Acquired thrombopathias should be suspected in animals with specific diseases and treated with certain drugs. Platelets can have increased (resulting in thrombosis) or decreased function (resulting in hemorrhage) in these situations. The risk of bleeding is unpredictable and typically less severe and consistent than inherited disorders. Although abnormal platelet function occurs in these diseases, there may be other causes for the excessive hemorrhage seen in these conditions, such as thrombocytopenia. However, it should be recognised that platelets are not functioning normally in these situations and drugs that may exacerbate this should be avoided in these patients.
Conditions in which there is decreased platelet function include neoplasia, monoclonal gammopathies, infectious disease, hepatic disease, renal disease, pancreatitis, DIC and immune-mediated thrombocytopenia.
- Neoplasia: In essential thrombocythemia and acute megakaryocytic leukemia, platelet aggregation and adhesion are defective. This can also occur in other neoplastic conditions, including chronic myeloid leukemia.
- Monoclonal gammopathy: Very high gamma globulin concentrations associated with some lymphoid or plasma cell neoplasms and atypical responses to some infectious diseases (e.g. Ehrlichiosis) can interfere sufficiently with platelet function in vivo to produce severe hemorrhage. The monoclonal protein (paraprotein) coats platelets, interfering with platelet aggregation, adhesion and phospholipid exposure.
- Infectious agents: Ehrlichia canis and platys can cause decreased platelet aggregation and adhesion (E. platys by activating platelets resulting in platelet exhaustion).
- Hepatic disease: Dogs with various types of hepatic disease have defective whole blood platelet aggregation thought to be due to circulating FDPs, increased bile acids, altered platelet phospholipids and increased proportions of older, less active platelets.
- Renal disease: Mucosal bleeding, reduced platelet retention and a prolonged BMBT are features of natural and experimental uremia in dogs. These abnormalities correlate to the degree of azotemia. Platelet aggregation is either normal or mildly decreased, implicating defective adhesion as the main hemostatic abnormality. The amount and multimeric composition of vWf are normal, indicating that the adhesion defects are not due to vWf abnormalities.
- Immune-mediated thrombocytopenia: Recent studies indicate that some dogs with ITP have abnormal platelet aggregation. This correlated to the immunoglobulin G fraction of the patients' sera. In human chronic ITP, most antibodies are directed against GPIIb/IIIa and GPIb-IX. Limited canine studies suggest that, in some dogs, there is an antibody against GPIIb/IIIa. As this glycoprotein has an essential role in platelet aggregation, it is not surprising that dogs with ITP will have concurrent platelet dysfunction. In ITP, the clinical signs of hemorrhage do not always correlate to the platelet count, for unknown reasons. It may be that the clinical signs of ITP correlate closer to the degree of platelet dysfunction, rather than the platelet count alone. However, further studies need to be performed in this area.
- DIC: In DIC, there is concurrent platelet dysfunction, mediated by FDPs (especially fragments D and E), which have a high affinity for platelet membranes and compete with fibrinogen for platelet receptors, thus impairing aggregation.
- Drugs: Drugs that inhibit platelet function include aspirin (which inhibits platelet function by irreversibly acetylating platelet cyclo-oxygenase, thus preventing thromboxane A2 generation, which is needed for secretion and aggregation), NSAIDs (which reversibly inhibit cyclo-oxygenase activity), phenothiazines, heparin and dextran.
Increased platelet function, which may predispose an animal to thrombosis, has been observed in dogs with lymphoma, nephrotic syndrome, and infectious agents (including RMSF, heartworm disease and FIPV infection). In nephrotic syndrome, the hyperaggregability is thought to be secondary to increased free arachadonic acid availability (for thromboxane production) due to hypoalbuminemia (which normally binds free arachadonic acid).
|
