Sepsis-Induced Coagulopathy

Sepsis induced coagulopathy is a haemostatic disorder in sepsis with thrombocytopenia, prolonged prothrombin time and microvascular thrombosis, and is an early stage of overt disseminated intravascular coagulation. Its recognition identifies patients at higher risk of death.

Epidemiology. It is found in about 30 to 60% of patients with sepsis, and overt disseminated intravascular coagulation in 10 to 30% of septic shock patients. Mortality rises with the degree of coagulopathy (about 30 to 50% with overt disease).

Scoring. The sepsis induced coagulopathy score uses platelets (under 150 x 10^9/L scores 1, under 100 x 10^9/L scores 2), prothrombin time-INR (over 1.2 scores 1, over 1.4 scores 2) and the SOFA score (2 or more scores 2). A total of 4 or more with a platelet and INR subtotal of 2 or more indicates sepsis induced coagulopathy. The overt DIC score (platelets, D-dimer, prothrombin time, fibrinogen) of 5 or more defines overt DIC.

Causes. Bacterial sepsis (Gram negative and Gram positive), viral sepsis and severe malaria, fungal infection, and trauma or burns with infection.

Pathophysiology. Pathogen products and cytokines induce tissue factor expression on monocytes and endothelium, driving thrombin generation. Natural anticoagulants (antithrombin, protein C, the tissue factor inhibitor) fall, fibrinolysis is suppressed (high plasminogen activator inhibitor-1), and microvascular thrombi cause organ dysfunction. Later consumption leads to bleeding.

Presentation is the septic picture with petechiae, bruising, oozing from lines, thrombosis (limb ischaemia, purpura fulminans), and bleeding in advanced disease. Organ failure out of proportion to haemodynamics suggests microvascular thrombosis.

Red flags.

• Platelets falling by over 30% in 24 hours, or under 100 x 10^9/L.
• Prolonged prothrombin time, low fibrinogen or very high D-dimer.
• Purpura, acral ischaemia or new bleeding.

Full blood count and film (fragmented red cells), prothrombin time-INR, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin and viscoelastic testing as available. Repeat every 6 to 24 hours. Calculate the sepsis induced coagulopathy and DIC scores. Look for the infective source, and exclude heparin induced thrombocytopenia, thrombotic thrombocytopenic purpura, liver failure, drug effect and massive transfusion.

Differential diagnosis. Heparin induced thrombocytopenia, thrombotic microangiopathy (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome), HELLP syndrome, liver failure, vitamin K deficiency, anticoagulant effect and dilutional coagulopathy.

Treat the sepsis. Source control, early antibiotics and haemodynamic support are the basis of treatment, since the coagulopathy improves as sepsis resolves.

Replacement therapy (only for bleeding or procedures).

• Platelets: transfuse for counts under 10 x 10^9/L without bleeding (under 20 x 10^9/L with high bleeding risk), under 50 x 10^9/L with active bleeding or before invasive procedures, and under 100 x 10^9/L with central nervous system bleeding.
• Fresh frozen plasma 10 to 15 mL/kg for bleeding with prolonged prothrombin time or activated partial thromboplastin time.
• Cryoprecipitate (2 pools, about 10 units) or fibrinogen concentrate 3 to 4 g IV for fibrinogen under 1.5 g/L with bleeding.
• Prothrombin complex concentrate is used for severe bleeding with caution because of thrombotic risk.
• Do not give plasma or platelets to correct laboratory values in non-bleeding patients.

Anticoagulation.

• Thromboprophylaxis: enoxaparin 40 mg SC daily (20 mg daily, or unfractionated heparin 5000 units SC every 8 to 12 hours, with creatinine clearance under 30 mL/min), unless platelets are under 20 to 30 x 10^9/L or there is active bleeding.
• Therapeutic heparin (unfractionated heparin 18 units/kg/h after bolus, adjusted to anti-factor Xa) for clinical thrombosis, purpura fulminans or acral ischaemia, with close monitoring.
• Recombinant thrombomodulin is available only in some countries, and antithrombin concentrate is not advised.

Avoid antifibrinolytics (tranexamic acid) in disseminated intravascular coagulation with thrombosis, except for life threatening bleeding with documented hyperfibrinolysis.

Purpura fulminans. Protein C concentrate 100 units/kg IV (specialist), with antibiotics and supportive care.

Monitoring. Platelets, INR, fibrinogen and D-dimer every 6 to 24 hours, limb perfusion, bleeding and organ function scores.

Referral and escalation. Haematology and intensive care. Infectious disease specialists for refractory sepsis.

Special groups. In liver failure, interpret coagulation with caution because of rebalanced haemostasis. In malignancy, balance thrombotic and bleeding risk. In pregnancy, consider obstetric causes (placental abruption, amniotic fluid embolism).