Background The recently reported c.1787G>A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. Objectives We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation. Patients and methods Nineteen family members were investigated, among whom 10 were carriers of the c.1787G>A mutation. In all subjects the clinical phenotype was determined and laboratory investigations of hemostatic parameters were performed. Results Six out of the 10 mutation carriers developed thromboembolic events, mainly deep venous and mesenteric vein thrombosis. The median age of the first thrombotic event was 26.5 (12-41) years, whereas the incidence rate of first thrombosis was 2.2% per year. In all mutation carriers prothrombin activity was significantly decreased in comparison with non-carriers, clearly distinguishing each group. However, the presence of the mutation did not affect the prothrombin antigen level in plasma. The endogenous thrombin potential was significantly increased in all carriers in comparison with non-carriers, indicating the presence of blood hypercoagulability. Interestingly, levels of D-dimer and the F1+2 fragment were similar in both groups. Conclusions Although rare, the prothrombin Belgrade mutation represents strong thrombophilia with early onset of thrombosis in the investigated family. According to our results, decreased prothrombin activity may be a simple screening test for detection of this mutation in thrombotic patients.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.

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Introduction. D-dimer is formed during plasmin-mediated proteolysis of cross-linked fibrin; hence it serves as a biomarker of activated coagulation and fibrinolysis. Clinical significance. Measurement of D-dimer is most commonly used to exclude venous thromboembolism, and in the diagnosis of disseminated intravascular coagulation. For the diagnosis of venous thromboembolism D-dimer is part of the validated algorithm, which includes an assessment of clinical pre-test probability to guide further investigation. Due to very high negative predictive values, average levels of D-dimer are sufficient for ruling out venous thromboembolism in patients with low-medium pre-test clinical probability. However, in patients with high pre-test probability, the measurement of D-dimer is of limited value. Similarly, normal values of D-dimer reliably exclude disseminated intravascular coagulation. On the other hand, elevated values of D-dimer have low specificity for this condition and should be evaluated in a validated scoring system developed for the diagnosis of disseminated intravascular coagulation. Recently, measurement of D-dimer has been increasingly applied to assess the risk of venous thrombosis recurrence in women and to decide on the duration of anticoagulant therapy after the first unprovoked venous thrombosis. Elevated D-dimer level is an essential characteristic of COVID-19 - associated coagulopathy. The degree of coagulopathy and D-dimer levels correlate with the clinical severity of the disease and higher mortality, most likely reflecting increased activation of the coagulation system in the microcirculation of various organs, primarily the lungs. Conclusion. D-dimer is one of the most often used hemostasis test, validated so far for diagnosis of venous thromboembolism and disseminated intravascular coagulation.

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