What are the causes of thrombocytopenia (low platelet count) in adults and neonates?

Causes of Thrombocytopenia

Primary Mechanism-Based Classification

Thrombocytopenia results from four fundamental mechanisms: decreased platelet production, increased platelet destruction, splenic sequestration, or dilution/clumping. 1, 2

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies impair megakaryocyte function and platelet release 1
• Bone marrow suppression occurs with chronic alcohol use, certain medications, viral infections (HIV, hepatitis C, parvovirus, CMV), and iron overload 1, 3
• Aplastic anemia presents with pancytopenia (anemia, thrombocytopenia, and neutropenia) due to hypocellular marrow with fatty replacement 4
• Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, and 22q11.2 deletion syndrome affect platelet production from birth 1

Increased Platelet Destruction

Immune-Mediated Destruction

• Primary immune thrombocytopenia (ITP) is an autoimmune disorder with antibody-mediated destruction of otherwise normal platelets, diagnosed only after excluding all secondary causes 1, 3

  • In adults, ITP typically has insidious onset with no preceding illness and follows a chronic course 3
  • In children, ITP usually follows viral infection and two-thirds recover spontaneously within 6 months 3, 1

• Secondary immune thrombocytopenia is associated with multiple conditions 1:

  • Autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome)
  • Viral infections (HIV, hepatitis C, CMV)
  • Lymphoproliferative disorders
  • Common variable immune deficiency
  • Bone marrow transplantation
  • Vaccination side effects

• Drug-induced immune thrombocytopenia can occur with antibiotics, GPIIb-IIIa inhibitors, quinine, sulfonamides, vancomycin, cefazolin, oxacillin, clindamycin, doxycycline, and SMX-TMP, typically presenting 5-14 days after drug exposure 1, 5

• Heparin-induced thrombocytopenia (HIT) typically presents with moderate thrombocytopenia (30-70 × 10⁹/L) occurring 5-10 days after heparin initiation, paradoxically associated with thrombosis rather than bleeding 1

Non-Immune Destruction

• Thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and HELLP syndrome cause platelet consumption through microvascular thrombosis 1, 2
• Disseminated intravascular coagulation (DIC) causes consumption of platelets and coagulation factors through widespread fibrin and platelet deposition 1
• Antiphospholipid syndrome causes thrombocytopenia with thrombosis, not bleeding 1
• Consumption thrombocytopenia occurs with extracorporeal circuits, intra-aortic balloon pumps, and cardiac surgery with cardiopulmonary bypass 1

Splenic Sequestration

• Hepatic disease with portal hypertension leads to splenomegaly and increased platelet sequestration 2, 6
• Up to one-third of total platelet mass can be sequestered in an enlarged spleen 6

Special Populations

Neonates and Children

• Neonatal alloimmune thrombocytopenia occurs when maternal antibodies cross the placenta and destroy fetal platelets 7
• Inherited thrombocytopenias may present in the neonatal period with characteristic features such as large platelets or associated congenital anomalies 1, 7

Pregnancy

• Gestational thrombocytopenia is the most common cause in pregnancy, typically presenting with mild thrombocytopenia (platelet count >70 × 10⁹/L) 1
• Pregnancy-induced hypertension/preeclampsia and HELLP syndrome can cause severe thrombocytopenia requiring emergency intervention 1

Cyanotic Congenital Heart Disease

• Polycythemia and hyperviscosity trigger platelet consumption, with platelet counts inversely correlating with hematocrit levels, resulting in mild thrombocytopenia (100,000-150,000/μL) more commonly than severe 1

Critical Diagnostic Pitfalls to Avoid

• Pseudothrombocytopenia from EDTA-dependent platelet clumping can falsely lower counts; always exclude by examining peripheral blood smear and repeating count in heparin or sodium citrate tubes 1, 2
• Missing secondary causes of ITP (HIV, hepatitis C, H. pylori) which have different natural histories and responses to therapy; test all adults with suspected ITP regardless of risk factors 1, 3
• Overlooking drug-induced thrombocytopenia; obtain detailed medication history including over-the-counter medications and herbal supplements 1
• Failing to recognize HIT early; calculate 4T score immediately if patient has received any heparin within the past 3 months 1
• Delaying recognition of thrombotic microangiopathies (TTP/HUS) which require prompt diagnosis and treatment to prevent catastrophic outcomes 1