Hyperfibrinolytic States

Etiology

Primary Hyperfibrinolytic States

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

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

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%)

Treatment


References

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