Bettina Dunkel
Disorders of Platelets
Platelets or thrombocytes are anucleate blood cells derived by budding off from the borders of polyploid precursors, megakaryocytes, in the bone marrow. In species other than the horse, platelet generation also takes place in the peripheral blood, particularly in the pulmonary circulation, which, besides the spleen, is one of the major storage sites for platelets. The daily production of platelets has been estimated to be approximately 35,000/µL. Radiolabeled equine platelets have an average life span of 4 to 5 days before they are removed from the circulation by macrophages residing in the liver, spleen, and bone marrow. Although they are fundamentally similar to platelets of other species, equine platelets have subtle morphologic and functional differences, such as the absence of an open canalicular system and differences in responsiveness to some mediators.
In recent years, it has become increasingly evident that platelets, besides their hemostatic functions, play a vital part in inflammation, immunity, and tissue regeneration and in the pathophysiology of many diseases. Platelets from other species not only contain and release a myriad of inflammatory and regenerative mediators, they also synthesize new factors, such as interleukin-1β (IL-1β), by rapid signal-dependent translation of messenger RNA acquired from the parent megakaryocyte. They also actively interact with other cells, particularly leukocytes and endothelial cells, and play an essential part in attracting leukocytes to sites of inflammation or tissue damage in human asthma and atherosclerosis and in animal models of ischemia-reperfusion injury and hemorrhagic and lipopolysaccharide-induced shock. Human platelets are also capable of active cell locomotion and gradient-driven chemotaxis in response to bacterial peptides and allergenic stimuli in asthma patients. In horses, platelet activation plays a role in recurrent airway obstruction, laminitis, and gastrointestinal disease, and this list is likely to expand with continuing research in the area. With increasing interest in equine platelets and more widely available facilities to assess multiple aspects of platelet function, including cell surface marker expression and interactions with other cells, our knowledge of equine platelets is bound to expand rapidly in the near future.
Disorders of Equine Platelets
Pseudothrombocytopenia is a common finding when automated platelet counts are performed on ethylenediaminetetraacetic acid (EDTA)-coagulated blood, but can also be seen with heparin-, and less frequently, citrate-anticoagulated blood. In blood anticoagulated with EDTA, platelets can form aggregates following calcium chelation, which results in artificially low platelet counts. Inspection of a blood smear, particularly along the feathered edge, and a manual platelet count can quickly establish whether the machine-reported platelet count is accurate. Rarely, true pseudothrombocytopenia might be encountered in individual horses, caused by EDTA-dependent antibody formation and subsequent platelet clumping. Use of a different anticoagulant should abolish platelet clumping in those rare instances.
Thrombocytopenia Secondary to Systemic Disease
Thrombocytopenia, commonly defined as a platelet count of less than 100 × 103/µL, is a relatively rare occurrence, affecting approximately 1.5% of hospitalized horses that had a complete blood count performed in one study. The most common reasons for thrombocytopenia, particularly in hospitalized horses, are increased utilization or destruction of platelets secondary to a primary disease process. Thrombocytopenia is frequently associated with infectious diseases and inflammatory or strangulating-ischemic gastrointestinal disorders, and platelet counts as low as 4000/µL might be encountered with these conditions. The decrease in platelet counts is often accompanied by an increased packed cell volume, increased percentage of band neutrophils, and leukocytosis, but plasma protein concentrations are frequently low, reflecting generalized systemic inflammation. Horses with subclinical or clinical disseminated intravascular coagulation (DIC) often have thrombocytopenia, which is regarded as a sensitive indicator for DIC. An association between thrombocytopenia and a poor prognosis has been demonstrated in hospitalized horses in general and in horses with colon torsion.
Thrombocytopenia is also frequently found in other diseases, such as equine infectious anemia, in which it is the result of a combined effect of immune-mediated platelet destruction and decreased production; Anaplasma phagocytophilum infection, in which it is presumed to be at least partially caused by bone marrow suppression; neoplasia, in which the thrombocytopenia is presumed to be immune mediated; and snake envenomation, which causes platelet sequestration and increased aggregation and consumption, and which is frequently associated with DIC.
Neonatal Alloimmune Thrombocytopenia
Immune-mediated destruction of platelets following ingestion of preformed antiplatelet antibodies with the colostrum has been reported in horse and mule foals and is suspected to be more common in the latter. Platelets can be the only cell type affected, or thrombocytopenia can occur in conjunction with neonatal isoerythrolysis. In mule foals, platelet destruction is suspected to be immunoglobulin G mediated, with targeting of the collagen receptor (GP Ia IIa). Platelet dysfunction secondary to adhering antibodies has been described in these foals, highlighting the fact that risk for bleeding is determined not only by platelet numbers but also by their functional state. It is reasonable to assume that platelet dysfunction might also play a role in other immune-mediated cases of thrombocytopenia.
A syndrome of ulcerative dermatitis, thrombocytopenia, and neutropenia has been described in six neonatal foals of various breeds. In that report, platelet counts varied from 0 to 30,000/µL, and four of six foals had petechiae or ecchymosis. All foals recovered completely, and thrombocytopenia appeared to be responsive to corticosteroid administration, suggesting an immune-mediated component. Although the exact etiology was not established, transmission of antibodies or other factors through the colostrum was strongly suspected (see Perkins et al in Suggested Readings).
Immune-Mediated Thrombocytopenia
Immune-mediated thrombocytopenia (ITP) is an uncommon disease in adult horses, and the diagnosis is arrived at by excluding other causes. The inappropriate immune response can be directed against intrinsic platelet antigens, antigens or substances bound to the platelet membrane, or infectious agents. The term immune thrombocytopenic purpura is occasionally used if autoantibodies are responsible for platelet destruction. However, differentiating between a primary and secondary immune response on the basis of clinical appearance can be difficult. Administration of penicillin in one case and trimethoprim-sulfadoxine in another was clinically suspected to be involved in ITP, but was not confirmed. The suspicion of ITP is strengthened by detection of antibodies on the platelet membrane or on megakaryocytes. A positive clinical response to immunosuppressive therapy is also strongly supportive. Platelet dysfunction secondary to bound antibodies might also be expected.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
