Treatment related changes in antifibrinolytic activity in patients with polycythemia vera

Abstract

Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.

Altered plasma fibrin clot properties in essential thrombocythemia

“…In 17 ET patients treated with anagrelide, Cacciola et al [36] observed a decrease in PF-4 and PAI-1 levels after reaching a platelet count of 5500 Â 109/l. Similarly, Sonmez et al [37] reported reduction in PAI-1 levels in 22 patients with polycythemia vera treated with hydroxyurea (this phenomenon was not observed in patients treated with phlebotomy). The lack of relationship between pharmacological treatment and the analyzed clot properties may in part result from a small size of the study group and its heterogeneity.…”

Hemoglobin combined with triglyceride and ferritin in predicting non‐alcoholic fatty liver

“…Third, excessive erythrocytosis may cause thrombosis and lead to the injury of the hepatocytes. 23 Fourth, as mentioned above, iron overload plays an important role in the pathogenesis and progression of NAFLD. It is well known that excessive erythrocytosis lead to iron overload in much status such as polycythemia vera and hemochromatosis.…”

“…So excessive erythrocytosis may lead to oxidative stress, which is the “second hit” of NAFLD. Third, excessive erythrocytosis may cause thrombosis and lead to the injury of the hepatocytes . Fourth, as mentioned above, iron overload plays an important role in the pathogenesis and progression of NAFLD.…”

Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation

“…The mechanisms underlying the thrombosis in PV are largely elusive and likely to be multifactorial. Increased haematocrit and whole-blood viscosity, quantitative/ qualitative abnormalities of blood cells, interactions between blood cells, and impaired fibrinolytic activity may all contribute to the thrombotic status in PV (2)(3)(4). However, causal relationships between any of these specific abnormalities and thrombosis have not been clearly established in that the clinical and pathogenetic significance of previously reported data has often been conflicting or difficult to interpret.…”