What are the causes and treatment options for thrombocytopenia (low platelet count)?

Causes and Treatment Options for Thrombocytopenia

Thrombocytopenia is primarily caused by decreased platelet production, increased destruction, splenic sequestration, or dilution, with treatment depending on the underlying cause, severity of thrombocytopenia, and presence of bleeding. 1

Definition and Clinical Presentation

• Thrombocytopenia is defined as a platelet count less than 150 × 10³ per μL 1
• Patients with platelet counts >50 × 10³ per μL are generally asymptomatic 1
• Mild skin manifestations (petechiae, purpura, ecchymosis) may occur with platelet counts between 20-50 × 10³ per μL 1
• High risk of serious bleeding occurs with platelet counts <10 × 10³ per μL 1

Common Causes of Thrombocytopenia

Primary Immune Thrombocytopenia (ITP)

• Diagnosis of exclusion based on history, physical examination, complete blood count, and peripheral smear examination 2
• Characterized by isolated thrombocytopenia without other abnormal findings 2
• Absence of splenomegaly (present in <3% of ITP patients) 2

Drug-Induced Thrombocytopenia

• Common causative medications include quinidine, heparin, sulfonamides, sulfonylureas, dipyridamole, and salicylates 2
• Alcohol can cause thrombocytopenia through direct effects and chronic liver disease 2
• Typically presents with severe thrombocytopenia (platelet nadir <20×10⁹/L) 3
• Onset usually 5-10 days after first drug exposure, or within hours of subsequent exposures 3

Infectious Causes

• Bacterial or viral infections can cause acute thrombocytopenia 2
• HIV infection is commonly associated with thrombocytopenia 2
• Hepatitis C infection can cause thrombocytopenia 4

Other Important Causes

• Thrombotic thrombocytopenic purpura (TTP) - associated with acute anemia, neurologic, or renal abnormalities 2
• Heparin-induced thrombocytopenia - can present with both thrombocytopenia and thrombosis 1
• Liver disease - causes thrombocytopenia through multiple mechanisms 2, 5
• Bone marrow disorders - decreased platelet production 5
• Pregnancy-related conditions including HELLP syndrome 1
• Antiphospholipid syndrome - can present with both bleeding and thrombosis 1

Diagnostic Approach

1. Confirm true thrombocytopenia

   • Rule out pseudothrombocytopenia (platelet clumping due to EDTA) by examining peripheral blood smear 2
   • Consider collecting blood in a tube containing heparin or sodium citrate if pseudothrombocytopenia is suspected 1

2. Determine if acute or chronic

   • Review previous platelet counts to distinguish between acute and chronic thrombocytopenia 1
   • Acute severe thrombocytopenia may require emergency hospitalization 1

3. Essential diagnostic tests

   • Complete blood count and peripheral blood smear examination 2
   • Assess for abnormal red or white blood cell morphology that may suggest other diagnoses 2

4. Additional testing based on clinical suspicion

   • HIV testing for patients with risk factors 2
   • Abdominal imaging (CT/ultrasound) if splenomegaly is suspected 2
   • Bone marrow examination for persistent thrombocytopenia (>6-12 months) or non-response to therapy 2
   • Testing for drug-dependent platelet antibodies when drug-induced thrombocytopenia is suspected 3

Treatment Approach

General Principles

• Treatment should be directed at the underlying cause 1, 5
• Platelet transfusion is recommended for active hemorrhage or platelet counts <10 × 10³ per μL 1
• Activity restrictions to avoid trauma-associated bleeding are advised for patients with platelet counts <50 × 10³ per μL 1

Treatment of ITP

1. Initial Management

   • Observation alone for patients with no bleeding or mild bleeding (skin manifestations only), regardless of platelet count 2
   • For patients requiring treatment, first-line options include:
     • Single dose of IVIg (0.8-1 g/kg) 2
     • Short course of corticosteroids 2
     • Single dose of anti-D in Rh-positive, non-splenectomized patients 2

2. Second-line Treatments

   • Rituximab for patients with significant ongoing bleeding despite first-line treatment 2
   • High-dose dexamethasone as an alternative to splenectomy 2
   • Splenectomy for chronic or persistent ITP with significant bleeding and lack of response to other therapies 2
   • Thrombopoietin receptor agonists (romiplostim, eltrombopag) for patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy 6, 4

Treatment of Drug-Induced Thrombocytopenia

• Discontinuation of the suspected causative drug 3
• Platelet transfusions if bleeding is present 3
• Counseling on future drug avoidance 3

Treatment of Thrombocytopenia in Special Populations

Pregnant Women with ITP

• No routine treatment needed if platelet count >50,000 2
• Treatment required for platelet counts <10,000, or 10,000-30,000 with bleeding in second/third trimester 2
• IVIg is appropriate initial treatment for women with platelet counts <10,000 in third trimester 2

Patients with SLE-associated Thrombocytopenia

• First-line treatment includes moderate/high doses of glucocorticoids with immunosuppressive agents 2
• Initial therapy with pulses of intravenous methylprednisolone (1-3 days) is encouraged 2
• Rituximab should be considered in patients with no response to glucocorticoids 2

Important Considerations and Pitfalls

• Thrombocytopenia does not protect against thrombosis; antithrombotic therapy may still be required despite low platelet counts 7
• Avoid attempting to normalize platelet counts with thrombopoietin receptor agonists, as this is not indicated and may increase thrombotic risk 6
• Bone marrow examination is not necessary in children with typical features of ITP or before initiating IVIg therapy 2
• Splenomegaly suggests an alternative diagnosis to ITP 2
• Drug-induced thrombocytopenia must always be considered and may be difficult to exclude 2