Search Results (624)

Transcatheter structural heart interventions, including aortic, mitral and tricuspid valve replacement or repair, and patent foramen ovale, atrial septal defect, and left atrial appendage closure, have dramatically expanded over the past two decades, providing substantial improvements in both clinical outcomes and quality of life. These interventions are performed in a high-risk patient population, which is at risk for both thrombotic and bleeding complications. The introduction of prosthetic devices into the arterial or venous circulation under heterogeneous hemodynamic conditions inevitably increases the risk for thrombotic events and thromboembolic complications. Consequently, the selection of antithrombotic therapy (AT) regimen and its duration is complex and should be tailored to each patient’s risk profile, balancing the expected risk and benefits. This state-of-the-art review critically examines the thrombotic risks inherent to transcatheter structural heart interventions, synthesizes available evidence and current guidelines recommendations on antithrombotic management, and defines persisting gaps in knowledge while discussing the most relevant ongoing clinical trials. Full article

Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1–7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4–10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies). Full article

Background and Clinical Significance: Isolated prolongation of activated partial thromboplastin time (aPTT) without a bleeding tendency presents a frequent diagnostic challenge and often leads to prolonged, inconclusive evaluations. Case Presentation: We report the case of a pregnant woman with long-standing isolated aPTT prolongation in whom clinical exome sequencing enabled a definitive diagnosis. Two compound heterozygous variants in F12 were identified: NM_000505.4:c.1561G>A, p.(Glu521Lys), previously reported in Factor XII deficiency, and a novel in-frame insertion, NM_000505.4:c.1423_1425dup, p.(Cys475dup), absent from population databases and the prior literature. Familial genetic testing confirmed a trans configuration. Factor XII activity was markedly reduced to 1%, and mixing studies showed complete correction, consistent with coagulation factor deficiency without inhibitors. Variant interpretation using ClinGen specifications within a Bayesian framework classified both variants as likely pathogenic. Despite significant laboratory abnormalities, the patient experienced no bleeding or thrombotic complications and underwent cesarean delivery without adverse events. Conclusions: This case highlights that early integration of next-generation sequencing and quantitative variant interpretation frameworks can facilitate timely diagnosis, clarify clinical significance, and support appropriate management in patients with unexplained isolated aPTT prolongation. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Severe congenital Protein C deficiency (SCPCD) is a rare autosomal recessive thrombophilia that typically presents in the neonatal period with early-onset life-threatening thrombotic complications. We report the case of a female infant who presented at birth with digital ischemic necrosis and laboratory evidence of consumptive coagulopathy consistent with neonatal purpura fulminans. Severe Protein C deficiency was confirmed by markedly reduced Protein C activity (<0.03 IU/mL) and compound heterozygous variants in the PROC gene. After initial stabilization and intermittent intravenous Protein C replacement, pharmacokinetic assessment showed marked peak–trough variability. Continuous subcutaneous infusion of Protein C concentrate was therefore initiated using a programmable insulin pump in combination with oral anticoagulation. This strategy achieved stable Protein C activity levels, allowed progressive reduction of the weight-adjusted replacement dose, and enabled removal of the central venous catheter. Continuous subcutaneous infusion of Protein C concentrate via an insulin pump, combined with oral anticoagulation, may represent a feasible long-term therapeutic option in selected patients with SCPCD. Full article

Carotid pseudoaneurysms are rare and potentially life-threatening, often necessitating urgent surgical intervention. Patients with myeloproliferative disorders (MPD) are predisposed to thrombotic and inflammatory complications. Pyoderma gangrenosum (PG), a rare neutrophilic dermatosis, is often misdiagnosed in postoperative settings. In the following article, we present a case of a 58-year-old woman with Philadelphia-negative MPD, neutrophilic leukocytosis, thrombocytosis, osteoporosis, and hypothyroidism, who presented with a giant left common carotid artery pseudoaneurysm. She underwent urgent surgical revascularization via bypass using an autologous reversed saphenous vein graft from the right thigh and external carotid artery ligation. Immediately postoperatively, the patient developed left hemiparesis. Initial CT scans showed bypass graft occlusion and right MCA stroke. Immediate thrombolysis resulted in complete motor recovery, although the bypass remained occluded. On postoperative day 10, necrotic wound lesions developed, initially treated as infectious. After worsening post-debridement, dermatologic evaluation raised suspicion for PG, confirmed by biopsy. She responded well to corticosteroid therapy. Four weeks later, the thigh wound became superinfected with Pseudomonas aeruginosa and Klebsiella pneumoniae, successfully treated with broad-spectrum antibiotics. The patient fully recovered within two months. This case illustrates the complex interplay between vascular, thrombotic, and inflammatory complications in patients with MPD and emphasizes the importance of multidisciplinary care and early recognition of PG. Full article

Background and Clinical Significance: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with a markedly increased risk of arterial and venous thrombosis. Superior mesenteric artery (SMA) thrombosis is an exceptionally rare but potentially fatal complication. Case Presentation: We report the case of a 25-year-old man with previously diagnosed, JAK2-negative PV who presented with acute abdominal pain, nausea, vomiting, abdominal distension, and absence of stool and flatus, consistent with clinical features of intestinal obstruction. Laboratory testing revealed marked leukocytosis, elevated inflammatory markers, and subtherapeutic anticoagulation (INR 1.2) despite ongoing oral therapy. Multislice computed tomography demonstrated occlusion of the SMA with developed collateral circulation and features of small-bowel ischemia. Due to progression to an acute abdomen, emergency laparotomy was performed, revealing jejunal perforation with preserved viability of the remaining bowel. Primary closure was carried out, followed by peritoneal lavage and drainage. The postoperative course was uneventful. After correction of anticoagulation and therapeutic INR monitoring, no recurrent thrombotic events were observed during follow-up. Conclusions: This case underscores the importance of strict anticoagulation control, early imaging, and prompt surgical intervention in patients with PV, even in young individuals and in atypical vascular territories. Full article

Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who develop immune complications secondary to the formation of auto-antibody responses that drive patients’ platelet counts lower or even cause infection, these patients stress the clearest need for prompt tests to discern the more likely thrombocytopenic-inducing cause. It is in this setting that looking at other platelet variables easily obtainable from modern hematology analyzers has gained traction. One of the elements found in extended platelet profiles are immature platelets (youngest and newly released platelets), also known as reticulated platelets, which are readily measurable from a complete blood count. One of the advantages of obtaining these counts is that they represent the immediate response of the bone marrow to the thrombocytopenia and, depending on etiology inducing the thrombocytopenia, they also provide information on the marrow’s response to therapeutic approaches. It is in this context that this review will present information of how these relatively novel platelet parameters can be used in clinical practice and how they can be a rapid gauge of the body’s response to disease processes leading to platelet losses. Thrombocytopenias resulting from infection (sepsis, viremia), autoantibody formation (immune thrombocytopenia and immune-mediated thrombotic thrombocytopenic purpura), immune dysregulation (systemic lupus erythematosus), and iatrogenic (drug-induced) will be discussed and used to explain how these young platelet measurements can provide valuable clinical information. Full article

The concept of ‘developmental hemostasis’ from birth to infancy and onwards to childhood and adulthood was introduced in the 1980s and is used to indicate the fundamental discrepancies of hemostatic mechanism between children and adults. The underlying differentiations are more pronounced in term and even more in preterm neonates. Hemostatic alterations tend to improve throughout childhood and adolescence but still imply a great example of the basic concept that children do not simply represent small adults. Many neonatal coagulation disorders lead to severe morbidities, such as intraventricular hemorrhage and intracerebral infarct, with critical consequences on long-term neurodevelopmental outcome. As the limits of viability have decreased and many preterm and severely affected neonates survive and grow up, a broad understanding of hemorrhagic and thrombotic complications in neonates is very important, in order to provide prompt identification and treatment. Coagulation abnormalities are usually induced by specific pathophysiologic disorders, and neonatal sepsis is a significant trigger of hemostatic derangement. Despite the initial protective role of coagulation activation during the early stages of sepsis, ultimately hemostatic abnormalities exert a substantial impact on clinical outcome and prognosis. This review explores developmental aspects of coagulation, particularly in relation to neonatal sepsis. Full article

Blood platelets are derived from megakaryocytes with functions extending beyond hemostasis to inflammation, immunity, and cancer. Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders driven by somatic mutations affecting JAK-STAT signaling, leading to excessive myeloid proliferation. Thrombosis affects approximately one-fifth of patients at diagnosis and remains elevated throughout the disease course, while the paradoxical coexistence of bleeding further complicates clinical management. In addition, MPNs may progress to advanced disease stages, including bone marrow fibrosis and transformation to acute myeloid leukemia, leading to ineffective hematopoiesis, worsening symptom burden, and poor clinical outcomes. This review outlines how peripherally circulating platelets provide a unique window into MPN pathophysiology, with emphasis on their functional and molecular abnormalities. We summarize current understanding of platelet-mediated hemostatic imbalance across MPN subtypes. We discuss the potential of platelet transcriptomics and proteomics to reveal disease-specific signatures. We further highlight emerging platelet-associated candidates with potential utility as dynamic biomarkers for both the pathological marrow niche and thrombotic and bleeding risk. Together, these insights underscore the potential of platelet-based approaches to complement existing diagnostic and prognostic strategies in MPNs. Full article

Clot-in-transit (CIT) is a free-floating thrombus in the right heart and can enter pulmonary circulation at any moment. Possible treatments include anticoagulation, systemic thrombolysis, surgical embolectomy, and endovascular catheter-based therapies. The optimal treatment is still undetermined, heavily relying on clinical judgment and multidisciplinary team discussion. We report a case of a 70-year-old woman presenting with tachydyspnoea following recent abdominal surgery, who was diagnosed with massive bilateral pulmonary embolism (PE) complicated by a clot-in-transit. Point-of-care ultrasonography revealed a large mobile thrombus in the right atrium with severe right ventricular dysfunction. Due to haemodynamic instability and a contraindication for systemic thrombolysis, mechanical thrombectomy was performed. A large thrombotic burden was aspirated from the right heart and pulmonary arteries, resulting in haemodynamic stabilization and recovery of right ventricular function. The patient remained stable throughout hospitalization and was discharged on oral anticoagulation therapy with complete recovery on follow-up. This case highlights several points. Firstly, CIT is a rare finding but should be considered in patients with massive pulmonary embolism and shock. Furthermore, POCUS is essential for diagnosing CIT. Finally, mechanical thrombectomy is a valuable therapeutic option in high-risk PE patients with contraindications to systemic thrombolysis and haemodynamic instability. Further studies are needed to establish adequate guidelines for the optimal management of CIT patients. Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology. Full article

The development of thrombocytopenia is common in cirrhosis. Further complex alterations in haemostasis also occur, resulting in a rebalanced state that predisposes patients to both thromboembolic and bleeding complications. Guidance on the management of thrombosis in patients with cirrhosis-related thrombocytopenia is limited and poses a common clinical dilemma. Anticoagulation in this population remains challenging due to altered drug pharmacokinetics, baseline abnormalities in conventional coagulation tests, limitations in laboratory monitoring, thrombocytopenia itself and concerns regarding bleeding risk. Low-molecular-weight heparin and vitamin K antagonists have traditionally been used; however, increasing data support the use of direct oral anticoagulants in patients with compensated cirrhosis. Management decisions should be individualised, incorporating liver disease severity, thrombotic burden, bleeding risk, and clinical factors such as portal hypertension. This review summarises current evidence on thromboembolic disease and antithrombotic therapy in cirrhosis-related thrombocytopenia. Further prospective studies are required to investigate key knowledge gaps, including optimal platelet thresholds for anticoagulation use and the role of functional coagulation testing in this population. Full article

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL) and is frequently associated with autoimmune phenomena. Clinically, AITL shows an aggressive disease course and poor prognosis with currently available treatment strategies. We here report the case of a 64-year-old female patient who was diagnosed with AITL and showed a complicated clinical course due to concurrent immune-mediated thrombotic thrombocytopenic purpura (iTTP). To our knowledge, the presented case highlights a previously unreported association of both conditions. Treatment, including chemotherapy and iTTP-directed treatments, resulted in rapid clinical improvement and sustained remission of both the AITL and the concurrent iTTP. In AITL, transformed T-follicular helper cells (TFHs) are particularly thought to mediate hypersecretion of cytokines and excessive autoantibody production. Immunological disturbances to large parts mediated through these transformed TFHs are thought to trigger autoimmune conditions, as seen with iTTP in this patient. At 36 months post-treatment, the patient remains in complete remission for both AITL and iTTP. This case highlights the complex immunopathological relationship between AITL and autoimmune disorders possibly impeding diagnosis and treatment in a timely manner. Full article

Inflammatory bowel disease is a recognized risk factor for venous thromboembolism, whereas arterial thrombotic events remain underappreciated despite their substantial clinical consequences. We report a 45-year-old man without significant comorbidities who developed severe ulcerative colitis complicated by diffuse arterial thrombosis, including cerebral infarctions, an ascending aortic mural thrombus, iliac artery thrombosis, and multi-organ infarctions. After stabilization with supportive care and anticoagulation, remission-directed ulcerative colitis therapy and a vascular safety–oriented maintenance strategy were initiated, including vedolizumab and individualized secondary thrombosis prevention. To contextualize this presentation, we integrate current evidence on the epidemiology, clinical phenotypes, underlying mechanisms, and risk factors for arterial thrombosis in inflammatory bowel disease, highlight disease activity as a dominant trigger, and summarize therapy-specific vascular safety considerations across IBD treatment classes. Full article