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Basics ⬇

Outline

BASICS

Definition!!navigator!!

A peripheral platelet (thrombocyte) count <100 000/μL (<100 × 109/L).

Pathophysiology!!navigator!!

  • Platelets are bone marrow-derived anucleate fragments of megakaryocytes; the smallest cellular particles in blood.
  • Platelets are integral to primary hemostasis via the formation of a platelet plug. They contribute to secondary hemostasis by localizing coagulation factors and providing cofactors.
  • Lifespan in circulation is ≈3–5 days.
  • Thrombopoiesis is stimulated by IL-3, IL-6, granulocyte–macrophage colony-stimulating factor, thrombopoietin.
  • 30–50% of mature platelets stored in the spleen.
  • In health, numbers are balanced between removal (circulation) and replacement (bone marrow).
  • Thrombocytopenia results from decreased production, increased consumption, increased destruction, or increased sequestration

Decreased Platelet Production

Causes include myelophthisis or aplastic anemia (intrinsic stem cell failure or disruption of interactions with other cells).

Increased Platelet Destruction

  • IMTPs are most common.
  • Nonimmune-mediated destruction may occur in response to infections and after exposure to various toxins and drugs.
  • Primary IMTP is associated with production of autoantibodies directed against normal platelet surface antigens or against novel platelet antigens that develop in response to a primary disease.
  • Neonatal alloimmune thrombocytopenia develops when a foal inherits a platelet alloantigen from the sire, the mare produces alloantibodies, and these are ingested by the foal.
  • Secondary IMTP occurs when either circulating immune complexes (against neoplasms, drugs, or infection) attach to platelets nonspecifically. Antibodies directed against antigens attach to platelets; or via molecular mimicry.
  • Platelets coated with antibody are removed from circulation by the reticuloendothelial system

Increased Platelet Consumption

  • DIC is the most common cause of thrombocytopenia.
  • Can also occur with localized activation of coagulation, trauma, severe hemorrhage

Platelet Sequestration

Caused by splenomegaly and vascular neoplasms.

Other

Pseudothrombocytopenia with collection of blood into EDTA or heparin tubes.

Systems Affected!!navigator!!

  • Hemic/lymphatic/immune.
  • Hemorrhage can occur when the platelet count is <30 000/μL (<30.0 × 109/L). Lesions mostly occur in the skin, renal/urologic, GI, and respiratory systems

Genetics!!navigator!!

  • Genetic basis to neonatal alloimmune thrombocytopenia.
  • Genetic basis of familial megakaryocytic and myeloid hypoplasia in Standardbreds is suspected

Incidence/Prevalence!!navigator!!

Unknown, but rare.

Signalment!!navigator!!

Breed Predilections

  • Standardbred horses may be at increased risk.
  • Mules at increased risk for neonatal alloimmune thrombocytopenia

Mean Age and Range

  • Neonatal alloimmune thrombocytopenia occurs in foals <7 days of age.
  • No age predilection for other forms

Predominant Sex

N/A

Signs!!navigator!!

General Comments

Signs of spontaneous hemorrhage are most common with platelet counts <10 000/μL (<10.0 × 109/L) or after trauma/surgery/venipuncture if platelet count is <30 000/μL (<30.0 × 109/L).

Historical Findings

  • Spontaneous or post-traumatic hemorrhage involving mucous membranes, skin, nasal cavity, GI, and urogenital tract.
  • Other signs related to primary disease

Physical Examination Findings

  • Petechial and ecchymotic hemorrhages of oral, ocular, vaginal, and nasal mucous membranes.
  • Mucosal hemorrhage from respiratory (epistaxis), GI (melena), or urinary (hematuria) tract.
  • Prolonged hemorrhage from venipuncture or surgical sites.
  • Hyphema

Causes!!navigator!!

Decreased Platelet Production

  • Myelophthisis—including myelofibrosis, myelodysplasia, leukoproliferative disorders, or lymphoproliferative disorders.
  • Aplastic anemia due to idiopathic pancytopenia, drugs (e.g. phenylbutazone, estrogens, chloramphenicol), infectious or immune-mediated disease.
  • Megakaryocytic and myeloid hypoplasia in Standardbreds

Increased Platelet Destruction

  • Primary IMTP—autoimmune or idiopathic.
  • Neonatal alloimmune thrombocytopenia.
  • Secondary IMTP due to neoplasia (e.g. lymphosarcoma), bacterial infection (sepsis), viral infection (e.g. EIA), drugs (e.g. heparin), or concurrent immune-mediated hemolysis.
  • Snake envenomation.
  • Toxin- or drug-induced platelet damage

Increased Platelet Consumption

  • DIC/systemic inflammatory response syndrome.
  • Localized intravascular coagulation due to hemangioma/hemangiosarcoma, hemolytic uremic syndrome, thrombosis.
  • Excessive hemorrhage.
  • Severe trauma.
  • Vasculitis

Platelet Sequestration

  • Splenomegaly.
  • Vascular neoplasms

Pseudothrombocytopenia

Collection of blood into EDTA.

Miscellaneous with Complex Mechanisms

  • Viral—including EIA, equine herpesvirus, equine viral arteritis, VEE, African horse sickness.
  • Bacterial—neonatal septicemia, EGE (Anaplasma phagocytophilum), equine monocytic ehrlichiosis (Neorickettsia risticii).
  • Neoplastic—lymphosarcoma.
  • Endotoxemia.
  • Fell Pony syndrome

Risk Factors!!navigator!!

  • Any drug may potentially precipitate IMTP. Most common with heparin and myelosuppressive drugs.
  • Certain viral and bacterial infections.
  • Neoplasia.
  • Immune-mediated diseases.
  • Systemic diseases triggering DIC

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Platelet dysfunction is a differential for abnormalities in primary hemostasis. This does not cause petechiae.
  • Vasculitis is a differential for petechiae.
  • Coagulopathy may also be associated with secondary deficits in hemostasis (e.g. anticoagulant therapy, vitamin K deficiency, hepatic failure, or congenital deficiencies)

CBC/Biochemistry/Urinalysis!!navigator!!

  • Platelet count <100 000/μL (<100 × 109/L).
  • Equine platelets are smaller than human platelets and laboratory equipment must be calibrated accordingly.
  • Decreased platelet production frequently has concurrent decreases in granulocytes, monocytes, and RBCs.
  • Concurrent anemia may occur with chronic disease, EIA, immune-mediated hemolysis, and hemorrhage.
  • Changes in RBC morphology.
  • Inclusions in neutrophils in EGE.
  • Inflammatory leukogram (neutrophilia or neutropenia ± left shift) may be seen with DIC.
  • Pseudothrombocytopenia (platelet clumping in EDTA)—rule out with manual platelet count and microscopic examination of smear or repeat platelet count on citrated blood sample.
  • Various biochemical derangements may be present with underlying conditions

Other Laboratory Tests!!navigator!!

  • Coggins test for EIA.
  • Serology for A. phagocytophilum, N. risticii, and various viral agents.
  • Coagulation panel (prothrombin time, activated partial thromboplastin time, d-dimer, fibrinogen) for diagnosis of DIC/consumptive coagulopathies.
  • Blood culture for septicemia.
  • Immunophenotypic techniques to classify leukemia.
  • Flow cytometry for detection of platelet-bound antibody.
  • Platelet factor 3 test as indirect test for IMTP.
  • Cytologic evaluation of fluid and aspirate samples in underlying disease

Imaging!!navigator!!

Ultrasonography and radiography of thorax and abdomen as indicated for identification of underlying disease.

Other Diagnostic Procedures!!navigator!!

  • Abdominocentesis.
  • Thoracocentesis.
  • Bone marrow biopsy to determine megakaryocyte numbers and evidence of myelophthisis or bone marrow hypoplasia.
  • Fine needle aspirate/biopsy of internal/external space-occupying lesion

Pathologic Findings!!navigator!!

  • Petechial and ecchymotic hemorrhages in various tissues.
  • Other findings dependent on specific underlying disease

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Severe thrombocytopenia necessitates hospitalization.
  • If severe hemorrhage has occurred, resuscitation will likely be required.
  • Less severe disease may respond to treatment on an outpatient basis

Nursing Care!!navigator!!

  • Minimize invasive procedures to limit potential for hemorrhage.
  • Apply prolonged pressure to venipuncture sites.
  • Prevent trauma.
  • Discontinue medications if IMTP is suspected.
  • Severe hemorrhage may be life-threatening—hypovolemic and/or anemic shock. Resuscitation with crystalloids for volume expansion and/or fresh whole blood.
  • Platelet replacement with fresh whole blood or platelet-rich plasma. Blood collection and processing should be in plastic containers to avoid activation associated with glass bottles

Activity!!navigator!!

Restricted

Client Education!!navigator!!

Thrombocytopenia indicates the presence of an underlying disease that requires diagnostic management.

Surgical Considerations!!navigator!!

  • Elective surgery should be avoided until platelet counts are normal.
  • Emergency surgery may require concomitant administration of fresh whole blood/platelet-rich plasma

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • For IMTP, initially dexamethasone (0.1 mg/kg IV or IM every 24 h, then reduce dose by 0.01 mg/kg/day when platelet count >100 000/μL. Longer term therapy with oral prednisolone (1–2 mg/kg PO or IM every 24 h).
  • EGE and equine monocytic ehrlichiosis—oxytetracycline (7 mg/kg IV every 12–24 h for 7 days).
  • Bacterial infection—appropriate antimicrobial therapy.
  • DIC—treatment of underlying disease

Contraindications!!navigator!!

  • Corticosteroids—preexistent laminitis or infectious disease.
  • NSAIDs (especially aspirin) in most circumstances owing to impairment of platelet function

Possible Interactions!!navigator!!

Avoid concurrent use of corticosteroids and NSAIDs—possible increased risk of GI damage

Alternative Drugs!!navigator!!

For refractory IMTP, azathioprine (3 mg/kg PO every 24 h) or vincristine (0.01–0.025 mg/kg IV every 7 days)

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Monitor for hemorrhagic diathesis.
  • Daily platelet count until stabilized, thereafter weekly until >100 000/μL

Prevention/Avoidance!!navigator!!

Avoid use of drugs suspected in development of IMTP.

Possible Complications!!navigator!!

Excessive hemorrhage.

Expected Course and Prognosis!!navigator!!

  • Variable, dependent on cause.
  • Most cases of secondary IMTP (drugs/infection) respond with withdrawal of the drug or successful treatment of the underlying infection.
  • Many cases recover in 3–4 weeks.
  • Myeloproliferative disorders have a grave prognosis.
  • EIA and neoplasia have a poor/grave prognosis.
  • Some cases are recurrent—require intermittent corticosteroid therapy.
  • Response to therapy is a useful prognostic indicator

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Immune-mediated hemolysis.
  • Bacterial, viral, or fungal infection.
  • Neoplasia.
  • DIC

Age-Related Factors!!navigator!!

Platelet counts in young animals (<3 years) are often higher than those in older animals.

Zoonotic Potential!!navigator!!

VEE

Abbreviations!!navigator!!

  • DIC = disseminated intravascular coagulation.
  • EGE = equine granulocytic ehrlichiosis.
  • EIA = equine infectious anemia.
  • GI = gastrointestinal.
  • IL = interleukin.
  • IMTP = immune-mediated thrombocytopenia.
  • NSAID = nonsteroidal anti-inflammatory drugs.
  • RBC = red blood cell.
  • VEE = Venezuelan equine encephalomyelitis

Suggested Reading ⬆ ⬇

Sellon DC. Disorders of the hematopoietic system. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine, 2e. St. Louis, MO: WB Saunders, 2004:721–768.

Author(s) ⬆

Author: Kira L. Epstein

Consulting Editors: David Hodgson, Harold C. McKenzie, and Jennifer L. Hodgson

Acknowledgment: The author and editors acknowledge the prior contribution of Kristopher Hughes.