Disorders

Overview of Hemostasis Disease States

• Hemostasis: The process of stopping bleeding, involving a balance between procoagulant and anticoagulant forces
• Disruption of Balance: Disease states arise when this balance is disrupted, leading to either:
  • Bleeding Disorders: Impaired clot formation or excessive clot breakdown
  • Thrombotic Disorders (Hypercoagulable States): Excessive clot formation or impaired clot breakdown

Key Components and Processes

• Vascular System: Endothelial cells regulate blood flow, platelet activation, and coagulation
• Platelets: Form a primary plug at the site of injury (primary hemostasis)
• Coagulation Cascade: A series of enzymatic reactions involving coagulation factors, leading to fibrin formation (secondary hemostasis)
• Fibrinolytic System: Breaks down fibrin clots to restore blood flow

Disease States

• Coagulation Factor Deficiencies: Bleeding Disorders

  • General Cause: Insufficient amount or impaired function of coagulation factors
  • Classification:
    • Hereditary: Genetic mutations affecting factor synthesis (e.g., Hemophilia A, Hemophilia B)
    • Acquired: External factors reducing factor levels (e.g., vitamin K deficiency, liver disease, DIC)
  • General Effect on Lab Tests: Prolonged PT and/or aPTT, depending on the factor affected
  • Common Examples:
    • Hemophilia A (Factor VIII Deficiency): X-linked recessive, affects intrinsic pathway. Prolonged aPTT, low Factor VIII activity
    • Hemophilia B (Factor IX Deficiency): X-linked recessive, affects intrinsic pathway. Prolonged aPTT, low Factor IX activity
    • Vitamin K Deficiency: Affects Factors II, VII, IX, and X. Prolonged PT and aPTT
    • Liver Disease: Impaired synthesis of multiple factors. Prolonged PT and aPTT

• Inhibitors: Bleeding or Thrombotic Disorders

  • General Cause: Antibodies that interfere with the function of coagulation factors or phospholipid-binding proteins
  • Classification:
    • Acquired: Autoantibodies (e.g., Factor VIII inhibitors, Lupus Anticoagulant)
  • General Effect on Lab Tests: Prolonged PT and/or aPTT that does not correct on mixing with normal plasma
  • Common Examples:
    • Factor VIII Inhibitors (Acquired Hemophilia A): Autoantibodies against Factor VIII. Prolonged aPTT that doesn’t correct, low Factor VIII activity
    • Lupus Anticoagulant (LA): Antibodies against phospholipids. Prolonged aPTT, increased risk of thrombosis

• Fibrinolytic Disorders: Bleeding or Thrombotic Disorders

  • General Cause: Imbalance in the fibrinolytic system, leading to either excessive clot breakdown or impaired clot removal
  • Classification:
    • Excessive Fibrinolysis (Hyperfibrinolysis): Increased breakdown of fibrin clots
    • Impaired Fibrinolysis (Hypofibrinolysis): Decreased breakdown of fibrin clots
  • Common Examples:
    • Excessive Fibrinolysis (e.g., DIC): Widespread activation of fibrinolysis leads to bleeding. Elevated D-dimer, decreased fibrinogen
    • Impaired Fibrinolysis: Often associated with increased risk of thrombosis (e.g., elevated PAI-1)

• Hypercoagulable States (Thrombophilia): Thrombotic Disorders

  • General Cause: Inherited or acquired conditions that increase the risk of thrombosis
  • Key Feature: Increased thrombin generation and/or impaired anticoagulant mechanisms
  • Classification:
    • Inherited (Genetic): Mutations in genes encoding coagulation factors or natural anticoagulants
    • Acquired: External factors affecting the coagulation system
  • Common Examples:
    • Factor V Leiden Mutation: Resistance to activated protein C (APC)
    • Prothrombin G20210A Mutation: Increased prothrombin production
    • Protein C Deficiency, Protein S Deficiency, Antithrombin Deficiency: Reduced levels of natural anticoagulants
    • Antiphospholipid Syndrome (APS): Autoantibodies against phospholipids, causing both thrombosis and pregnancy morbidity

• Disseminated Intravascular Coagulation (DIC): Bleeding and Thrombotic Disorder

  • Definition: A complex, acquired disorder involving widespread activation of coagulation and fibrinolysis
  • Key Features:
    • Not a Primary Disease: Always secondary to an underlying condition (e.g., sepsis, trauma, malignancy, obstetric complications)
    • Simultaneous Clotting and Bleeding: Microthrombi formation leads to organ damage, while consumption of clotting factors and platelets causes bleeding
  • Pathophysiology: Triggering event leads to:
    • Uncontrolled activation of coagulation
    • Consumption of clotting factors and platelets
    • Secondary activation of fibrinolysis
  • Laboratory Findings:
    • Prolonged PT and aPTT
    • Low fibrinogen
    • Thrombocytopenia
    • Elevated D-dimer
    • Schistocytes on peripheral blood smear

Summary Table

Disease State	Main Effect	Key Lab Findings
Hereditary Factor Deficiencies	Bleeding	Prolonged PT/aPTT, low factor activity
Acquired Factor Deficiencies	Bleeding	Prolonged PT/aPTT, low factor activity
Inhibitors	Bleeding or Thrombosis	Prolonged PT/aPTT, mixing study does not correct
Fibrinolytic Disorders	Bleeding or Thrombosis	Elevated D-dimer, abnormal lysis times
Hypercoagulable States	Thrombosis	(Often normal) May have specific genetic markers
DIC	Bleeding and Thrombosis	Prolonged PT/aPTT, low fibrinogen, elevated D-dimer, schistocytes