Platelet factor 4 (PF4) displaced from endothelial cells, or directly from the platelets, binds to heparin molecule to form an immunogenic complex. heparin treatment, in patients with ET carrying V617F mutation, as compared with patients without mutations (P=0.029). ET with V617F mutation seems to be associated with higher risk of thrombotic complications during heparin treatment. Monitoring platelet counts very closely during the course of heparin is essential especially in ET patients in which platelet drop may be hidden by constitutional thrombocytosis. Keywords: myeloproliferative neoplasms (MPNs), essential thrombocythemia, Heparin Treatment, Heparin-induced thrombocytopenia (HIT), V617F mutation Introduction Patients with Philadelphia chromosome negative myeloproliferative neoplasms are at increased risk of arterial and venous thrombosis. The cumulative incidence of all thromboembolic events amount to 2.5% to 5% per patient/year in Policytemia Vera (PV) and to 1.9% to 3% per patient in Essential thrombocythemia (ET) [1][2][3]. Only 30% of all vascular events in BCR-ABL1 negative MPNs patients are venous thromboembolism (VTE), while arterial thromboembolism is more frequent [2[3] [4][5][6]. The JAK2V617F mutation, commonly found in MPN, correlates with several clinical and laboratory characteristics. The frequency of JAK2 V617F mutation for PV, idiopathic myelofibrosis (IMF), and ET is 92%, 58%, 50% respectively [7]. The role of JAK2 V617F allele burden as risk Gabapentin enacarbil factor for thrombosis in MPNs remains debated to date [8][9][10][11][12][13][14]; however, recent advances showed that higher JAK2 mutation allele burden (> 75%) predispose patients to higher thrombotic and haemorrhagic risk [15] [16]. Recently other recurrent Gabapentin enacarbil mutations have been identified in MPN including the MPL W 515 L/K mutation and mutations of Calreticulin (CALR). MPL mutations are present in 8.5% of Gabapentin enacarbil JAK2 V617F negative patients while CALR mutations in around 20-25% [18][19]. CALR mutations are associated with younger age, male sex, higher platelet count, lower haemoglobin level, lower leukocyte count and lower incidence of thrombotic events [20]. Because frequently MPNs patients have had previous exposure to heparin, the presence of heparin-related anti-platelet antibodies typical for heparin-induced thrombocytopenia (HIT) is one underlying possible mechanism of thrombosis despite masked normal platelet count. HIT is an adverse drug reaction caused by immunoglobulin (Ig) G platelet-activating antibodies that bind to platelet factor 4/heparin (PF4/H) complexes on the surface of platelets [21]. Although a significant proportion of patients exposed to heparin will develop anti-PF4/heparin antibodies, a much smaller fraction will develop clinical features of HIT with overt thromboembolic manifestations (HITT). Platelet factor 4 (PF4) displaced from endothelial cells, or directly from the platelets, binds to heparin molecule to form an immunogenic complex. The anti-heparin/PF4 Ig G immune-complexes activates platelets through binding with the Fc gamma RII a (CD32) receptor inducing endothelial lesions. The resulting Gabapentin enacarbil thrombin generation causes consumptive thrombocytopenia and can lead to devastating venous and arterial thromboembolic complications. Cytokines are generated during this process and inflammation could play an additional role in the pathogenesis of thromboembolic manifestations [22] [23] The diagnosis of HIT is generally established when a platelet drop of at least 50% occurs in the absence Gabapentin enacarbil of obvious explanations for thrombocytopenia, and by demonstration of heparin-dependent IgG antibodies. However, HIT in the presence of normal-high platelet counts presents a diagnostic challenge and requires a high index of suspicion. It has been suggested that the observed risk of HIT is higher in patients with MPNs. [24] [25][26][27]. The aim of our study is to evaluate the occurrence of new thrombotic events among patients with ET with JAK2 V617F mutation treated with un-fractioned (UFH) or low molecular weight heparin (LMWH). Patients and methods This retrospective analysis considered a consecutive series of ET patients exposed to heparin because of previous thrombotic events in usual or in unusual sites or in thromboprophilaxis for surgery This retrospective study lasted from March 2006 to March 2017. The patients were divided into two subgroups : group 1: ET patients carrying JAK2 V617F mutations; group 2: Ednra ET patients without JAK2 V617F mutation (control group). All patients were followed in two University Hospitals. The study was conducted according to the ethical principles stated in the Declaration of Helsinki, and the Institutional.
Platelet factor 4 (PF4) displaced from endothelial cells, or directly from the platelets, binds to heparin molecule to form an immunogenic complex
