What are the causes of coagulation factor inhibitors in patients with burns?

From the Guidelines

Coagulation factor inhibitors in burn patients are primarily caused by the development of autoantibodies against coagulation factors, such as factor X, due to exposure to normally sequestered proteins from extensive tissue damage and inflammatory response. The development of these inhibitors can lead to significant morbidity and mortality in burn patients. According to a recent study 1, acquired factor X deficiency can be caused by various factors, including primary amyloidosis, severe liver disease, vitamin K antagonist therapy, and exposure to topical thrombin, with some patients developing inhibitors to factor X.

The clinical characteristics of patients with acquired factor X deficiency can vary, with bleeding manifestations resembling those in patients with hereditary factor X deficiency, but with marked heterogeneity 1. The presence of a specific inhibitor can be suggested by anomalous findings, such as factor X assays that are inconsistent with the extent of hemorrhagic symptoms. Testing for inhibitory activity typically involves mixing patient and normal plasmas and measuring factor X activity following dilution, with additional tests including ELISA testing for immunoglobulin M and G antiphospholipid antibodies and platelet neutralization testing 1.

In terms of treatment, there is no standardized approach for acquired factor X deficiency, but limited success has been achieved with various treatments, including vitamin K plus fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), dual-factor concentrate, or recombinant activated factor VIIa with oral corticosteroids 1. However, the most effective treatment approach may involve addressing the underlying cause of the inhibitor, such as removing precipitant medications or treating underlying conditions like inflammatory bowel disease or malignancy 1.

Key considerations in the management of coagulation factor inhibitors in burn patients include:

• Early identification and diagnosis of the inhibitor
• Careful monitoring of coagulation parameters
• Consultation with a hematologist
• Treatment of the underlying cause of the inhibitor
• Use of bypassing agents like recombinant factor VIIa or activated prothrombin complex concentrate for acute bleeding
• Immununosuppressive therapy with corticosteroids and cyclophosphamide or rituximab for severe inhibitors.

Overall, the management of coagulation factor inhibitors in burn patients requires a multidisciplinary approach, with careful consideration of the underlying cause of the inhibitor and the most effective treatment strategy to prevent life-threatening hemorrhagic complications.

From the Research

Causes of Coagulation Factor Inhibitors in Patients with Burns

• The development of coagulation factor inhibitors in patients with burns is a complex process, involving multiple factors and pathways 2, 3.
• Severe burns can lead to the activation of coagulation and fibrinolytic pathways, consumption of coagulation factors, and depletion of coagulation regulatory proteins, resulting in disseminated intravascular coagulation (DIC) 2.
• The introduction of cellular debris with strong thromboplastic activity into the circulation can trigger massive thrombin generation and activate the extrinsic pathway of coagulation, contributing to the development of coagulopathy 2.
• Systemic coagulopathy in patients with severe burns is characterized by procoagulant changes, impaired fibrinolytic and natural anticoagulation systems, and is associated with increased comorbidity and mortality 3.
• Hemodilution and hypothermia, which can occur as a result of aggressive fluid resuscitation, can also contribute to the development of coagulopathy in patients with severe burns 3.

Risk Factors for Coagulation Factor Inhibitors

• The severity of the burn injury is a significant risk factor for the development of coagulopathy, with more severe burns associated with a higher risk of coagulation factor inhibitors 2, 3.
• The size of the burn area and the presence of third-degree burns also increase the risk of coagulopathy and coagulation factor inhibitors 2.
• Sepsis and multiple organ failure can also contribute to the development of coagulopathy and coagulation factor inhibitors in patients with severe burns 2, 4.

Diagnosis and Treatment of Coagulation Factor Inhibitors

• The diagnosis of coagulopathy and coagulation factor inhibitors in patients with severe burns can be challenging, and there is currently no consensus on the definition or treatment of coagulopathy in these patients 4.
• Standard coagulation tests, such as prothrombin time and activated partial thromboplastin time, are commonly used to monitor coagulation abnormalities in burn patients, but may not accurately reflect the presence of coagulation factor inhibitors 4.
• Plasma transfusion and specific coagulation factor substitution, such as cryoprecipitate and fibrinogen concentrate, may be used to treat coagulopathy and coagulation factor inhibitors in patients with severe burns, but the evidence for these interventions is limited 4.