Etiology

Primary Hyperfibrinolytic States

• Alpha-2 Antiplasmin Deficiency (see Alpha-2 Antiplasmin Deficiency, [[Alpha-2 Antiplasmin Deficiency]])
• Plasminogen Activator Inhibitor-1 (PAI-1) Deficiency (see Plasminogen Activator Inhibitor-1 Deficiency, [[Plasminogen Activator Inhibitor-1 Deficiency]])

Secondary Hyperfibrinolytic States

• Cardiopulmonary Bypass (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])
  • Coagulopathy after cardiopulmonary bypass is multi-factorial and may include a component of hyperfibrinolysis
• Cirrhosis (see End-Stage Liver Disease, [[End-Stage Liver Disease]]): due to decreased tPA clearance from the circulation and decreased alpha-2 antiplasmin synthesis by the liver
• Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]]): due to release of tPA, resulting in the generation of plasmin at site of injury
  • Acute Promyelocytic Leukemia (APML) (see Acute Promyelocytic Leukemia, [[Acute Promyelocytic Leukemia]])
  • Prostate Cancer (see Prostate Cancer, [[Prostate Cancer]])
    • DIC with secondary hyperfibrinolysis
    • Excessive production of urinary-type plasminogen activators by the malignant cells
    • Decreased alpha-2 antiplasmin synthesis
• Factor XI Deficiency (see Factor XI Deficiency, [[Factor XI Deficiency]]): due to decreased thrombin synthesis, resulting in decreased activation of thrombin activatable fibrinolysis inhibitor (TAFI)
• Heat Stroke (see Heat Stroke, [[Heat Stroke]])
• Hemophilia A (Factor VIII Deficiency) (see Hemophilia A, [[Hemophilia A]]): due to decreased thrombin synthesis, resulting in decreased activation of thrombin activatable fibrinolysis inhibitor (TAFI)
• Hemophilia B (Factor IX Deficiency) (see Hemophilia B, [[Hemophilia B]]): due to decreased thrombin synthesis, resulting in decreased activation of thrombin activatable fibrinolysis inhibitor (TAFI)
• Orthotopic Liver Transplantation (see Liver Transplant, [[Liver Transplant]]): due to decreased tPA clearance from the circulation and decreased alpha-2 antiplasmin synthesis (both of which occur during the anhepatic period of the transplant)
• Trauma
• Thrombolytics (see Thrombolytics, [[Thrombolytics]]): due to depletion of alpha-2 antiplasmin, plasminogen, and fibrinogen
  • Streptokinase (see Streptokinase, [[Streptokinase]])
  • Urokinase (see Urokinase, [[Urokinase]])

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Physiology

• Fibrin Degradation Products (FDP): plasmin cleaves polymerized fibrin at multiple sites and releases fibrin degradation products
  • D-Dimers: a type of fibrin degradation product which consists of two domains from adjacent fibrin monomers which have been cross-linked by activated factor XIII
    • D-dimers are generated from cross-linked fibrin (not fibrinogen), an elevated D-dimer concentration indicates the presence of recent or ongoing intravascular coagulation

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Clinical Differentiation of Abnormal Fibrinolytic States

Primary Hyperfibrinolysis

• Platelet Count: normal
• Fibrinogen: decreased
• Fibrin Degradation Products: increased
• D-Dimer: increased
• Anti-Thrombin: normal
• Schistocytes: absent
• Plasma Clotting Times (INR and PTT): prolonged
• Euglobulin Lysis Time: shortened
• ADAMTS13 Level: normal

Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]])

• Platelet Count: decreased
• Fibrinogen: decreased
• Fibrin Degradation Products: increased
• D-Dimer: increased
• Anti-Thrombin: decreased
• Schistocytes: present
• Plasma Clotting Times (INR and PTT): prolonged
• Euglobulin Lysis Time: shortened
• ADAMTS13 Level: normal (although may be decreased in the presence of sepsis)

Thrombotic Thrombocytopenic Purpura (TTP) (see Thrombotic Thrombocytopenic Purpura, [[Thrombotic Thrombocytopenic Purpura]])

• Platelet Count: decreased
• Fibrinogen: normal
• Fibrin Degradation Products: normal
• D-Dimer: normal
• Anti-Thrombin: normal
• Schistocytes: present
• Plasma Clotting Times (INR and PTT): normal
• Euglobulin Lysis Time: normal
• ADAMTS13 Level: decreased (usually <10%)

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Treatment

• Epsilon Aminocaproic Acid (Amicar) (see Epsilon Aminocaproic Acid, [[Epsilon Aminocaproic Acid]])
• Tranexamic Acid (see Tranexamic Acid, [[Tranexamic Acid]])

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References

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