From the Guidelines
Liver coagulopathy should be managed by addressing the underlying liver disease, and prophylactic correction of laboratory values without active bleeding is generally not recommended due to the risk of thrombosis, as evidenced by a study showing that PCC administration was associated with thromboembolic events in 5.5% of patients with cirrhosis 1. When managing liver coagulopathy, it is essential to consider the patient's overall clinical condition and the risk of bleeding or thrombosis. The liver plays a crucial role in producing clotting factors, including factors I, II, V, VII, IX, X, XI, and XIII, as well as proteins C and S. In liver disease, coagulopathy occurs due to decreased synthesis of these factors, leading to prolonged prothrombin time (PT) and international normalized ratio (INR).
Some key points to consider in managing liver coagulopathy include:
- Fresh frozen plasma (FFP) can be administered at 10-15 mL/kg to temporarily replace clotting factors in acute bleeding situations.
- Vitamin K (10 mg IV or subcutaneously for 3 days) may help if deficiency is contributing to the coagulopathy.
- Prothrombin complex concentrate (PCC) at 25-50 IU/kg provides concentrated clotting factors for urgent reversal, but its use is considered off-label outside of correction of an elevated INR due to vitamin K antagonist treatment, and dosage is problematic in patients with cirrhosis due to altered INR values 1.
- Recombinant factor VIIa (90 μg/kg) may be used in severe, refractory bleeding.
- Importantly, liver coagulopathy represents a rebalanced hemostatic state with both pro- and anti-coagulant factors reduced, so patients may not bleed despite elevated INR values.
It is crucial to weigh the benefits and risks of correcting coagulopathy in patients with liver disease, as evidenced by a recent in vitro study showing an exaggerated procoagulant response after addition of PCCs to the plasma of patients with cirrhosis compared to healthy individuals 1. Therefore, prophylactic correction of laboratory values without active bleeding is not recommended, and treatment should focus on addressing the underlying liver disease and managing acute bleeding risks.
From the FDA Drug Label
Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) aqueous dispersion of vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The resulting gamma-carboxy-glutamic acid residues convert the precursors into active coagulation factors that are subsequently secreted by liver cells into the blood. The liver coagulopathy factors that are affected by vitamin K include:
- Prothrombin (factor II)
- Proconvertin (factor VII)
- Plasma thromboplastin component (factor IX)
- Stuart factor (factor X) 2
From the Research
Liver Coagulopathy Factors
- The liver plays a central role in hemostasis, as it is the site of synthesis of clotting factors, coagulation inhibitors, and fibrinolytic proteins 3
- Coagulopathy in liver disease is characterized by thrombocytopenia and impaired humoral coagulation, with the most common coagulation disturbances including thrombocytopenia and impaired humoral coagulation 3
- Therapy for coagulopathy in liver disease aims to achieve hemostasis, rather than complete correction of laboratory value abnormalities 3
Treatment Options
- Fresh frozen plasma (FFP) is traditionally used for correction of coagulopathy to manage and prevent bleeding in patients with liver disease 4, 5
- Prothrombin complex concentrates (PCCs) offer an attractive alternative to FFP, as they are more readily available and avoid large-volume transfusion 4, 5
- Recombinant activated factor VIIa (rFVIIa) may be used in patients with significantly prolonged prothrombin time and contraindications to FFP therapy 3, 6
- Vitamin K therapy may be useful in patients with increased prothrombin time due to vitamin K deficiency, but evidence for its effectiveness is lacking 7
Efficacy and Safety
- PCCs have been shown to be effective in improving coagulation test results in patients with liver disease, with statistically significant reductions in prothrombin time and international normalized ratio (INR) 4
- FFP, PCCs, and rFVIIa have been compared in terms of their ability to lower INR and facilitate procedures in critically ill patients with coagulopathy from liver disease, with PCCs and rFVIIa appearing to be more effective than FFP 6
- Thromboembolic events have been reported in patients receiving PCCs, but the risk appears to be low 4, 5
- Hypervolemia is a common adverse event in patients receiving FFP, but is less likely to occur in patients receiving PCCs or rFVIIa 6