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.
- Immune mediated:
- 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.