Management of Sepsis-Associated Coagulopathy and Disseminated Intravascular Coagulation
Treat the underlying infection aggressively—this is more important than any supportive coagulation measure—and reserve blood product replacement strictly for active bleeding or immediately before invasive procedures, not to "normalize" laboratory values. 1
Diagnostic Strategy: Two-Step Algorithm
Step 1: Screen with Sepsis-Induced Coagulopathy (SIC) Criteria
- Apply SIC scoring to every septic patient with platelet count <150 × 10⁹/L to detect the compensated (early) phase of coagulopathy before overt DIC develops. 1, 2
- SIC score ≥4 points defines sepsis-induced coagulopathy and carries ≥30% mortality, making it the threshold for intensified monitoring and potential anticoagulant consideration. 1, 2
- SIC scoring components (total ≥4 points):
- Fibrinogen is deliberately excluded from SIC criteria because it is usually normal or elevated in sepsis due to acute-phase response, unlike malignancy-associated DIC. 1
Step 2: Confirm Overt DIC with ISTH Criteria
- If SIC ≥4, then calculate ISTH overt-DIC score (≥5 points confirms overt DIC). 1, 2
- ISTH overt-DIC scoring components (total ≥5 points):
- Overt DIC represents decompensated coagulopathy with hemorrhage, microvascular thrombosis, tissue ischemia/necrosis, and schistocytes on peripheral smear. 2
Laboratory Monitoring Frequency
- Daily in acute severe DIC with active bleeding or rapid deterioration 2
- Every 2–3 days in stable ICU patients with diagnosed DIC 2
- Trend analysis over hours to days is more diagnostically important than single absolute values—a ≥30% drop in platelet count is diagnostic of subclinical DIC even when absolute values remain normal. 2
- Normal D-dimer effectively rules out DIC (sensitivity 91–100%), making it the single most useful screening test to exclude the diagnosis. 3
Blood Product Replacement: Strict Indications Only
Platelet Transfusion Thresholds
- <10 × 10⁹/L: prophylactic transfusion in the absence of bleeding 1
- <20 × 10⁹/L: transfusion when significant bleeding risk exists 1
- ≥50 × 10⁹/L: target for active bleeding, surgery, or invasive procedures 1
Fresh Frozen Plasma (FFP)
- Reserve FFP strictly for active bleeding with prolonged PT/aPTT—do not use to normalize laboratory values in non-bleeding patients. 1
- FFP is indicated for documented factor deficiency with hemorrhage or immediately before invasive procedures. 1
Fibrinogen Replacement
- Indicated only when fibrinogen <1.5 g/L (150 mg/dL) persists despite FFP and the patient has active bleeding, using cryoprecipitate or fibrinogen concentrate. 1
- Do not treat elevated fibrinogen—it reflects acute-phase response in sepsis and does not require correction. 1
- Hypofibrinogenemia is uncommon in sepsis-associated DIC due to excessive suppression of fibrinolysis (via plasminogen activator inhibitor-1), contrasting with malignancy-associated DIC where fibrinolytic phenotype predominates. 1
Anticoagulant Therapy: Evidence and Indications
Heparin (Low-Molecular-Weight or Unfractionated)
- Therapeutic-dose heparin is FDA-approved for "acute and chronic consumptive coagulopathies (disseminated intravascular coagulation)" 4
- Start therapeutic-dose heparin (preferably LMWH) in thrombosis-predominant DIC when any of the following are present: 2
- Arterial or venous thromboembolism
- Severe purpura fulminans with acral ischemia
- Vascular skin infarction
- Cancer-associated DIC with documented thrombotic events
- Prolonged PT/aPTT alone should not preclude anticoagulation in thrombosis-predominant DIC. 2
- Prophylactic-dose heparin (5,000 units subcutaneously every 8–12 hours) may be considered in high-risk septic patients without active bleeding. 4
- Monitor aPTT to maintain 1.5–2 times normal (or whole blood clotting time 2.5–3 times control) when using therapeutic-dose heparin. 4
Antithrombin Supplementation: Do Not Use
- Antithrombin provides no mortality benefit in septic shock and increases bleeding risk, especially when combined with heparin (KyberSept Phase III trial). 1
- Do not use antithrombin therapy regardless of measured levels. 1
Recombinant Thrombomodulin
- A phase III trial showed a 2.6% absolute mortality reduction (not statistically significant overall), but in patients meeting SIC criteria at baseline, the mortality difference was approximately 5% without increased bleeding. 5
- Thrombomodulin is not FDA-approved in the United States but may be considered in regions where available, specifically in patients with SIC score ≥4. 5, 6
Critical Pitfalls to Avoid
- Do not correct elevated fibrinogen as a therapeutic target—it is excluded from SIC criteria and does not correlate with sepsis severity or mortality. 1
- Do not give FFP prophylactically to "normalize" lab values in non-bleeding patients. 1
- Do not rely on fibrinogen level alone to grade DIC severity in sepsis—falling platelet count and PT prolongation are the key prognostic markers. 1
- Normal PT and aPTT do not rule out DIC—they remain normal in approximately 50% of cases of sepsis or subclinical cancer-associated DIC. 3
- Do not use the intramuscular route for heparin due to frequent hematoma formation. 4
- Distinguish DIC from thrombotic microangiopathy and heparin-induced thrombocytopenia, which require different management. 7
Pathophysiology Context
- The dominant coagulation disturbance in sepsis is suppression of fibrinolysis caused by excess plasminogen activator inhibitor-1, rather than a consumptive coagulopathy. 1
- Endothelial injury is an essential component of DIC pathophysiology; antithrombin activity and von Willebrand factor are candidate biomarkers for assessing endothelial dysfunction when available. 1, 2
- Neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and glycocalyx shedding contribute to thromboinflammation in sepsis-induced DIC. 7, 5