Definition

Platelet count below the lower limit of reference interval, which varies with the method of platelet counting. Grade of thrombocytopenia-Grade 1: 100,000/µL to lower limit of reference range; Grade 2: 50,000–99,000/µL; Grade 3: 25,000–49,000/µL; Grade 4: <25,000/µL.

Pathophysiology

• Platelets are produced by bone marrow megakaryocytes and released into the blood, where they normally circulate 5–10 days.
• Thrombocytopenia is caused by one or more of decreased production; increased sequestration, utilization, destruction of platelets.
• Thrombocytopenia may cause spontaneous or excessive hemorrhage.

Systems Affected

• Hemorrhage may occur into any organ system.
• Clinical hemorrhage-most commonly recognized in the skin/exocrine and gastrointestinal systems, followed by the renal/urologic and respiratory systems; less commonly recognized in the ophthalmic, nervous, and reproductive systems.

Incidence/Prevalence

• Thrombocytopenia is a common hematologic abnormality.
• Severe hemorrhage due to thrombocytopenia is uncommon (dogs) or rare (cats) in general practice.

Signalment

Signs

Causes

• Decreased production-hereditary; bone marrow neoplasia; Sertoli cell tumor; infectious agents; immune-mediated; drugs; irradiation. Thrombocytopenia varies from mild to severe and may be an isolated hematologic abnormality or a feature of pancytopenia.
• Increased sequestration-splenomegaly; severe thrombocytopenia is uncommon.
• Increased utilization-DIC; local thrombosis (e.g., portal vein); vasculitis; severe thrombocytopenia is uncommon.
• Increased destruction-primary IMT or IMT secondary to neoplasia, infectious agents, aseptic inflammation, drugs. Most common cause of severe thrombocytopenia in dogs.
• Increased loss-hemorrhage due to vitamin K antagonist poisoning may result in mild to moderate thrombocytopenia; hemorrhage due to major trauma may result in mild to severe thrombocytopenia after volume resuscitation.

Risk Factors

• Potentially any infection-most commonly associated with thrombocytopenia: FeLV; FIV; distemper; parvoviruses; Ehrlichia spp.; Anaplasma spp., Rocky Mountain spotted fever; leptospirosis; Borrelia burgdorferi; bacterial sepsis; histoplasmosis; Cytauxzoon felis; Babesia spp.; Rangelia spp.; Hepatozoon canis, Leishmania spp.; Theileria spp. heartworm, Angiostrongylus vasorum, and aberrant larva migrans.
• Potentially any non-infectious inflammation, e.g., vasculitis.
• Potentially any neoplasm-most commonly identified include hemangiosarcoma, thyroid carcinoma, lymphoma, histiocytic sarcoma and acute leukemias.
• Large-field radiation therapy and cytotoxic drug therapy-predictable myelosuppression; lomustine causes a cumulative thrombocytopenia.
• Potentially any drug-drugs with known risk for unpredictable myelosuppression or IMT include estrogen, gold compounds, phenylbutazone, phenobarbital (dogs); chloramphenicol, griseofulvin, propylthiouracil, methimazole and carbimazole (cats); drugs with reported idiosyncratic reactions causing myelosuppression include cephalosporins and albendazole (dogs, cats), fenbendazole, sulfonamides, ACE inhibitors (dogs), and ribavirin.
• Vaccination within 1 month-for IMT.
• Toxins and venoms-zinc, autumn crocus (myelosuppression); mycotoxins, xylitol (acute hepatic injury-DIC); snake bite.
• Hyperthermia-DIC.

Differential Diagnosis

• Measurement error due to platelet clumping-most likely with traumatic venipuncture and in cats. EDTA-induced platelet clumping may occur in dogs (rare).
• Clerical error.
• Local hemorrhage-rule out trauma, gastrointestinal ulceration, primary intranasal, urinary, and reproductive tract disorders.
• von Willebrand disease-petechiae, ecchymoses, and ocular hemorrhages unusual.
• Coagulopathy-petechiae, gastrointestinal hemorrhage, and epistaxis unusual; subcutaneous swellings, swollen joints, hemothorax, and hemoabdomen may be present.

CBC/Biochemistry/Urinalysis

• Confirm thrombocytopenia reported by a hematology analyzer by examination of a blood smear; examine feather edge for platelet clumps; estimate platelet count from red cell monolayer where about 50% of cells are touching; each platelet-per-oil immersion field represents 15,000–25,000/µL.
• Mean platelet volume and platelet distribution width are inversely related to platelet count and usually do not assist in differentiating causes of thrombocytopenia. Platelet morphology changes are nonspecific.
• Plateletcrit (analogous to hematocrit)-best method to diagnose pathologic thrombocytopenia in a Cavalier King Charles spaniel.
• Regenerative anemia-rule out hemorrhage or IMHA concurrent with IMT.
• Neutrophilia and left shift-rule out sepsis, non-septic inflammation, and nonspecific stimulation of granulopoiesis.
• Eosinophilia-rule out heartworm and other helminth infections.
• Concurrent non-regenerative anemia and neutropenia-thrombocytopenia probably due to decreased production.
• Schistocytes-DIC.
• Organisms in blood cells.
• Abnormalities on a biochemistry profile and urinalysis reflect primary disease.

Other Laboratory Tests

• von Willebrand factor antigen.
• PT, APTT, ACT-prolonged times increase likelihood of DIC; normal PT rules out vitamin K antagonism.
• Fibrinogen degradation products and D-dimer-positive result increases likelihood of DIC or local thrombosis.
• Cultures of abnormal organs, blood, and urine for bacterial or fungal sepsis.
• Serologic and PCR tests for infectious organisms.
• Fecal floatation and Baermann tests for parasitic larvae.
• Antiplatelet/antimegakaryocyte antibody tests-negative results help rule out IMT.
• Coombs' test-positive result increases likelihood of concurrent IMHA.
• Antinuclear antibody test-positive result increases likelihood of SLE.
• Flow cytometry for immature reticulated platelets (analogous to reticulocyte count).

Imaging

Identify splenomegaly, hepatomegaly, neoplasms, infection, and internal bleeding.

Diagnostic Procedures

Bone marrow biopsy-rule out reduced platelet production: neoplasia in bone marrow, histoplasmosis, maturation arrest, marrow aplasia, myelofibrosis, and marrow necrosis; no specific finding that rules in or out immune-mediated megakaryocytic hypoplasia; low diagnostic yield if the only hematologic abnormalities are thrombocytopenia causing bleeding and regenerative anemia (likely IMT). Not contraindicated in severe thrombocytopenia.

Pathologic Findings

Internal bleeding; other findings reflect primary disease.

Appropriate Health Care

• Treatment of primary disorder.
• Platelet transfusion-20 mL/kg (minimum 10 mL/kg) fresh whole blood, platelet-rich plasma, or fresh frozen plasma (contains platelet particles), or 1 unit/10 kg (minimum 1 unit/30 kg) platelet concentrate (fresh, room-temperature stored, cryopreserved, and lyophilized) or cryoprecipitate (where 1 canine unit refers to product derived from a 450 mL unit of whole blood); transfuse if critical hemorrhage is noted and consider prophylactic transfusion if platelet count <5,000–10,000/µL; transfusions may be needed q1–3d if severe thrombocytopenia persists; most useful when thrombocytopenia is due to reduced production or loss and rapid resolution is anticipated; less useful in splenomegaly and DIC and least useful in IMT.
• Whole blood or packed red cell transfusion to correct anemia-bleeding due to thrombocytopenia is worse in the presence of anemia.
• Do not drain hematomas unless necessary (e.g., tracheal compression).

Nursing Care

• Minimize IM and SC injections. Apply extended pressure after IV injection/catheterization and invasive procedures. Avoid jugular venipuncture.
• Avoid overexuberant fluid therapy.

Activity

Restrict activity with moderate-to-severe thrombocytopenia.

Diet

Avoid hard foods with severe thrombocytopenia (gingival bleeding).

Surgical Considerations

Extensive perioperative transfusion may be needed.

Drug(s) Of Choice

• See specific chapters for diseases causing thrombocytopenia.
• Acepromazine has negligible effects on platelet function in dogs and cats and may be used to sedate animals to reduce risk of hemorrhage associated with excessive activity.

Contraindications

NSAIDs that interfere with platelet function-opioids are preferred for analgesia; if NSAID use required, use selective cyclooxygenase-2 inhibitors (e.g., deracoxib).

Precautions

• Heparin (used in DIC) may aggravate hemorrhage due to thrombocytopenia.
• Corticosteroid therapy may exacerbate infection and promote gastrointestinal ulceration.

Possible Interactions

Corticosteroids are prothrombotic.

Alternative Drug(s)

• Thrombopoietic stimulants: Oprelvekin-50 µg/kg SC q24h for maximum of 2 weeks (to avoid risk of neutralizing antibody formation); most useful when thrombocytopenia caused by cytotoxic therapy; expensive. Romiplostim, eltrombopa, lithium carbonate-not recommended.
• Plasmin inhibitors: aminocaproic acid, tranexamic acid; as for IMT; contraindicated in DIC; Melatonin and 5-methoxytryptamine-as for IMT.

Patient Monitoring

• Amount of bleeding-control of clinical hemorrhage is most important parameter to monitor to judge effectiveness of treatment.
• Serial platelet counts using same method
• Serial coagulation profiles-if DIC suspected.

Prevention/Avoidance

Varies with cause.

Possible Complications

• Hemorrhagic shock
• Uveitis
• Mild-to-severe neurologic signs (CNS bleeding)

Expected Course and Prognosis

Varies with cause. If underlying cause of severe thrombocytopenia cannot be treated, prognosis poor because of limited ability to provide extensive platelet transfusions.

Associated Conditions

• If thrombocytopenia is from reduced production, may be concurrent anemia and neutropenia.
• IMT may be solitary or associated with other immune-mediated disorders.

Age-Related Factors

Varies with cause-e.g., FeLV in younger cats, IMT in middle-aged dogs, neoplasia in older dogs.

Zoonotic Potential

Thrombocytopenia may be due to a zoonotic infection (e.g., leptospirosis).

See Also

• Anemia, Immune-Mediated
• Disseminated Intravascular Coagulation
• Hyphema
• Pancytopenia
• Petechia, Ecchymosis, Bruising
• Splenic Torsion
• Splenomegaly
• Thrombocytopathies
• Thrombocytopenia, Primary Immune-Mediated
• Vasculitis, Systemic
• Specific chapters for various infectious diseases

Abbreviations

• ACE = angiotensin converting enzyme
• ACT = activated clotting time
• APTT = activated partial thromboplastin time
• DIC = disseminated intravascular coagulation
• EDTA = ethylene diamine tetra-acetic acid
• FeLV = feline leukemia virus
• FIV = feline immunodeficiency virus
• IMHA = immune-mediated hemolytic anemia
• IMT = immune-mediated thrombocytopenia
• NSAID = nonsteroidal anti-inflammatory drug
• PCR = polymerase chain reaction
• PT = prothrombin time
• SLE = systemic lupus erythematosus

Internet Resources

https://ahdc.vet.cornell.edu/sects/clinpath/modules/coags/acqtbtp.htm