Overcoming the diagnostic and therapeutic challenges of canine immune-mediated thrombocytopenia - Veterinary Medicine
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Overcoming the diagnostic and therapeutic challenges of canine immune-mediated thrombocytopenia
Determining that the immune system is the cause of a dog's decreased platelet count can be difficult. These clinicians walk you through the diagnostic and treatment process so you can help patients with this life-threatening bleeding disorder.


VETERINARY MEDICINE


Platelets play an essential role in normal hemostasis. In primary hemostasis, platelets bind to the damaged vessel wall, forming an initial platelet plug. The platelet plug is then stabilized by fibrin, which is generated through the activation of clotting factors in secondary hemostasis.

Immune-mediated thrombocytopenia is the most common acquired cause of abnormal primary hemostasis in dogs.1 It involves antibodies binding to the surface of platelets, causing premature platelet destruction by macrophages.2 Besides increased platelet destruction, other non-immune-mediated mechanisms of thrombocytopenia include decreased platelet production by the bone marrow, platelet sequestration (primarily in the spleen), and increased platelet consumption or loss.3

Immune-mediated thrombocytopenia is often diagnostically and therapeutically challenging. Understanding the underlying pathophysiology and principal differential diagnoses for thrombocytopenia in dogs is vital to develop an appropriate diagnostic and therapeutic approach.

PATHOPHYSIOLOGY

Platelets are produced from the fragmentation of bone marrow megakaryocytes and are then released into the circulation where their average life span is eight to 12 days. Aged platelets are removed from the circulation by tissue macrophages, especially in the spleen.1,4 Immune-mediated thrombocytopenia is mainly a disorder of accelerated platelet destruction.2 In this disease, antibodies bind to platelet membranes, enhancing platelet clearance by the mononuclear phagocytic system. This process usually occurs in the spleen although the liver also plays a role.1,2 Thrombocytopenia develops as platelet destruction exceeds compensatory production by the bone marrow.1

Antiplatelet antibodies are directed against normal platelet surface antigens.2 Platelet integrin alphaIIBbeta3 (formerly glycoprotein IIb/IIIa) on the platelet surface is highly immunogenic and is thought to be the most frequent target antigen.5 Platelet-surface-bound antibodies in dogs with immune-mediated thrombocytopenia are frequently immunoglobulin G (IgG).2 Antiplatelet antibodies may also alter platelet function and further compromise primary hemostatic function.1,5 However, the clinical relevance of this altered platelet function is unclear since immature platelets have increased hemostatic function that may compensate for the platelet dysfunction.1

Immune-mediated thrombocytopenia can be classified as primary or secondary.1

Primary immune-mediated thrombocytopenia

Primary immune-mediated thrombocytopenia has also been called idiopathic thrombocytopenic purpura. In this spontaneous autoimmune disorder, autoantibodies are directed against specific portions of the platelet membrane. It occurs in the absence of an underlying disease1,2 and can only be diagnosed once causes of secondary immune-mediated thrombocytopenia have been ruled out.6

Secondary immune-mediated thrombocytopenia

In secondary immune-mediated thrombocytopenia, antibodies bind to antigens adsorbed to the platelet surface or immune complexes nonspecifically bind to the platelet.5 Secondary immune-mediated thrombocytopenia occurs as a result of an underlying disorder.1,2 Many underlying causes of secondary immune-mediated thrombocytopenia have been reported. Often there is an association between a disease and thrombocytopenia, but the causative role has not been confirmed experimentally.1 Conditions that have been associated with immune-mediated thrombocytopenia include autoimmune disorders, drug therapy, blood product transfusion, vaccine administration, various neoplasms, and infectious agents.

Autoimmune diseases. Immune-mediated thrombocytopenia may occur in association with other autoimmune diseases in dogs such as systemic lupus erythematosus, rheumatoid arthritis, and immune-mediated hemolytic anemia.3

Drug and blood product therapy. Although any drug could provoke this disease, several drugs have been associated with immune-mediated thrombocytopenia in dogs, including auranofin (gold salts), cefazedone, and trimethoprim-sulfonamide combinations.1,2 Drugs generally act as haptens, which combine with platelets to form a drug-platelet complex that is antigenic.7 Drug-related immune-mediated thrombocytopenia usually develops weeks to months after initial therapy, resolves within two weeks of discontinuing therapy, and does not recur unless the drug is readministered.2,8 Severe thrombocytopenia caused by the production of antiplatelet antibodies has been reported in dogs within weeks after blood product transfusion.3


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Source: VETERINARY MEDICINE,
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