Coagulopathy

General:

• Vit K dependent clotting factors = PT/INR = Factors II, VII, X
• PTT = VIII, IX, XI, XII
• Measured via PT/INR or PTT. Can use Thromboelastography (TEG)

Hemophilia

• Hemophilia A and B (deficiency of factors VIII and IX, respectively) are X-linked hereditary bleeding disorders primarily found in male patients
• Prolonged PTT with normal PT
• Antifibrinolytic agents (such as ε-aminocaproic acid and tranexamic acid) are useful in controlling bleeding from dental procedures
• Patients with moderate or severe hemophilia often require virally inactivated factor concentrates or recombinant factor replacement
  • Some pts develop acquired factor inhibitors after replacement therapy (25% of patients with hemophilia A and 3% to 5% of patients with hemophilia B). Manifests as ongoing bleeding despite factor replacement therapy.
• Hemophilia A
  • More common
  • Factor VIII deficiency
  • Treatment: desmopressin which stimulates release of preformed factor VIII from endothelial cells.
• Hemophilia B
  • Factor IX deficiency
• Hemophilia C
  • Factor XI deficiency, very rare
  • Seen predominantly in persons of Ashkenazi Jewish heritage

Von Willebrand Disease

• most common hereditary bleeding disorder
• Typically presents with mucocutaneous bleeding
• Caused be deficiency of vWF (quantity or function)
• Diagnosis is confirmed by finding a reduction in von Willebrand antigen (quantitative analysis) and reduced vWF ristocetin cofactor activity (a measurement of the functional effect)
• Subtypes:
  • Type 1: Low vWF (<30%) but normal function
    • Treatment: Desmopressin is effective, causing release of pre-formed vWF and factor VIII from endothelial cells
  • Type 2: Abnormal vWF function
    • 2A: Selective deficiency of high-molecular-weight fragments of vWF
      • Treatment: Desmopressin or vWF concentrate
    • 2B: Increased binding of high-molecular-weight fragments of vWF to platelet receptors
    • Treatment: vWF concentrate
      • Desmopressin contraindicated; induces platelet aggregation, which may cause secondary thrombocytopenia
  • Type 3: Severe deficiency
    • Treatment: vWF concentrate
    • Desmopressin is ineffective
  • Acquired:
    • Causes:
      • High circulatory shear stress (valvular heart disease, hypertrophic cardiomyopathy, circulatory assist devices, and extracorporeal membrane-oxygenation systems)
      • Autoimmune disease (SLE),
      • Lymphoproliferative disease (monoclonal gammopathy, and myeloproliferative disease)
    • Treatment: Desmopressin and vWF concentrates have been used for management

Coagulopathy of Liver Disease

• Measuring the factor VIII level may be useful, because factor VIII is often elevated in liver disease but consumed in DIC. Nonetheless many patients have mixed pathology, so this is not perfect.
• Patients experiencing bleeding may require blood product replacement, with cryoprecipitate to increase fibrinogen levels to greater than 100 mg/dL
• For routine procedures (para, thora, EGD) ok if platelet count >75k and INR <2
  • FFP for INR > 2
• #ChoosingWisely prothrombin complex concentrates should not be routinely used to manage the coagulopathy of liver disease because of their cost and association with prothrombotic complications.

Acquired Factor Inhibitors:

Acquired Factor VIII (Acquired Hemophilia A):

• Mixing study does not correct, showing that inhibitor is blocking the factor 8 from the healthy plasma
• Treatment: Recombinant porcine factor VIII, which is not cross-reactive with human factor VIII, thus the inhibitor does not block it.