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Thrombocytopenia

Last updated: May 5, 2021

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Thrombocytopenia is a platelet count below the normal range (< 150,000/mm3) that is most commonly due to either impaired platelet production in the bone marrow or increased platelet turnover in the periphery. Common causes of impaired platelet production include bone marrow failure, infection, malignancy, and chemotherapy/radiation. Additional etiologies include hereditary syndromes, such as Wiskott-Aldrich syndrome and Alport syndrome. In contrast, increased peripheral platelet turnover may be caused by autoimmune conditions, (e.g., immune thrombocytopenia), drugs (e.g., heparin), and other conditions (e.g., TTP/HUS, DIC/sepsis). Thrombocytopenia is often asymptomatic and found incidentally on routine bloodwork. Patients may notice petechiae or mucosal bleeding (e.g., bleeding gums, epistaxis) at lower platelet counts. Other patients with thrombocytopenia are clinically ill and have multisystem findings (e.g., acute infection, liver disease, TTP/HUS, DIC). Diagnosis should be confirmed with repeat testing (to rule out pseudothrombocytopenia) and underlying causes should be investigated and treated. Patients with active bleeding or neurological symptoms require emergency platelet transfusion, and in cases of immune-mediated etiologies, IVIG. Observation may be sufficient for patients who have stable medium-low platelet levels and no serious underlying condition. Patients with suspected ITP and low platelet counts (e.g., < 30,000/mm3) are typically treated with corticosteroids, IVIG, or splenectomy.

See also “Immune thrombocytopenia”.

Impaired platelet production in bone marrow [1]

Bone marrow conditions → megakaryocytes thrombopoiesis

If platelet production is impaired, the number of megakaryocytes on bone marrow biopsy will also be decreased.

Increased platelet turnover in the periphery

Increased peripheral turnover also increases numbers of megakaryocytes on bone marrow biopsy!

Redistribution, dilution, and other causes

References:[1][4][4][5][5][6][7][8]

Clinical features according to platelet count [1][9]
Platelet count Symptoms [9]
Mild
  • > 70,000–149,999/mm3
  • Typically: no abnormal bleeding, i.e., asymptomatic thrombocytopenia
Moderate
  • 20,000–70,000/mm3
Severe
  • < 20,000/mm3

References:[1][5][7]

Approach [1]

  • Confirm the diagnosis in all patients:
  • Investigate for underlying causes with a thorough history and routine laboratory studies.
  • If the etiology remains unclear:
    • Evaluate recent medication (see “Etiology”).
    • Order additional investigations based on clinical suspicion, e.g., evaluation for MDS or other malignancies in patients > 60 years old with new-onset thrombocytopenia.
  • See “ITP” if isolated thrombocytopenia with no other underlying cause detected.
  • Evaluate for complications:

Do not delay treatment for diagnostic testing in patients with significant bleeding or new neurological symptoms.

Routine laboratory studies [1]

A rapidly falling platelet count is worrisome, even if it is within the normal range (e.g., in HIT).

Additional investigations

Consider additional laboratory studies or imaging depending on clinical features and results of routine laboratory studies

Additional diagnostic studies for thrombocytopenia by etiology [1][10]
Suspected etiology Supporting clinical features Diagnostics
Infectious
Autoimmune disease
  • History of autoimmune disease
  • Features of systemic autoimmune diseases, e.g., fever, rash, arthralgia
Heparin-induced thrombocytopenia
HELLP syndrome
Malignancy
Thrombotic microangiopathy
  • TTP
    • Patient is systemically unwell
    • Purpura
    • Neurological features may be seen.
  • HUS
    • Recent gastrointestinal illness, typically with bloody diarrhea
Liver disease and/or hypersplenism

See Differential diagnosis of platelet disorders for a comparison of findings in various etiologies of thrombocytopenia.

The differential diagnoses listed here are not exhaustive.

Patients with thrombocytopenia may be asymptomatic or acutely unwell if the thrombocytopenia is a feature of a wider syndrome such as DIC or TTP. Management depends on symptoms, initial platelet count, and the underlying condition.

Approach [1][15]

  • All patients
    • Treat any significant bleeding (see “Emergency management of thrombocytopenia”).
    • Treat underlying cause (See “Etiology”).
      • Immediately treat serious or life-threatening underlying illnesses (See “Treatment” in “TTP”, “HIT”, “HUS”, and “DIC”).
      • Benign or mild illnesses may resolve spontaneously.
    • Consider empiric treatment for ITP (e.g., corticosteroids, IVIG) if platelet count < 30,000/mm3 without another apparent cause (see “Treatment” in “ITP”).
    • Consider stopping medications that impair platelet function and increase bleeding risk, e.g., NSAIDs. [15]
  • Mildly symptomatic or asymptomatic patients with a platelet count < 50,000/mm3: Consult hematology.
  • Asymptomatic patients with a platelet count > 50,000/mm3: Repeat CBC in 1–4 weeks or if the patient becomes symptomatic. [1]

Emergency management of thrombocytopenia [15][16]

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