Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Apr 2006
ReviewClinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications.
Microvascular disturbances in essential thrombocythemia (ET) and polycythemia vera (PV), including erythromelalgia, and atypical and typical transient cerebral, ocular, and coronary ischemic attacks, are caused by platelet-mediated transient and occlusive thrombosis in the end-arterial circulation. ET patients with microvascular disturbances have shortened platelet survival, increased beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), and thrombomodulin (TM) levels, and increased urinary thromboxane B2 (TXB2) excretion, indicating platelet-mediated thrombotic processes. Inhibition of platelet cyclooxygenase-1 by aspirin is followed by relief of microvascular disturbances; correction of shortened platelet survival; correction of increased plasma beta-TG, PF4, and TM levels; and correction of increased TXB2 excretion to normal. ⋯ Homozygous JAK2 mutation with pronounced kinase activity is associated with trilinear megakaryocyte, erythroid, and granulocytic myeloproliferation, myeloid metaplasia, and secondary myelofibrosis (MF), with the most frequent clinical picture of classical PV complicated by major thrombosis in addition to the platelet-mediated microvascular thrombotic syndrome of thrombocythemia. The positive predictive value of a JAK2 V617F polymerase chain reaction test for the diagnosis of MPDs is high (near to 100%), but only half of ET and MF (sensitivity 50%) and the majority of PV (sensitivity 85 to 97%) are JAK2 V617F positive. Bone marrow histopathology, when used in combination with specific markers such as serum erythropoietin, PRV-1, endogenous erythroid colony formation, peripheral blood parameters and red cell mass, has a high sensitivity and specificity (near 100%) to detect the early and overt stages of the MPDs and to differentiate between ET, PV, and CIMF in both JAK2 V617F-positive and -negative MPDs.
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Semin. Thromb. Hemost. · Apr 2006
ReviewMechanism of action of factor VIIa in the treatment of coagulopathies.
Recombinant factor VIIa (rFVIIa) has been developed for treatment of bleeding in patients with hemophilia who have inhibitors against factor VIII (FVIII) or FIX, and has been found to induce hemostasis during major orthopedic surgery. The use of rFVIIa treatment for hemophilia is a new concept and is based on the low-affinity binding of FVIIa to the surface of thrombin-activated platelets. Administration of pharmacologic doses of exogenous rFVIIa enhances thrombin generation on the platelet surface at the site of injury independently of the presence of FVIII or FIX. ⋯ A tight fibrin plug will aid in resisting the overwhelming local release of fibrinolytic activity triggered by vast tissue damage occurring in extensive trauma. Local fibrinolytic activity also occurs in the gastrointestinal tract as well as during profuse postpartum bleeding. Pharmacologic doses of rFVIIa induce hemostasis in these cases also.