| Causes of thrombocytopenia fall into one or a combination of the following
Remember that platelet clumping in blood samples (as evident in peripheral
blood smears) will artifactively decrease the platelet count (obtained
by any method) and, in some instances, may result in a pseudothrombocytopenia.
There have been rare reports in human patients (with isolated reported
case in horses) of an EDTA-dependent pseudothrombocytopenia. This only
occurs in blood collected into EDTA (not citrate or heparin) due to EDTA-induced
unmasking of platelet antigens by EDTA with binding of antibodies and
subsequent platelet aggregation. In these circumstances, platelet counts
need to be determined from citrated or heparinized blood samples (although
citrate is preferred as heparin can also produce platelet clumping).
- Decreased production of platelets in the marrow
- Increased consumption of platelets in coagulation
- Increased destruction of platelets by macrophages
- Sequestration of platelets in the spleen or microvasculature
- Acute, severe hemorrhage
- Decreased platelet production
Most causes of decreased platelet production are not just selective
for megakaryocytes but affect the erythroid and myeloid (granulocyte)
lines as well. Therefore, thrombocytopenia due to decreased production
is usually accompanied by neutropenia and or/anemia without reticulocytosis.
Remember that neutrophils survive in the circulation for approximately
12 hours, whereas platelets survive for up to 7-10 days. Therefore,
thrombocytopenia and neutropenia may precede anemia in animals with
these bone marrow conditions (as red cells have a much longer lifespan).
Acquired causes of decreased bone marrow production of platelets include
1) Bone marrow aplasia or hypoplasia: Causes include drug toxicities
(estrogen, griseofulvin, trimethoprim-sulfonamides, albendazole), bracken
fern poisoning in cattle, infectious agents (Ehrlichia canis
infection), and idiopathic (likely immune-mediated).
2) Leukemia: An acute leukemia (acute myeloid leukemia or acute
lymphoid leukemia) arising in the bone marrow wipes out the remaining
hematopoietic cells. Animals may present with pancytopenia with or without
circulating blasts. Some animals have a leukocytosis comprised only
of leukemic blasts, with a concurrent neutropenia, thrombocytopenia
and non-regenerative anemia.
3) Infiltrative neoplasia: This is due to replacement of the
bone marrow by extramedullary neoplasia, such as lymphoma. Metastatic
carcinomas (breast, prostate) are a common tumor that metastasizes to
the bone marrow in man, but not in animals.
4) Ineffective hematopoiesis: Some animals with pancytopenia
have a cellular marrow, but hematopoiesis is not effective, likely due
to increased intramedullary cell death. Causes include neoplastic conditions
(myelodysplastic syndromes in cats, histiocytic sarcoma in dogs), infectious
agents (Ehrlichia canis) and immune-mediated disease.
5) Necrosis: Necrosis of the bone marrow from ischemic, radiation
or toxic injury or secondary to infectious agents can result in a pancytopenia.
This is a very rare cause of pancytopenia in animals.
- Increased platelet consumption
Thrombocytopenia of variable severity is a fairly consistent finding
in disseminated intravascular coagulation (DIC). Vasculitis, whether
caused by infectious agents or immune complexes, can produce thrombocytopenia
even without laboratory results indicative of DIC; the thrombocytopenia
of Rocky Mountain spotted fever is thought to be due primarily to generalized
- Increased platelet destruction
Immune-mediated destruction of platelets can occur as a clinical syndrome
of idiopathic (primary) immune-mediated thrombocytopenia - called ITP
or IMT - or as a component of other infectious, neoplastic or systemic
immunologic diseases, such as systemic lupus erythrematosis (SLE). There
is no routinely available, reliable method for detecting antiplatelet
antibodies in animals at this time. The platelet factor 3 (PF3) release
test widely mentioned in the veterinary literature is no longer available
and never was a very reliable test. Detection of IgG on megakaryocytes
of thrombocytopenic animals by direct immunofluorescence methods is
considered as supportive evidence of antibodies with antiplatelet activity;
this procedure is neither sensitive nor specific and is not a routinely
offered test either. Newer procedures using flow cytometery to detect
anti-platelet antibodies are now available at certain referral institutions.
Antiplatelet antibodies confirm an immune-mediated pathogenesis for
the thrombocytopenia, but do not distinguish between primary and secondary
ITP. Positive results are seen in animals with infectious disorder (e.g.
Ehrlichiosis in dogs), neoplasia
and other immune-mediated disease (e.g. SLE). ITP is diagnosed most
frequently in dogs but rare cases of ITP in cats and horses have been
seen. Examination of a peripheral blood smear in animals with ITP show
very few or no platelets in severe cases (as illustrated by the image
on the right which is a smear from a dog with ITP).
Primary ITP usually presents as a clinical syndrome of acute
onset small vessel type bleeding in a dog without signs of severe systemic
illness. The degree of anemia is variable and depends on the amount
of blood lost through hemorrhage and the presence of concurrent immune-mediated
destruction of red cells (hemolytic anemia). The diagnosis of ITP is
based on finding thrombocytopenia, normal coagulation test results,
exclusion of other diseases, and favorable response to immunosuppressive
therapy. Bone marrow aspiration is generally not indicated in the initial
work-up of a patient with ITP; results show normal erythroid and granulocytic
lines and, in most cases, normal to increased numbers of megakaryocytes.
Rare dogs with ITP have no or few megakaryocytes in marrow; such patients
are considered to have immune-mediated destruction of megakaryocytes
as well. These dogs are thought to respond more poorly to immunosuppressive
therapy than dogs with megakaryocytic hyperplasia. Platelet destruction
in some animals can be quickly controlled with fairly mild immunosuppression
(corticosteroids alone) but in others prolonged treatment with cytotoxic
drugs (azathioprine and/or vincristine in combination with corticosteroids)
is necessary to increase the platelet count. Dogs in the latter category
need intense supportive care to manage the side effects of the immunosuppressive
drugs and the loss of blood. Since the spleen is a major site of platelet
destruction, splenectomy is done in rare cases refractory to control
by drugs. Because ITP can be a part of more generalized immune-mediated
disease, clinical signs, physical findings, history, and laboratory
results should be evaluated for evidence of abnormalities of other organs,
particularly skin, joints, and kidneys, that may lead to recognition
Secondary ITP occurs with infectious diseases, neoplasia and
drugs. Immune-mediated destruction of platelets is one of several possible
mechanisms by which infectious diseases can cause thrombocytopenia.
Thrombocytopenia is seen in some viral infections and may occur within
7-10 days of vaccination with modified-live viruses (especially canine
distemper virus). This post-vaccinal thrombocytopenia is generally mild
(platelet counts rarely decrease < 100,000/Ál), with the most severe
decreases seen in puppies. Immune-mediated destruction is partly responsible
for the thrombocytopenia of canine ehrlichiosis (E. canis) and
infectious canine cyclic thrombocytopenia (E. platys). The severe
thrombocytopenia in some cows with BVD appears to be due in part to
antibody-mediated destruction. Babesia, a protozoan erythroparasite,
can cause thrombocytopenia.
Many drugs have been reported to cause ITP in human patients and therefore
are potential causes of thrombocytopenia in animals. In general, if
an animal with the clinical syndrome of ITP is receiving drugs, these
should be discontinued if at all possible and reintroduced with caution
when a normal platelet count is restored.
Documented cases of drug-related ITP in animals are few but include
gold compounds, PTU (propylthiouracil, an anti-
|Petechiae and gingival hemorrhage
in a Doberman with primary ITP
thyroid drug), sulfonamides, and penicillin.
Immune-mediated thrombocytopenia is associated with neoplastic diseases
in some animals. Neoplasms such as lymphoma and a variety of benign
and malignant solid tumors have been implicated in some cases.
Immune-mediated thrombocytopenia due to blood transfusions (so-called
post-transfusion purpura) is a rare condition in human patients characterized
by a severe thrombocytopenia 1 to 2 weeks after blood or blood product
transfusion. This has been reported in a dog with hemophilia A. The
dog developed a severe thrombocytopenia (platelet count < 10,000/Ál),
on 2 occasions after being transfused (the first occurred 8 days after
a second blood transfusion; the second, 5 days after cryoprecipitate
infusions). On both occasions, the platelet counts normalized within
4 to 6 days of corticosteroid therapy (but the dog may have recovered
spontaneously without treatment).
Neonatal thrombocytopenic purpura has been recognized in pigs, mules
and one Quarterhorse foal. In pigs, agglutinating antibodies against
sire and piglet platelets have been documented in the dam. The piglets
are generally born healthy, then develop thrombocytopenia after 5 to
9 days, with the nadir occurring at 10 to 13 days. Thrombocytopenia
is due to increased platelet destruction and decreased platelet production.
Clinical signs of cutaneous hemorrhage are seen. Death may result at
2 to 3 weeks of age. Surviving piglets appear clinically and hematologically
normal by 16 weeks of age. Severe thrombocytopenia was discovered in
a 1 day old Quarterhorse foal presenting for weakness and failure to
suckle. His dam's serum contained antibodies that bound to his and a
full brother's platelets.
- Increased platelet sequestration
Excessive platelet pooling in spleens enlarged due to a variety of reasons
may cause thrombocytopenia. Thrombocytopenia in animals with bacteremia
or endotoxemia is due in part to sequestration of damaged platelets
in organs such as lung, liver and spleen. However, animals with these
diseases are likely to have DIC as well, which contributes to the thrombocytopenia
by consumption in coagulation.Severe, acute hemorrhage due to trauma
or deficiency of coagulation factors can result in mild to moderate
thrombocytopenia (usually not < 50,000/Ál).
- Acute severe hemorrhage
Severe, acute hemorrhage due to trauma or deficiency of coagulation
factors can result in mild to moderate thrombocytopenia (usually not
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