What is the initial treatment for a patient with acute on chronic liver failure, a prolonged activated Partial Thromboplastin Time (APTT) and spontaneous intramuscular bleeding?

From the Guidelines

The initial treatment for a patient with acute on chronic liver failure, prolonged APTT, and spontaneous intramuscular bleeding should focus on correcting coagulopathy and controlling hemorrhage with prothrombin complex concentrate (PCC) at 25-50 IU/kg, rather than fresh frozen plasma (FFP), due to the potential risks and limited efficacy of FFP in this setting, as suggested by recent guidelines 1.

Key Considerations

• The use of FFP is not recommended for correcting coagulopathy in patients with cirrhosis undergoing invasive procedures, due to its limited efficacy and potential risks, including transfusion-related acute lung injury, transfusion-associated circulatory overload, and allergic reactions 1.
• PCCs offer a more rapid and effective correction of coagulopathy, with a lower volume of administration, and may be considered for patients with acute on chronic liver failure and prolonged APTT 1.
• The dosage of PCCs should be based on the patient's weight and INR, with a recommended dose of 25-50 IU/kg 1.
• Concurrently, the underlying liver failure should be addressed by identifying and treating precipitating factors, and supportive care including fluid management, electrolyte correction, and prevention of hepatic encephalopathy is essential.

Additional Interventions

• Platelet transfusion may be necessary if the platelet count is below 50,000/μL.
• Cryoprecipitate (1 unit per 10 kg body weight) may be needed if fibrinogen levels are low.
• Vitamin K administration (10 mg intravenously) may be considered to support hepatic synthesis of clotting factors.

Rationale

The management of coagulopathy in patients with acute on chronic liver failure and prolonged APTT requires a careful consideration of the potential risks and benefits of different interventions. Recent guidelines suggest that PCCs may be a more effective and safer alternative to FFP for correcting coagulopathy in this setting 1. By prioritizing the use of PCCs and addressing the underlying liver failure, clinicians can optimize the management of coagulopathy and improve patient outcomes.

From the FDA Drug Label

Treatment with human fibrinogen concentrate in congenital fibrinogen deficiency has been associated with risk of thrombosis at target fibrinogen levels that were less than 150 mg/dL. The risk of thrombosis may be greater when the target fibrinogen plasma level is 150 mg/dL.

The initial treatment for a patient with acute on chronic liver failure, a prolonged activated Partial Thromboplastin Time (APTT) more than 150, and spontaneous intramuscular bleeding is fibrinogen replacement therapy.

• The goal of treatment is to increase the fibrinogen level to a target level that will help control the bleeding.
• Fibrinogen (IV), such as FIBRYGA, can be used to treat bleeding and/or for perioperative management in patients with acquired fibrinogen deficiency.
• However, the risk of thrombosis should be weighed against the benefits of FIBRYGA administration, and patients receiving FIBRYGA should be monitored for signs and symptoms of thrombosis 2.

From the Research

Initial Treatment for Acute on Chronic Liver Failure with Prolonged APTT and Spontaneous Intramuscular Bleeding

The initial treatment for a patient with acute on chronic liver failure, a prolonged activated Partial Thromboplastin Time (APTT) more than 150, and spontaneous intramuscular bleeding involves correcting the coagulopathy to manage and prevent bleeding.

• Prothrombin Complex Concentrates (PCCs): PCCs offer an attractive alternative to fresh frozen plasma for correction of coagulopathy in liver disease, as they are more readily available and avoid large-volume transfusion 3.
• Fresh Frozen Plasma (FFP): FFP is traditionally used for correction of coagulopathy, but its effectiveness in correcting the coagulopathy of chronic liver disease is limited, with only 12.5% of patients achieving correction of their prothrombin time to less than 3 seconds longer than control time 4.
• Cryoprecipitate: Cryoprecipitate may be a viable alternative to FFP in patients with liver disease at risk of pulmonary edema, and it has been shown to improve the coagulopathy of liver disease, although four units of FFP may be more efficacious than five units of cryoprecipitate 5.
• Combined Use of FFP and PCC: The combined use of FFP and prothrombin complex concentrates has been shown to correct abnormal coagulation in chronic liver disease, with no clinical or laboratory evidence of thrombotic complications 6.
• Prophylactic Management: The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known, with no evidence to favor a specific product (FFP or PCC) over another 7.

Treatment Options

Treatment options for a patient with acute on chronic liver failure, prolonged APTT, and spontaneous intramuscular bleeding may include:

• Administration of PCCs to correct coagulopathy
• Use of FFP to correct coagulopathy, although its effectiveness may be limited
• Cryoprecipitate as an alternative to FFP in patients at risk of pulmonary edema
• Combined use of FFP and PCC to correct abnormal coagulation.