Differential Diagnosis

When seeing a patient with thrombocytopenia, there are several ways to approach the differential diagnosis. For the last 2 classification schemes, click on the links for more detail:

1. According to whether or not the thrombocytopenia is real:

  • Pseudothrombocytopenia
  • True thrombocytopenia

2. According to whether the thrombocytopenia is congenital or acquired:

  • Congenital (familial)
  • Acquired

3. According to other changes in the complete blood count:

  • Isolated thrombocytopenia – no other significant changes in the complete blood count.
  • Thrombocytopenia associated with other abnormalities in blood counts.

4. According to the mechanism of thrombocytopenia:

  • Decreased production
  • Increased consumption/destruction
  • Sequestration – hypersplenism, especially in setting of cirrhosis

5. According to clinical context:

  • Outpatient
  • Emergency department
  • Inpatient (new onset)

The most useful of these classifications is clinical context. The classification scheme, which is detailed here, can be conveniently organized as a flow chart:

* New onset thrombocytopenia in hospital. APS, antiphospholipid syndrome; ITP, immune thrombocytopenia; primary BM, primary bone marrow process such as myelodysplasia or leukemia, including treatment effect; TMA, thrombotic microangiopathy; post op, postoperative; ICU, intensive care unit; Extracorporeal, extracorporeal membrane, for example ECMO; L&D, labor and delivery.

In our case, we can focus on the differential diagnosis of isolated thrombocytopenia in an outpatient. The most common conditions include:

Differential diagnosisHistory & physicalLabs
PseudothrombocytopeniaIn vitro artifact, so patients are asymptomatic.Peripheral smear to examine for platelet clumping. Repeat complete blood count in non-EDTA-containing tube.
Immune thrombocytopeniaBleeding and easy bruising. Symptoms associated with causes of secondary ITP. Signs of mucocutaneous bleeding. HCV, HIV, H. pylori to rule out secondary causes.
Drug-induced thrombocytopeniaHistory of drug intake, negative in this patient.No specific testing.
Familial (congenital) thrombocytopenia (FT)Family history of thrombocytopenia and/or bleeding.Peripheral blood smear to examine for giant platelets (present in some but not all causes of FT).
Alcohol abuseHistory of heavy drinking, which was negative in this patient. No specific testing.
CirrhosisHistory/findings of liver disease, jaundice, encephalopathy, spider nevi, palmar erythema, splenomegaly. Negative history/physical exam in this patient.Transaminases, bilirubin, PT, aPTT, albumin.
Antiphospholipid syndrome (APS)History of thrombosis (or in case of women, pregnancy loss), livedo reticularis and other cutaneous manifestations, symptoms associated with secondary causes such as systemic lupus erythematosus. Negative history/physical exam in this patient.Thrombocytopenia is usually mild (platelet count 50-150 × 109/L) and asymptomatic. Severe thrombocytopenia is extremely rare outside the context of APS-associated thrombotic microangiopathy.
ITP, immune thrombocytopenia; HCV, hepatitis C virus; PT, prothrombin time; aPTT, activated partial thromboplastin time; APS, antiphospholipid antibody syndrome.

At this point, we only have a history and physical exam. We have not yet ordered lab tests. Based on what we know so far:

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