Infective endocarditis (IE) arises from complex interactions between microbial pathogens and host hemostasis systems, where dysregulated coagulation mediates microbial persistence and systemic thromboembolic complications. Alterations in primary, secondary, and tertiary hemostasis in the acute IE phase have direct clinical implications for vegetation formation and detachment. Staphylococcus aureus is one of the most common pathogens that causes IE, and it is capable of profoundly altering the coagulation cascade through several mechanisms, such as platelet activation, prothrombin activation through staphylocoagulase release, and plasminogen stimulation via staphylokinase production. Understanding these complex and yet unmasked mechanisms is of pivotal importance to promoting targeted therapeutic intervention aimed at reducing IE morbidity and mortality. Moreover, the management of antiplatelet and anticoagulant treatment during IE onset is a controversial issue and needs to be tailored to patient comorbidities and IE-related complications, such as cerebral embolism. This review provides a roadmap to promote clinicians' understanding of the complex interactions between hemostasis and IE clinical manifestations and complications, discussing pathogen-specific coagulation profiles while addressing critical knowledge gaps for IE management.

Around 10% of patients with acute coronary syndrome are treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants for various indications. The initial management of these patients is highly complex, and new guidelines specify that, only during percutaneous coronary intervention, a bolus of unfractionated heparin is recommended in one of the following circumstances: (1) if the patient is receiving a non-vitamin K antagonist oral anticoagulant; or (2) if the international normalized ratio is<2.5 in a patient being treated with a vitamin K antagonist. In this review, we report on five key messages essential for the management of these patients. There are no randomized studies to date, and we propose two diagnostic and/or therapeutic decision algorithms. However, randomized studies are needed to validate these strategies.

Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein, carrying high rates of morbidity and mortality.

We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver failure. Pylephlebitis was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal veins. To our knowledge, this is the first documented case of acute liver failure as a potential life-threatening complication of pylephlebitis.

Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain, especially if there are co-existing risk factors for hypercoagulability. We also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the United States. VTE is caused by genetic and acquired conditions, but the genetic variants that increase the risk of VTE are not fully characterized. Recent genome-wide association studies (GWAS) have discovered novel genetic loci linked to VTE. Some of these loci have been characterized, uncovering new pathways that regulate VTE. Functional characterization of candidate genes discovered by GWAS may reveal new therapeutic targets to treat and prevent abnormal thrombosis or bleeding.

The occurrence of coronary artery embolism (CE) has been associated with various clinical conditions, including aortic and mitral prosthetic heart valve implantation, atrial fibrillation (AF), dilated cardiomyopathy, neoplasia, infective endocarditis, atrial septal defect, cardiac tumors, and hypercoagulable states. CE is also a rare cause of myocardial infarction (MI), with a prevalence of about 5%, a figure probably underestimated. The purpose of this article was to determine the current state of knowledge on acute coronary syndrome (ACS) related to CE. We thus performed a comprehensive structured literature search of the MEDLINE database for articles published between 1 January 1990 and 31 December 2021. The diagnosis of CE remains difficult despite the currently used Shibata classification, which is based on major criteria, including angiographic characteristics: globular filling defects, saddle thrombi or multiple filling defects and absence of atherosclerosis in the coronary arteries. Suspected or confirmed CE requires the identification of an etiology. There are only two published series on CE, including about 50 cases each. The three main causes in these series were: 1) atrial fibrillation (73% vs 28.3%), 2) cardiomyopathy (9.4% vs 25%) and 3) malignancy (9.6% vs 15.1%). Finally, 26.3% of the MI patients with CE had no identifiable cause of CE. When anatomically possible, analyzing the thrombus after thrombectomy may help. MI due to CE requires systematic assessment of other locations, i.e. multiple coronary and extracardiac locations. Simultaneous systemic embolization to the brain (67%), limbs (25%), kidneys (25%) or spleen (4%) is frequent, occurring in approximately 25% of CE-related MI. In the setting of acute MI, CE is associated with significant morbidity and mortality. Coronary artery thromboembolism is a rare, non-atherosclerotic, cause of ACS, and prospective studies are needed to evaluate a systematic diagnostic approach and personalized therapeutic strategies.

Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis.

Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical.

Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study.

The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.

We investigated the frequency of factor 5 Leiden (FVL) and prothrombin gene (PTG) mutations in patients with severe coronavirus disease 2019 (COVID-19). Our primary aim is to reveal whether these mutations are associated with severity of disease and mortality. A total of 249 patients were included in this cross-sectional study. Severe COVID-19 cases (with oxygen saturation of less than 90 mmHg and who received ventilation support invasively or noninvasively) were included. FVL and PTG mutations were identified by real time- PCR technique. Frequency of mutations for FVL was 11.7%, whereas for PTG was 3.5%. The frequency of FVL and PTG's mutations in our patient group was found to be significantly higher than the normal population ( P  < 0.0001, 0.004, respectively). There was no difference in the frequency of mutations of FVL and PTG between the patients ventilated - invasively and noninvasively. There was also no difference in D-dimer, ferritin, fibrinogen, ex status, and entubational status between the groups of FVL and PTG mutated and wild-type. To the best of our knowledge, it is the first time that we have examined the frequencies of FVL and PGM's mutations in severe COVID-19 disease on such a large scale. The frequencies of both mutations in severe COVID-19 patients were higher than in the healthy population. We believe that studies prospectively designed, including asymptomatic and mild COVID-19 patients, will provide more comprehensive information on the subject.

The term myocardial infarction with non-obstructive coronary arteries (MINOCA), defines a puzzling event occurring in the absence of obstructive coronary artery disease on coronary angiography and without an overt potential cause. However, a practical diagnostic work-up is often difficult, due to the heterogeneous etiologies and pathophysiology of MINOCA. This review aims to provide a comprehensive overview focusing on epidemiology, etiopathogenesis, diagnostic tools and therapeutic strategies for subjects with MINOCA, in order to provide a prompt and accurate diagnostic work-up and an adequate therapeutic approach in this subset population.

This educational review was carried out by following the standard methods of the Cochrane Collaboration and the PRISMA statement. The terms "MINOCA" OR ("myocardial infarction" AND ("non-obstructive" OR "non-obstructive")) were searched in PubMed and Embase databases (in Title and/or Abstract) from 1st January 2003 until 31st May 2022.

Etiologic findings, clinical presentation and the degree of hemodynamic impairment play a pivotal role in defining the patient's natural history and prognostic outcome, and may significantly impact on the decision-making strategies and therapeutic approaches.

Despite further advances in diagnostic and therapeutic strategies, MINOCA remains a challenging conundrum in clinical practice. Clinicians should be aware of the different potential etiologies and pathogenic mechanisms of MINOCA, in order to carry out a comprehensive diagnostic work-up and implement a tailored therapeutic approach.

In young patients, especially with no traditional coronary risk factors, hypercoagulable states may always be considered as an alternative cause of acute coronary syndromes. The concomitant thrombotic and bleeding risk associated with myeloproliferative disorders complicates the decision-making, particularly regarding long-term dual antiplatelet therapy. The chosen therapy may need to be frequently revisited, depending on the patient's bleeding complications. We reported the case of a 49-year-old woman with acute myocardial infarction with no traditional risk factors for coronary artery disease where a myeloproliferative neoplasm was diagnosed.

Inherited thrombophilic disorders are well-established predisposing factors for venous thromboembolism, but their role in arterial ischaemic stroke is uncertain. The exact mechanism of arterial thrombosis in thrombophilias remains elusive. Herein, we report a case of a 30-year-old woman who was admitted to our facility with sudden-onset right-sided ptosis and ophthalmoplegia. Detailed clinical features, neuroimaging and laboratory evaluation clinched the diagnosis of ischaemic stroke in midbrain due to microvascular obstruction associated with isolated protein S deficiency. She was treated with oral anticoagulant (warfarin) and physiotherapy; without any improvement of her symptoms at 2 months of follow-up. A high index of clinical suspicion is needed in any case of young ischaemic stroke in absence of common cardiac and vascular risk factors, to recognise the presence of inherited thrombophilia.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is defined by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries on angiography. This condition is present in about 5% to 25% of patients presenting with acute coronary syndromes. MINOCA is a working diagnosis. Current guidelines and consensus recommend identification of underlying causes of MINOCA in order to optimize treatment, improve prognosis, and promote prevention of recurrent myocardial infarction. An accurate evaluation of patient history, symptoms and use of invasive and non-invasive imaging should lead to identification of epicardial or microvascular causes of MINOCA and differentiation from non-ischemic myocardial injury due to both cardiac (e.g. myocarditis) and non-cardiac disease (e.g. pulmonary embolism). In this review, we highlight the role of coronary imaging in differential diagnosis of patients presenting with MINOCA. Intravascular ultrasound and optical coherence tomography are well known technologies used in different settings from acute to chronic coronary syndromes. In MINOCA patients, coronary imaging could help to identify pathological alterations of the epicardial vessels that are not visible by coronary angiography such as plaque disruption, coronary dissection, coronary thromboembolism, coronary spasm, and coronary artery disease in patients presenting with takotsubo syndrome. In future, the widespread use of these technologies, in the right clinical context, could lead to optimization and personalization of treatment, and to better prognosis of patients presenting with MINOCA.

Background: The last two decades have seen a growing number of pregnancies in women who needed the donation of oocytes. With oocyte donation pregnancies, studies on obstetric outcomes among these women revealed an increased incidence of pre-eclampsia and pregnancy-induced hypertension. Furthermore, several studies have found a higher incidence of low birth weight, preterm birth, and delivery by cesarean section in oocyte donation rather than in women subjected to assisted reproduction techniques (ART) with autologous oocytes. Numerous studies have also shown a deep connection between cardiovascular and thrombotic risk factors and adverse pregnancy outcomes. In this setting, to strictly assess the preconceptional risk for women who undergo egg donation to achieve pregnancy, the aim of our study is to draw a detailed assessment of the vascular risk profile of patients with gamete donation ART indications through the evaluation of comorbidities and cardiometabolic and thrombophilic markers Materials and Methods: Patients undergoing ART with oocyte or sperm donation or double donation of gametes underwent a careful clinical assessment through a detailed personal and family anamnesis and they were evaluated for cardiometabolic and thrombophilic profile. Clinical and demographic characteristics, comorbidities, and biohumoral parameters were collected. The study was approved by the Regional Ethical Committee(Em 2018-017 CINECA 10189). Results: We evaluated 525 women. Around 73.1% were >40 years and 35% of them were older than 45 years. There was a high prevalence of dyslipidemias (58.1%), smoking habit (24.6%), a body mass index >25 in 28.6% of patients, a high abdominal circumference in 58.1% of cases, a prevalence of acquired thrombophilia in about 7% and hereditary of 19.2%. Around 39.2% of patients had total cholesterol >200 mg/dL, 19.5% had high-density lipoprotein <48 mg/dL and 43.6% had low-density lipoprotein >115 mg/dL, and 6.9% had triglyceride values >150 mg/dL. Conclusions: A careful assessment of the preconceptional status of patients undergoing ART programs with oocyte donation can be highly recommended.

: Hereditary protein S deficiency is an autosomal dominant disorder associated with a high risk of venous thromboembolism (VTE) and usually results from mutations of PROS1. Historically heparin and warfarin have been applied as recommended treatment of VTE. Recent researches showed that rivaroxaban provided more consistent and predictable anticoagulation than warfarin. However, it is unknown whether rivaroxaban is effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report two cases of recurrent VTE in two patients with hereditary protein S deficiency, owing to the same nonsense mutation in PROS1, which were successfully treated by rivaroxaban monotherapy.

How thrombophilia may contribute to the development of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. We searched on PubMed and EMBASE (until 15 April 2018), studies on CTEPH reporting data on inherited or acquired thrombophilia. Starting from 367 articles mentioning the search terms, 347 were excluded mainly as duplicate articles or articles not in English. After reading the full text of remaining articles, ten were excluded for being reviews, editorials, letters or case reports, and two were further removed from the analysis because of the potential selection bias. All the eight considered studies provided the proportion of patients positive for antiphospholipid (aPL) antibodies. The crude rate of aPL in CTPEH patients is 11.8% (95% CI 10.09-13.8%). The meta-analysis considering the weighted mean proportion and 95% confidence intervals (CIs) yields a rate of aPL antibody-positive profile of 12.06% (95% CI 8.12-16.65%) among the patients with CTEPH in the random effects model (I² 76.33%; 95% CI 52.75-88.14%, p = 0.0001). The sensibility analysis confirms the result. No predictors of heterogeneity are found in a meta-regression analysis. Our results suggest that aPL antibodies are frequently associated with CTEPH underlining the need to test for aPL antibodies in young patients with "idiopathic" and "provoked" PE caused by mild provoking risk factors.

To review the use of the direct oral anticoagulant (DOAC) agents in inherited thrombophilia based on the literature. MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1970-May 2016) were conducted for case reports, case series, retrospective cohorts, or clinical trials using the key words: protein C deficiency, protein S deficiency, antithrombin deficiency, activated protein C resistance, Factor V Leiden, hypercoagulable, NOACs, dabigatran, apixaban, rivaroxaban, betrixaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Results were limited to English-only articles. Clinical studies evaluating the use of DOACs for hypercoagulable states related to inherited thrombophilia were selected and evaluated. Thrombophilia, a predisposition to thrombosis, manifests predominantly as venous thromboembolism. Causes of inherited thrombophilia include antithrombin deficiency, deficiencies of proteins C and S, and Factor V Leiden mutation. Many patients with thrombophilia receive anticoagulant therapy for primary or secondary prevention of VTE, historically either warfarin or a heparin product. DOAC's have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports and a post-hoc analysis of a clinical trial have indicated positive results in patients with inherited thrombophilia and VTE. Positive results have been reported for the use of DOACs in inherited thrombophilia. Further robust studies are needed for definitive decision making by clinicians.

This issue provides a clinical overview of deep venous thrombosis, focusing on prevention, diagnosis, treatment, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.