Hematology and Bone Marrow Transplantation
Contributions
Type: Publication Only
Background
Arterial or venous thrombotic events occurs in 15 % of essential thrombocythemia (ET) cases at presentation and in 10% to 20% during the disease course. The pathogenesis of thrombosis in ET is multifactorial and not yet clear. Prevention of thrombohaemorrhagic events is the important goal of the ET therapy.
Aims
The aim of this study was to examine biomarkers for prediction of possible prothrombotic condition in patients with essential thrombocythemia.
Methods
Diagnosis of ET based on the WHO criteria (2008). The study was approved by the Ethics Committee of the Medical University of Wroclaw and was performed in accordance with the Declaration of Helsinki. Each patient has been tested using Ceveron alpha (Technoclone) for fibrinogen (F) (Fibrynogen Reagent, Technoclone), factor VIII (Siemens test), D-dimer (Technoclone), protein C (PC) (TECHNOCHROM® Protein C, Technoclone), activated protein C resistance (APCR) (APC Restance Kit Technoclone), thrombin generation and microparticles (MPs) (TECHNOTHROMBIN® TGA (Technoclone). The activation markers thrombin-antithrombin complexes (TAT) and prothrombin fragment F1+2 (F1+F2) were determined by ELISA using kits from Enzygnost micro, Simens). Testing for the factor V Leiden mutation (FVL mutation) and prothrombin gene mutation was accomplished by the PCR on peripheral blood leukocyte DNA.
Material: The study group consisted of 45 patients with ET (13 males and 32 females; mean age 61) and 45 healthy subjects (28 males and 17 females; mean age 62). The JAK2V617F mutation was present in 25 ET patients. Twenty-one patients experienced thrombotic events, 12 had arterial thrombosis ( myocardial infarction in 6, TIA in 3, and peripheral arterial disease in 3 and 8 had deep venous thrombosis in 8 patients. Out of 45 ET patients 35 were treated with anagrelide and 8 with hydroxyurea.
Results
In ET patients the median level D-dimer was significantly higher compared to control (183.2 vs 18.5 ng/ml; p=0.00018), but not fibrinogen level, TAT, F1+F2, FVIII activity and protein C activity. Neither thrombin generation (TG) nor microparticles (MPs) were elevated in ET patients. Five of 45 ET patients had the activated protein C resistance (APCR), and in two of them the heterozygous type of FVL was confirmed. Prothrombin gene mutation was not present in the ET group.
Summary
Conclusions: D-dimer has been shown as a valuable biomarker for prediction of thrombotic events in patients with essential thrombocythemia, and the knowledge of carriership of FVLeiden can be used in the individual thrombosis risk assessment.
Keyword(s): Essential Thrombocytemia, Thrombosis
Type: Publication Only
Background
Arterial or venous thrombotic events occurs in 15 % of essential thrombocythemia (ET) cases at presentation and in 10% to 20% during the disease course. The pathogenesis of thrombosis in ET is multifactorial and not yet clear. Prevention of thrombohaemorrhagic events is the important goal of the ET therapy.
Aims
The aim of this study was to examine biomarkers for prediction of possible prothrombotic condition in patients with essential thrombocythemia.
Methods
Diagnosis of ET based on the WHO criteria (2008). The study was approved by the Ethics Committee of the Medical University of Wroclaw and was performed in accordance with the Declaration of Helsinki. Each patient has been tested using Ceveron alpha (Technoclone) for fibrinogen (F) (Fibrynogen Reagent, Technoclone), factor VIII (Siemens test), D-dimer (Technoclone), protein C (PC) (TECHNOCHROM® Protein C, Technoclone), activated protein C resistance (APCR) (APC Restance Kit Technoclone), thrombin generation and microparticles (MPs) (TECHNOTHROMBIN® TGA (Technoclone). The activation markers thrombin-antithrombin complexes (TAT) and prothrombin fragment F1+2 (F1+F2) were determined by ELISA using kits from Enzygnost micro, Simens). Testing for the factor V Leiden mutation (FVL mutation) and prothrombin gene mutation was accomplished by the PCR on peripheral blood leukocyte DNA.
Material: The study group consisted of 45 patients with ET (13 males and 32 females; mean age 61) and 45 healthy subjects (28 males and 17 females; mean age 62). The JAK2V617F mutation was present in 25 ET patients. Twenty-one patients experienced thrombotic events, 12 had arterial thrombosis ( myocardial infarction in 6, TIA in 3, and peripheral arterial disease in 3 and 8 had deep venous thrombosis in 8 patients. Out of 45 ET patients 35 were treated with anagrelide and 8 with hydroxyurea.
Results
In ET patients the median level D-dimer was significantly higher compared to control (183.2 vs 18.5 ng/ml; p=0.00018), but not fibrinogen level, TAT, F1+F2, FVIII activity and protein C activity. Neither thrombin generation (TG) nor microparticles (MPs) were elevated in ET patients. Five of 45 ET patients had the activated protein C resistance (APCR), and in two of them the heterozygous type of FVL was confirmed. Prothrombin gene mutation was not present in the ET group.
Summary
Conclusions: D-dimer has been shown as a valuable biomarker for prediction of thrombotic events in patients with essential thrombocythemia, and the knowledge of carriership of FVLeiden can be used in the individual thrombosis risk assessment.
Keyword(s): Essential Thrombocytemia, Thrombosis