21. Thrombocytopenia

Definition: platelet count <150K. Generally, platelets >50K are not associated with significant bleeding. Spontaneous bleeding risk increases when <10K.

Differential Diagnosis

  • Decreased production
    • Aplastic anemia.
    • Cirrhosis.
    • Megaloblastic anemia: B12 or folate deficiency.
    • Hematologic malignancies: myelodysplasia.
    • Marrow infiltration: lymphoma, leukemia, myelofibrosis, metastatic tumor, TB, Gaucher's disease.
    • Drug-induced: numerous including EtOH, valproic acid, thiazides, estrogens, trimethoprim- sulfamethoxazole, chemotherapy, cimetidine, famotidine.
    • Paroxysmal nocturnal hemoglobinuria (PNH): rare and associated with pancytopenia.
    • Infections: HIV, HCV, CMV, EBV, rubella.
  • Increased destruction: classically associated with large platelets on the smear.
    • Immune mediated:
      • Primary ITP: sending platelet associated antibody has low sens/spec and should not be ordered, treat with steroids, IVIG, splenectomy.
      • Secondary ITP: SLE, RA.
      • Neoplasia-associated: CLL.
      • Drug-induced: e.g. quinidine, HIT, rifampin, sulfa, indomethacin, gold.
      • HIV-associated thrombocytopenia.
    • Non-immune mediated:
      • DIC.
      • HUS.
      • TTP: always increased LDH. Decreased platelet, and normal PT/PTT.
      • Pre-ecclampsia/ecclampsia.
      • Hemophagocytosis.
      • HELLP syndrome.
      • Toxic shock syndrome.
      • Vasculitis.
      • Infections: sepsis, CMV, EBV, malaria, rickettsia, ehrlichiosis, hantavirus, dengue hemorrhagic fever.
  • Sequestration: hypersplenism.
  • Pseudo-thrombocytopenia: platelet clumping or satellitism due to EDTA anticoagulant. Peripheral smear occasionally reveals clumping but not always. Send a repeat platelet count in citrate tube for any new diagnosis of thrombocytopenia.

Evaluation

  • Ask about “B”-symptoms (such as fevers, night sweats, weight loss), GI bleed, epistaxis, gum bleeding.
  • Look for lymphadenopathy, splenomegaly, ecchymosis, petechiae, purpura. Petechiae indicate a significant risk for intracerebral hemorrhage.
  • For labs, get CBC with differential (repeat in citrate tube), peripheral smear, PT/PTT, fibrinogen, D-dimers, LDH (MAHA), BUN/Cr (HUS/TTP).
  • Otherwise, work up may be guided by the suspected etiology – consider HIV, HCV Ab, ANA when indicated, and consider toxoplasmosis, EBV, and CMV serology if lymphadenopathy, splenomegaly, or “B”-symptoms are detected. If HIT is suspected (see section Heparin Induced Thrombocytopenia), test platelet factor-4 antibody.

Management

  • Consider platelet transfusions (see section Blood Products for parameters), except when TTP is suspected.
  • Otherwise, treatment is based on etiology, with steroids for ITP, vitamin supplementation when appropriate.
  • Once the diagnosis of ITP is made, corticosteroids, IVIG, rituximab, thrombopoetin receptor agonists, and splenectomy may also be considered.

Key Points

  • ITP is always a diagnosis of exclusion. The number of diagnoses that should be excluded depend on the patient.
  • Consider bone marrow biopsy in the elderly or those who are HIV+ and when more than one cell lineage is affected.

 

Aster RH, Bougie DW. Current Concepts: Drug-induced Thrombocytopenia. New Engl J Med 2007 357: 580-587.

Kuter DJ.Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med. 2009;60:193-206.