APS diagnosis is dependent on accurate detection and interpretation of antiphospholipid antibodies (aPL). Lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis. In the 2023 ACR/EULAR APS classification criteria, the type of laboratory parameters remain essentially unchanged compared to the updated Sapporo classification criteria, and aCL and aβ2GPI antibody measurement is still restricted to enzyme-linked immunosorbent assays (ELISA) with moderate and high titer aPL thresholds defined as 40 and 80 units, respectively, and a cutoff calculated by the 99 percentile has been abandoned. We must differentiate between classification criteria and assessment of aPL in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader meant to diagnose each APS patient to optimize their management. Nowadays, there is increasing use of measurement of aPL by methods other than ELISA, the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes IgM and IgA, and the role of other aPL, such as antiphosphatidylserine/prothrombin antibodies. Patients diagnosed with the disease may or may not fulfill the classification criteria and inappropriate use of classification criteria may lead to mis(under)diagnosis. The aim of this guidance, based on literature and expert opinion, is to provide guidance recommendations for laboratory workers and clinicians, on routine diagnostic assessment of patients with suspected APS.

Understanding of the hemostatic and complement alterations associated with cardiopulmonary bypass (CPB) in pediatric patients and the impact of these alterations on outcome is limited.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by quantitative or qualitative defects of VWF. The p.M771V VWF variant leads to a severe bleeding phenotype in homozygous patients. However, the exact molecular mechanism remains unclear, which prevents personalized treatment of those VWD patients.

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein that inhibits FXa, the TF-FVIIa-FXa complex, and early forms of the prothrombinase complex. Concizumab is a monoclonal antibody that blocks FXa inhibition by TFPI and reduces bleeding in hemophilia.

Increasing evidence in females with Hemophilia A has shown significant bleeding symptoms. Accurate factor VIII activity (FVIII:C) measurement is essential to assign correct diagnosis/severity. Assay discrepancies reported in Hemophilia A male patients, are not well studied in females.

Fibrinogen and its insoluble degradation product fibrin are pivotal plasma proteins that play important roles in blood coagulation, wound healing, and immune responses. This review highlights research from the last 24 months connecting our progressing view of fibrin(ogen)'s structure, and in particular its conformational flexibility and post-translational modifications (PTMs), to its (patho)physiological roles, molecular interactions, mechanical properties, use as a biomaterial, and potential as a therapeutic target. Recent work suggests that fibrinogen structure is highly dynamic, sampling multiple conformations, which may explain its myriad physiological functions and the presence of cryptic binding sites. Investigations into fibrin clot structure elucidated the impact of PTMs, therapeutic interventions, and pathological conditions on fibrin network morphology, offering insights into thrombus formation and embolization. Studies exploring the mechanical properties of fibrin reveal its response to blood flow and platelet-driven contraction, offering implications for clot stability and embolization risk. Moreover, advancements in tissue engineering leverage fibrin's biocompatibility and customizable properties for diverse applications, from wound healing to tissue regeneration and biomaterial interactions. These findings underscore the structural origins of fibrin(ogen)'s multifaceted roles and its potential as a target for therapeutic interventions.

A 56-year-old woman required urgent cardiac surgery for Streptococcus mitis mitral valve infective endocarditis complicated by severe autoimmune HIT (aHIT). We reasoned that the combination of high-dose IVIG (to mitigate aHIT antibody-mediated platelet activation in the presence of heparin) together with the high concentrations of heparin attained during cardiac surgery (which typically produce less platelet activation in-vitro versus usual therapeutic heparin concentrations) might prove effective. Accordingly, our patient underwent cardiac surgery with heparin following high-dose IVIG (1g/kg×2), without intra- or postoperative thrombosis. Serial serotonin-release assays, using blood obtained pre-/post-IVIG, showed minimal platelet activation (∼30% serotonin-release) post-IVIG at heparin concentrations typically obtained during cardiac surgery (2-5 U/mL), and significantly less than pre-IVIG serum in heparin's absence (∼85% serotonin-release). In the setting of urgent cardiac surgery, preoperative high-dose IVIG appears to be a reasonable strategy to reduce platelet-activating effects of HIT (including aHIT) antibodies, permitting safe use of standard intraoperative heparin dosing.

Aplastic anemia (AA) is a bone marrow failure disease for which the means of assessing and predicting the therapeutic effectiveness are still relatively limited. Thrombocytopenia is often the earliest and most severe symptom in patients newly diagnosed with AA (Dx-AA). While clinical consideration is usually given to the quantitative changes in platelets during treatment, there is little focus on the resolution of the molecular characteristics of platelets in AA.

Following the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted dichotomously, with test results categorized as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear.

Catheter-related thrombosis (CRT) is a complication of central venous access devices (CVADs). Evidence is variable regarding the significance of the side of catheter insertion. The role of the patient's hand dominance in predisposition to CRT remains uncertain.

Following proteolytic activation, activated blood coagulation factor VIII (FVIIIa) binds to activated platelet membranes, forming the intrinsic tenase complex with activated factor IX (FIXa). Previous studies have identified the C1 and C2 domains as the membrane binding domains of FVIII through conserved arginine residues. A membrane binding model for the FVIII C domains proposes that surface exposed hydrophobic and positively charged residues at each C domain interact with the membrane, yet a comprehensive thermodynamic and structural description of this interaction is lacking.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are not responsive to standard rituximab in approximately 10-15% of cases, and oral immunosuppressants showed controversial results with significant toxicity. Targeting plasma cells with bortezomib appears promising, but available evidence is scarce and stems only from isolated reports in the pre-caplacizumab era.

While the number of models for predicting the risk of cancer-associated thrombosis has been rising, there is still a lack of comprehensive assessment for machine learning prediction models.

Immediate factor Xa (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases.

Many research investigations for pulmonary embolism (PE) rely on the International Classification of Diseases 10th Revision (ICD-10) codes for analyses of electronic databases. The validity of ICD-10 codes in identifying PE remains uncertain.

Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor VIII (FVIII). The goals of treatment are two-fold, namely immunosuppressive therapy (IST) to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a factor VIIIa (FVIIIa) mimetic, has seen growing use in AHA following its approval for congenital hemophilia A (cHA). This review provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of AHA. Registry, trial, and case series data are assimilated and summarized with an emphasis on a standardized approach that integrates the use of emicizumab. With recent registry data suggesting the need to focus on immunosuppression-related mortality in AHA, we provide treatment recommendations in an algorithmic format that have become the standard of care at our institution. These recommendations are intended to minimize hemostatic product usage and potential toxicity related to IST, while reducing morbidity and re-hospitalization rates for bleeding. The proposed treatment algorithm, which includes key interventions by phase of therapy, can be readily implemented at centers that have rapid access to plasma FVIII activity using a one-stage assay. A case is presented to illustrate the proposed diagnostic and management considerations.

Here, we summarize the EHA-ISTH-EAHAD-ESO Clinical Practice Guidance document recommendations on antithrombotic therapy for cardiovascular indications among patients with hemophilia. This summary includes discussion on primary and secondary prevention of venous and arterial thrombosis. The guidance document considers distinct and controversial challenges presented by various clinical scenarios in this aging patient population and provides thoughtful recommendations to assist the hemophilia care provider in clinical decision-making.

The availability of direct oral anticoagulants rapidly changed the landscape of anticoagulation between 2010 and the present. Randomized controlled trials demonstrating efficacy with similar or superior safety compared with warfarin led to the widespread use of direct oral anticoagulants in male and female patients of all ages. Years later, postmarketing data demonstrated a markedly increased rate of heavy menstrual bleeding (HMB) with rivaroxaban that had gone undetected in registry trials. Factor (F)XI inhibitors are currently being investigated as another alternative to available anticoagulation agents. While generally mild, the phenotype of inherited FXI deficiency includes bleeding in tissues with enhanced fibrinolysis, including HMB. Thus, we aimed to perform a systematic review of published studies on FXI inhibitors in order to estimate rates of HMB. However, we found that few studies included menstruating individuals, and even fewer specifically reported on uterine bleeding, highlighting once again a flaw in our approach to conducting trials of new anticoagulants.

Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE).

Hypertrophic synovium (HS) is a marker of disease activity in patients with haemophilia (PwH). Although some recommendations suggest intensifying prophylaxis in PwH with HS, no validated schedules are available. We explored the efficacy of intensive Factor VIII (FVIII) replacement treatment in PwH with HS.

Long term-recurrence risk following a pregnancy associated venous thromboembolism (VTE) is sparsely assessed.