We report a case of hyperacute multiple graft thrombosis following an uneventful coronary artery bypass graft (CABG) surgery in a 69-year-old female with chronic immune thrombocytopenia (ITP). Detailed evaluation revealed the presence of anti-PF4/heparin antibodies, confirming the diagnosis of heparin-induced thrombocytopenia (HIT). The co-existence of chronic ITP masked the thrombocytopenia typically associated with HIT, complicating the recognition of the thrombotic and hematologic abnormalities. This case emphasizes the importance of promptly discontinuing heparin when HIT is suspected or confirmed. Additionally, maintaining a low threshold for suspecting HIT in patients with ITP undergoing cardiac surgery is crucial, as this complex interplay may increase the risk of severe postoperative complications.

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, including low molecular weight heparins (LMWHs) like dalteparin. While LMWHs reduces the risk of HIT compared to unfractionated heparin, vigilance remains essential.

An 82-year-old male with chronic kidney disease (CKD) developed HIT during hemodialysis anticoagulation with dalteparin, resulting in a platelet count of 17,000/µL and positive HIT antibodies. Dalteparin was replaced with nafamostat mesilate. Following confirmed HIT antibody seronegativity, elective aortic valve replacement was performed under cardiopulmonary bypass using heparin. Postoperative dialysis was managed using nafamostat mesilate, preventing HIT recurrence. His platelet count recovered after dalteparin replacement, and no recurrence of HIT was observed.

Even LMWHs, such as dalteparin, pose a HIT risk, necessitating vigilant monitoring. Confirming HIT antibody seronegativity and appropriately timing surgery are critical for patients with a history of HIT. Proper postoperative follow-up and alternative anticoagulation strategies can prevent HIT recurrence.

Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH.

Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019.

Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01).

SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is associated with antibodies that target platelet factor 4 (PF4) and are heparin-independent. VITT antibodies are implicated in acute, transient prothrombotic disorders that are triggered by adenoviral vector vaccines against coronavirus disease 2019 or by adenovirus infection. We describe chronic prothrombotic disorders featuring anticoagulant-refractory thromboses and intermittent thrombocytopenia that were associated with VITT-like antibodies in five patients (four patients with newly reported cases and the index patient). The patients had low levels of M proteins (median level, 0.14 g per deciliter); in each patient, we found that the M protein was the VITT-like antibody. The antibody clonotype profiles and binding epitopes on PF4 were different from those observed with the acute disorders occurring after vaccination or viral infection, features that reflect distinct immunopathogenesis. Treatment strategies besides anticoagulation alone are needed for the chronic disorders, referred to as VITT-like monoclonal gammopathy of thrombotic significance. (Funded by the Canadian Institutes of Health Research and others.).

In this review, we aim to highlight the extent of inappropriate hemostasis testing and provide practical guidance on how to prevent it. We will focus on the acute setting, including but not limited to the emergency department and intensive care unit. To this end, we will first discuss the significance of inappropriateness, in the general context of laboratory medicine. This includes acknowledging the importance of the phenomenon and attempting to define it. Next, we describe the harmful consequences of inappropriate testing. Finally, we focus on the inappropriate use of hemostasis testing in the acute setting. The second section describes how interventions-in particular, the implementation of guidance for testing-can efficiently reduce inappropriateness. In the third section, we summarize the available recommendations for rational use of hemostasis testing (platelet count, activated partial thromboplastin time, prothrombin time/international normalized ratio, fibrinogen, thrombin time, D-dimer, anti-Xa assay, antithrombin, ADAMTS13 activity, antiheparin-PF4 antibodies, viscoelastometric tests, coagulation factors, and platelet function testing), as supported by guidelines, recommendations, and/or expert opinions. Overall, this review is intended to be a toolkit in the effort to promote the appropriate use of hemostasis testing. Hopefully, the new In Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR) should help in improving the availability of evidence regarding clinical performance of hemostasis assays.

Hemorrhagic complications associated with regional anesthesia are extremely rare. The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy reviews the published evidence since 2018 and provides guidance to help avoid this potentially catastrophic complication.The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy uses similar methodology as previous editions but is reorganized and significantly condensed. Therefore, the clinicians are encouraged to review the earlier texts for more detailed descriptions of methods, clinical trials, case series and pharmacology. It is impossible to perform large, randomized controlled trials evaluating a complication this rare; therefore, where the evidence is limited, the authors continue to maintain an 'antihemorrhagic' approach focused on patient safety and have proposed conservative times for the interruption of therapy prior to neural blockade. In previous versions, the anticoagulant doses were described as prophylactic and therapeutic. In this version, we will be using 'low dose' and 'high dose,' which will allow us to be consistent with other published guidelines and more accurately describe the dose in the setting of specific patient characteristics and indications. For example, the same 'high' dose may be used in one patient as a treatment for deep venous thrombosis (DVT) and in another patient as prophylaxis for recurrent DVT. Due to the increasing ability to obtain drug-specific assays, we have included suggestions for when ordering these tests may be helpful and guide practice. Like previous editions, at the end of each recommendation the authors have clearly noted how the recommendation has changed from previous editions.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare prothrombotic disorder with a unique clonality-restricted immunological profile. The study by Petito and Bury et al. provides insight into the role of HLA polymorphisms and an inherent predisposition to VITT. Commentary on: Petito et al. Association of human leucocyte antigen loci with vaccine-induced immune thrombotic thrombocytopenia: Potential role of the interaction between platelet factor 4-derived peptides and MHC-II. Br J Haematol 2025; 206:290-295.

Coronavirus disease-19 (COVID-19) vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious clinical condition with high mortality rate in apparently healthy individuals without noticeable risk factors. VITT typically arises due to the administration of vaccines that possess recombinant adenoviral vectors, including ChAdOx1 nCov-19 (AstraZeneca) and Ad26 COV2.S (Johnson & Johnson/Janssen). Thrombosis frequently occurs at atypical sites, such as the cerebral or splanchnic circulations, in this particular pathological state. Similar to heparin-induced thrombotic thrombocytopenia (HITT), it seems that the cause of VITT is the misdirection of anti-platelet factor 4 antibodies (anti-PF4 Abs), an ancient antimicrobial mechanism. Anti-PF4 Abs in patients with VITT activates the coagulation system, leading to thrombosis. This process occurs through the stimulation of platelets (Plts) and neutrophils and subsequently release of neutrophil extracellular traps (NETs). Due to the potentially fatal consequences of VITT, early diagnosis is mandatory. In addition to thrombocytopenia, thrombosis, and the presence of anti-PF4 Abs, the day of symptoms onset and the elevation of D-dimer are also required for definitive diagnosis of VITT. The absence of one or more criteria can result in the exclusion of definitive VITT and lead to the diagnosis of probable, possible, or unlikely VITT.

Heparin is given for anticoagulation during and after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Our objective was to add to the limited data available on the incidence, management and outcomes of suspected heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

This retrospective single-centre study included consecutive patients with suspected heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy done in 2005-2018. Confirmed heparin-induced thrombocytopaenia was defined as positive findings from both the antibody test and the platelet aggregation test. Patients with versus without confirmed heparin-induced thrombocytopaenia were compared, as well as patients with versus without heparin replacement therapy within the group with unconfirmed heparin-induced thrombocytopaenia. The platelet counts over time were compared to those in controls without suspected heparin-induced thrombocytopaenia.

Heparin-induced thrombocytopaenia was suspected in 86 (6.3%) of 1360 patients and confirmed in 16 (16/86, 19%), all of whom received heparin replacement therapy and survived to intensive care unit discharge. Of the remaining 70 patients, 28 (40%) received heparin replacement therapy and less often experienced bleeding compared to the other 42 (3.6% vs 21.4%, P = 0.043). Intensive care unit mortality was 17/70 (24.3%) and was lower in the subgroup given heparin replacement therapy (10.7% vs 33.3%; P = 0.046). Confirmed heparin-induced thrombocytopaenia was associated with a sharp platelet-count drop on Day 5. In unconfirmed suspected heparin-induced thrombocytopaenia, the early platelet-count decline was similar to that in the controls without suspected heparin-induced thrombocytopaenia, but the baseline count was lower.

Clinical features suggesting heparin-induced thrombocytopaenia after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension were associated with excess mortality. Relay heparin replacement therapy was associated with lower mortality and fewer bleeding events.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.

Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin. Other HIT-like syndromes are increasingly recognised, mediated by antibodies binding to platelet factor 4, with or without identifiable polyanions. The history of heparin exposure is atypical for classical HIT and standard HIT laboratory tests may be negative. This manuscript describes subtypes of HIT-like syndromes and highlights practical tips for diagnosis and therapy.

Heparin-induced thrombocytopenia (HIT) is clinically the most relevant non-hemorrhagic complication of heparin, which is associated with the increased risk of thrombosis and mortality. This study was conducted to determine platelet activation in HIT-II in hospitalized patients with surgery or deep vein thrombosis (DVT). The clinical outcomes of the patients was also assayed.

In this descriptive/cross-sectional study, 754 heparin-receiving-hospitalized patients with surgery or DVT were evaluated for the incidence of thrombocytopenia 7 days after heparin therapy. Clinical assessment 4Ts and ELISA for heparin-platelet factor 4 (HPF4) antibodies were performed to diagnose HIT-II. Production of platelet microparticles (PMPs), soluble P-selectin (sP-selectin), IL-1, IL-6, and tumor necrosing factor-α (TNF-α) were evaluated in the HIT suspected patients.

The frequency of HIT-II was 4.50%. More HIT-II was diagnosed in the elder patients (P = 0.008) and female (P = 0.005). Thrombosis rate was higher in the HIT-II (P = 0.0001). More PMPs, sP-selectin, IL-1, IL-6, and TNF-α was detected in the HIT-II patients. The length of hospital stay was significantly different in HIT-II (P = 0.015). Mortality rate of the HIT-II patients was higher than non-HIT ones (P = 0.0007).

Platelet activation in the HIT-II patients mediated more thrombosis formation. It was associated with the increased length of hospital stay and mortality.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated disease with severe thromboembolic complications. HIT during percutaneous coronary intervention (PCI) can be fatal without prompt treatment. We report an unusual case of HIT observed during PCI for acute coronary syndrome (ACS). A 74-year-old female with a history of pulmonary embolism managed with unfractionated heparin (UFH) 2 years previously presented with intermittent chest pain. Coronary angiography revealed total occlusion of the mid-right coronary artery. Before and during the primary PCI, 14000 UFH units were administered. However, abundant thrombus formation in the non-culprit lesion was refractory to repeated thrombus aspiration. We suspected HIT, discontinued UFH, and administered argatroban. Despite repeated thrombus aspirations and balloon dilatation, coronary obstruction persisted; consequently, ventricular fibrillation refractory to multiple cardioversions occurred. Therefore, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was required. Platelet counts rapidly decreased to <50 % of the baseline value, and serum was highly positive for IgG-specific antiplatelet factor 4/heparin antibodies. The patient was discharged with independent gait and no major neurological disorders. This is a clinically noteworthy case of rapidly developing HIT during primary PCI for ACS, requiring VA-ECMO management, with no major neurological complications. HIT may occur immediately after re-exposure to heparin long after the first exposure.

Without prompt treatment, heparin-induced thrombocytopenia (HIT) during percutaneous coronary intervention (PCI) can be fatal. It may lead to refractory coronary obstruction, which may need to be managed by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We present a clinically noteworthy case of rapidly developing HIT during primary PCI for acute coronary syndrome, requiring VA-ECMO management, with no major neurological complications. Physicians must be mindful that HIT may occur immediately after re-exposure to heparin long after the first exposure.

In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used in critically ill patients with respiratory or cardiac failure. Heparin is usually used as anticoagulation therapy during ECMO support. However, heparin-induced thrombocytopenia (HIT) in ECMO-supported patients, which results in considerable morbidity and mortality, has not yet been well described. This meta-analysis and systematic review aimed to thoroughly report the incidence of HIT on ECMO, as well as the characteristics and outcomes of HIT patients.

We searched the PubMed, Embase, Cochrane Library, and Scopus databases for studies investigating HIT in adult patients supported by ECMO. All studies conforming to the inclusion criteria were screened from 1975 to August 2023. Nineteen studies from a total of 1,625 abstracts were selected. The primary outcomes were the incidence of HIT and suspected HIT.

The pooled incidence of HIT in ECMO-supported patients was 4.2% (95% CI: 2.7-5.6; 18 studies). A total of 15.9% (95% CI: 9.0-22.8; 12 studies) of patients on ECMO were suspected of having HIT. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used immunoassay. The median optical density (OD) of the ELISA in HIT-confirmed patients ranged from 1.08 to 2.10. In most studies, the serotonin release assay (SRA) was performed as a HIT-confirming test. According to the subgroup analysis, the pooled incidence of HIT in ECMO patients was 2.7% in studies whose diagnostic mode was functional assays, which is significantly lower than the incidence in studies in which the patients were diagnosed by immunoassay (14.5%). Argatroban was most commonly used as an alternative anticoagulation agent after the withdrawal of heparin. Among confirmed HIT patients, 45.5% (95% CI: 28.8-62.6) experienced thrombotic events, while 50.1% (95% CI: 24.9-75.4) experienced bleeding events. Overall, 46.6% (95% CI: 30.4-63.1) of patients on ECMO with HIT died.

According to our study, the pooled incidence of HIT in ECMO-supported patients is 4.2%, and it contributes to adverse outcomes. Inappropriate diagnostic methods can easily lead to misdiagnosis of HIT. Further research and development of diagnostic algorithms and laboratory assays are warranted.

Hematology is a clinical specialty with strong roots in the laboratory; accordingly, the lab can help solve perplexing clinical problems. This review highlights clinical-pathological conundrums addressed during my 35-year hematology career at McMaster University. Heyde syndrome is the association between aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia where the bleeding is usually cured by aortic valve replacement; the chance reading of a neonatal study showing reversible deficiency of high-molecular-weight (HMW) multimers of von Willebrand factor (vWF) following surgical correction of congenital heart disease provided the key insight that a subtle deficiency of HMW multimers of vWF explains Heyde syndrome. The unusual immunobiology of heparin-induced thrombocytopenia (HIT)-a highly prothrombotic, antibody-mediated, anti-platelet factor 4 (PF4) disorder featuring rapid appearance and then disappearance (seroreversion) of the pathological heparin-dependent platelet-activating antibodies-permitted identification of key clinical features that informed development of a scoring system (4Ts) to aid in HIT diagnosis. Atypical clinical presentations of HIT prompted identification of heparin-independent anti-PF4 antibodies, now recognized as the explanation for vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as VITT-like disorders triggered by adenovirus infection. Another unusual feature of HIT is its strong association with limb ischemia, including limb necrosis secondary to deep-vein/microvascular thrombosis (venous limb gangrene). The remarkable observation that supratherapeutic warfarin anticoagulation predisposes to HIT- and cancer-associated venous limb gangrene provided insight into disturbed procoagulant/anticoagulant balance; these concepts are relevant to microvascular thrombosis in critical illness (symmetrical peripheral gangrene), including a pathophysiological role for proximate "shock liver" (impaired hepatic synthesis of natural anticoagulants).

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice.

To evaluate the current diagnostic practice for managing the suspicion of HIT.

This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT.

Suspicion of HIT.

The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests.

Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively.

In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet severe adverse complication first identified during the global vaccination effort against SARS-CoV-2 infection, predominantly observed following administration of the ChAdOx1-S (Oxford-AstraZeneca) and Ad26.CoV2.S (Johnson & Johnson/Janssen) adenoviral vector-based vaccines. Unlike other anti-platelet factor 4 (PF4) antibody-mediated disorders, such as heparin-induced thrombocytopenia (HIT), VITT arises with the development of platelet-activating anti-PF4 antibodies 4-42 days post-vaccination, typically featuring thrombocytopenia and thrombosis at unusual sites.

To explore the unique properties, pathogenic mechanisms, and long-term persistence of VITT antibodies in patients, in comparison with other anti-PF4 antibody-mediated disorders.

This review highlights the complexity of VITT as it differs in antibody behavior and clinical presentation from other anti-PF4-mediated disorders, including the high incidence rate of cerebral venous sinus thrombosis (CVST) and the persistence of anti-PF4 antibodies, necessitating a re-evaluation of long-term patient care strategies. The nature of VITT antibodies and the underlying mechanisms triggering their production remain largely unknown.

The rise in awareness and subsequent prompt recognition of VITT is paramount in reducing mortality. As vaccination campaigns continue, understanding the role of adenoviral vector-based vaccines in VITT antibody production is crucial, not only for its immediate clinical implications, but also for developing safer vaccines in the future.

Antibodies against the chemokine platelet factor 4 (PF4) occur often, but only those that activate platelets induce severe prothrombotic disorders with associated thrombocytopenia. Heparin-induced thrombocytopenia (HIT) is the prototypic anti-PF4 disorder, mediated by strong activation of platelets through their FcγIIa (immunoglobulin G [IgG]) receptors (FcγRIIa). Concomitant pancellular activation (monocytes, neutrophils, endothelium) triggers thromboinflammation with a high risk for venous and arterial thrombosis. The classic concept of HIT is that anti-PF4/heparin IgG, recognizing antigen sites on (cationic) PF4 that form in the presence of (anionic) heparin, constitute the heparin-dependent antibodies that cause HIT. Accordingly, HIT is managed by anticoagulation with a nonheparin anticoagulant. In 2021, adenovirus vector COVID-19 vaccines triggered the rare adverse effect "vaccine-induced immune thrombotic thrombocytopenia" (VITT), also caused by anti-PF4 IgG. VITT is a predominantly heparin-independent platelet-activating disorder that requires both therapeutic-dose anticoagulation and inhibition of FcγRIIa-mediated platelet activation by high-dose intravenous immunoglobulin (IVIG). HIT and VITT antibodies bind to different epitopes on PF4; new immunoassays can differentiate between these distinct HIT-like and VITT-like antibodies. These studies indicate that (1) severe, atypical presentations of HIT ("autoimmune HIT") are associated with both HIT-like (heparin-dependent) and VITT-like (heparin-independent) anti-PF4 antibodies; (2) in some patients with severe acute (and sometimes chronic, recurrent) thrombosis, VITT-like antibodies can be identified independent of proximate heparin exposure or vaccination. We propose to classify anti-PF4 antibodies as type 1 (nonpathogenic, non- platelet activating), type 2 (heparin dependent, platelet activating), and type 3 (heparin independent, platelet activating). A key concept is that type 3 antibodies (autoimmune HIT, VITT) require anticoagulation plus an adjunct treatment, namely high-dose IVIG, to deescalate the severe anti-PF4 IgG-mediated hypercoagulability state.

To identify risk factors and develop a pretest scoring system to differentiate patients with heparin-induced thrombocytopenia (HIT) in the mechanical circulatory support (MCS) population. The authors present a modified "4TMCS" scoring system, which considers the "type of mechanical circulatory support" that may help identify patients at risk for developing postoperative HIT.

A retrospective cohort study. Patients who underwent cardiac surgery were categorized into 3 groups: (1) normal platelet count, (2) thrombocytopenia with a negative HIT test, and (3) thrombocytopenia with a positive HIT test. A comparison of diagnostic accuracy between the 4Ts and 4TMCS probability scores was performed.

At a single adult tertiary-care center.

A total of 5,314 patients who underwent cardiac surgery between May 1, 2008 and December 31, 2016.

None.

In total, 125 out of 5,314 patients (2.4%) were diagnosed with HIT, of whom 75 out of 5,314 (1.4%) had clinical evidence of thrombosis. Overall, in-hospital mortality was 25.6%, 11.7%, and 1.5% in the HIT(+), HIT(-), and control groups, respectively (p < 0.001). Mechanical circulatory support was associated with a significantly increased risk for HIT, with an incidence of 5.9% in patients receiving MCS versus 1.9% in those without (p < 0.001). Area under the receiver operator curve (AUC) analysis demonstrated improved diagnostic accuracy of the 4TMCS score compared with the 4Ts (AUC = 0.83 v 0.77, p < 0.044). The 4TMCS score had higher sensitivity than the 4Ts, using the guideline-recommended score cutoff of ≥4 (95.2% v 85.7%).

Heparin-induced thrombocytopenia is associated with worse outcomes and increased morbidity and mortality in the MCS population. Awareness of patient risk factors and the application of a modified 4TMCS probability score may allow for more accurate screening and treatment of HIT in the MCS population.

Autoimmune thrombocytopenia (aHIT) is a severe subtype of heparin-induced thrombocytopenia (HIT) with atypical clinical features caused by highly pathological IgG antibodies ("aHIT antibodies") that activate platelets even in the absence of heparin. The clinical features of aHIT include: the onset or worsening of thrombocytopenia despite stopping heparin ("delayed-onset HIT"), thrombocytopenia persistence despite stopping heparin ("persisting" or "refractory HIT"), or triggered by small amounts of heparin (heparin "flush" HIT), most cases of fondaparinux-induced HIT, and patients with unusually severe HIT (e.g., multi-site or microvascular thrombosis, overt disseminated intravascular coagulation [DIC]). Special treatment approaches are required. For example, unlike classic HIT, heparin cessation does not result in de-escalation of antibody-induced hemostasis activation, and thus high-dose intravenous immunoglobulin (IVIG) may be indicated to interrupt aHIT-induced platelet activation; therapeutic plasma exchange may be required if high-dose IVIG is ineffective. Also, aHIT patients are at risk for treatment failure with (activated partial thromboplastin time [APTT]-adjusted) direct thrombin inhibitor (DTI) therapy (argatroban, bivalirudin), either because of APTT confounding (where aHIT-associated DIC and resulting APTT prolongation lead to systematic underdosing/interruption of DTI therapy) or because DTI inhibits thrombin-induced protein C activation. Most HIT laboratories do not test for aHIT antibodies, contributing to aHIT under-recognition.

Intermittent hemodialysis (HD) is almost invariably performed with heparin, and thus HD patients are at risk of developing the immune-mediated adverse effect heparin-induced thrombocytopenia (HIT), caused by anti-platelet factor 4/heparin IgG, which strongly activates platelets. HIT patients develop hypercoagulability with greatly increased risk of thrombosis, both venous and arterial. Certain HIT-associated complications are more likely to develop among HD patients, including hemofilter thrombosis despite heparin, intravascular catheter and/or arteriovenous fistula-associated thrombosis, post-heparin bolus anaphylactoid/anaphylactic reactions, and thrombotic stroke and acute limb artery thrombosis (reflecting the high frequency of underlying arteriopathy in many patients with renal failure). Management of HIT in HD usually requires use of an alternative (non-heparin) anticoagulant; for example, danaparoid sodium (outside the USA) or argatroban (USA and elsewhere). Whether heparin-grafted hemodialyzers (without systemic heparin) can be used safely in acute HIT is unknown. The HIT immune response is remarkably transient and usually not retriggered by subsequent heparin administration. Accordingly, since renal failure patients often require long-term HD, there may be the opportunity-following seroreversion (loss of platelet-activating HIT antibodies)-to restart heparin for HD, a practice that appears to have a low likelihood of retriggering HIT.

Platelet factor 4 (PF4, CXCL4), the most abundant α-granule platelet-specific chemokine, forms tetramers with an equatorial ring of high positive charge that bind to a wide range of polyanions, after which it changes conformation to expose antigenic epitopes. Antibodies directed against PF4 not only help to clear infection but can also lead to the development of thrombotic disorders such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombocytopenia and thrombosis (VITT). This review will outline the different mechanisms through which PF4 engagement with polyanions combats infection but also contributes to the pathogenesis of inflammatory and thrombotic disease states.

Recent work has shown that PF4 binding to microbial polyanions may improve outcomes in infection by enhancing leukocyte-bacterial binding, tethering pathogens to neutrophil extracellular traps (NETs), decreasing the thrombotic potential of NET DNA, and modulating viral infectivity. However, PF4 binding to nucleic acids may enhance their recognition by innate immune receptors, leading to autoinflammation. Lastly, while HIT is induced by platelet activating antibodies that bind to PF4/polyanion complexes, VITT, which occurs in a small subset of patients treated with COVID-19 adenovirus vector vaccines, is characterized by prothrombotic antibodies that bind to PF4 alone.

Investigating the complex interplay of PF4 and polyanions may provide insights relevant to the treatment of infectious disease while also improving our understanding of the pathogenesis of thrombotic disorders driven by anti-PF4/polyanion and anti-PF4 antibodies.

Cerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the so-called venous stroke. Current guidelines recommend anticoagulants as first-line therapy in the treatment of venous stroke. With complicated causes of cerebral venous thrombosis, treatment is difficult, especially when combined with autoimmune diseases, blood diseases, and even COVID-19.

This review summarizes the pathophysiological mechanisms, epidemiology, diagnosis, treatment, and clinical prognosis of cerebral venous thrombosis combined with autoimmune diseases, blood diseases, or infectious diseases such as COVID-19.

A systematic understanding of particular risk factors that should not be neglected when unconventional cerebral venous thrombosis occurs and for a scientific understanding of pathophysiological mechanisms, clinical diagnosis, and treatment, thus contributing to knowledge on special types of venous stroke.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector-based vaccines against SARS-CoV-2. This syndrome is caused by antibodies against platelet factor 4 (PF4; CXCL4) that lead to platelet activation and is characterized by thrombocytopenia and thrombosis in unusual locations, including cerebral venous sinus thrombosis (CVST). VITT can be classified based on anti-PF4 antibodies properties in vitro: those that require PF4 to activate platelets (PF4-dependent) and those that can activate platelets without additional PF4 (PF4-independent) in the serotonin release assay.

We aim to characterize the relationship of VITT platelet-activating profiles with CVST.

We conducted a retrospective cohort study involving patients with confirmed VITT who were tested between March and June 2021. Data were collected with an anonymized form and cases were identified as VITT with high clinical suspicion according to platelet activation assays. Anti-PF4 antibody binding regions on PF4 were further characterized with alanine scanning mutagenesis.

Of the patients with confirmed VITT (n = 39), 17 (43.6%) had PF4-dependent antibodies and 22 (56.4%) had PF4-independent antibodies. CVST occurred almost exclusively in PF4-independent patients (11 of 22 vs 1 of 17; P < .05). Additionally, PF4-independent antibodies bound to 2 distinct epitopes on PF4, the heparin-binding region and a site typical for heparin-induced thrombocytopenia antibodies, whereas PF4-dependent antibodies bound to only the heparin-binding region.

These findings suggest that VITT antibodies that cause PF4-independent platelet activation represent a unique subset of patients more likely to be associated with CVST, possibly due to the 2 different types of anti-PF4 antibodies.

An effective worldwide vaccination campaign started and is still being carried out in the face of the coronavirus disease 2019 (COVID-19) pandemic. While vaccines are great tools to confront the pandemic, predominantly adenoviral vector-based vaccines can cause a rare severe adverse effect, termed vaccine-induced immune thrombocytopenia and thrombosis (VITT), in about 1 in 100,000 vaccinated individuals. VITT is diagnosed 5-30 days post-vaccination and clinically characterized by thrombocytopenia, strongly elevated D-dimer levels, platelet-activating anti-platelet factor 4 (PF4) antibodies and thrombosis, especially at atypical sites such as the cerebral venous sinus and/or splanchnic veins. There are striking similarities between heparin-induced thrombocytopenia (HIT) and VITT. Both are caused by anti-PF4 antibodies, causing platelet and leukocyte activation which results in massive thrombo-inflammation. However, it is still to be determined why PF4 becomes immunogenic in VITT and which constituent of the vaccine triggers the immune response. As VITT-like syndromes are increasingly reported in patients shortly after viral infections, direct virus-PF4 interactions might be most relevant. Here we summarize the current information and hypotheses on the pathogenesis of VITT and address in vivo models, especially murine models for further studies on VITT.

Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are highly prothrombotic (thrombosis frequency ≥50%). Both are caused by platelet-activating anti-platelet factor 4 (PF4) antibodies, forming PF4/IgG-containing immune complexes that engage platelet FcγIIa receptors, producing strong platelet activation. In HIT, heparin crosslinks several PF4 molecules, whereas in VITT, anti-PF4 antibodies alone crosslink PF4. Sufficient levels of circulating anti-PF4 antibodies are needed to create the pathogenic immune complexes on platelet surfaces; this explains why certain serum (plasma)-based assays are highly sensitive for detecting HIT/VITT antibodies. Accordingly, HIT and VITT are "clinical-pathological" disorders, that is, positive testing for such antibodies-together with a compatible clinical picture-is integral for diagnosis. Heparin (low concentrations) enhances HIT antibody-induced platelet activation, but platelet activation by VITT sera is usually inhibited by heparin. For both HIT and VITT, high sensitivity (>99% and >95%, respectively) characterizes PF4-dependent enzyme immunoassays (EIAs) and PF4-enhanced platelet activation assays; in contrast, certain rapid immunoassays have high sensitivity for HIT (>90-97%) but poor sensitivity (<25%) for VITT. HIT and VITT antibodies are directed at distinct sites on PF4: solid-phase EIAs and platelet activation assays are indifferent to these distinct antigen targets, but rapid immunoassays are not. We discuss a conceptual model where PF4 is viewed as a "globe," with the heparin-binding site the "equator"; in this model, HIT antibodies are primarily directed at antigen site(s) at the north and south "poles" of PF4 (formed when PF4 binds to heparin), whereas VITT antibodies recognize sites on the equator.

Rapid diagnosis and treatment has improved outcome of patients with vaccine-induced immune thrombocytopenia and thrombosis (VITT). However, after the acute episode, many questions on long-term management of VITT remained unanswered.

To analyze, in patients with VITT, the long-term course of anti-platelet factor 4 (PF4) antibodies; clinical outcomes, including risk of recurrent thrombosis and/or thrombocytopenia; and the effects of new vaccinations.

71 patients with serologically confirmed VITT in Germany were enrolled into a prospective longitudinal study and followed for a mean of 79 weeks from March 2021 to January 2023. The course of anti-PF4 antibodies was analyzed by consecutive anti-PF4/heparin immunoglobulin G enzyme-linked immunosorbent assay and PF4-enhanced platelet activation assay.

Platelet-activating anti-PF4 antibodies became undetectable in 62 of 71 patients (87.3%; 95% CI, 77.6%-93.2%). In 6 patients (8.5%), platelet-activating anti-PF4 antibodies persisted for >18 months. Five of 71 patients (7.0%) showed recurrent episodes of thrombocytopenia and/or thrombosis; in 4 of them (80.0%), alternative explanations beside VITT were present. After further COVID-19 vaccination with a messenger RNA vaccine, no reactivation of platelet-activating anti-PF4 antibodies or new thrombosis was observed. No adverse events occurred in our patients subsequently vaccinated against influenza, tick-borne encephalitis, varicella, tetanus, diphtheria, pertussis, and polio. No new thrombosis occurred in the 24 patients (33.8%) who developed symptomatic SARS-CoV-2 infection following recovery from acute VITT.

Once the acute episode of VITT has passed, patients appear to be at low risk for recurrent thrombosis and/or thrombocytopenia.

A proactive and systemic approach is imperative to preventing wounds due to disorders of non-malignant haematologic disease. Here, the authors provide several examples of patients with either a known history or acute diagnosis of a coagulation disorder with the aim of reviewing potential cutaneous injuries as well as diagnosis and treatment. A description of the wound and treatment course along with recommendations where appropriate are presented. The article serves as a general review for health professionals who may encounter patients with this disorder and who are involved in treatment decisions. After reviewing the article, the practitioner will be able to identify cutaneous injuries that may be secondary to an underlying haematological disorder, review the diagnosis and treatment recommended, and understand the need for a multidisciplinary approach to patient care.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect from unfractionated or low-molecular-weight heparin that results in thrombocytopenia and potentially catastrophic thrombosis. HIT occurs due to the development of platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin. Given the frequency of thrombocytopenia and heparin use among hospitalized patients, calculation of the 4Ts Score is recommended to identify patients at increased likelihood of HIT and direct further evaluation. In patients with an intermediate or high probability 4Ts Score, an immunoassay and functional assay are recommended to confirm or refute the diagnosis of HIT. Heparin avoidance and initiation of nonheparin anticoagulation are the mainstays of acute HIT management. In this illustrated review, we provide visual summaries of the diagnosis and management of HIT, highlighting connections between pathophysiology and clinical care as well as summarizing efforts in quality improvement in the field. We further emphasize common pitfalls and pearls in diagnosis and management to encourage evidence-based care. We include graphical representation of the unique challenges of HIT with cardiopulmonary bypass and also delineate autoimmune HIT and its subtypes.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic disorder caused by anti-PF4 antibodies that activate platelets and neutrophils, leading to thrombosis. Heparin-induced thrombocytopenia (HIT) is a related anti-PF4 mediated disorder, with similar pathophysiology and clinical manifestations but different triggers (i.e., heparin vs adenoviral vector vaccine). Clinically, both HIT and VITT typically present with thrombocytopenia and thrombosis, although the risk of thrombosis is significantly higher in VITT, and the thromboses occur in unusual anatomical sites (e.g., cerebral venous sinus thrombosis and hepatic vein thrombosis). The diagnostic accuracy of available laboratory testing differs between HIT and VITT; for VITT, ELISAs have better specificity compared to HIT and platelet activation assays require the addition of PF4. Treatment of VITT and HIT is anticoagulation non-heparin anticoagulants; however, heparin may be considered for VITT if no other option is available.

A woman that suffered burns previously presented with leg swelling and was diagnosed with venous thromboembolism. Heparin was given until she suddenly developed myocardial infarction. Ventricular septal rupture was detected and managed by transcatheter closure. She developed massive bleeding and extensive thrombosis that made treatment paradoxical and eventually died.

Anti-platelet factor 4 (PF4) antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) appear to be transient, with discrepant persistence depending on the platform used for detection.

We aimed to report a longitudinal study of antibody persistence using 2 ELISA platforms and 2 platelet-activating functional assays in a clinical cohort of patients with VITT referred for follow-up testing.

In total, 32 Australian patients with VITT or pre-VITT, confirmed by expert adjudication, with samples referred for clinical follow-up were included. Clinical follow-up assays, including Stago and Hyphen ELISAs, procoagulant platelet flow cytometry, and modified PF4-serotonin-release assay, were performed according to the pattern of reactivity for that patient at diagnosis.

The median follow-up was 24 weeks after diagnosis. A general decline in anti-PF4 antibody levels and platelet-activating capacity over time was observed with a more rapid median time to resolution of 16 weeks by functional assay vs 24 weeks by Stago ELISA. Decline in platelet-activating antibody levels detected by functional assays mirrored Stago ELISA titer but not Hyphen. However, 87% of patients received a documented second vaccination and 74% received an mRNA booster with no reported adverse events.

Anti-PF4 antibodies persist longer than functional platelet-activating antibodies in VITT but do not warrant avoidance of subsequent vaccinations. Persistence detection is assay-dependent. Stago ELISA may be a surrogate where functional assays are unavailable for follow-up testing of confirmed patients with VITT.

Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are rare, iatrogenic immune-mediated conditions with high rates of thrombosis-related morbidity and mortality. HIT is a long-recognized reaction to the administration of the common parenterally administered anticoagulant heparin (or its derivatives), while VITT is a new, distinct syndrome occurring in response to adenovirus-based vaccines against coronavirus disease 2019 and potentially other types of vaccines. A feature of both HIT and VITT is paradoxical thrombosis despite a characteristic low platelet count, mediated by the presence of platelet-activating antibodies to platelet factor 4. Several additional factors have also been suggested to contribute to clot formation in HIT and/or VITT, including monocytes, tissue factor, microparticles, endothelium, the formation of neutrophil extracellular traps, complement, procoagulant platelets, and vaccine components. In this review, we discuss the literature to date regarding mechanisms contributing to thrombosis in both HIT and VITT and explore the pathophysiological similarities and differences between the two conditions.

High-dose intravenous immunoglobulin (IVIg) can be effective for patients with refractory autoimmune heparin-induced thrombocytopenia (HIT). We report two patients with autoimmune HIT (aHIT) successfully treated with early high-dose IVIg.

Case 1 was a 48-year-old male who had persisting HIT with recurrent ischemic stroke after mitral valve replacement. Case 2 was a 71-year-old male who had flush heparin HIT with cerebral venous thrombosis after total hip arthroplasty. High-dose IVIg was administered 6 and 4 days after starting argatroban due to non-improved thrombocytopenia and persistently high D-dimer values, respectively. Both patients achieved favorable functional recovery at discharge as well as improvements of thrombocytopenia and hypercoagulation.

Early high-dose IVIg may be effective for patients with aHIT and hypercoagulability.

Heparin-induced thrombocytopenia (HIT) is a major issue in cardiac surgery requiring cardiopulmonary bypass (CPB). HIT represents a severe adverse drug reaction after heparin administration. It consists of immune-mediated thrombocytopenia paradoxically leading to thrombotic events. Detection of antibodies against platelets factor 4/heparin (anti-PF4/H) and aggregation of platelets in the presence of heparin in functional in vitro tests confirm the diagnosis. Patients suffering from HIT and requiring cardiac surgery are at high risk of lethal complications and present specific challenges. Four distinct phases are described in the usual HIT timeline, and the anticoagulation strategy chosen for CPB depends on the phase in which the patient is categorized. In this sense, we developed an institutional protocol covering each phase. It consisted of the use of a non-heparin anticoagulant such as bivalirudin, or the association of unfractionated heparin (UFH) with a potent antiplatelet drug such as tirofiban or cangrelor. Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients.

We report a case of cerebral venous sinus thrombosis, bilateral adrenal hemorrhage, and thrombocytopenia in a 70-year-old man found dead. He had previously received the ChAdOx1 nCoV-19 vaccine (Vaxzevria®, AstraZeneca) 18 days before, and had since developed unspecific and undiagnosed characteristics of what proved to be a rare case of vaccine-associated thrombocytopenia with thrombosis syndrome (TTS). He was found dead 1 week after the beginning of symptoms (day 25 post-vaccine). Autopsy yielded venous hemorrhagic infarction with the presence of thrombi within dural venous sinuses, and extensive hemorrhagic necrosis of the central part of the adrenal glands. Antibodies against platelet factor 4 (PF4) were strongly positive in postmortem fluids, as measured with an enzyme-linked immunosorbent assay (ELISA). This difficult diagnosis is usually made during the patient's lifetime. After eliminating differential diagnoses, we concluded on a fatal case of vaccine-induced immune TTS with positive anti-PF4 antibodies in cadaveric blood, 3 weeks after ChAdOx1 nCoV-19 vaccination. Specific search for anti-PF4 antibodies in cadaveric blood appears therefore paramount to assess postmortem cases of TTS associated with anti-COVID vaccines.

We present the case of a 39-year-old pregnant woman who had intrauterine fetal death and imminent uterine rupture and underwent cesarean section. She also underwent catheter embolization for hemorrhagic shock due to bleeding from the uterine artery, and heparin-containing saline was used. On day 7 of hospitalization, she felt severe pain in her right lower leg, and computed tomography (CT) revealed focal nonocclusive thrombus formations in the right common and external iliac artery. After intravenous heparin administration, she suddenly developed dyspnea, her blood pressure dropped, and her platelet count decreased. We diagnosed her with heparin-induced thrombocytopenia (HIT). Although we discontinued heparin and switched to argatroban, CT after 5 days revealed subtotal occlusion of the right iliac artery by a massive thrombus. We performed surgical thrombectomy using a Fogarty catheter, but blood flow was not restored. Therefore, we administered urokinase continuously with catheter-directed thrombolysis (CDT). The thrombus in the iliac artery gradually cleared and was successfully eliminated. However, the patient developed gangrene in her right lower leg, and we decided to perform an above-knee amputation of the right leg. She was discharged with a prosthetic leg and prescribed 15 mg of rivaroxaban per day.

HIT is a known serious side effect of heparin administration, and it can sometimes be fatal. HIT treatment using aggressive thrombectomy procedures may be ineffective since such procedures may accelerate thrombus formation when the coagulation cascade is highly activated. In this case, CDT may have to be considered as the first-line treatment before Fogarty thrombectomy when argatroban therapy fails.

Heparin-induced thrombocytopenia (HIT) is an important adverse drug reaction that can occur postcardiac surgery. Preoperative exposure to unfractionated heparin (UFH) is common, raising the issue of how frequently cardiac surgery-associated HIT occurs after immunizing preoperative exposure to heparin.

To determine the frequency and clinical picture of HIT occurring within 4 days of cardiac surgery (early presentation) versus later presentations (typical, delayed).

We identified patients with laboratory-confirmed HIT following cardiac surgery over 30 years in a single cardiac surgery center. Three different clinical presentations of HIT were identified: typical (HIT-related platelet count fall beginning between postoperative days [PODs] 5-10), delayed (patients with falls after POD10 or who presented following hospital discharge), and early (established before POD5, including during cardiac surgery [acute intraoperative HIT]).

Of 129 patients identified with HIT complicating cardiac surgery, 100 had typical and 16 had delayed presentation of HIT; only 13 patients (10.1%) presented with early HIT, all of whom had received exposure to UFH during the 10 days before cardiac surgery. No patient was identified in whom remote preoperative UFH exposure was implicated in explaining early HIT. Notably, five patients appeared to have had acute intraoperative HIT, without immediate adverse consequences.

Approximately 90% of patients with HIT after cardiac surgery appear to develop this complication due to immunization triggered by cardiac surgery; however, in approximately 10% of patients, early presentation during the first four PODs (or intraoperatively) can be explained by recent immunizing exposure to heparin.

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin products, but not warfarin. HIT usually occurs 5‒10 days after exposure to heparin. Here, we report a case of HIT with multiple thrombotic events and severe thrombocytopenia resulting from intermittent intravenous heparin flushes for maintenance of a newly placed subclavian central venous catheter (CVC) for stem cell transplant. The patient is a woman in her forties with multiple myeloma who presented to the emergency department (ED) with dyspnea, pleuritic-type chest pain, hemoptysis, and worsening left-leg swelling. Heparin had been used to flush the CVC. Her platelet count began dropping approximately one week after insertion. The patient was receiving other medications known to cause thrombocytopenia. She had undergone multiple platelet transfusions. In the ED, her lab results showed thrombocytopenia), anemia; renal insufficiency; and elevated troponin, prothrombin time, and D-dimer levels. Because of the hemoptysis and thrombocytopenia, she initially received platelet transfusion and oxygen. She was found to have deep vein thrombosis of the lower extremity and started a referral to interventional radiology for inferior vena cava (IVC) filter placement. However, further review and consultation of the Benign Hematology service, discussion about the timing of decreased platelet count shortly after CVC placement and heparin administration, and the presence of thrombosis, suggested a high pre-test probability of HIT. Anticoagulation with argatroban was initiated, and IVC filter insertion was canceled. Further workup confirmed HIT diagnosis and saddle pulmonary embolism. During the patient's hospitalization, her platelets continued to improve and reached baseline upon discharge. She was transitioned to fondaparinux at the time of discharge. A few weeks later, she had successful stem cell transplantation. Emergency physicians treating patients with thrombocytopenia receiving heparin, even in small amounts, should consider the possibility of HIT and be familiar with its management.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is primarily a complication of adenoviral vector-based covid-19 vaccination. In VITT, thrombocytopenia and thrombosis mediated by anti-platelet factor 4 (PF4) antibodies can be severe, often characterized by thrombosis at unusual sites such as the cerebral venous sinus and splanchnic circulation. Like in heparin-induced thrombocytopenia (HIT) and spontaneous HIT, VITT antibodies recognize PF4-polyanion complexes and activate PF4-treated platelets but additionally bind to un-complexed PF4, a critical finding that could be leveraged for more specific detection of VITT. Intravenous immunoglobulin and non-heparin-based anticoagulation remain the mainstay of treatment. Second dose/boosters of mRNA covid-19 vaccines appear safe in patients with adenoviral vector-associated VITT. Emerging data is consistent with the possibility that ultra-rare cases of VITT may be seen in the setting of mRNA and virus-like particle (VLP) technology-based vaccinations and until more data is available, it is prudent to consider VITT in the differential diagnosis of all post-vaccine thrombosis and thrombocytopenia reactions.