What is the management approach for low fibrinogen (Fibrinogen) levels in patients with Disseminated Intravascular Coagulation (DIC)?

From the Guidelines

Management of low fibrinogen levels in DIC primarily involves treating the underlying cause while providing supportive care with fibrinogen replacement, with the most recent guidelines suggesting an initial fibrinogen supplementation of 3–4 g if major bleeding is accompanied by hypofibrinogenemia (viscoelastic signs of a functional fibrinogen deficit or a plasma Clauss fibrinogen level ≤ 1.5 g/L) 1.

Key Considerations

• Fibrinogen replacement should be considered in patients with DIC and active bleeding, or those at high risk of bleeding, with a focus on maintaining fibrinogen levels above 1.5 g/L 1.
• Cryoprecipitate and fibrinogen concentrate are both viable options for fibrinogen replacement, with the choice depending on availability and patient-specific factors 1.
• The initial dose of fibrinogen concentrate can be 3-4 g, which is equivalent to 15-20 single donor units of cryoprecipitate 1.
• Repeat dosing should be guided by viscoelastic monitoring and laboratory assessment of fibrinogen levels 1.
• Treatment should continue until the underlying cause of DIC is controlled and coagulation parameters begin to normalize.

Additional Blood Components

• Platelets and fresh frozen plasma may also be necessary in the management of DIC, depending on the patient's laboratory values and clinical condition 1.
• Antifibrinolytic agents like tranexamic acid should be avoided unless there is predominant hyperfibrinolysis 1.

Monitoring and Adjustments

• Continuous monitoring of fibrinogen levels is essential to guide repeat dosing and adjust the treatment plan as needed 1.
• Viscoelastic monitoring can also be useful in guiding fibrinogen replacement and assessing the effectiveness of treatment 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION For intravenous use only. Dose (mg/kg body weight) = [Target level (mg/dL) - measured level (mg/dL)] 1.7 (mg/dL per mg/kg body weight) Dose when fibrinogen level is unknown: 70 mg/kg body weight. (2.1) Monitoring of patient's fibrinogen level is recommended during treatment. A target fibrinogen level of 100 mg/dL should be maintained until hemostasis is obtained. (2.1) RIASTAP dose when baseline fibrinogen level is known Dose should be individually calculated for each patient based on the target plasma fibrinogen level based on the type of bleeding, actual measured plasma fibrinogen level and body weight, using the following formula [see Clinical Pharmacology (12.3)]: [Target level (mg/dL) - measured level (mg/dL)] 1. 7 (mg/dL per mg/kg body weight) RIASTAP dose when baseline fibrinogen level is not known. If the patient's fibrinogen level is not known, the recommended dose is 70 mg per kg of body weight administered intravenously. Monitor patient's fibrinogen level during treatment with RIASTAP. Maintain a target fibrinogen level of 100 mg/dL until hemostasis is obtained.

The management approach for low fibrinogen levels in patients with Disseminated Intravascular Coagulation (DIC) involves administering fibrinogen concentrate (IV). The dose can be calculated using the formula: Dose (mg/kg body weight) = [Target level (mg/dL) - measured level (mg/dL)] 1.7 (mg/dL per mg/kg body weight). If the fibrinogen level is unknown, a dose of 70 mg/kg body weight is recommended. The goal is to maintain a target fibrinogen level of 100 mg/dL until hemostasis is obtained 2, 2, 2.

• Key points:
  • Calculate the dose based on the target plasma fibrinogen level, actual measured plasma fibrinogen level, and body weight.
  • Monitor the patient's fibrinogen level during treatment.
  • Maintain a target fibrinogen level of 100 mg/dL until hemostasis is obtained.
  • Administer the dose intravenously at a rate not exceeding 5 mL per minute.

From the Research

Management Approach for Low Fibrinogen Levels in DIC

The management of low fibrinogen levels in patients with Disseminated Intravascular Coagulation (DIC) involves several strategies, including:

• Removing the underlying trigger or disease that is causing DIC 3, 4, 5
• Correcting the consumption of coagulation constituents with cryoprecipitate, platelet concentrates, and fresh frozen plasma if needed 3
• Using anticoagulation therapy, such as heparins, in patients with compensated DIC, but avoiding its use in patients who are bleeding 3
• Administering concentrates of natural anticoagulants, such as antithrombin, protein C, or tissue factor pathway inhibitor, which may be safer than heparins and do not exacerbate the bleeding tendency 3, 5

Diagnostic Considerations

Diagnosing DIC can be challenging and relies on a combination of clinical suspicion, laboratory tests, and molecular markers of in vivo hemostasis activation 3, 6. Laboratory tests that support the diagnosis of DIC include:

• Decreasing fibrinogen levels and platelet counts 3
• Elevated D-dimer, fibrin(ogen) split products (FSP), and soluble fibrin monomer (FM) levels 3
• Molecular markers of in vivo hemostasis activation, such as thrombin-antithrombin (TAT) complexes, prothrombin fragment 1 + 2 (F 1 + 2), or plasmin-antiplasmin (PAP) complexes 3, 6

Treatment Strategies

Treatment strategies for DIC focus on addressing the underlying causes and may involve supportive care, anticoagulation therapy, and other supportive measures 7, 4, 5. The use of anticoagulants, such as unfractionated heparin, low-molecular-weight heparin, or recombinant tissue factor pathway inhibitor, may be considered in certain cases 5. However, the efficacy and safety of these treatments have not been objectively assessed, and further research is needed to improve diagnostic accuracy and treatment efficacy 4, 6, 5.