Drug-induced thrombocytopenia

A variety of drugs may cause thrombocytopenia. Although it occurs more often than drug-induced anemia it is less well understood because techniques for studying drug-platelet-immune interactions have been unavailable until recently. The mechanisms by which drugs cause thrombocytopenia are varied. Bone marrow suppression or increased peripheral destruction of platelets could be involved. Nonimmunologic as well as immunologic mechanisms may also occur. These different mechanisms of drug-induced thrombocytopenia are reveiwed. Diagnostic methods and treatment are also summarized.     

Possible causal association of idiopathic inflammatory bowel disease with thrombocytopenia in the dog

Extraintestinal manifestations of inflammatory bowel disease (IBD) are commonly observed in humans but are poorly documented in companion animals. Thrombocytopenia is an uncommon but well-documented extraintestinal hematological abnormality in humans; however, there are no previous reports of IBD and concurrent thrombocytopenia in the veterinary literature. Seven dogs having idiopathic IBD and concurrent thrombocytopenia were identified and evaluated retrospectively (this represents an incidence of 2.5% in the authors' IBD population). Obvious known causes for thrombocytopenia were eliminated by diagnostic testing as deemed appropriate by the clinician of record. Thrombocytopenia resolved with treatment for the IBD in some but not all patients. This is similar to reports in humans. Thrombocytopenia typically appears to be subclinical, and the severity does not correlate with the degree of intestinal inflammation defined histopathologically. However, quantitative platelet counts should be monitored during IBD therapy, as additional immunosuppression may be required to treat thrombocytopenia, despite resolution of gastrointestinal signs. It is speculated that thrombocytopenia may be causally associated with canine IBD, possibly secondary to immune stimulation from lumenal bacterial antigens, altered immunological regulation, or both.     

Thrombocytopenia associated with vaccination of a dog with a modified-live paramyxovirus vaccine

Thrombocytopenia (10,000/mm3), with hematochezia and melena, appeared in a dog 8 days after it was given modified-live canine distemper, virus vaccine and persisted for approximately 5 days. Clinical investigation discounted other possible causes of thrombocytopenia; the condition was considered to be associated with vaccination. The problem spontaneously resolved. The appearance of thrombocytopenia after modified-live canine distemper virus vaccination is not unknown and may assume a severe form. This condition may be mistaken for idiopathic thrombocytopenia of immune origin, and in other instances, it may contribute significantly to surgical risk if concurrent coagulation disorders are present. Administration of levamisole HCl may alleviate the decrease in platelet count in affected animals.     

Resolution of severe thrombocytopenia in two standard Poodles with surgical correction of splenic torsion

Objective: To describe the diagnosis and treatment of 2 cases of severe thrombocytopenia associated with splenic torsion and to discuss the pathophysiologic mechanisms underlying the thrombocytopenia. Summary: We report 2 cases of severe thrombocytopenia associated with splenic torsion. Each dog presented with non‐specific clinical signs, radiographic evidence of an intra‐abdominal mass, and platelet counts of less than 25,000 platelets/μL. The diagnosis of splenic torsion was made with abdominal ultrasonography and was confirmed during exploratory laparotomy. Both dogs recovered rapidly following splenectomy. The cause of thrombocytopenia associated with splenic torsion is not fully elucidated, but may be because of either platelet sequestration within the torsed spleen, platelet consumption in disseminated intravascular coagulation, or a combination of both. New information provided: This report provides previously unreported evidence that the degree of thrombocytopenia associated with splenic torsion may be of a severity at which primary hemostasis is compromised, and resolution of thrombocytopenia occurs after splenectomy.     

Diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia: 58 cases (1994-2004)

OBJECTIVE: To determine the diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia. DESIGN: Retrospective case series. ANIMALS: 58 dogs with thrombocytopenia. PROCEDURES: Medical records were searched and reviewed for dogs with thrombocytopenia. Dogs that had thrombocytopenia and cytologic examination of bone marrow were included in the study. Dogs with other hematologic abnormalities, with a previous diagnosis of hematopoietic neoplasia, or that had previous treatment with cytotoxic drugs were excluded. Bone marrow cytologic findings were reviewed. Results were compared between dogs with severe thrombocytopenia (< 20,000 platelets/microL) and dogs with mild to moderate thrombocytopenia (20,000 to 200,000 platelets/microL). RESULTS: 58 dogs met the inclusion criteria. Of 55 dogs with diagnostic bone marrow aspirates, 36 had severe thrombocytopenia. Cytologic evaluation of bone marrow did not reveal substantial nonmegakaryocytic bone marrow abnormalities or result in a definitive diagnosis in any of these dogs. Nineteen dogs with mild to moderate thrombocytopenia had diagnostic bone marrow aspirates. Bone marrow cytologic findings revealed nonmegakaryocytic abnormalities in 4 of these dogs. Significantly fewer dogs with severe thrombocytopenia had abnormalities identified on cytologic examination of bone marrow, compared with dogs with mild to moderate thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Cytologic examination of bone marrow is unlikely to provide specific diagnostic or prognostic information in dogs with severe thrombocytopenia.     

A Drug-induced Cerebrospinal Lipodystrophy in the Domestic Chicken (Gallus domesticus)

A drug-induced lipidosis of the central nervous system of chickens is reported. Membranous cytoplastic neuronal inclusions similar to those seen in Tay-sach's disease in man and in spontaneous or drug-induced disease in swine were seen by electron microscopy. Fat was demonstrated in frozen sections.     

Presumed primary immune-mediated thrombocytopenia in four cats

Feline primary immune-mediated thrombocytopenia (pIMT) is a rare hematological disorder. Platelet-bound antibody assays for cats have variable specificity and sensitivity and are not widely available. Diagnosis of pIMT is made on the basis of exclusion of other identifiable causes of thrombocytopenia and the response to immunosuppressive therapy. This report describes four cats with severe thrombocytopenia and no detectable underlying disease. One cat was euthanased because of pulmonary hemorrhage, while the other cats had frequent relapses, two of these cats developed diabetes mellitus due to long-term corticosteroid therapy. In these cats IMT had a chronic course and responded poorly to therapy with prednisolone. Alternative immunomodulatory drugs may be considered in the treatment of feline IMT.     

Concurrent bartonellosis and babesiosis in a dog with persistent thrombocytopenia

A 12-year-old castrated male West Highland White Terrier was referred because of recurrent episodes of collapsing. The dog was mildly anemic and severely thrombocytopenic and had high serum alanine aminotransferase activity. Infection with Bartonella vinsonii (berkhoffii) was initially diagnosed on the basis of serologic testing. Despite treatment with a series of antimicrobials and prolonged use of immunosuppressive drugs, thrombocytopenia persisted. After 5 months of treatment, Babesia canis organisms were seen during examination of a direct blood smear. The dog was treated with imidocarb dipropionate for babesiosis, after which thrombocytopenia resolved, and administration of immunosuppressive drugs was discontinued. Retrospective review of blood smears failed to identify organisms; however, polymerase chain reaction (PCR) analysis of multiple stored blood samples obtained during the 5-month period of persistent thrombocytopenia identified DNA of B. canis vogeli. Babesiosis may cause persistent, unexplained thrombocytopenia in dogs that are not anemic. A PCR assay can facilitate a diagnosis of babesiosis when organisms are not evident or when serologic testing fails to detect Babesia-specific antibodies.     

Flow cytometric detection of platelet-bound antibody in three horses with immune-mediated thrombocytopenia

Immune-mediated thrombocytopenia (IMT) is a sporadic cause of thrombocytopenia in horses for which it is difficult to establish a definitive diagnosis. In this report, we describe 3 horses with severe thrombocytopenia in which flow cytometric analysis of platelets for surface-bound IgG was used in an attempt to substantiate a provisional diagnosis of IMT. A distinct proportion (4.28%, 5.04%, and 7.95%) of platelets with surface-bound IgG was detected in the 3 thrombocytopenic horses, but not in 6 healthy horses (0.03% to 0.15%) or 6 horses with colic (0.00% to 1.21%). These results, in conjunction with elimination of other potential causes of the thrombocytopenia, established a diagnosis of IMT. The horses were treated with glucocorticoids alone or in combination with azathioprine, and the thrombocytopenia gradually resolved. Flow cytometric detection of platelet-bound IgG was readily performed and may be a useful adjunct for the diagnosis of IMT.     

Epidemiologic survey of thrombocytopenia in dogs: a report on 987 cases

Thrombocytopenia was documented in 987 of 18,910 (5.2%) dogs admitted to North Carolina State University, College of Veterinary Medicine, Veterinary Teaching Hospital, between 1983 and 1989. Classifying thrombocytopenic dogs by etiologic groups revealed the following proportionate ratios: 5% (48/987) immune-mediated thrombocytopenia; 13% (130/987) neoplasia-associated thrombocytopenia; 23% (224/987) inflammatory/infectious thrombocytopenia; and 59% (585/987) miscellaneous thrombocytopenia. Dogs with immune-mediated thrombocytopenia had significantly (P < 0.05) lower platelet counts (mean 36,760 +/- 50,288 microliter) than dogs in the other three groups, and Doberman Pinschers were overrepresented in all groups except the immune-mediated thrombocytopenic group. We conclude that thrombocytopenia is a prevalent and potentially important diagnostic finding in a variety of disease states.     

Hereditary and acquired thrombopathias

Normal platelet function is essential for hemostasis. The pathophysiologic processes that result in acquired quantitative platelet abnormalities are detailed. Platelet pathophysiology associated with acquired qualitative disorders, either drug-induced or secondary to disease, is discussed. Numerous hereditary platelet defects also exist. Their functional and biochemical features are presented.     

Pseudothrombocytopenia secondary to the effects of EDTA in a dog

Pseudothrombocytopenia (PTCP) secondary to the effects of ethylenediaminetetraacetic acid (EDTA) has been noted in horses and pigs and should be considered in dogs with moderate thrombocytopenia and no clinical bleeding tendency. This type of pseudothrombocytopenia is not a pathological process by itself, but it can be clinically significant if diagnostics and medical treatments are initiated based on the reported thrombocytopenia. Platelet clumping occurs with EDTA-dependent PTCP, resulting in inaccurate hematology analyzer platelet concentrations. A nontraumatic venipuncture may be sufficient to obtain an accurate platelet count. However, rare cases in the dog may require blood drawn into a different anticoagulant, such as sodium citrate, to help discriminate a true thrombocytopenia from PTCP.     

Thrombocytopenia Associated With Neoplasia in Dogs

Ten percent (214/2,059) of all dogs with cancer at North Carolina State University Veterinary Teaching Hospital had thrombocytopenia. The thrombocytopenia was associated with infectious/inflammatory etiologies in 4%, miscellaneous disorders (therapy, bone marrow failure, disseminated intravascular coagulation) in 35%, and neoplasia without identifiable secondary factors in 61% of cancer-bearing dogs. Classifying these dogs by tumor groups revealed the following proportionate ratios: lymphoid, 29%; carcinoma, 28%; sarcoma, 20%; hemic neoplasia, 7%; multiple, 5%; unclassified, 3%; benign, 3%; brain, 3%; and endocrine, 3%. Dogs with hemangiosarcoma, lymphoma, and melanoma were at increased risk of developing thrombocytopenia. Cytotoxic therapy was the major factor increasing the risk of thrombocytopenia in dogs with melanoma. Golden Retrievers were the only breed recognized with a predisposition to develop thrombocytopenia. If thrombocytopenia is identified in a dog with cancer, we recommend thorough evaluation of the coagulation system before surgery or therapy, and careful consideration of the risks and potential benefits of myelosuppressive or L-asparaginase therapy.     

Evaluation of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy

OBJECTIVE: To determine accuracy of a manual technique for detection of neutropenia and thrombocytopenia in dogs receiving chemotherapy. DESIGN: Masked prospective study. ANIMALS: 11 dogs treated with chemotherapy for neoplasia. PROCEDURE: 124 blood samples from dogs being treated with chemotherapy for various neoplasms were processed through an automated cell counter, and results were compared with those obtained by use of a rapid manual technique for estimating neutrophil and platelet concentrations to determine whether the manual technique could accurately detect dogs with neutropenia or thrombocytopenia. RESULTS: By use of automated techniques, neutropenia (< 3,000 cells/microl) was detected in 17 of 124 blood samples, and thrombocytopenia (< 100,000 platelets/microl) was detected in 3 of 124 blood samples. The manual technique correctly identified 16 of 17 (94%) blood samples with neutropenia, with a specificity of 92% (98/107). The manual technique correctly identified 3 of 3 (100%) blood samples with thrombocytopenia, with specificity of 94% (114/121). CONCLUSIONS AND CLINICAL RELEVANCE: Manual estimates of neutrophil and platelet counts are sensitive and specific; however, a full differential cell count is still preferable.     

Idiopathic thrombocytopenic purpura in a cat

An 11-year-old, castrated, male domestic shorthair cat was presented for hematuria and pollakiuria. The cat had a marked thrombocytopenia, and a bone-marrow core biopsy demonstrated megakaryocytic hyperplasia with many megakaryocyte-associated neutrophils (i.e., emperipolesis). On peripheral blood, collected at initial presentation, what appeared to be platelets were noted to be within or adherent to occasional neutrophils. The thrombocytopenia was idiopathic in that no definitive cause could be found. However, platelet concentrations appeared to increase and decrease in response to changes in prednisone and cyclosporine therapy, suggesting a possible immune-mediated pathogenesis. As tests to detect increased feline platelet-associated antibodies are unavailable, immune-mediated thrombocytopenia can only be tentatively diagnosed in cats by exclusion and response to therapy.     

Persistent thrombocytopenia in a case of equine infectious anemia

Persistent thrombocytopenia was detected in a horse with equine infectious anemia (EIA). The thrombocytopenia was considered to be immune-mediated, developing secondary to infection with EIA virus. Epistaxis, petechial hemorrhages, subcutaneous hematomas, and edema resolved after treatment with corticosteroids; however, the owners requested that the mare by euthanatized because of infection with EIA virus. Although clinical signs attributable to immune-mediated thrombocytopenia may resolve with appropriate treatment, horses with immune-mediated thrombocytopenia secondary to EIA have a guarded to grave prognosis, because of the risk of recurrence and transmission of the EIA virus.     

Relationship between splenic sequestration and thrombocytopenia in Trypanosoma evansi infection in rats

Trypanosoma evansi infections in domestic animals are characterized by anemia and thrombocytopenia. The cause of the platelets decrease is unknown, but researchers suggest that thrombocytopenia may result from damage of the bone marrow, reduced survival of platelets, auto-immune thrombocytopenia, disseminated intravascular coagulation and splenic sequestration. Some of these causes have already been tested by our research group and found to be unrelated. Therefore, this study has the objective of testing the hypothesis that splenic sequestration might be responsible for thrombocytopenia in T. evansi-infected rats. A total of 28 rats assigned to four groups were used in the experiment. Group A rats were splenectomized and infected with T. evansi, group B rats were infected with T. evansi, group C rats were splenectomized, but not infected and group D rats were normal controls. Five days post-infection all rats were anesthetized and blood was collected in order to measure the number of circulating platelets, fibrinogen levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT). The spleens of groups B and D were weighed at necropsy. The infected animals (groups A and B) showed a significant reduction in platelets and increased PT and aPTT when compared to negative control groups (groups C and D). Animals from group A showed increased levels of fibrinogen. The mean weight of spleen differed between group B (2.62 g) and group D (0.55 g). It was concluded that there is no relationship between thrombocytopenia and splenic sequestration in infection by T. evansi.     

Neonatal Alloimmune Thrombocytopenia in a Quarter Horse Foal

Neonatal alloimmune thrombocytopenia is recognized as a spontaneous disease of human infants, piglets, and possibly mules, but it has not been previously reported in horses. A 1–day-old Quarter Horse foal presented to Michigan State University Large Animal Clinic with severe thrombocytopenia of unknown origin. Immunoglobulins that bound to the foal's platelets were identified in the mare's plasma, serum, and milk by indirect assays. The immunoglobulins were further shown to recognize platelets from the foal's full brother, born 1 year earlier. These findings, coupled with the clinical course of the foal during its period of hospitalization, strongly suggest that neonatal alloimmune thrombocytopenia can spontaneously occur in neonatal horses. This diagnosis should be considered for foals with severe thrombocytopenia when other causes can be excluded, and platelet antibody assays should be used to support this diagnosis.     

Histopathology of incidental findings in beagles used in toxicity studies

The purpose of our publication is to widely communicate the pictures of spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly in beagles. Frequent sites of arteritis are the heart, spleen, pancreas, epididymis and spinal cord. Morphological similarities between spontaneous and drug-induced arterial lesions may cause confusion when evaluating vascular toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory lesions are occasionally seen in the lung and may be associated with aspiration of food particles or of unknown causes. A cystic change with copious mucin production occurs occasionally in the mucosal epithelium of the gall bladder. Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring frequently in beagles must be distinguished from drug-induced damage of the seminiferous tubules in toxicity studies. The morphological differences of the female genital system in each cycle need to be understood; therefore, we present the normal features of the cyclic changes of the female genital organs. Further, we provide more information on spontaneous findings in beagles for exact diagnoses in toxicity studies.     

Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier

A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, apparent throughout the entire lungfield, but particularly marked within the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia was made and the dog was treated with vincristine and immunosuppressive doses of prednisolone. Initially anaemia developed following gastrointestinal haemorrhage; however, after symptomatic treatment the dog showed a marked clinical improvement. Evaluation for an underlying cause of the disease revealed Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with fenbendazole was commenced. The dog made a full clinical recovery with all treatment was withdrawn within five weeks of diagnosis. This is the second report of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection and it is the first to be successfully managed. The report highlights that Angiostrongylus vasorum should be considered in young dogs presented with thrombocytopenia.