Ventilation/perfusion lung scanning, spiral computed tomography (CT) or pulmonary angiography in case of suspected pulmonary embolism

Ventilation/perfusion lung scanning, spiral computed tomography (CT) or pulmonary angiography in case of suspected pulmonary embolism. 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 unfavorable 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 unfavorable MPNs patients are venous thromboembolism (VTE), while arterial thromboembolism is usually 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 usually 92%, 58%, 50% respectively [7]. The role of JAK2 V617F allele burden as risk 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 mutations have been recognized in MPN including the MPL W 515 L/K mutation and mutations of Calreticulin (CALR). MPL mutations are present in 8.5% of JAK2 V617F negative patients while CALR mutations in around 20-25% [18][19]. CALR mutations are associated with more youthful 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 common for heparin-induced thrombocytopenia (HIT) is usually 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 Hederagenin 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 producing 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 of obvious explanations for thrombocytopenia, and by demonstration of heparin-dependent IgG antibodies. However, Mouse monoclonal to PR 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 this observed risk of HIT is usually higher in patients with MPNs. Hederagenin [24] [25][26][27]. The aim of our study is usually to evaluate the occurrence of new thrombotic events among patients Hederagenin with ET with JAK2 V617F mutation treated with un-fractioned (UFH) or low molecular excess weight heparin (LMWH). Patients and methods This retrospective analysis considered a consecutive series of ET patients Hederagenin Hederagenin exposed to heparin because of previous thrombotic events in usual.