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• Thrombosis


  The formation or presence of a blood clot within a blood vessel

  
• Thrombophilia


  A hereditary or acquired disorder marked by an abnormal increase in the tendency of blood to clot and higher than normal risk of thrombosis

  
• Thrombosis


  • Inappropriate formation of platelet or fibrin clots that obstruct blood vessels
  • Causes ischemia and necrosis
• Classification of Thrombosis


  • Venous thrombosis
  • Arterial thrombosis

  
• Venous Thrombosis


  • Blood clot blocks a vein
  • Caused by stasis and hypercoagulability

  
• Arterial Thrombosis


  • Blood clot blocks an artery
  • Usually occurs after the erosion or rupture of an atherosclerotic plaque

  
• Deep Vein Thrombosis (DVT)


  • Most prevalent venous thromboembolic event (VTE)
  • Caused by clots that form in the iliac, popliteal, and femoral veins of the calves and upper legs

  
• Pulmonary Embolism (PE)


  • Follows DVT
  • Nearly 95% of pulmonary emboli arise from thrombi in the deep leg and calf veins

  
• Ischemic Stroke


  Most strokes (87%) are ischemic strokes. Blood clots block arteries that supply blood to the brain

  
• Myocardial Infarction (MI)


  The irreversible death of heart muscle secondary to prolonged lack of oxygen supply (ischemia)

  
• Symptoms of Thrombosis


  • Pain in one leg
  • Swelling in the leg or arm
  • Chest pain
  • Numbness or weakness on one side of the body
  • Sudden change in mental state
• Nondisease Risk Factors That Contribute to Thrombotic Disease

  • Markers of Arterial Thrombosis Risk

  
• Thrombophilia


  • Once called hypercoagulability
  • Increased tendency to develop thrombosis
  • Predisposition to thrombosis secondary to a congenital or acquired disorder
• Two Categories of Thrombophilia


  • Primary disorders
  • Secondary disorders
• Primary Disorders


  • Deficiency in regulatory proteins (Antithrombin III, Protein C and S deficiency)
  • Fibrinolytic system disorders
  • Genetic mutations
• Secondary Disorders


  • Antipospholipid syndrome
  • Hemostatic protein abnormalities (postoperative state, malignancy, pregnancy, oral contraceptives)
  • Platelet abnormalities (DM, hyperlipidemia, MPD's, HIT)
  • BV and flow abnormalities (artificial surfaces, damaged BVs, abnormal blood flow)

  
• Antithrombin Deficiency


  AT inhibits IIa, IXa, Xa, and XIa
• Protein C Deficiency


  • PC Hydrolyzes factor Va and VIIIa
  • Type I (antigen and activity low), type II (only activity is low)
• Protein S Deficiency


  PS is a stabilizing factor for APC
• Fibrinolytic System Disorders


  • Deficiency in FXII, PK, and HMWK
  • Plasminogen deficiency
• Factor V Leiden (FVL)


  • Activated Protein C Resistance (APCR)
  • Substitution of arginine with glutamine at position 506 in factor V
  • FVL can't be inactivated by protein C
  • Most common hereditary cause of thrombosis
• Prothrombin G20210A


  • Second most common hereditary cause of thrombosis
  • Caused by an amino acid substitution
  • May have slightly elevated prothrombin level
• Dysfibrinogenemia


  • Autosomal-dominant trait
  • Associated with either bleeding or thrombosis
  • Abnormal structure of fibrinogen - fibrin resistant to fibrinolysis
• Antiphospholipid Syndrome (APS)


  • Antiphospholipid (APL) antibodies include: Lupus anticoagulant (LA), Anticardiolipin (ACL) antibodies, Anti–β2-glycoprotein I (anti–β2-GPI)
  • Antibodies interfere with PPL portion of the complex (factor Xa-Va-Ca++-platelet PPL) which converts prothrombin to thrombin
  • Binding of antibody to phospholipid binding proteins leads to platelet activation
• Disseminated Intravascular Coagulation (DIC)


  • Generalized activation of hemostasis secondary to a systemic disease
  • Fibrin microthrombi partially occlude small vessels
  • Consumption of platelets, coagulation factors, coagulation control proteins, and fibrinolytic enzymes
• Heparin-Induced Thrombocytopenia (HIT)


  IgG antibody binds platelet Fc receptors leading to platelet activation, thrombocytopenia, and microvascular thrombi formation
• Other Secondary Thrombotic Disorders


  • Post-operative status
  • Malignancy
  • Pregnancy
  • Estrogen or oral contraceptives
  • Morbid obesity
  • Hyperhomocysteinemia
• Thrombophilia Laboratory Test Profile


  • Current Antithrombotics, Mode of Action, Measurement, Reversal