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Karasu M, Berber İ, Karaca Y, Cansel M, Ulutaş Z. Unveiling cardiac insights: Exploring early left ventricular dysfunction in polycythemia vera through 4D-STE and fragmented QRS analysis. Echocardiography 2023; 40:1365-1373. [PMID: 37965911 DOI: 10.1111/echo.15715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 10/18/2023] [Accepted: 11/02/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND Polycythemia vera (PV), characterized by elevated red blood cell counts, poses challenges to cardiovascular health with potential impacts on cardiac function. Myocardial infarction (MI) and heart failure are major causes of mortality in PV patients. Early detection of left ventricular systolic dysfunction is crucial for optimizing outcomes. METHODS Fifty-two PV patients and 45 healthy controls were recruited. Four-dimensional speckle tracking echocardiography (4D-STE) and fragmented QRS complexes (fQRS) on electrocardiograms were utilized to assess cardiac mechanics. Hematological and echocardiographic parameters were measured, and statistical analyses were performed. RESULTS PV patients exhibited significantly higher hematocrit and red cell distribution width compared to controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) were lower in PV patients. fQRS complexes were associated with longer disease duration and reduced GCS and GAS values. Hematocrit correlated positively with LV-GCS and LV-GAS. Multiple linear regression revealed that disease duration and fQRS presence independently predicted LV-GAS. CONCLUSION This study underscores the intricate link between elevated red blood cell counts, disease duration, and cardiac function in PV patients. Combining 4D-STE and fQRS complexes enhances the identification of early left ventricular systolic dysfunction. These findings offer potential improvements in recognizing and managing cardiovascular complications in PV patients, with implications for future research and clinical practice. Further investigations are needed to elucidate underlying mechanisms and validate these markers in larger cohorts.
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Affiliation(s)
- Mehdi Karasu
- Department of Cardiology, Fethi Sekin Sehir Hastanesi, Elazıg, Turkey
| | - İlhami Berber
- İç hastalıkları ABD, Hematoloji BD, İnönü Üniversitesi, Malatya, Turkey
| | - Yücel Karaca
- Department of Cardiology, Fethi Sekin Sehir Hastanesi, Elazıg, Turkey
| | - Mehmet Cansel
- Department of Cardiology, İnönü Üniversitesi, Malatya, Turkey
| | - Zeynep Ulutaş
- Department of Cardiology, İnönü Üniversitesi, Malatya, Turkey
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Kuipers RS, Kok L, Virmani R, Tefferi A. Essential thrombocytosis: diagnosis, differential diagnosis, complications and treatment considerations of relevance for a cardiologist. Neth Heart J 2023; 31:371-378. [PMID: 36757576 PMCID: PMC10516821 DOI: 10.1007/s12471-023-01757-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2022] [Indexed: 02/10/2023] Open
Abstract
Essential thrombocytosis (ET) is a rare haematological malignancy, with an incidence rate of 1.5-2.5/100,000 per year. For many patients with ET the first manifestation of their underlying disease is a thrombotic or haemorrhagic complication. A recent retrospective study revealed an incidence rate of at least 2.1% in people under 40 years presenting with an acute coronary syndrome, although the diagnosis was initially missed in all cases. Thus, cardiologists face a much higher than average incidence rate of ET in their daily practice, but seem insufficiently aware of the disease. The current review summarises symptoms, (differential) diagnosis, complications and treatment considerations of ET of relevance for a cardiologist. Typical symptoms, besides thrombosis and haemorrhage, include erythromelalgia and aquagenic pruritus, while platelets > 450 × 109/l are a diagnostic for ET once other myeloproliferative neoplasms, secondary and spurious thrombocytosis have been excluded. With regard to treatment, timing of revascularisation depends on the presence of ischaemia and concurrent platelet counts. In the presence of ischaemia, revascularisation should not be delayed and adequate platelet counts can be achieved by platelet apheresis. In the absence of ischaemia, revascularisation can be delayed until adequate platelet counts have been achieved by cytoreductive therapies. Cardiologists should be aware of/screen for possible ET.
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Affiliation(s)
- R S Kuipers
- OLVG Heart Centre, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
- Department of Cardiology, Dijklander Hospital, Purmerend/Hoorn, The Netherlands.
| | - L Kok
- OLVG Heart Centre, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
- Department of Cardiology, Spaarne Hospital, Haarlem, The Netherlands
| | - R Virmani
- CVPath Institute, Gaithersburg, MD, USA
| | - A Tefferi
- Divisions of Hematology and Hematopathology, Mayo Clinic, Rochester, MN, USA
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Muacevic A, Adler JR, Verbeek EC, van de Wetering M, Voogel AJ, Oosterom L, Herrman JPR, Kuipers RS. Essential Thrombocytosis in Patients <40 Years Old With Acute Coronary Syndromes: A Not So Uncommon Underlying Diagnosis Often Overlooked. Cureus 2022; 14:e32638. [PMID: 36654555 PMCID: PMC9842111 DOI: 10.7759/cureus.32638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND In patients under <40 years, traditional cardiovascular (CV)-risk factors are a less likely cause of acute coronary syndromes (ACS) compared to older counterparts. AIMS To estimate the prevalence of essential thrombocytosis (ET), a hematological disorder and less-prevalent risk factor, in young patients presenting with ACS. METHODS We constructed a retrospective database of all patients <40 years (n=271) that had consecutively undergone coronary angiography (CAG) after their first ACS within our hospital within the last ten years (2010-2020) and had known thrombocyte counts (n=241). Patients with thrombocytes >450x10*9/L were screened for this hematological disorder. RESULTS In our database, we identified 15 subjects with thrombocytosis. One was previously known as ET. Of the remaining 14 patients, five were considered reactive/secondary thrombocytosis, and four were lost to follow-up, four were eventually diagnosed with ET, one remains uncertain. The diagnosis was newly established before the initiation of this study in two patients (average delay: six years). Two patients were identified as a result of this study. Conclusion: With a prevalence of at least 2.1%, ET appears not uncommon in patients <40 years with ACS. Moreover, screening patients with ACS and elevated thrombocytes yielded a novel diagnosis of ET in 27% of patients. The diagnosis was initially missed in all cases. Since the timing of revascularization should be adjusted to thrombocyte count/initiation of ET therapy to prevent thrombotic complications, cardiologists should know, recognize and screen for this pathology in ACS-patients, notably in those with absent traditional CV-risk factors: an 'ACS-protocol' aimed at less-prevalent risk factors could support this.
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Murphy AJ, Febbraio MA. Immune-based therapies in cardiovascular and metabolic diseases: past, present and future. Nat Rev Immunol 2021; 21:669-679. [PMID: 34285393 DOI: 10.1038/s41577-021-00580-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2021] [Indexed: 02/02/2023]
Abstract
Cardiometabolic disorders were originally thought to be driven primarily by changes in lipid metabolism that cause the accumulation of lipids in organs, thereby impairing their function. Thus, in the setting of cardiovascular disease, statins - a class of lipid-lowering drugs - have remained the frontline therapy. In the past 20 years, seminal discoveries have revealed a central role of both the innate and adaptive immune system in driving cardiometabolic disorders. As such, it is now appreciated that immune-based interventions may have an important role in reducing death and disability from cardiometabolic disorders. However, to date, there have been a limited number of clinical trials exploring this interventional strategy. Nonetheless, elegant preclinical research suggests that immune-targeted therapies can have a major impact in treating cardiometabolic disease. Here, we discuss the history and recent advancements in the use of immunotherapies to treat cardiometabolic disorders.
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Affiliation(s)
- Andrew J Murphy
- Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia.
| | - Mark A Febbraio
- Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
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Ielasi A, Loffi M, Buono A, De Blasio G, Tespili M. Intracoronary cangrelor administration-assisted primary percutaneous coronary intervention in a patient with essential thrombocythemia and recurrent ST-segment elevation myocardial infarction. J Cardiovasc Med (Hagerstown) 2021; 21:825-828. [PMID: 32740411 DOI: 10.2459/jcm.0000000000001006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Alfonso Ielasi
- Clinical and Interventional Cardiology Unit, Sant'Ambrogio Cardio-Thoracic Center GSD, Milan
| | - Marco Loffi
- Cardiology Unit, Azienda Socio Sanitaria Territoriale (ASST) di Cremona, Cremona
| | - Andrea Buono
- Clinical and Interventional Cardiology Unit, Sant'Ambrogio Cardio-Thoracic Center GSD, Milan
| | | | - Maurizio Tespili
- Clinical and Interventional Cardiology Unit, Sant'Ambrogio Cardio-Thoracic Center GSD, Milan
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Cengiz B, Aytekin V, Bildirici U, Sahin ST, Yurdakul S, Aytekin S, Kucukkaya R. A rare cause of acute coronary syndromes in young adults - myeloproliferative neoplasms: A case series. Rev Port Cardiol 2019; 38:613-617. [PMID: 31784298 DOI: 10.1016/j.repc.2018.09.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 09/12/2018] [Accepted: 09/30/2018] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Acute coronary syndromes (ACS) mostly occur in patients with traditional risk factors. Especially in young adults without major cardiovascular (CV) risk factors, one of the less common causes of ACS is myeloproliferative neoplasms (MPNs). METHODS We retrospectively collected data on 11 consecutive patients (nine men, two women, mean age 40.18±8.4 years) with a diagnosis of MPN who presented with ACS. The demographic characteristics of the study population, type of MPN, clinical manifestations, location of myocardial infarction (MI), coronary angiography findings, complete blood count and other related findings, and treatment strategy before and after diagnosis were analyzed. RESULTS Six patients were diagnosed with polycythemia vera, four with essential thrombocytosis and one with primary myelofibrosis. A JAK2 mutation was found in nine patients. Mean time to diagnosis of MPN was 2.81 years after presenting ACS and mean age at first MI was 32.9±6 years. Six patients had no major CV risk factors. Ten patients had anterior MI and one had inferior MI. After initiation of specific treatment for MPN, no recurrent thrombotic events were observed in a mean follow-up of 4±2.44 years. CONCLUSIONS In young adults presenting with ACS, MPNs should be considered, especially in the absence of atherosclerotic coronary artery lesions. It is also important to pay attention to blood cell count abnormalities seen in intracoronary thrombotic events. Early diagnosis and treatment of MPNs is essential to prevent recurrence of thrombotic events and may reduce mortality and morbidity related to thrombotic complications.
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Affiliation(s)
- Betul Cengiz
- Department of Cardiology, Istanbul Bilim University, Istanbul, Turkey
| | - Vedat Aytekin
- Department of Cardiology, Florence Nightingale Hospital, Istanbul, Turkey
| | - Ulas Bildirici
- Department of Cardiology, Kocaeli University Faculty of Medicine, Koaceli, Turkey
| | | | - Selen Yurdakul
- Department of Cardiology, Istanbul Bilim University, Istanbul, Turkey
| | - Saide Aytekin
- Department of Cardiology, Florence Nightingale Hospital, Istanbul, Turkey.
| | - Reyhan Kucukkaya
- Department of Internal Medicine, Istanbul Bilim University, Istanbul, Turkey
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Cengiz B, Aytekin V, Bildirici U, Sahin ST, Yurdakul S, Aytekin S, Kucukkaya R. A rare cause of acute coronary syndromes in young adults – myeloproliferative neoplasms: A case series. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2019. [DOI: 10.1016/j.repce.2019.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Gurrieri C, Smith BB, Nuttall GA, Pruthi RK, Said SM, Smith MM. Essential Thrombocythemia and Cardiac Surgery: A Case Series and Review of the Literature. Ann Thorac Surg 2018; 106:482-490. [DOI: 10.1016/j.athoracsur.2018.03.057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 02/09/2018] [Accepted: 03/19/2018] [Indexed: 10/17/2022]
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Shintaku M, Miura S, Asagoe K, Yutani C. Chronic recurrent pulmonary thromboembolism in a patient with essential thrombocythemia, complicating acute right ventricular infarct. Pathol Int 2018; 68:202-204. [PMID: 29318735 DOI: 10.1111/pin.12622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Masayuki Shintaku
- Department of Pathology, Shiga Medical Center for Adults, Moriyama, Shiga
| | - Satoshi Miura
- Department of Hematology and Oncology, Shiga Medical Center for Adults, Moriyama, Shiga
| | - Kohsuke Asagoe
- Department of Hematology and Oncology, Shiga Medical Center for Adults, Moriyama, Shiga
| | - Chikao Yutani
- Department of Pathology, Amagasaki Central Hospital, Amagasaki, Hyogo, Japan
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10
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Michiels JJ. Aspirin responsive erythromelalgia in JAK2-thrombocythemia and incurable inherited erythrothermalgia in neuropathic Nav1.7 sodium channelopathy: from Mitchell 1878 to Michiels 2017. Expert Opin Orphan Drugs 2016. [DOI: 10.1080/21678707.2017.1270822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Jan Jacques Michiels
- Department of Hematology & Coagulation, Academic Hospital Dijkzigt and Erasmus University, Rotterdam, The Netherlands
- Department of Blood and Coagulation Disorders, University Hospital Antwerp, Edegem, Belgium
- Blood, Coagulation and Vascular Medicine Research Center, Goodheart Institute & Foundation in Nature Medicine & Health, Freedom of Science and Education, European Free University, Erasmus Tower, Rotterdam
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11
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Gül C, Kürüm T, Demir M, Ozbay G, Vural O, Iqbal O, Fareed J. Acute Myocardial Infarction in a Patient with Essential Thrombocythemia Treated with Glycoprotein Ilb/Illa Inhibitor. Clin Appl Thromb Hemost 2016; 10:77-9. [PMID: 14979411 DOI: 10.1177/107602960401000114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Essential thrombocythemia (ET) rarely causes obstruction of coronary arteries or acute myocardial infarction. Treatment of acute myocardial infarction in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. There is no reported case of acute myocardial infarction with essential thrombocythemia treated with a glycoprotein lIb/Illa inhibitor. In this report, a 49-year-old woman with essential thrombocythemia, admitted with a diagnosis of acute inferolateral myocardial infarction, was treated with tirofiban, a glycoprotein IIb/IIIa receptor blocker.
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Affiliation(s)
- Cetin Gül
- Department of Cardiology, Division of Hematology, Trakya University, Edirne, Turkey
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12
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Murphy AJ, Tall AR. Disordered haematopoiesis and athero-thrombosis. Eur Heart J 2016; 37:1113-21. [PMID: 26869607 PMCID: PMC4823636 DOI: 10.1093/eurheartj/ehv718] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 11/22/2015] [Accepted: 12/07/2015] [Indexed: 12/25/2022] Open
Abstract
Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis.
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Affiliation(s)
- Andrew J Murphy
- Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia Department of Immunology, Monash University, Melbourne, Victoria 3165, Australia
| | - Alan R Tall
- Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA
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13
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Khaheshi I, Memaryan M, Taherkhani M, Serati A, Movahed MR. Acute ST-segment elevation myocardial infarction as the first manifestation of essential thrombocytosis successfully treated with thrombectomy alone. Cardiovasc Interv Ther 2015; 31:275-8. [PMID: 26296385 DOI: 10.1007/s12928-015-0347-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 07/14/2015] [Indexed: 10/23/2022]
Abstract
A patient with no conventional cardiovascular risk factors presented with inferior ST-elevation myocardial infarction which was finally diagnosed as a case of essential thrombocytosis. This case demonstrated that thrombectomy alone was sufficient for the treatment of his coronary occlusion. Furthermore, this case report highlights the importance of evaluating rare causes of myocardial infarction other than atherosclerosis and that internists and cardiologists should be aware of essential thrombocytosis as a known cause of myocardial infarction, particularly in patients with no underlying cardiovascular risk factors.
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Affiliation(s)
- Isa Khaheshi
- Cardiovascular Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Memaryan
- Cardiovascular Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Taherkhani
- Cardiovascular Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Serati
- Cardiovascular Research Center, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Movahed
- CareMore Arizona, 7091 East Speedway, Tucson, AZ, 85710, USA. .,University of Arizona College of Medicine, Tucson, AZ, USA.
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Tsai MS, Chou SE, Lai HS, Jeng LB, Lin CL, Kao CH. Long-term risk of acute coronary syndrome in splenectomized patients due to splenic injury. Medicine (Baltimore) 2015; 94:e610. [PMID: 25738485 PMCID: PMC4553951 DOI: 10.1097/md.0000000000000610] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We aimed to assess the magnitude and duration of risk of acute coronary syndrome (ACS) associated with splenectomy for splenic injury.We identified 5139 splenectomized patients (the splenectomy cohort) to compare with 2 other cohorts for assessing the magnitude and risk of ACS: the first cohort comprising subjects without splenic injury and without splenectomy (control cohort), and the second cohort comprising nonsplenectomized patients with splenic injury (nonsplenectomy cohort; n = 6391). For each splenic injury patient (n = 11530), 4 control comparisons were frequency-matched by the year of index date, age, and sex (n = 46120).The adjusted risk of ACS was significantly higher in the splenectomy group than in the control group (2.08 vs 1.68 per 1000 person-years; adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.01-1.68). The sex-specific data showed that the adjusted HR for the splenectomy group, compared with the control group, was 1.29 in men (95% CI, 0.97-1.73) and 1.36 in women (95% CI, 0.79-2.33). The age-specific analyses failed to demonstrate a significantly higher adjusted HR of ACS in the splenectomized patients in any age subgroup, compared with their counterparts in the control group. Furthermore, no difference in the risk of ACS was detected between the splenectomy and nonsplenectomy cohorts within the splenic injury patients.In comparison with the control cohort, patients undergoing splenectomy for splenic injury exhibited an elevated risk of ACS.
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Affiliation(s)
- Ming-Shian Tsai
- From the Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung (M-ST, S-EC); Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei (H-SL); Department of Surgery, Organ Transplantation Center, China Medical University Hospital (L-BJ); Graduate Institute of Clinical Medical Science, China Medical University (L-BJ, C-HK); Management Office for Health Data, China Medical University Hospital (C-LL); College of Medicine, China Medical University (C-LL); and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (C-HK)
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Darwazah AK, Madi H, Zagha R, Hawash Y. Off-pump myocardial revascularization in a high-risk patient with essential thrombocythemia. Tex Heart Inst J 2014; 41:537-42. [PMID: 25425991 DOI: 10.14503/thij-13-3508] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Essential thrombocythemia is a rare type of myeloproliferative disorder. Cerebral, myocardial, and peripheral thrombosis are all frequent complications of the disease. A 71-year-old man presented with severe coronary artery disease, associated with cerebral vascular ischemic changes and erythromelalgia. His platelet count was 1,486 ×10(3)/μL. The patient underwent successful myocardial revascularization by means of an off-pump technique after his platelet count had been reduced by hydroxycarbamide administration. We conclude that the use of off-pump cardiopulmonary bypass in high-risk patients with essential thrombocythemia is safe. Reducing platelet count via the administration of hydroxycarbamide and the careful balancing of antiplatelets and anticoagulants is crucial in determining the outcome of surgery.
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Michiels JJ, Berneman Z, Gadisseur A, Lam KH, De Raeve H, Schroyens W. Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia vera. Acta Haematol 2014; 133:56-63. [PMID: 25116182 DOI: 10.1159/000360388] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Accepted: 02/04/2014] [Indexed: 01/03/2023]
Abstract
Migraine-like cerebral transient ischemic attacks (MIAs) and ocular ischemic manifestations were the main presenting features in 10 JAK2(V617F)-positive patients studied, with essential thrombocythemia (ET) in 6 and polycythemia vera (PV) in 4. Symptoms varied and included cerebral ischemic attacks, mental concentration disturbances followed by throbbing headaches, nausea, vomiting, syncope or even seizures. MIAs were frequently preceded or followed by ocular ischemic events of blurred vision, scotomas, transient flashing of the eyes, and sudden transient partial blindness preceded or followed erythromelalgia in the toes or fingers. The time lapse between the first symptoms of aspirin-responsive MIAs and the diagnosis of ET in 5 patients ranged from 4 to 12 years. At the time of erythromelalgia and MIAs, shortened platelet survival, an increase in the levels of the platelet activation markers β-thromboglobulin and platelet factor 4 and also in urinary thromboxane B2 were clearly indicative of the spontaneous in vivo platelet activation of constitutively JAK2(V617F)-activated thrombocythemic platelets. Aspirin relieves the peripheral, cerebral and ocular ischemic disturbances by irreversible inhibition of platelet cyclo-oxygenase (COX-1) activity and aggregation ex vivo. Vitamin K antagonist, dipyridamole, ticlopidine, sulfinpyrazone and sodium salicylate have no effect on platelet COX-1 activity and are ineffective in the treatment of thrombocythemia-specific manifestations of erythromelalgia and atypical MIAs. If not treated with aspirin, ET and PV patients are at a high risk of major arterial thrombosis including stroke, myocardial infarction and digital gangrene.
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17
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Michiels JJ, Ten Kate FWJ, Koudstaal PJ, Van Genderen PJJ. Aspirin responsive platelet thrombophilia in essential thrombocythemia and polycythemia vera. World J Hematol 2013; 2:20-43. [DOI: 10.5315/wjh.v2.i2.20] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2012] [Accepted: 01/06/2013] [Indexed: 02/05/2023] Open
Abstract
Essential thrombocythemia (ET) and polycythemia vera (PV) frequently present with erythromelalgia and acrocyanotic complications, migraine-like microvascular cerebral and ocular transient ischemic attacks (MIAs) and/or acute coronary disease. The spectrum of MIAs in ET range from poorly localized symptoms of transient unsteadiness, dysarthria and scintillating scotoma to focal symptoms of transient monocular blindness, transient mono- or hemiparesis or both. The attacks all have a sudden onset, occur sequentially rather than simultaneously, last for a few seconds to several minutes and are usually associated with a dull, pulsatile or migraine-like headache. Increased hematocrit and blood viscosity in PV patients aggravate the microvascular ischemic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Phlebotomy to correct hematocrit to normal in PV significantly reduces major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated erythromelalgia and MIAs. Complete long-term relief of the erythromelalgic microvascular disturbances, MIAs and major thrombosis in ET and PV patients can be obtained with low dose aspirin and platelet reduction to normal, but not with anticoagulation. Skin punch biopsies from the erythromelalgic area show fibromuscular intimal proliferation of arterioles complicated by occlusive platelet-rich thrombi leading to acrocyanotic ischemia. Symptomatic ET patients with erythromelalgic microvascular disturbances have shortened platelet survival, increased platelet activation markers β-thromboglobulin (β-TG), platelet factor 4 (PF4) and thrombomoduline (TM), increased urinary thromboxane B2 (TXB2) excretion, and no activation of the coagulation markers thrombin fragments F1+2 and fibrin degradation products. Inhibition of platelet cyclooxygenase (COX1) by aspirin is followed by the disappearance and no recurrence of microvascular disturbances, increase in platelet number, correction of the shortened platelet survival times to normal, and reduction of increased plasma levels of β-TG, PF4, TM and urinary TXB2 excretion to normal. These results indicate that platelet-mediated fibromuscular intimal proliferation and platelet-rich thrombi in the peripheral, cerebral and coronary end-arterial microvasculature are responsible for the erythromelalgic ischemic complications, MIAs and splanchnic vein thrombosis. Baseline platelet P-selectin levels and arachidonic acid induced COX1 mediated platelet activation showed a highly significant increase of platelet P-selectin expression (not seen in ADP and collagen stimulated platelets), which was significantly higher in JAK2V617F mutated compared to JAK2 wild type ET.
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Cheng CW, Hung MJ. Coronary spasm-related acute myocardial infarction in a patient with essential thrombocythemia. World J Cardiol 2011; 3:278-80. [PMID: 21876778 PMCID: PMC3163243 DOI: 10.4330/wjc.v3.i8.278] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Revised: 07/18/2011] [Accepted: 07/25/2011] [Indexed: 02/06/2023] Open
Abstract
We report a case of essential thrombocythemia (ET) in a 30-year-old female who exhibited inferior wall ST-elevation acute myocardial infarction (AMI) without significant obstructive coronary artery disease. Right coronary vasospasm was observed after intra-coronary methylergonovine administration and she received verapamil 120 mg/dthereafter and hydroxyurea 1500 mg/d for thrombocythemia. After discontinuation of the hydroxyurea for 9 mo based on the impression of coronary spasm-related instead of coronary thrombosis-related AMI, her platelet count rose but no chest pain was observed. It is suggested that coronary spasm potentially plays a role in patients with ET, AMI and no significant coronary artery stenosis.
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Affiliation(s)
- Chi-Wen Cheng
- Chi-Wen Cheng, Ming-Jui Hung, Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung City 20401, Taiwan, China
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Zhang Z, Wan X, Liu Y, Lin X, Ni Z, Yang X, Zhang L. Non-ST-segment Elevation Myocardial Infarction in a Patient With Essential Thrombocythemia Treated With Glycoprotein IIb/IIIa Inhibitor. Clin Appl Thromb Hemost 2010; 17:532-4. [PMID: 20724303 DOI: 10.1177/1076029610379846] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Essential thrombocythemia (ET) can cause systemic vascular thrombosis but rarely cause obstruction of coronary arteries or acute myocardial infarction (MI). Treatment of acute MI in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. In this report, a 63-year-old man presented with acute chest pain and a greatly increased platelet count. The patient was successfully treated with intravenous tirofiban, a glycoprotein IIb/IIIa receptor blocker. Essential thrombocythemia was diagnosed based on bone marrow findings, clinical presentation, and laboratory analysis. Thrombocythemia had been controlled with hydroxyurea.
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Affiliation(s)
- Zhiyong Zhang
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xinhong Wan
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yuanyuan Liu
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xiangmin Lin
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Zhuhua Ni
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xinchun Yang
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lin Zhang
- Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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20
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Michiels JJ, Berneman Z, Schroyens W, Koudstaal PJ, Lindemans J, Neumann HAM, van Vliet HHDM. Platelet-mediated erythromelalgic, cerebral, ocular and coronary microvascular ischemic and thrombotic manifestations in patients with essential thrombocythemia and polycythemia vera: a distinct aspirin-responsive and coumadin-resistant arterial thrombophilia. Platelets 2007; 17:528-44. [PMID: 17127481 DOI: 10.1080/09537100600758677] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Microvascular circulation disturbances including erythromelalgia, its microvascular ischemic complications, and migraine-like atypical or typical transient ischemic cerebral, ocular, and coronary ischemic attacks are specific clinical manifestations in patients with essential thrombocythemia (ET), and polycythemia vera (PV) associated with thrombocythemia. Thrombocythemia (ET and PV) patients with microvascular disturbances have shortened platelet survival, increased beta-thromboglobulin (beta-tg), platelet factor 4 (PF4), and thrombomoduline (TM) levels, and increased urinary thromboxane B2 (TxB2) excretion indicating platelet-mediated processes in vivo. Inhibition of platelet cyclooxygenase (COX 1) by aspirin is followed by relief of microvascular disturbances, correction of shortened platelet survival, and return of plasma levels of beta-tg, PF4, TM levels and TxB2 excretion to normal. The transient ischemic attacks and thrombotic complications in thrombocythemia are very likely caused by hypersensitive platelets produced by spontaneously proliferating enlarged megakaryocytes in the bone marrow of ET and PV patients. In contrast to normal platelets in healthy individuals the circulating hypersensitive thrombocythemic platelets spontaneously activate and secrete their products, thus forming aggregates that transiently plug the microcirculation, or result in occlusive platelet thrombi in arterioles or small arteries. Clear evidence is presented that the microvascular transient ischemic and occlusive thrombotic complications in thrombocythemia patients are relieved by treatment with aspirin and by reduction of platelet counts to normal (<400 x 109/l), but not by coumadin. In patients with thrombocythemia associated with PV, increased hematocrit and whole blood viscosity aggravate the platelet-mediated microvascular ischemic and thrombotic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Correction of hematocrit and blood viscosity by phlebotomy significantly reduces the major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated microvascular circulation disturbances in PV patients because thrombocythemia persists. Complete relief and prevention of microvascular and major thrombosis in PV patients are obtained by treatment with low-dose aspirin on top of phlebotomy or by treatment with the platelet lowering agents, anagrelide, interferon or hydroxyurea.
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Affiliation(s)
- Jan Jacques Michiels
- Department of Hematology, University Hospital Antwerp, Hemostasis Thrombosis Research, Antwerp, Belgium.
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21
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Landolfi R, Cipriani MC, Novarese L. Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: Pathogenetic mechanisms and prevention. Best Pract Res Clin Haematol 2006; 19:617-33. [PMID: 16781491 DOI: 10.1016/j.beha.2005.07.011] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Polycythemia vera and essential thrombocythemia are chronic myeloproliferative disorders, the benign clinical course of which can be complicated by both thrombotic and hemorrhagic diatheses. Thrombotic diathesis is characterized by microcirculatory disturbances and by an increased risk of arterial and venous thromboses. Thrombotic accidents often manifest at diagnosis or in the preclinical phase of the disease so that the search for a latent myeloproliferative disorder has become widely recommended in screenings for acquired thrombophilia, particularly when venous thromboses manifest at an unusual site. Hemorrhagic diathesis is more rare, less ominous and mostly affects patients with a very high platelet count. In these subjects, an altered degradation and function of von Willebrand factor can cause minor mucocutaneous hemorrhages, which are sometimes a prelude to major gastrointestinal bleedings. The bleeding tendency can be effectively treated by cytoreduction. Pathogenesis and treatment of thrombotic diathesis are still controversial. The nature of disease-related hemostatic abnormalities and the role of common risk factors are far from being elucidated. In polycythemic subjects, treatment of blood hyperviscosity is essential and low-dose aspirin, which has an established antithrombotic efficacy, should always be used in the absence of contraindications. These are mostly constituted by conditions of increased bleeding risk, which, in particular, have to be evaluated when considering aspirin use in patients with essential thrombocythemia. Future clinical research should primarily aim to assess the risk/benefit ratio of aspirin use in this disease, to better characterize the determinants of vascular risk and to reduce the high incidence of leukemias in patients with these diseases. This might require either the availability of safer cytoreductive agents or, alternatively, the use of more aggressive antiplatelet regimens in patients at high thrombotic risk.
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Affiliation(s)
- Raffaele Landolfi
- Internal Medicine Head of Hemostasis and Thrombosis Unit, Catholic University of Rome, Italy.
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22
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Michiels JJ, Berneman Z, Schroyens W, Koudstaal PJ, Lindemans J, van Vliet HHDM. Platelet-mediated thrombotic complications in patients with ET: Reversal by aspirin, platelet reduction, and not by coumadin. Blood Cells Mol Dis 2006; 36:199-205. [PMID: 16510297 DOI: 10.1016/j.bcmd.2005.12.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2005] [Accepted: 12/16/2005] [Indexed: 12/22/2022]
Abstract
The broad spectrum of aspirin-sensitive erythromelalgia, its microvascular ischemic complications, migraine-like atypical or typical transient ischemic attacks (cerebral and ocular) as well as acute coronary syndromes in thrombocythemia vera (essential thrombocythemia and thrombocythemia associated with polycythemia vera in maintained remission by phlebotomy) is caused by platelet cyclo-oxygenase-mediated arteriolar inflammation, fibromuscular intimal proliferation without and with occlusive thrombosis by platelet-rich thrombi in the end-arterial microvasculature of the peripheral, cerebral, ocular and coronary circulation. These microvascular ischemic and thrombotic complications does not respond to Coumadin, but are immediately relieved by a loading dose of 500 mg aspirin, and does not recur when the patient is maintained on low dose aspirin (50 mg per day) or after reduction of platelet counts to normal (<400.000/microl).
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Affiliation(s)
- Jan Jacques Michiels
- Hemostasis Thrombosis Research, Department of Hematology, University Hospital Antwerp, Belgium.
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23
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Michiels JJ, Berneman ZN, Schroyens W, Van Vliet HHDM. Pathophysiology and treatment of platelet-mediated microvascular disturbances, major thrombosis and bleeding complications in essential thrombocythaemia and polycythaemia vera. Platelets 2004; 15:67-84. [PMID: 15154599 DOI: 10.1080/09537100310001646969] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Essential thrombocythaemia (ET) is associated with a broad spectrum of microvascular circulation disturbances including erythromelalgia and its ischaemic complications, episodic neurological symptoms of atypical and typical transient ischaemic attacks (TIAs), transient ocular ischaemic attacks, acute coronary syndromes, and superficial 'thrombophlebitis'. The microvascular circulation disturbances are caused by spontaneous activation and aggregation of hypersensitive thrombocythaemic platelets at high shear stress in the endarterial microcirculation involving the peripheral, cerebral and coronary circulation. As this microvascular syndrome is a pathognomonic feature of essential thrombocythaemia and of thrombocythaemia associated with polycythaemia vera (PV) in complete remission with normal haematocrit, we have labelled these two variants of thrombocythaemia as thrombocythaemia vera. The arterial thrombophilia of microvascular circulation disturbances in thrombocythaemia vera already occur at platelet counts in excess of 400 x 10(9)/l. Complete relief of microvascular circulation disturbances in thrombocythaemia vera is obtained with the platelet cyclooxygenase inhibitor aspirin 50-100 mg/day, but not with dipyridamole, ticlopidine, coumarin or heparin. Haemorrhagic thrombocythaemia (HT) is a clinical syndrome of recurrent spontaneous mucocutaneous and secondary haemorrhages associated with extremely high platelet counts far in excess of 1000 x 10(9)/l. The paradoxical occurrence of microvascular circulation disturbances and mucocutaneous bleeding is usually seen at platelet counts between 1000 and 2000 x 10(9)/l. At increasing platelet counts from below 1000 to in excess of 2000 x 10(9)/l, the arterial thrombophilia of thrombocythaemia vera changes into a spontaneous bleeding tendency of HT as a consequence of platelet-mediated increased proteolysis of the large von Willebrand factor multimers leading to a type 2 acquired von Willebrand syndrome. As PV is usually associated with thrombocythaemia, the vascular complications in PV patients are microvascular circulation disturbances typical of thrombocythaemia. On top of this, major arterial and venous thrombotic events and haemorrhages are related to increased haematocrit, red cell mass and its concomitant increased blood viscosity. Correction of increased blood viscosity and haematocrit to normal values (0.40-0.44) by bloodletting alone will significantly reduce the risk of major thrombotic complications, but does not prevent the microvascular circulation disturbances because thrombocythaemia persists. The microvascular syndrome associated with thrombocythaemia in PV patients in remission after bloodletting is best controlled by low-dose aspirin (50-100 mg/day) or by reduction of platelet count to normal (< 350 x 10(9)/l).
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Affiliation(s)
- Jan Jacques Michiels
- Department of Haematology, Haemostasis Thrombosis Research, University Hospital Antwerp, Antwerp, Belgium.
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24
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Abstract
Essential thrombocythemia is a distinct clinical entity within the spectrum of myeloproliferative disorders. There is as yet no pathognomonic diagnostic test, and patients who currently fall into the category of essential thrombocythemia are likely to be heterogeneous. This article discusses diagnostic criteria, clinical features, prognosis, and management.
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Affiliation(s)
- Claire N Harrison
- Department of Haematology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
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25
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Fujimura M, Akaike M, Kato M, Takamori N, Abe M, Nishiuchi T, Azuma H, Matsumoto T. Aggressive antiplatelet therapy before coronary stent implantation in acute coronary syndrome with essential thrombocythemia--a case report. Angiology 2003; 54:485-90. [PMID: 12934770 DOI: 10.1177/000331970305400414] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
A 52-year-old man was admitted to the hospital because of unstable angina pectoris. Coronary angiography revealed severe stenosis at a proximal site of the left anterior descending artery. Essential thrombocythemia (ET) was diagnosed on the basis of findings of marked thrombocytosis (106 x 10(4)/microL) and an increased number of immature megakaryocytes in the bone marrow. Because hyperaggregability of platelets was demonstrated by an ex vivo platelet aggregation assay and by elevated plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), antiplatelet therapy with aspirin and ticlopidine and cytoreduction therapy with hydroxyurea were started. This combination treatment resulted in a decrease in the platelet count to less than 60 x 10(4)/microL and decreases in plasma levels of both beta-TG and PF4 to almost normal values. Percutaneous coronary angioplasty and stenting were then performed successfully without thrombotic complications. These findings suggest that combination therapy with antiplatelet and cytoreduction agents before catheter intervention is useful for the prevention of thrombotic complications in patients with acute coronary syndrome associated with essential thrombocythemia.
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Affiliation(s)
- Mitsunori Fujimura
- First Department of Internal Medicine, University of Tokushima School of Medicine, Kuramoto-3-18-15, Tokushima 770-8503, Japan.
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26
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Michiels JJ. Platelet-mediated microvascular inflammation and thrombosis in thrombocythemia vera: a distinct aspirin-responsive arterial thrombophilia, which transforms into a bleeding diathesis at increasing platelet counts. PATHOLOGIE-BIOLOGIE 2003; 51:167-75. [PMID: 12781799 DOI: 10.1016/s0369-8114(03)00038-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Erythromelalgia is the main, pathognomonic and presenting symptom in patients with essential thrombocythemia and thrombocythemia associated with polycythemia vera. Complete relief from erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine. Thus, cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers beta-thromboglobulin, thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients suffering from erythromelalgia. Aspirin treatment of erythromelalgia in thrombocythemia patients resulted in the disappearance of the erythromelalgic, thrombotic signs and symptoms, correction of the shortened platelet survival times, and a significant reduction of the increased levels of beta-TG, PF4, TM and urinary TxB2 excretion to normal. Erythromelalgia is frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic symptoms, which specifically respond to low-dose aspirin or reduction of platelet counts to normal. The broad spectrum of acropareshesias, erythromelalgia and acrocyanotic ischemia together with the episodic and transient atypical TIAs and ocular or coronary ischemic symptoms are caused by spontaneous activation and aggregation of hypersensitive platelets in the end-arterial microvasculature involving the peripheral, cerebral and coronary circulation of thrombocythemia patients. These microvascular circulation ischemic disturbances in thrombocythemia vera already occur at platelet counts in excess of 400 x 10(9) l(-1). Low-dose aspirin is highly effective and safe in the cure and prevention of thrombotic and ischemic events and does not elicit bleedings at platelet counts below 1000 x 10(9) l(-1). Spontaneous hemorrhages usually occur at very high platelet counts far in excess of 1000 x 10(9) l(-1) (HT) due to an acquired von Willebrand factor deficiency at increasing platelet counts. At platelet counts between 1000 and 2000 x 10(9) l(-1), thrombosis and bleeding (ETT and HT) frequently occur in sequence or paradoxically and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count to below 1000 x 10(9) l(-1) by platelet lowering agents usually results in the disappearance of the bleeding tendency and improvement of the von Willebrand syndrome, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal.
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Affiliation(s)
- J J Michiels
- Hemostasis, Thrombosis and Vascular Research, Department of Hematology, University Hospital, Antwerp, Belgium.
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Affiliation(s)
- Claire N Harrison
- Department of Haematology, Guy's and St Thomas' Hospital NHS Trust, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
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28
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Laguna MS, Kornblihtt LI, Marta RF, Michiels JJ, Molinas FC. Effectiveness of anagrelide in the treatment of symptomatic patients with essential thrombocythemia. Clin Appl Thromb Hemost 2000; 6:157-61. [PMID: 10898276 DOI: 10.1177/107602960000600307] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
We prospectively evaluated the effect of anagrelide on platelet counts and the clinical manifestations of microvascular circulation disturbances in 17 newly diagnosed patients with essential thrombocythemia. Ten patients had symptoms related to thrombocythemia, eight at the time of starting anagrelide treatment. The platelet counts before anagrelide treatment and during maintained remission of essential thrombocythemia by anagrelide were 980 (range, 610-2030) and 378 (range, 212-546) x 10(9)/L, respectively. Spontaneous platelet aggregation was found in 6 patients (35%), which disappeared on remission of essential thrombocythemia in five cases (P = 0.02). Essential thrombocythemia-related microvascular thrombotic and hemorrhagic symptoms disappeared with the normalization of platelet count in all cases during maintained remission of essential thrombocythemia by long term continuous anagrelide treatment with a follow-up period of between 2 and 6 years. However, ET-related symptoms reappeared in three patients, coinciding with increased platelet count up to 600 x 10(9)/L caused by anagrelide dose reduction. We conclude that reduction of increased platelet to normal (< 400 x 10(9)/L) in symptomatic patients with essential thrombocythemia through use of maintained anagrelide treatment is associated with the disappearance of spontaneous platelet aggregation and the complete relief of thrombotic and hemorrhagic manifestations.
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Affiliation(s)
- M S Laguna
- Sección Hematología Investigación, Instituto de Investigaciones Médices Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina
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Michiels JJ, Barbui T, Finazzi G, Fuchtman SM, Kutti J, Rain JD, Silver RT, Tefferi A, Thiele J. Diagnosis and treatment of polycythemia vera and possible future study designs of the PVSG. Leuk Lymphoma 2000; 36:239-53. [PMID: 10674896 DOI: 10.3109/10428190009148845] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The present study describes clinicopathological criteria to distinguish the 5 sequential stages proposed by Wasserman et al in the natural history of newly diagnosed PV patients. The European Working Group on MPD (EWG.MPD) extended and modified the PVSG diagnostic criteria of PV by including bone marrow histopathology. From the results of prospective randomized studies in PV it became evident that new clinical trials in previously untreated PV patients should focus on comparing interferon-alpha, a non-leukemogenic approach, versus a potential leukemogenic myelosuppressive treatment modality. Hydroxyurea appears to be the least leukemogenic myelosuppressive agent in long-term prospective clinical PV-studies extending observation periods of more than 10 years. The rational for using IFN-alpha as a first-line treatment option in newly diagnosed PV-patient include its effectiveness to abate constitutional symptoms and to induce a complete remission thereby avoiding phlebotomy, iron deficiency, and macrocytosis associated with hydroxyurea. Moreover IFN-alpha may prevent or delay the development of postpolycythemic myelofibrosis if used early in the course of the disease. Clinicians will be reluctant to postpone the use of hydroxyurea in early stage PV as long as a conservative approach using phlebotomy aiming at a hematocrit below 0.45, plus low-dose aspirin for the control platelet function or anagrelide for the control platelet number is used to keep the patient healthy. Low-dose aspirin will prevent the microvascular thrombotic complications of thrombocythemia associated with PV in remission after phlebotomy, but lacks myelosuppressive activity. Control of megakaryocyte maturation and reduction of platelet production to normal (<400 x 10(9)/l) by relatively low doses of anagrelide will predict a significant reduction of vascular complications in the early stages of PV, may prevent progression to myelofibrosis during follow-up of PV and very probable will postpone the use of hydroxyurea treatment for controlling the platelet count in PV. Large scale randomized clinical trials in PV are proposed, which should aim not only for clinical and hematological response, safety, efficacy, but should also assess toxicity, the need for phlebotomy and whether the development of progressive disease such as splenomegaly, pruritus, myelofibrotic myeloid metaplasia, spent phase, myelodysplasia and acute leukemia can be delayed or prevented by IFN-alpha as compared to a conservative approach of phlebotomy plus low-dose aspirin or anagrelide followed by hydroxyurea when signs of myeloproliferative activity became evident.
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Affiliation(s)
- J J Michiels
- Goodheart Institute, Rotterdam, The Netherlands.
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30
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Michiels JJ. Acquired von Willebrand disease due to increasing platelet count can readily explain the paradox of thrombosis and bleeding in thrombocythemia. Clin Appl Thromb Hemost 1999; 5:147-51. [PMID: 10725999 DOI: 10.1177/107602969900500301] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
The arterial microvascular thrombotic events in thrombocythemia including erythromelalgia, atypical and typical cerebral and ocular transient ischemic attacks, and acute coronary syndromes already occur at platelet counts > 400 x 10(9)/L and are sensitive to low-dose aspirin, which does not elicit bleedings at platelet counts < 1,000 x 10(9)/L. An increasing platelet count in thrombocythemia to above 1,000 x 10(9)/L is accompanied by the acquisition of a von Willebrand factor deficiency due to the loss of intermediate and large von Willebrand factor multimers. The arterial thrombotic condition in thrombocythemia changes into an overt spontaneous bleeding tendency at mean platelet counts of about 2,000 +/- 1,000 x 10(9)/L due to an acquired von Willebrand disease type II with normal values for von Willebrand factor antigen concentration but absence of intermediate and large von Willebrand factor multimers in plasma. At platelet counts between 1,000 and 2,000 x 10(9)/L, thrombosis and bleeding frequently occur in sequence or paradoxically, and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count < 1,000 x 10(9)/L significantly restores the von Willebrand factor deficiency with the reappearance of the intermediate and some of the large von Willebrand factor multimers and the disappearance of the bleeding tendency, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal. The acquisition of von Willebrand factor deficiency at increasing platelet counts can readily explain the paradox of thrombosis and bleeding in thrombocythemia and has important clinical implications.
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Affiliation(s)
- J J Michiels
- Goodheart Institute Rotterdam, European Working Group on Myeloproliferative Disorders, Amsterdam, The Netherlands
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31
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Michiels JJ. Normal life expectancy and thrombosis-free survival in aspirin treated essential thrombocythemia. Clin Appl Thromb Hemost 1999; 5:30-6. [PMID: 10725980 DOI: 10.1177/107602969900500107] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Focusing on platelet-mediated erythromelalgia as a specific, presenting, and single sign of essential thrombocythemia (ET) we were able to define the characteristic peripheral blood and bone marrow findings in ET patients. From 1974 to 1986 we treated 20 symptomatic ET patients with microvascular circulation disturbances including erythromelalgia (N = 18), atypical or typical transient ischemic attacks (N = 6), or acute coronary ischemic syndrome (N = 3) with aspirin and one course of busulfan. The mean platelet counts before and after busulfan treatment were 1,009 (range 545-1,525) and 241 (range 159-315) x 10(9)/L, respectively. After induction of a complete remission, treatment with busulfan and aspirin was discontinued until symptoms returned. All 20 patients remained asymptomatic as long as ET was in maintained remission (platelet < 350 x 10(9)/L) for 4 to 61 (mean 36) months. Eight patients became symptomatic and 4 patients remained asymptomatic at relapse of ET after a follow-up period of 19 to 61 and 31 to 46 months, respectively. Platelet counts at time of symptomatic relapse in the 8 patients were 410, 450, 490, 500, 515, 545, 548, and 635 x 10(9)/L and at time of asymptomatic relapse in 4 ET patients 577, 600, 648, and 725 x 10(9)/L. Based on these observations, since 1986 we followed the strategy to treat ET patients with aspirin as long as the platelet count was between 400 and 1,000 up to 1,250 x 10(9)/L. Clear indications to reduce the platelet count were bleeding, aspirin side effects, and platelets counts above 1500 x 10(9)/L. This nonleukemogenic or least toxic approach in ET is the rationale behind the normal life expectancy and subsequent thrombosis-free survival in 68 ET patients after a mean follow-up period of 6.2 years.
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Affiliation(s)
- J J Michiels
- Thrombocythemia Vera Study Group, Goodheart Institute, Rotterdam, The Netherlands
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32
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Cortelazzo S, Marchetti M, Orlando E, Falanga A, Barbui T, Buchanan MR. Aspirin increases the bleeding side effects in essential thrombocythemia independent of the cyclooxygenase pathway: role of the lipoxygenase pathway. Am J Hematol 1998; 57:277-82. [PMID: 9544970 DOI: 10.1002/(sici)1096-8652(199804)57:4<277::aid-ajh2>3.0.co;2-r] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for patients with essential thrombocythemia (ET) who are at an increased risk of thrombotic events. However, ASA is also associated with an increased risk of bleeding in these patients as compared to the risk of bleeding in other patients treated with ASA. Recent data suggest that while ASA inhibits platelet thromboxane A2 (TxA2) synthesis in all individuals, ASA has little effect or inhibits the lipoxygenase pathway (i.e., 12-hydroxyeicosatetranoic acid or 12-HETE synthesis) in some individuals, and enhances 12-HETE synthesis in others. These differential effects are associated with a pronounced prolongation of the bleeding time vs. no prolongation of the bleeding time, respectively, i.e., in ASA responders and ASA nonresponders, respectively. To determine if the increased risk of ASA-induced bleeding seen in ET patients is associated with an effect on 12-HETE synthesis, we compared the relative effects of ASA on the bleeding time, platelet TxA2 and 12-HETE synthesis, and platelet aggregation and adhesion in ET patients and healthy volunteers. ASA (300 mg, taken orally) prolonged the bleeding time in 82% of the ET patients but only 27% of the healthy volunteers although platelet TxA2 synthesis and ADP- and collagen-induced aggregation were inhibited significantly in both groups. In contrast, platelet 12-HETE synthesis was unchanged and platelet adhesion was decreased in those patients and volunteers whose bleeding times were prolonged by ASA, whereas platelet 12-HETE synthesis was increased significantly and platelet adhesion was unaffected in those patients and volunteers whose bleeding times were not prolonged, and in some cases shortened by ASA. These results confirm previous data that demonstrate that ASA has different effects on platelet 12-HETE synthesis and platelet adhesion in different individuals, i.e., inhibitory or no effect in ASA responders (in whom ASA prolonged bleeding) vs. enhancing effects in ASA nonresponders (in whom ASA did not prolong bleeding). These results also indicate that there is a greater percentage of ASA responders in patients with ET than that seen in the general population, a difference that is associated with an effect of ASA on the lipoxygenase pathway. This may explain the increased bleeding side effects seen in the ET patient population.
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Abstract
Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.
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Affiliation(s)
- B Hermanns
- Medical Faculty of the Technical University of Aachen, Department of Pathology, Würselen, Germany
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34
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Michiels JJ, van Genderen PJ, Jansen PH, Koudstaal PJ. Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders. Leuk Lymphoma 1996; 22 Suppl 1:65-70. [PMID: 8951774 DOI: 10.3109/10428199609074362] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Neurological symptoms of transient unsteadiness, dysarthria, dysphasia, dysbasia, transient monoor hemiparesis, hemiparesis, scintillating scotomas, amaurosis fugax, vertigo, dizziness, migraine accompaniments, syncope and seizures were the presenting manifestations of thrombocythemia in various myeloproliferative disorders. Erythromelalgia preceded or followed the neurologic ischemic attacks. The neurologic and ocular attacks usually had a sudden onset, lasted for a few seconds to several minutes and occurred independently or sequentially rather than simultaneously. This clinical syndrome is caused by platelet-mediated ischemic and thrombotic processes in the end-arterial microvasculature and reflects the existence of a platelet dependent and aspirin responsive arterial thrombophilia in thrombocythemia as novel disease entity, which confirms and elucidates Mitchell's hypothesis.
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Affiliation(s)
- J J Michiels
- Department of Hematology, University Hospital Dijkzigt, Erasmus University Medical School, Rotterdam, The Netherlands
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35
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Michiels JJ, van Genderen PJ, Lindemans J, van Vliet HH. Erythromelalgic, thrombotic and hemorrhagic manifestations in 50 cases of thrombocythemia. Leuk Lymphoma 1996; 22 Suppl 1:47-56. [PMID: 8951772 DOI: 10.3109/10428199609074360] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Fifty consecutive patients with thrombocythemia (35 men and 15 women) were diagnosed as primary thrombocythemia (PT) in 30 and thrombocythemia associated with polycythemia vera (PV) in 20. The symptoms were platelet-mediated erythromelalgia in 16 PT and 15 PV, coronary artery disease in 3 PT and 2 PV, atypical cerebral ischemic attacks in 8 PT and 3 PV, paradoxical thrombosis and bleeding in 3 PT and 2 PV and hemorrhages alone in 6 PT and 2 PV patients. Erythromelalgia was localized in the forefoot sole and toes in 28, the fingertips in 9, the handpalm in 2. Untreated erythromelalgia progressed to acrocyanosis or peripheral ischemia with necrosis in a toe or fingertip in 14 cases. Painful red, warm and indurated erythromelalgic hot spots in the skin of the upper legs were misdiagnosed as superficial thrombophelebitis in 5 PT and 2 PV patients. Erythromelalgia in thrombocythemia already occurred at slightly increased platelet counts above 400 x 10(9)/l. The curative effect of aspirin on erythromelalgia in thrombocythemia was consistently accompanied by a significant increase of platelet counts. Erythromelalgia and bleeding paradoxically occurred in 5 patients at platelet counts between 1000 and 2000 x 10(9)/l. In this situation aspirin prevents erythromelalgic and microcirculatory circulation disturbances, but further increases the risk of serious bleeding complications. Presenting hemorrhagic manifestations in thrombocythemia were observed at platelet counts in excess of 1000 x 10(9)/l in 9 PT and 4 PV patients as severe epistaxis in 5, atypical ecchymoses in 3, gastrointestinal bleeding in 2 and secondary bleeding in 3. The concept of platelet-mediated erythromelalgia, thrombosis and hemorrhages in thrombocythemia is discussed.
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Affiliation(s)
- J J Michiels
- Department of Hematology, Hemostasis and Thrombosis Research, University Hospital Dijkzigt, Erasmus University Medical School, Rotterdam, The Netherlands
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36
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Michiels JJ. The myeloproliferative disorders. An historical appraisal and personal experiences. Leuk Lymphoma 1996; 22 Suppl 1:1-14. [PMID: 8951768 DOI: 10.3109/10428199609074356] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
According to strict morphological, biochemical and cytogenetic criteria Philadelphia chromosome positive essential thrombocythemia and chronic granulocytic leukemia constitute a separate malignant and individual disease entity, whereas Philadelphia chromosome negative essential thrombocythemia, polycythemia vera and agnogenic or megakaryocytic myeloid metaplasia form a chronic proliferation of three hematopoietic cell lines. Histopathology from bone marrow biopsies permits the characterization and diagnostic differention of the various myeloproliferative disorders and appears to be a main and specific diagostic criterion for polycythemia vera and essential thrombocythemia. Hemorrhagic thrombocythemia is a clinical syndrome of recurrent spontaneous mucocutaneous and secondary hemorrhages often preceded by thromboses, extremely high platelet counts, pseudohyperkalemia, increased bone marrow cellularity and frequently splenomegaly. The diagnostic criteria of essential thrombocythemia with paradoxical occurrence of thrombotic events and hemorrhagic manifestations are a platelet count in excess of 1000 x 10(9)/L and increased bone marrow cellularity in the majority of the cases. Erythromelalgia and other microcirculatory ischemic or thrombotic events or accidents in essential thrombocythemia and polycythemia vera already occur at platelet counts in excess of the upper limit of normal. First line treatment options in essential thrombocythemia and polycythemia vera are control of platelet function with low-dose aspirin and reductive control of platelet count and erythrocytes by bloodletting, interferon and busulfan or hydroxyurea monochemotherapy.
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Affiliation(s)
- J J Michiels
- Department of Hematology, University Hospital Dijkzigt, Erasmus University Medical School Rotterdam, The Netherlands
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37
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Barbui T, Finazzi G, Dupuy E, Kiladjian JJ, Brière J. Treatment strategies in essential thrombocythemia. A critical appraisal of various experiences in different centers. Leuk Lymphoma 1996; 22 Suppl 1:149-60. [PMID: 8951786 DOI: 10.3109/10428199609074373] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The therapeutic strategy in patients with Essential Thrombocythemia (ET) is a difficult balance between the prevention of bleeding and thrombotic complications and the risks of drug side effects and toxicity. Major bleeding is rare and seem to be related to higher platelet counts: therefore, a platelet count over 1500 x 10(9)/L is generally regarded as an indication for cytoreduction. Thrombotic complications include microvascular occlusive symptoms, which are reversible with low-dose aspirin, and large vessels thrombosis. The risk of major thrombosis is higher in ET patients aged more than 60 ys. and with previous occlusive event. In this high-risk group, the non-alkylating agent hydroxyurea (HU) significantly reduces the rate of vascular complications and has emerged as the treatment of choice. However, the long-term risk/benefit of HU remains disputed because its leukemogenic potential has not been ruled out. This holds also for other myelosuppressive agents, such as busulphan and pipobroman. Other drugs of particular interest for young patients include recombinant alpha-interferon (IFN) and Anagrelide. Both of them are effective in lowering platelet count, but their efficacy in reducing clinical complications remains to be demonstrated. However, both IFN and Anagrelide have shown to have frequent and clinically important side effects. Thus, further clinical studies are required to establish their role in the strategy of ET patient treatment.
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Affiliation(s)
- T Barbui
- Division of Hematology, Ospedali Riuniti Bergamo, Italy
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38
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Flores NA. Platelet activation during myocardial ischaemia: a contributory arrhythmogenic mechanism. Pharmacol Ther 1996; 72:83-108. [PMID: 8981572 DOI: 10.1016/s0163-7258(96)00100-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Experimental and clinical observations of the involvement of platelets in the pathophysiology of myocardial ischaemia indicate the importance of interactions between these formed elements and the heart. The aim of this review is to outline evidence linking platelet activation, myocardial ischaemia and infarction, and to present evidence for a link between platelet activation, arrhythmogenesis and sudden death. A brief review of platelet physiology and pharmacology is provided, with a review of the cardiac electrophysiological effects of ischaemia and the electrophysiological effects of platelet-derived substances. The concept that platelet activation during myocardial ischaemia is a contributory arrhythmogenic mechanism is discussed.
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Affiliation(s)
- N A Flores
- Academic Cardiology Unit, Imperial College School of Medicine at St. Mary's, London, UK
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39
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Landolfi R, Rocca B, Patrono C. Bleeding and thrombosis in myeloproliferative disorders: mechanisms and treatment. Crit Rev Oncol Hematol 1995; 20:203-22. [PMID: 8748010 DOI: 10.1016/1040-8428(94)00164-o] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Affiliation(s)
- R Landolfi
- Centro Ricerche Fisiopatologia dell'Emostasi, Università Cattolica del S. Coure, Roma, Italy
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40
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41
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Wright SD, Tuddenham EG. Myeloproliferative and metabolic causes. BAILLIERE'S CLINICAL HAEMATOLOGY 1994; 7:591-635. [PMID: 7841603 DOI: 10.1016/s0950-3536(05)80101-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- S D Wright
- Department of Haematology, St. Mary's Hospital, London, UK
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42
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van Genderen PJJ, Michiels JJ. Arterial Thrombophilia in Primary Thrombocythemia. Angiology 1994. [DOI: 10.1177/0003319794045006121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The clinical course of a case of primary thrombocythemia is described, complicated by a variety of recurrent and sequential thrombotic manifestations, involving the peripheral as well as the cerebrovascular and coronary microvasculature, demonstrating that throm bocythemia should be considered as an important risk factor for thrombosis, already at platelet count states in excess of 400 x 109/L.
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Affiliation(s)
| | - Jan J. Michiels
- Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
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43
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Affiliation(s)
- J J Michiels
- Department of Hematology, Hemostasis Thrombosis and Vascular Research, Erasmus University Medical School, Rotterdam, The Netherlands
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44
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Affiliation(s)
- J P Drenth
- Department of Hematology, Hemostasis Thrombosis and Vascular Research, Erasmus University Medical School, Rotterdam, The Netherlands
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45
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Abstract
The clinical course of a case of primary thrombocythemia is described, complicated by a variety of recurrent and sequential thrombotic manifestations, involving the peripheral as well as the cerebrovascular and coronary microvasculature, demonstrating that thrombocythemia should be considered as an important risk factor for thrombosis, already at platelet count states in excess of 400 x 10(9)/L.
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Affiliation(s)
- P J van Genderen
- Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
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46
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Michiels JJ, Van Genderen PJ, Van Vliet HH. Erythromelalgia and arterial thrombophilia in thrombocythemia. Ann N Y Acad Sci 1994; 714:318-21. [PMID: 8017789 DOI: 10.1111/j.1749-6632.1994.tb12067.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- J J Michiels
- Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
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47
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Schlemper RJ, van der Maas AP, Eikenboom JC. Familial essential thrombocythemia: clinical characteristics of 11 cases in one family. Ann Hematol 1994; 68:153-8. [PMID: 8167182 DOI: 10.1007/bf01727421] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Reports on familial occurrence of essential thrombocythemia (ET) are scanty. Many clinical and hematological aspects of familial ET have not been clarified yet. We studied 16 family members in four successive generations. By laboratory tests and bone marrow examination they were divided into a non-thrombocythemia group (n = 5) and into ET patients (n = 11). Five ET patients were asymptomatic, three patients had both vaso-occlusive and hemorrhagic symptoms, and three patients only vaso-occlusive symptoms. The platelet count ranged from 500 to 1700 x 10(9)/l. Symptoms correlated with age but not with platelet count. ADP-induced platelet aggregation distinguished best between patients and non-ET subjects. Four patients and four non-ET subjects had factor VIII:C or von Willebrand factor antigen abnormalities; all but one had blood group O. These abnormalities were not due to inherited von Willebrand's disease according to haplotype analysis. Two patients and three non-ET subjects had a bleeding diathesis. One of these two patients and all three non-ET subjects had a decreased factor VIII:C or vWF:Ag. No chromosome abnormalities were found. In conclusion, familial ET has a relatively benign course with clinical manifestations similar to nonfamilial cases, and it is probably transmitted by an autosomal dominant mode of inheritance.
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Affiliation(s)
- R J Schlemper
- Department of General Internal Medicine, Academic Hospital, Leiden, The Netherlands
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48
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Abyad A, Kligman E. Primary polycythaemia vera in the elderly. J Int Med Res 1994; 22:121-9. [PMID: 8020639 DOI: 10.1177/030006059402200209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
At presentation the history of an 87-year-old woman included progressive memory loss, repeated transient ischaemic attack, increasing fatigue, dizziness, palpitations and frequent falls. Investigations revealed erythrocytosis, leukocytosis, thrombocytosis, normal arterial oxygen concentration and an increased red cell volume. Polycythaemia vera was diagnosed and was successfully managed by phlebotomy with half a unit twice a week and rechecks of her haematocrit, initially; she reported marked improvement after 2 weeks of treatment. The alternative treatments for polycythaemia vera are discussed; in addition to venesection, conventional treatments include bone-marrow depressive agents such as phosphorus-32 and chemotherapy with agents such as hydroxyurea. More recent developments include isovolumic erythrocytophoresis, alpha-interferon and ticlopidine. All of the treatments are associated with complications, or other disadvantages, thrombotic complications in the case of phlebotomy, malignancies in the case of most myelosuppressive treatments, and problems of compliance in others. The optimal treatment for polycythaemia vera is a judicious combination of the alternatives, depending on the phase of the disease, the age of the patient, and other prognostic factors.
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Affiliation(s)
- A Abyad
- Department of Family Medicine, American University of Beirut, Lebanon
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49
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Michiels JJ, Koudstaal PJ, Roelandt JR, van Vliet HH. Arterial thrombosis in thrombocythemia. Am Heart J 1993; 126:1495-6. [PMID: 8249822 DOI: 10.1016/0002-8703(93)90573-r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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50
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van Genderen PJ, Michiels JJ. Primary thrombocythemia: diagnosis, clinical manifestations and management. Ann Hematol 1993; 67:57-62. [PMID: 8347730 DOI: 10.1007/bf01788127] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- P J van Genderen
- Department of Hematology, University Hospital Dijkzigt, Erasmus University Rotterdam, The Netherlands
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