How do I manage sepsis-associated coagulopathy, including antibiotics, source control, fluids, vasopressors, blood product replacement, vitamin K, antithrombin/protein C supplementation, and thromboprophylaxis?

Management of Sepsis-Associated Coagulopathy

The cornerstone of managing sepsis-associated coagulopathy is aggressive early resuscitation with source control, antibiotics, fluids, and vasopressors—NOT routine correction of laboratory coagulation abnormalities with blood products or anticoagulants. 1

Initial Resuscitation (First Hour)

Early goal-directed therapy must begin immediately upon recognition:

• Obtain blood cultures (at least two sets, aerobic and anaerobic) before starting antibiotics 1, 2
• Administer broad-spectrum antibiotics within 1 hour of recognizing septic shock 1, 3
• Measure serum lactate as a marker of tissue hypoperfusion and mortality predictor 1, 2
• Begin aggressive fluid resuscitation with crystalloids, targeting a minimum of 30 mL/kg as initial fluid challenge 1

Source Control

Identify and control the anatomic source of infection within 12 hours of diagnosis whenever feasible 1

• Use the least physiologically invasive intervention (e.g., percutaneous drainage over surgical drainage when appropriate) 1
• Remove intravascular access devices promptly if they are a possible infection source, after establishing alternative vascular access 1
• For intra-abdominal sepsis, consider damage control surgery with open abdomen management in severe cases to facilitate source control and manage inflammatory mediators 1

Fluid Therapy

Use crystalloids (either balanced or saline) as the initial fluid of choice for resuscitation 1

• Continue fluid challenges as long as hemodynamic parameters improve, guided by dynamic (pulse pressure variation, stroke volume variation) or static (arterial pressure, heart rate) variables 1
• Add albumin when patients require substantial amounts of crystalloids 1
• Never use hydroxyethyl starches—they are contraindicated in sepsis 1

Vasopressor Support

If mean arterial pressure (MAP) remains <65 mmHg despite adequate fluid resuscitation, initiate vasopressors immediately 1

• Norepinephrine is the first-line vasopressor of choice 1, 4
• Dopamine is an alternative in select patients, though norepinephrine is preferred 1
• Early vasopressor use reduces organ failure incidence 1
• Vasopressin (0.01-0.04 units/min) or terlipressin can be used as rescue therapy in refractory shock 1

Blood Product Management

Red Blood Cells

Transfuse RBCs only when hemoglobin drops below 7.0 g/dL in the absence of myocardial ischemia, severe hypoxemia, or acute hemorrhage, targeting 7.0-9.0 g/dL 1, 2

Platelets

Transfuse platelets prophylactically based on these thresholds: 1, 2

• <10,000/mm³ without apparent bleeding
• <20,000/mm³ with significant bleeding risk
• ≥50,000/mm³ for active bleeding, surgery, or invasive procedures

Fresh Frozen Plasma

Do NOT use FFP to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures 1, 2

This is a critical pitfall—coagulopathy labs alone are not an indication for FFP transfusion.

Vitamin K

The guidelines do not specifically address vitamin K supplementation in sepsis-associated coagulopathy. In clinical practice, consider vitamin K (10 mg IV) if there is concern for nutritional deficiency or warfarin effect, but this is not a primary intervention.

Anticoagulant Therapy

Do NOT use antithrombin concentrate for treatment of sepsis and septic shock—this is a strong recommendation based on moderate quality evidence 1, 5, 2

• No recommendation exists for routine use of thrombomodulin or heparin in sepsis 1
• Heparin is indicated only for septic thrombosis of great central veins and arteries, not for routine peripheral vein thrombosis 5
• Recombinant activated protein C was withdrawn from the market after failing clinical trials 6

The key pitfall here is attempting to "correct" DIC with anticoagulants—this approach has consistently failed to improve outcomes 6, 7

Protein C Supplementation

Recombinant activated protein C is no longer available and should not be used 1, 6

Despite initial promise, it failed to demonstrate survival benefit in subsequent trials and was withdrawn from the market in 2011 6

Thromboprophylaxis

Initiate DVT prophylaxis in all septic patients unless contraindicated 3

This represents standard critical care practice for immobilized patients, though specific sepsis guidelines focus primarily on acute management.

Corticosteroids

Use IV hydrocortisone (200 mg/day) only if adequate fluid resuscitation and vasopressor therapy fail to restore hemodynamic stability 1

This is a weak recommendation with low quality evidence, reserved for refractory septic shock 1

Monitoring and Reassessment

Continuously monitor these parameters: 1, 2

• MAP ≥65 mmHg
• Urine output ≥0.5 mL/kg/hour
• Lactate clearance
• Central venous oxygen saturation (ScvO₂) >70% if available
• Blood glucose every 1-2 hours until stable, targeting <150 mg/dL 2, 3

Key Clinical Pitfalls to Avoid

1. Do not delay antibiotics or source control while attempting to correct coagulation parameters 1, 3
2. Do not transfuse FFP based solely on abnormal PT/INR without bleeding 1
3. Do not use antithrombin, protein C, or other anticoagulants as routine therapy 1, 5
4. Do not use hydroxyethyl starches for volume resuscitation 1
5. Do not extrapolate VTE treatment guidelines to septic emboli or sepsis-associated coagulopathy 5