Thrombosis risk assessment in patients with congenital thrombophilia during COVID - 19 infection.

BACKGROUND: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. METHODS: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 patients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. RESULTS: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with thrombophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. CONCLUSION: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.

Genotype phenotype correlation in a pediatric population with antithrombin deficiency.

Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases.Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients. What is Known: • Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene. • The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients. What is New: • The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3). • In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.

Endothelial biomarkers in the light of new sepsis definition.

The aim of our study was to compare usefulness of endothelial biomarkers for severity and outcome prediction in patients with positive Sepsis-3 criteria with traditionally used biomarkers. A total of 150 patients were included in our study. Patients were divided into two groups: patients with sepsis and those with infectious systemic inflammatory response syndrome. Development of septic shock and 28-day mortality were assessed. Endocan and thrombomodulin showed better discriminative power than procalcitonin for the presence of sepsis. Endocan showed good discriminative power for septic shock prediction. Addition of endocan significantly contributed to sequential (sepsis-related) organ failure assessment score in logistic regression model. Conclusion: Endothelial biomarkers have a good diagnostic potential for sepsis. Endocan is useful as a predictor of the severity and fatality of sepsis.

The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications.

BACKGROUND: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. METHODS: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. RESULTS: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P = 0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. CONCLUSION: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers.

INTRODUCTION: The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. METHODS: One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. RESULTS: A significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. CONCLUSION: In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

: Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

Clinical and laboratory characteristics of antithrombin deficiencies: A large cohort study from a single diagnostic center.

INTRODUCTION: Inherited antithrombin (AT) deficiency is a heterogeneous disease. Due to low prevalence, only a few studies are available concerning genotype-phenotype associations. The aim was to describe the clinical, laboratory and genetic characteristics of AT deficiency in a large cohort including children and to add further laboratory data on the different sensitivity of functional AT assays. PATIENTS AND METHODS: Non-related AT deficient patients (n=156) and their family members (total n=246) were recruited. Clinical and laboratory data were collected, the mutation spectrum of SERPINC1 was described. Three different AT functional assays were explored. RESULTS: Thirty-one SERPINC1 mutations including 11 novel ones and high mutation detection rate (98%) were detected. Heparin binding site deficiency (type IIHBS) was the most frequent (75.6%) including AT Budapest3 (ATBp3), AT Padua I and AT Basel (86%, 9% and 4% of type IIHBS, respectively). Clinical and laboratory phenotypes of IIHBS were heterogeneous and dependent on the specific mutation. Arterial thrombosis and pregnancy complications were the most frequent in AT Basel and AT Padua I, respectively. Median age at the time of thrombosis was the lowest in ATBp3 homozygotes. The functional assay with high heparin concentration and pH7.4 as assay conditions had low (44%) sensitivity for ATBp3 and it was insensitive for AT Basel and Padua I. CONCLUSION: Type IIHBS deficiencies behave differently in clinical and laboratory phenotypes from each other and from other AT deficiencies. Heparin concentration and pH seem to be the key factors influencing the sensitivity of AT functional assays to IIHBS.

Endogenous thrombin potential as marker of procoagulant response that can be useful in early stage of sepsis.

: Sepsis is associated with complex procoagulant and anticoagulant changes that modify inflammatory response. Identification of coagulation markers that can differentiate useful procoagulant response from adverse alteration of clotting mechanism in patient with sepsis. In total, 150 patients who fulfilled criteria for diagnosis of sepsis were included in this study. Patients were categorized in two groups according to sepsis severity in the first 24 h from intensive care unit admission: sepsis and septic shock. In total, 28-day mortality was assessed. Platelet count, activated partial thromboplastin time, prothrombin time, D-dimer, fibrinogen, protein C, protein S, antithrombin levels, and endogenous thrombin potential were determined within first 24 h from ICU admission. Differences between groups of septic patients were assessed by Mann-Whitney U test. Categorical variables were compared using χ test. Receiver operating characteristic curves were plotted to determine predictive values of variables for sepsis severity prediction. Activated partial thromboplastin time and prothrombin time were significantly prolonged with higher D-dimer, lower fibrinogen, and natural anticoagulant levels (protein C, protein S, and antithrombin) in patients with more severe form of the disease and worse outcome (P < 0.05). Endogenous thrombin potential [area under the curve (AUC) %] was significantly decreased in patients with more severe form of sepsis (66.01 ±â€Š41.51 vs. 83.21 ±â€Š28.83; AUC 0.76) and in patients with worse outcome (67.66 ±â€Š37.79 vs. 81.79 ±â€Š32.15; AUC 0.68; P < 0.05). Evaluation of initial thrombin generation is useful to distinguish between beneficial coagulation activation and hazardous haemostatic alteration, and to predict multiorgan dysfunction development and poor outcome in septic patients.

Early pregnancy angiogenic proteins levels and pregnancy related hypertensive disorders.

INTRODUCTION: Normal placental vascular development depends on multiple interactions of many regulatory molecules including pro and antiangiogenic proteins. It is considered that these vascular modulators might be one of the factors responsible for development hypertensive disorders in pregnancy. OBJECTIVE: To evaluate and compare the early pregnancy (11-14 week of gestation) serum level of angiogenic proteins sFlt1, VEGF i PIGF between different types of pregnancy related hypertensive disorders. MATERIALS AND METHODS: The study included 177 pregnant women between 11 and 14 weeks of gestation, divided into four study subgroups (preeclampsia group-41, gestational hypertension group-31, chronic hypertension group-32 and miscarriage group-19) and control group-54. Blood samples (serum) were taken for measuring sFlt1, VEGF i PIGF by a quantitative ELISA technique and measuring other biochemical and hematological parameters. RESULTS: Significantly higher levels of sFlt1 were in the subgroups with preeclampsia and miscarriages, significantly lower level of VEGF in the all study subgroups and lover level of PIGF were in miscarriage group. In the groups with chronic and gestational hypertension there were higher level of sFlt1 and lover level of VEGF than in the control group, but the differences did not reach statistical significance. CONCLUSION: Early pregnancy imbalance between antiangiogenic protein sFlt1 and proangiogenic molecules VEGF and PIGF could have impact on pathophysiology of placental disorders which leads to development of pregnancy related hypertensive disorders.

Early onset of abdominal venous thrombosis in a newborn with homozygous type II heparin-binding site antithrombin deficiency.

: The overall incidence of thromboembolic events in the neonatal period is 5 per 100 000 births, wherein more than 40% of all such manifestations are symptomatic renal vein thromboses. We describe the case of a newborn female who developed extensive thrombosis, which filled the inferior vena cava and renal vein and was diagnosed in the first weeks of life. A homozygous type II heparin-binding site antithrombin deficiency (c. 391C>T, p. Leu131Phe) was detected in the background. Despite the timely diagnosis and appropriate treatment, clinical signs of renal insufficiency, because of left kidney atrophy and arterial hypertension, were observed. Our case demonstrates the seriousness of the consequences arising after early onset of venous thrombosis caused by homozygous type II heparin-binding site antithrombin deficiency. In addition to prompt diagnosis, of huge importance is the determination of inherited thrombophilia, as it significantly affects therapeutic treatment and indicates that long-term follow-up is mandatory.

Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats.

BACKGROUND: Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats. METHODS: Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining. RESULTS: Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals. CONCLUSIONS: Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical-induced hepatotoxicity should be more in-depth investigated.

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis.

BACKGROUND/AIM: Clinical manifestations of sepsis are not caused directly by the invading pathogens, but rather mostly by systemic inflammation that leads to activation of the coagulation system. The aim of this study was to determine whether levels of hemostasis- related parameters measured in intensive care unit admissions are associated with mortality and severity in patients with sepsis. MATERIALS AND METHODS: Eighty-five patients who fulfilled criteria for a diagnosis of sepsis were included in our study. Platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time, D-dimer, and fibrinogen levels were determined within the first 24 h from sepsis onset. Differences between groups of septic patients were assessed by Mann-Whitney U test and Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. RESULTS: Prolonged aPTT and PT with higher D-dimer concentrations in patients with sepsis are associated with more severe forms of the disease, aPTT was prolonged in nonsurvivors, while platelet count and fibrinogen levels were higher in survivors. Platelet count and aPTT ratio are independent predictors of fatal outcome in our logistic regression model. CONCLUSION: Hemostasis-related parameters have a significant impact on severity and outcome in sepsis.

Reticulated platelets and antiplatelet therapy response in diabetic patients.

Increased platelet turnover and high level of reticulated platelets are associated with low response to antiplatelet therapy in diabetes mellitus type 2. This study evaluated association between percentage of reticulated platelets (%RP) and the response to antiplatelet therapy in patients with type 2 diabetes mellitus (T2DM). This prospective, pilot, case-control, clinical trial included 79 subjects stratified in three groups: group I included 30 patients with T2DM, group II included 34 non-diabetic patients and 15 healthy age and sex matched healthy volunteers were enrolled in control group. Platelet response to clopidogrel and aspirin was assessed by Multiplate(®) aggregometry analyzer. Individual response to dual antiplatelet therapy was estimated by the percentage of decrease in overall platelet aggregability (%DPA) obtained after antiplatelet therapy, calculated by presented formulas: %DPAadp = 100 × (1 - ADP/TRAP) and %DPAaspi = 100 × (1 - ASPI/TRAP). %RP was significantly higher in diabetics, than in non-diabetics, (3.17 ± 1.26 vs. 2.39 ± 1.56; p < 0.05). Significantly lower response to clopidogrel (31.55 ± 13.02 vs. 50.24 ± 11.38; p < 0.001) and aspirin (52.33 ± 22.67 vs. 64.31 ± 16.47; p < 0.05) therapy was observed in diabetics. %RP negatively correlated with response to clopidogrel therapy, but positively with metabolic profile indicators in diabetics (p < 0.05, all). Correlation of %RP with metabolic profile indicators and poor response to antiplatelet therapy suggest that altered metabolic profile can affect platelet turnover in T2DM leading to low responsiveness to antiplatelet therapy in these patients.

COMPARISON OF STANDARD COAGULATION TESTS AND ROTATIONAL THROMBOELASTOMETRY FOR HEMOSTATIC SYSTEM MONITORING DURING ORTHOTOPIC LIVER TRANSPLANTATION - RESULTS FROM A PILOT STUDY.

INTRODUCTION: During liver transplantation, continuous laboratory monitoring of complex changes of the hemostatic system is necessary. The aim of this study was to compare two methods of monitoring: standard coagulation tests and rotational thromboelastometry. MATERIAL AND METHODS: The study included 17 patients who had undergone orthotopic liver transplantation in the Clinical Centre of Vojvodina, Serbia in the period from June 2008 to October 2012. The coagulation parameters (platelet count, activated partial thromboplastin time, prothrombin time and fibrinogen level) were compared with the thromboelastometric parameters (coagulation time, clot formation time and maximal clot firmness). RESULTS: The results showed a statistically significant correlation between the platelet count and maximum clot firmness of the intrinsically (r=0.51, p<0.001) and extrinsically activated thromboelastometric assays (r=0.64, p<0.001). The fibrinogen level and maximum clot firmness of the fibrinogen thromboelastometric test correlated significantly as well (r=0.44, p=0.002). No significant correlations were found among the activated partial thromboplastin time, prothrombin time, coagulation time and clot formation time. CONCLUSION: For an adequate perioperative monitoring of the dynamic intraoperative hemostatic changes and the optimal use of blood derivatives during liver transplantation, the combined application of standard coagulation tests and rotational thromboelastometry should be considered whenever possible.

Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis.

BACKGROUND: Biomarkers of endothelial dysfunction are not recommended for routine laboratory investigation of the outcome prognosis and prediction of the course of sepsis. METHODS: A total of 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Development of multiorgan dysfunction syndrome (MODS) in the first 48 hours was assessed. Differences between groups of patients with sepsis were assessed by Mann-Whitney U test and by Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. RESULTS: Level of thrombomodulin was significantly higher in group of patients with MODS than without MODS (P = .015). Levels of antithrombin (P = .026) and protein C (P = .035) were significantly lower in patients with MODS. Level of thrombomodulin was the strongest predictor in MODS development in first 48 hours (P = .028). CONCLUSION: The level of thrombomodulin not only was able to distinguish the severity of sepsis but also was a significant predictor of MODS development.

Clinical characteristics of first venous thrombosis among women under and over 45 years of age.

INTRODUCTION: Venous thromboembolism is a multifactorial disease defined by multiple interactions between genetic and acquired risk factors. After coronary heart disease and stroke, venous thromboembolism is the most common cause of cardiovascular death and disability. MATERIAL AND METHODS: In order to investigate the clinical characteristics of first venous thromboembolism, 447 women younger than 45 and 174 over 45 years of age with confirmed venous thromboembolism, who had been tested for the presence of thrombophilia in the period 1998-2012, were included in the study. RESULTS: Proximal deep vein thrombosis occurred most often among young women, while distal deep vein thrombosis was the most frequent in the older group. The most common reported risk for venous thromboembolism observed in 49.8% of the young women was pregnancy and puerperium, while 25.2% of them developed venous thromboembolism without any obvious cause. Among women over the age of 45, venous thromboembolism developed without an obvious cause in 38.5%, while malignant disease was identified as the most important risk factor in 23% of them. Thrombophilia was observed in 48.7% of the young women in comparison to 28.7% of the older ones (p < 0.0001). As for venous thromboembolism recurrence, it developed in 26.3% of young women and 17.8% of the older ones (p = 0.03). CONCLUSION: Younger women developed more severe forms of thrombosis than the older ones. Inherited risk factor for thrombosis was detected in almost half of all young women, and in every fourth elderly women. With the exception of factor V Leiden mutation, other types of congenital thrombophilia are almost negligible among older women. Therefore, thrombophilia testing in case of first thrombosis is fully justified only in young women.