title: Relation of platelet abnormalities to thrombosis and hemorrhage in chronic myeloproliferative disorders.
abstract: The chronic myeloproliferative disorders (MPD), predominantly polycythemia vera and essential thrombocythemia, are characterized by a high incidence of thromboembolic and, to a lesser degree, hemorrhagic complications. The disease process in chronic MPD affects a pluripotent progenitor cell and results in trilineage hematopoietic proliferation. Clonal involvement of megakaryocytopoiesis is regarded as the main origin of thromboembolism in MPD and results in abnormal platelet production. These platelets show increased size heterogeneity and ultrastructural abnormalities, and their function in vitro is in many ways impaired with a high degree of individual variability. Elevated levels of platelet-specific proteins, increased thromboxane generation, and expression of activation-dependent epitopes on the platelet surface are common on chronic MPD, and may reflect an inappropriate state of platelet activation. Although a variety of platelet receptor deficiencies and some defects of intracellular signaling pathways have been identified, the different platelet defects in MPD could not be traced back to an underlying general pathogenetic mechanism. On progression of chronic MPD to more advanced stages of the disease, the number of platelet abnormalities tend to increase. Cytoreductive drugs may partly improve platelet dysfunction, and platelet inhibitory agents reduce symptoms of platelet activation. However, neither of these therapeutic principles is able to normalize platelet function in MPD. As an alternative to conventional treatment, specific suppression of clonal megakaryocyte growth and recovery of polyclonal hematopoiesis may be achieved by biologic agents such as interferon alpha. Such treatment strategies may prevent thromboembolic complications together with hematologic symptoms and progression of the disease and should be further evaluated in prospective studies.
authors.affiliation: Department of Internal Medicine, Hematology, Oncology and Clinical Immunology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wehmeier
authors.forename: T
authors.initials: T
authors.lastname: Südhoff
authors.forename: F
authors.initials: F
authors.lastname: Meierkord
mesh_terms: D000477:Alkylating Agents / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D006410:Hematopoiesis; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006474:Hemorrhagic Disorders / Q000097:blood / Q000209:etiology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000150:complications; D008533:Megakaryocytes / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D018962:Phlebotomy; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D015398:Signal Transduction; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D013927:Thrombosis / Q000097:blood / Q000209:etiology*
chemical_list: D000477:Alkylating Agents; D016898:Interferon-alpha; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D016718:Arachidonic Acid; D001241:Aspirin