Cryoprecipitate Dosing for Cirrhosis with Prolonged INR Unresponsive to Vitamin K
Direct Answer
Do not give cryoprecipitate to correct INR in cirrhotic patients—INR does not predict bleeding risk in cirrhosis and cryoprecipitate is indicated only for low fibrinogen levels, not for INR correction. 1
Why INR Correction is Not the Goal
- INR is not a valid predictor of bleeding in cirrhosis because it reflects hepatic synthetic dysfunction rather than actual hemostatic capacity 1
- Vitamin K typically has minimal impact on INR in cirrhosis (only 16.7% of patients achieve meaningful INR reduction) and is effective primarily in cholestatic disease or malabsorption, not parenchymal liver disease 2, 3
- Fresh frozen plasma (FFP) should not be used to correct INR in cirrhosis—even high volumes fail to meaningfully correct INR in 86% of patients, and FFP dangerously increases portal pressure 1
When Cryoprecipitate IS Indicated in Cirrhosis
Active Bleeding Scenario
Cryoprecipitate is indicated only when:
- The patient has active bleeding (not prophylaxis for procedures) 1
- Fibrinogen level is <120 mg/dL (the consensus threshold for actively bleeding cirrhotic patients) 1
Dosing Protocol
Standard dose: 5–10 units of cryoprecipitate 1
- Each unit contains 10–20 mL volume 1
- Weight-based calculation: 1 unit per 10 kg body weight raises fibrinogen by approximately 50 mg/dL 1
- For a 70 kg patient: 7 units would raise fibrinogen by ~50 mg/dL 1
- Alternative dosing: 15–20 single-donor units (approximately 50 mg/kg) for severe hypofibrinogenemia 4
Target Fibrinogen Level
- Maintain fibrinogen >120 mg/dL during active bleeding in cirrhosis 1
- Some guidelines suggest targeting 100–200 mg/dL, but 120 mg/dL is the most widely accepted threshold in clinical practice 1
Evidence Against Prophylactic Use
- A retrospective study of 237 critically ill cirrhotic patients showed that cryoprecipitate transfusion (given to achieve fibrinogen >100–120 mg/dL) had no independent effect on bleeding complications or mortality 1
- This calls into question whether fibrinogen itself directly causes bleeding in cirrhosis, or merely reflects disease severity 1
Alternative Approaches for Active Bleeding
If Fibrinogen is Adequate (>120 mg/dL)
Consider these interventions instead of cryoprecipitate: 1
- Platelet transfusion to achieve count >50,000/μL 1
- Antifibrinolytic agents (aminocaproic acid 4–5 g IV over 1 hour then 1 g/h, or tranexamic acid 1 g IV every 6 hours) for suspected hyperfibrinolysis 1
- Red blood cell transfusion to hematocrit 25% to improve platelet margination 1
- Treat infection aggressively—active infection releases endothelial-derived heparinoids that worsen coagulopathy 1
- Optimize renal function—uremia causes platelet dysfunction 1
Prothrombin Complex Concentrate (PCC)
- Off-label use of 4-factor PCC has been reported in cirrhosis with the advantage of minimal volume (10–20 mL) 1
- However, dosing based on INR is problematic in cirrhosis because INR does not reflect true coagulation status 1
- Role remains undefined and requires further study 1
Critical Pitfalls to Avoid
- Do not transfuse FFP to "correct" INR—it increases portal pressure and bleeding risk without improving hemostasis 1
- Do not give cryoprecipitate prophylactically before procedures based on INR alone 1
- Do not use vitamin K expecting INR improvement in parenchymal liver disease—it works only in cholestasis or malabsorption 1, 2, 3
- Measure fibrinogen level before giving cryoprecipitate—do not assume low fibrinogen based on INR 1
- Minimize volume expansion from blood products as this worsens portal hypertension and bleeding 1
Procedure-Related Bleeding Prevention
For elective procedures in cirrhosis (not active bleeding):
- Low-risk procedures (paracentesis, thoracentesis, endoscopy with banding) require no prophylactic correction of INR, platelets, or fibrinogen 1
- Higher-risk procedures: Target platelets >50,000/μL (using transfusion or thrombopoietin agonists like avatrombopag/lusutrombopag) and fibrinogen >120 mg/dL only if baseline is low 1