thromboplastin and Myeloproliferative-Disorders

Thrombotic complications in patients with hematologic malignancies are as frequent as in those with solid tumors and significantly affect morbidity and mortality. In acute leukemia, thrombosis and bleeding manifestations may occur concomitantly as a part of the same thrombo-hemorrhagic syndrome. In patients with Philadelphia chromosome-negative chronic myeloproliferative disorders (i.e., essential thrombocythemia [ET] and polycythemia vera [PV]), a thrombosis rate as high as 40% has been recorded. A hypercoagulable state is present in virtually all of these patients, even without clinical manifestations. In this review, we focus on the pathogenic mechanisms underlying the hypercoagulable state of these two hematologic malignancies. Although the pathogenesis of hypercoagulability is complex, a central role is played by the fundamental molecular changes of both the leukemic cells and of the progeny arising from the hematopoietic progenitor cells that have undergone clonal rearrangement. These cells overexpress procoagulant factors, as well as adhesion molecules and cytokines capable of inducing procoagulant changes in the vascular wall and stimulating increased cellular interactions. Recent molecular studies in experimental models of human tumors have demonstrated for the first time that oncogene- and repressor gene-mediated neoplastic transformation induces activation of blood coagulation. Similarly, in cells from patients with acute promyelocytic leukemia, the T15-17 translocation induces hyperexpression of tissue factor (TF) and renders the patient hypercoagulable. Furthermore, in blood cells from patients with PV or ET, the presence of the JAK2V617F mutation translates into activation of hemostasis, with increased expression of platelet-associated TF microparticles and the formation of increased platelet/neutrophil aggregates. Understanding the pathophysiology of hypercoagulability is critical to the design of appropriate measures for intervention in these hematologic disorders to prevent thromboembolic complications.

Topics: Hematologic Neoplasms; Hemostasis; Humans; Leukemia, Promyelocytic, Acute; Myeloproliferative Disorders; Neovascularization, Pathologic; Polycythemia Vera; Thrombocythemia, Essential; Thrombophilia; Thromboplastin; Up-Regulation

Topics: Arthritis; Blood Coagulation Factors; Collagen Diseases; Diabetes Complications; Endocrine Glands; Glucocorticoids; Humans; Myeloproliferative Disorders; Obesity; Sex Factors; Thromboembolism; Thrombophlebitis; Thromboplastin; Thyroid Diseases

Topics: Aged; Blood Platelets; CD11b Antigen; Fibrinolytic Agents; Humans; Hydroxyurea; Leukocytes; Middle Aged; Myeloproliferative Disorders; Nitrates; Nitric Oxide Donors; Thromboplastin

Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin.. We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 microm). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucyl-phenylalanine-induced PMN TF expression.. In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.

Topics: Aged; Aged, 80 and over; Blood Platelets; Cell Aggregation; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Humans; Hydroxyurea; In Vitro Techniques; Male; Middle Aged; Myeloproliferative Disorders; Neutrophils; P-Selectin; Platelet Adhesiveness; Reference Values; Thromboplastin

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Blood Coagulation Tests; Blood Platelets; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Male; Middle Aged; Myeloproliferative Disorders; Platelet Adhesiveness; Polycythemia Vera; Primary Myelofibrosis; Thromboplastin

Topics: Blood Platelets; Centrifugation; Humans; Methods; Myeloproliferative Disorders; Thromboplastin

Topics: Adenine Nucleotides; Adenosine Diphosphate; Blood Coagulation Factors; Blood Platelet Disorders; Humans; Kaolin; Myeloproliferative Disorders; Thromboplastin

Topics: Adenine Nucleotides; Aged; Blood Coagulation Factors; Blood Platelet Disorders; Bone Marrow Diseases; Carbon Isotopes; Cell Aggregation; Collagen; Epinephrine; Female; Hematocrit; Hemorrhage; Humans; Male; Microscopy, Electron; Middle Aged; Myeloproliferative Disorders; Phosphates; Serotonin; Sodium; Thromboplastin