What causes thrombocytopenia (low platelet count) in sepsis?

Causes of Thrombocytopenia in Sepsis

Thrombocytopenia in sepsis is primarily caused by pathological activation of hemostasis and consumptive coagulopathy, often manifesting as disseminated intravascular coagulation (DIC). 1

Pathophysiological Mechanisms

1. Consumptive Coagulopathy

• Disseminated Intravascular Coagulation (DIC): The primary mechanism causing thrombocytopenia in sepsis is DIC, which reduces platelet counts through pathological activation of hemostasis and consumptive coagulopathy 1
• Platelet Activation: Pathogens (both bacterial and viral) directly activate platelets, leading to systemic thrombosis that contributes to multi-organ failure in DIC 2
• Fibrinolysis Suppression: Sepsis-associated DIC is characterized by excessive suppression of fibrinolysis caused by overproduction of plasminogen activator inhibitor-1, with potential prothrombotic effects 1

2. Endothelial Dysfunction

• Inflammatory Mediators: Markers of inflammation (e.g., tumor necrosis factor alpha, heat shock protein 70) and endothelial dysfunction (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1) are negatively associated with platelet count 3
• Microvascular Thrombosis: Endothelial damage promotes microvascular thrombosis, particularly in distal extremities, which can lead to symmetrical peripheral gangrene in severe cases 1

3. Altered Thrombopoiesis

• Growth Factors: Thrombopoiesis growth factors (e.g., thrombopoietin) are negatively associated with platelet count during sepsis, suggesting dysregulation of platelet production 3
• Decreased Production: Sepsis can lead to decreased platelet production in the bone marrow, contributing to thrombocytopenia 4

4. Additional Contributing Factors

• Hemodilution: Surrogates of hemodilution (hypoprotidemia and higher fluid balance) are associated with thrombocytopenia in septic shock 3
• Hepatic Dysfunction: Impaired hepatic synthesis of crucial natural anticoagulants (antithrombin and protein C) can exacerbate coagulopathy 1

Clinical Significance and Assessment

Diagnostic Approach

• Two-Step Diagnostic Approach: The International Society on Thrombosis and Haemostasis (ISTH) recommends a two-step approach for diagnosing coagulopathy in sepsis 5:

  1. Initial evaluation using Sepsis-Induced Coagulopathy (SIC) criteria
  2. Evaluation for overt DIC using ISTH criteria if SIC is positive

• SIC Scoring System (≥4 points for diagnosis) 5:

  • Platelet count: 2 points (<100 × 10^9/L) or 1 point (≥100, <150 × 10^9/L)
  • Prothrombin time ratio: 2 points (>1.4) or 1 point (>1.2, ≤1.4)
  • SOFA score: 2 points (≥2) or 1 point (1)

• DIC Scoring System (≥5 points for diagnosis) 1, 5:

  • Platelet count: 2 points (<50 × 10^9/L) or 1 point (≥50, <100 × 10^9/L)
  • Fibrin degradation products/D-dimer: 3 points (strong increase) or 2 points (moderate increase)
  • Prothrombin time: 2 points (≥6 seconds prolonged) or 1 point (≥3, <6 seconds prolonged)
  • Fibrinogen: 1 point (<100 g/mL)

Prognostic Implications

• Thrombocytopenia is an independent predictor of poor outcomes in patients with sepsis 4
• Platelet count declines and PT prolongation are correlated with increased mortality in sepsis 1
• Early identification of SIC is crucial for guiding anticoagulant therapy and improving outcomes 5

Management Considerations

Treatment Approaches

• Control Underlying Infection: The primary treatment focus should be controlling the underlying infection 5

• Anticoagulant Therapy: Consider in patients with positive SIC diagnosis 5

  • Unfractionated heparin (UFH) has been associated with reduced 28-day and hospital mortality without increasing major bleeding risk 5
  • Antithrombin supplementation may benefit septic patients with DIC who have decreased antithrombin activity 5
  • Recombinant thrombomodulin has shown lower mortality rates compared to heparin in some studies 5

• Platelet Support: For patients with severe thrombocytopenia, recombinant human thrombopoietin (rhTPO) has shown efficacy in increasing platelet counts and shortening ICU stay time 6

Monitoring

• Serial monitoring of coagulation parameters improves detection of progression to DIC 5
• Monitor for acute kidney injury through urine output, serum creatinine, and blood urea nitrogen 5

Pitfalls and Caveats

• Thrombocytopenia in sepsis may be multifactorial, with different mechanisms predominating in different patients 3
• Treating only the thrombocytopenia without addressing the underlying sepsis will not improve outcomes 5
• Anticoagulant therapy should be carefully considered, as it may increase bleeding risk in already thrombocytopenic patients 7
• Not all septic patients with thrombocytopenia have DIC; other causes such as drug-induced thrombocytopenia should be considered