What is thrombocytopenia?

What is Thrombocytopenia

Thrombocytopenia is a platelet count below 150 × 10⁹/L (150,000/μL), resulting from decreased platelet production, increased destruction, splenic sequestration, or dilution. 1, 2

Definition and Clinical Thresholds

• The normal platelet count ranges from 150,000 to 450,000 per microliter, with thrombocytopenia defined as any count below this lower threshold 3, 2
• However, counts below 100 × 10⁹/L are more clinically relevant and warrant further investigation 4
• Severity classification directly correlates with bleeding risk: mild (50-150 × 10⁹/L) is typically asymptomatic, moderate (20-50 × 10⁹/L) may cause cutaneous bleeding like petechiae and purpura, and severe (<20 × 10⁹/L) carries significant risk of serious hemorrhage 1, 2
• Spontaneous serious bleeding is rare when platelet counts exceed 10 × 10⁹/L, occurring in less than 5% of patients, but increases to approximately 40% when counts fall below this threshold 5

Primary Mechanisms

Thrombocytopenia develops through four fundamental pathways 1, 2:

• Decreased production: Bone marrow disorders including myelodysplastic syndromes, leukemias, malignancies, viral infections suppressing megakaryocyte function, and chronic alcohol use 6, 7
• Increased destruction: Immune-mediated mechanisms (primary or secondary immune thrombocytopenia), drug-induced thrombocytopenia, and thrombotic microangiopathies 6, 7
• Splenic sequestration: Hypersplenism from liver disease or portal hypertension 8
• Dilution: Massive transfusion or fluid resuscitation 2

Major Etiologic Categories

Immune-Mediated Destruction

• Primary immune thrombocytopenia (ITP) represents autoimmune destruction of otherwise normal platelets and remains a diagnosis of exclusion after ruling out all secondary causes 6, 7
• Secondary immune thrombocytopenia associates with HIV, hepatitis C, H. pylori infection, autoimmune disorders (lupus, antiphospholipid syndrome), lymphoproliferative disorders, common variable immune deficiency, and post-vaccination 6, 7
• HIV and HCV infections produce thrombocytopenia clinically indistinguishable from primary ITP and may precede other symptoms by years 7
• Antiphospholipid antibodies are found in approximately 40% of otherwise typical adult ITP patients, though their presence does not affect treatment response 7

Drug-Induced Thrombocytopenia

• Over 200 medications can cause thrombocytopenia through either bone marrow suppression or immune-mediated platelet destruction 9
• Most commonly implicated drugs include heparin, quinidine, sulfonamides, sulfonylureas, dipyridamole, salicylates, and GPIIb-IIIa inhibitors 5, 7
• Heparin-induced thrombocytopenia (HIT) typically presents with moderate thrombocytopenia (30-70 × 10⁹/L) occurring 5-10 days after heparin initiation 6
• Drug-induced thrombocytopenia usually resolves with discontinuation of the offending medication 7

Infection-Related Causes

• Viral infections including HIV, HCV, parvovirus, and cytomegalovirus cause thrombocytopenia through platelet consumption from inflammation-induced coagulation, sequestration by phagocytosis, and cytokine-induced myelosuppression 7
• Acute bacteremia or viral infection may manifest as acute and severe thrombocytopenia 5
• H. pylori infection, particularly in high-prevalence regions, can cause thrombocytopenia that normalizes with eradication therapy 7

Pregnancy-Related Thrombocytopenia

• Gestational thrombocytopenia is the most common cause during pregnancy, accounting for approximately 75% of cases, typically presenting with mild thrombocytopenia (platelet count >70 × 10⁹/L) occurring in late gestation that resolves spontaneously after delivery 5, 6
• Pregnancy-induced hypertension/preeclampsia occurs in about 10% of pregnancies, with thrombocytopenia developing in up to 25% of these patients 5
• HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) accounts for most remaining cases of pregnancy-associated thrombocytopenia 5, 6

Inherited Thrombocytopenias

• Congenital disorders including thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, and 22q11.2 deletion syndrome affect platelet production 6, 7
• 22q11.2 deletion syndrome characteristically presents with lower platelet counts, large platelets, and reduced platelet quality, though usually mild 7

Critical Diagnostic Paradox

Certain thrombocytopenic conditions paradoxically increase thrombotic risk rather than bleeding risk, including heparin-induced thrombocytopenia, thrombotic microangiopathies, and antiphospholipid syndrome. 6, 1

• In cancer patients with thrombocytopenia, venous thromboembolism risk is not reduced despite low platelet counts, and prolonged thrombocytopenia (>30 days) associates with greater than four-fold increased risk of recurrent VTE 1
• Antiphospholipid syndrome and disseminated intravascular coagulation cause thrombocytopenia with thrombosis, not bleeding 6

Essential First Step: Exclude Pseudothrombocytopenia

• Pseudothrombocytopenia occurs in approximately 0.1% of adults due to EDTA-dependent platelet agglutination causing platelet clumping in the presence of anticoagulant EDTA 5
• Thrombocytopenia must be confirmed by direct examination of the peripheral blood smear in every patient before proceeding with further evaluation 5, 7
• If pseudothrombocytopenia is suspected, repeat the platelet count using blood collected in heparin or sodium citrate tube 7, 2

Clinical Presentation

• Patients with platelet counts greater than 50 × 10⁹/L are generally asymptomatic 2
• Patients with counts between 20 and 50 × 10⁹/L may develop cutaneous bleeding manifestations including petechiae, purpura, or ecchymosis 2
• Patients with counts less than 10 × 10⁹/L have high risk of serious bleeding including intracranial hemorrhage 2
• Physical examination should assess bleeding severity and exclude other causes: splenomegaly provides evidence against primary ITP (present in less than 3% of ITP patients), while lymphadenopathy or signs of liver disease suggest lymphoproliferative or autoimmune disorders 5, 6

Activity Restrictions and Safety

• Patients with platelet counts below 50 × 10⁹/L should avoid contact sports and activities that increase trauma risk to prevent bleeding complications 1, 2
• A sedentary individual may tolerate lower platelet counts than patients whose profession or hobbies involve high exertion or potential trauma 5
• Medications that impair platelet function, including aspirin and NSAIDs, must be avoided as they increase bleeding risk even with moderate thrombocytopenia 6