Background: Percutaneous coronary intervention (PCI) is the treatment metod of ischemic heart disease. Platelet hyperactivity is associated with stent thrombosis so this patients need antiplatelet therapy. Such therapy usually includes clopidogrel and aspirin. It might be useful to assess total procoagulant activity using a global coagulation test in patients on dual antiplatelet therapy (DAPT) Aims: To estimate the plasma coagulation potential level in patients with a different response to antiplatelet therapy. Methods: This research included 46 patients after the successful coronary stent placement. All of them were given 75 mg clopidogrel and 150 mg aspirin per day. The antiplatelet therapy efficiency was assessed with light transmission aggregometry performed with a Hronolog 4‐channel platelet aggregometer using the adenosine diphosphate (ADP, 5 μM) and collagen (2 μg/ml) as agonists. Maximal platelet aggregation (MA, %) was determined. Thrombin generation was measured in platelet‐rich plasma by Calibrated Automated Thrombinogram Assay method (CAT) using reagent containing recombinant tissue factor (Trombinoscope BV, The Netherlands) as a trigger. Following parameters were derived: endogenous thrombin potential (ETP, nM‐min), peak thrombin (Peak, nM), and rate of thrombin generation (R, nM/min). STATISTICA 6.0 package was used in data analysis. Results are presented as median with 95% confidence intervals, p < 0.05 was considered statistically significant. Results: The results of aggregometry are presented in table. 30 (65%) patients (group №1) had a significant decrease in aggregation response only to collagen compared with controls, the response to ADP was not considerably lower. 16 (35%) patients (group №2) had a significant decrease in aggregation response to both collagen and ADP. The results of platelet aggregation suggest that the patients in the group №2 were more sensitive to antiplatelet therapy. There was a significant decrease in ETP, Peak and R in the group №2 compared with group №1 (ETP:Мe‐1636,5, CI: 1168,6‐1919,9 vs. Me‐1785,0, CI: 1415,7‐2576,2, p < 0,05; Peak: Me‐112,8, CI: 72,3‐138,9 vs. Me‐134,7, CI: 80,6‐180,2, p < 0,001; R: Me‐9,2, CI: 4,1‐13,3 vs. Me‐ 12,4, CI: 4,5‐21,2, p < 0,01). Summary/Conclusion: Patients with a better sensitivity to DAPT had lower plasma coagulation potential. It might be associated with the lower risk of stent thrombosis in patients with good response to DAPT.. Individual assessment of plasma coagulation potential using thrombin generation test could be useful for prediction of the thrombosis risk in the stent in patients after PCI. More research is clearly needed. image
Introduction: A frequent clinical manifestation of Ph-negative myeloproliferative neoplasms (MPN) is the development of thrombosis. To identify the state of hypercoagulation it is relevant and promising to introduce global tests for evaluating the hemostasis — the thrombin generation test (TGT) and thromboelastography (TEG). Aim: to evaluate the parameters of thrombin generation and thromboelastography in patients with Ph-negative MPN. Material and methods. In total, 62 patients with MNP were included in the study: 27 with polycythemia vera (PV), 14 with essential thrombocythemia (ET) and 21 with primary myelofibrosis (PMF). The control group included 55 practically healthy individuals, comparable in gender and age (19 people in the study of TEG, 36 people in the study of TGT). The TEG was performed using a “TEG 5000” thromboelastograph. TGT was measured with Calibrated Automated Thrombinography. Results: Ly30 and Ly60 in TEG in patients were significantly lower (0.35 (0.20–0.48), 0.00 (0.00–0.40) and 0.00 (0.00 — 0.43) and 3.15 (2.45–3.60), 1.25 (0.10–3.58) and 0.60 (0.00–3.05) respectively), than in the control (1.60 (1.05–2.75) and 6.20 (4.15–8.30), respectively), which indicates the ineffectiveness of fibrinolysis. The values of MA and G in patients with ET and PV significantly exceeded the control (69.15 (67.98–70.78) mm and 65.20 (59.65–63.83) mm versus 62.00 (57.75–6.75) mm and 11.20 (10.60–12.15) din/cm 2 and 9.40 (7.40–11.60) din/cm 2 versus 8.20 (6.85–8.75) din/cm 2 , respectively. The most pronounced change in sensitivity to TM was observed in patients with ET (27.94 (17.35–43.58) % and 13.29 (-3.48–23.60) %, respectively; p < 0.05). A significant decrease in ETP was observed in patients with PV and PMF. Conclusion. The study of hemostasis in patients with MPN using TEG and TGT revealed the presence of multidirectional changes associated with the disease. The TEG showed that an increase in the time required for the onset of fibrin formation is combined with increased clot strength and inhibited fibrinolysis, which are risk factors for the development of thromboembolic complications. The study of TGT determined a decrease in the quantitative characteristics of thrombin generation and at the same time the failure of the anticoagulant system of protein C, leading to the development of hypercoagulation.
The new coronavirus infection (COVID-19) is considered a systemic disease, often complicated by thrombotic events, impacting respiratory, cardiovascular, gastrointestinal, hematopoietic, and immune systems. The development of a hypercoagulable state accompanying the disease involves inflammatory reactions, endothelial dysfunction, hemostatic system activation, and autoimmune disorders, including antiphospholipid antibodies (aPA). Despite the high prevalence of aPA in COVID-19 patients, its impact on thrombotic complications and disease outcome is not significant. The transient nature of these antibodies and conflicting study results suggest uncertainty about their influence on clinical outcomes in COVID-19 patients.
Background: Thrombotic complications contribute significantly to morbidity and mortality in Ph‐negative myeloproliferative neoplasms, including primary myelofibrosis (PMF). The majority of PMF patients have JAK2V617F mutation that is associated with increased thrombotic risk, CALR gene mutations are also common in PMF. Clonal myeloproliferation in PMF followed by secondary inflammation with pathologic cytokine production induce endothelium, leukocytes and platelets activation resulting in coagulation activation. Natural anticoagulants protein C (PC) and protein S (PS) deficiencies with activated protein C resistance development are supposed among the crucial procoagulant features in Polycythemia Vera and Essential Thrombocythemia, while the data on hemostatic abnormalities in PMF and their relationship with JAK2V617F burden is scarce. Aims: To evaluate the hemostatic parameters in PMF patients, predisposing high thrombosis risk, and their relationship with JAK2V617F presence and allele burden. Methods: The study included 36 PMF patients (age 30‐86 years, median 60 years). Somatic mutations ( JAK2V617F and CALR) presence and JAK2V617F allele burden were assessed using allele specific polymerase‐chain reaction. The control group consisted of 68 healthy persons (30‐73 years, median 46 years). Coagulation assays (factors VIII, V, von Willebrand (VWF), antithrombin and PC activities, fibrinogen concentration, VWF antigen and free PS level) were performed by standard clotting, chromogenic and immunoturbidimetric techniques. STATISTICA 6.0 was used for data analysis. The results were presented as median with 95% confidence interval (CI). Mann‐Whitney and Spearman rank tests were applied, the differences considered statistically significant with p < 0.05(∗). Results: 23 (63.9%) PMF patients in the study were JAK2V617F ‐positive, 8 (22.2%) had mutation in CALR gene. JAK2V617F allele burden data was available in 13 PMF patients with median 8.1% (95%CI 3.4‐43.8%). The results of hemostatic parameters in PMF patients and controls are shown in Table 1. Unexpectedly there were no significant differences in studied parameters between PMF patients with JAK2V617F and CALR mutations. However, a statistically significant inverse correlation was revealed between JAK2V617F allele burden and PC activity (r = ‐0.68301, p = 0.01). image Summary/Conclusion: PC and, especially, PS activities were decreased in PMF, predisposing hypercoagulation. The increased FVIII activity and fibrinogen in PMF patients confirm the hypercoagulability and also reflect high inflammation level, while VWF:Ag increase suggests the endothelium damage and dysfunction, enhancing prothrombotic state in PMF. An inverse relationship between JAK2V617F allele burden and PC activity can serve as one of the mechanisms contributing to the higher thrombosis incidence depending on JAK2V617F burden.
Background : COVID-19 course is characterized of thrombosis complications, respiratory failure, and a multiple organ failure development. One of the central pathogenic mechanism of COVID-19 is endothelial dysfunction which can lead to the hypercoagulability. Studying of the endothelial dysfunction markers in patients with COVID-19 could be useful for improving of disease's outcomes. Aims : To estimate potential endothelial damage in COVID-19 patients by measuring biomarkers of endothelial disfunction. Methods : The study included 221 patients with COVID-19 and 68 healthy controls. We studied ristocetin-cofactor von Willebrand's factor activity (vWF:RCo, %), antigen von Willebrand's factor (vWF:Ag,%), and homocysteine (HCY, μmol/l) . STATISTICA 12.0 package was used. Statistical analysis was performed by non-parametric methods (median (Me), 95% confidence interval (95% CI), Mann-Whitney U test), P < 0.05 was considered statistically significant. Results : Conclusions : The increase of vWF:RCo activity, vWF:Ag and HCY may indicate endothelial damage in COVID-19 patients that can lead to hypercoagulability and predispose to thromboembolic complications. High vWF:Ag could be predictive marker of poor outcomes in COVID-19 patients.
Aim . To evaluate the effect of ruxolitinib therapy on hemostasis in patients with primary myelofibrosis (PMF). Materials and methods . 30 patients with PMF were examined, 16 of them received ruxolitinib (group 1) at the time of examination and 14 were untreated (group 2). The control group consisted of 30 healthy individuals. A complete blood count was performed, the platelets aggregation, the activity of Willebrand factor, factor VIII and natural anticoagulants were evaluated. In the thrombin generation test, the endogenous thrombin potential (ETP, nM×min) was determined; sensitivity to thrombomodulin and coagulation index were calculated. Kruskal-Wallis test with post hoc Dunn test was used to compare groups. Results . Hemoglobin and platelet count were lower in group 1 compared to group 2 and control. Platelet aggregation with collagen was lower in patients with PMF than in the control group, and lower in group 1 than in group 2: 2.2 (1.6; 5.7) % vs 41.6 (3.4; 64.8) %, p < 0.05. In patients in group 1, the activity of Willebrand factor – 150.0 (122.5; 195) % and factor VIII – 173 (148.5; 200) % was higher ( p < 0.05) than in the control: 97 (84.8; 110) % and 104 (85; 130) % respectively. Antithrombin did not differ in the PMF and control group. Protein S was reduced in both groups with PMF: group 1 – 70 (58; 86,6) %, group 2 – 65 (43,6; 107,5) %, control – 102 (86; 109,0) %, p < 0.001. ETP and sensitivity to thrombomodulin in groups 1 and 2 were low, p < 0.001. The coagulation index tended to higher values than in the control: 5.3 (3.0; 11.4) – group 1; 3.2 (2.4; 7.3) – group 2; control – 1.9 (1.6; 2.2), p = 0.073. Conclusion . Ruxolitinib therapy leads to the failure of the platelet hemostasis, the procoagulant activity of plasma with an increase in the activity of Willebrand factor and factor VIII and a decrease in the activity of protein S.
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