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Hypercoagulable states (Thrombophilia)

• Where is the problem?
  • Clotting Factors
    • Too many
    • Too active
  • Platelets
    • Too many
    • Too active
  • Vascular injury
    • Surgery
    • Trauma
  • Stasis
• Virchow’s triad
  • Stasis
  • Hypercoagulable state
  • Vascular injury
  • German doctor and scientist who first described the mechanism for a pulmonary embolism. The name Virchow’s triad was not used until well after his death.
• Congenital Causes
  • Factor V Leiden
    • The most commonly inherited thrombophilia
    • Protein C would normally have an inhibitory affect on Factor V, but can not bind to this mutant form of factor V.
    • It was first discovered in the Netherlands in the city of Leiden.
  • Factor II – Prothrombin G20210A mutation
    • The second most commonly inherited thrombophilia
    • The mechanism is not entirely understood.
    • There other prothrombin mutations which can cause varying degrees of thrombophilia or an increased risk of bleeding.
  • There are many anticoagulant deficiencies which are more rare
    • Antithrombin III deficiency is one example
  • Stasis
    • Sedentary patient
    • Atrial fibrillation
    • Sickle cell disease
    • Polycythemia vera – excess production of red blood cells
• Acquired
  • Antiphospholipid syndrome
    • Autoimmune disease where the patient creates antibodies to cell membrane
    • Blood clots occur throughout the vascular system
  • Nephrotic syndrome
  • Cancer especially in metastatic disease
  • Pregnancy
  • Inflammatory bowel diseases
  • Estrogen – Think birth control
  • Obesity
  • Trauma – Think surgery

Clinical Presentation

• This depends on where the clot occurs
• Deep venous thrombosis
  • Calf pain or tenderness
• Pulmonary embolism (PE)
  • Shortness of breath
  • Elevated heart rate
• Superficial vein thrombosis
  • Pain and irritation at the site

Labs & Studies

• CBC
  • Hematocrit
  • RBC
  • Platelet count
• Prothrombin time & Partial thromboplastin time – PT/PTT
• D-Dimer
  • Elevated with active clotting

Treatment

• Treat the underlying cause if possible
• Short term
  • Heparin
• Long term
  • Oral agent like Warfarin
  • Warfarin is teratogenic so women who may become pregnant should use low molecular weight heparin

HUS, HEELP, HIT, TTP and DIC

• Treat the underlying condition
• Supportive care
• Blood or blood product transfusion
• Steroids

HUS – Hemolytic uremic syndrome

• Most cases are caused by ingesting contaminated food. Most commonly E. Coli producing the Shiga toxin is the causative agent.
• Low platelets
  • They are activated and consumed
• Low RBCs
  • Hemolysis is part of the process
• Acute Kidney failure

HELLP – Hemolysis, Elevated Liver Enzymes, Low Platelet Count

• A complication of pregnancy
• Occurs in the third trimester or shortly after delivery
• Associated with pre-eclampsia
• Deliver the baby as soon as possible.

HIT – Heparin-induced thrombocytopenia

• Heparin may bind to a protein (PF4) that is released from an activated platelet.
• This may lead to the formation of larger complexes that the immune system responds too by creating antibodies to these complexes.
• Some of these antibodies can activate platelets thereby increasing the amount of circulating PF4 and compounding the problem.
• Stop the heparin

TTP – Thrombotic Thrombocytopenic Purpura

• Very rare disorder causing microscopic clots throughout the small blood vessels of the body
• Large vWF complexes are formed and can not be broken down under the normal processes. These complexes cause damage to the blood vessels resulting in more clot formation. The constant use of clotting factors and platelets depletes the bodies supply.
• Petechiae and purpura
• Low platelet count
• Labs tests showing <5% normal ADAMTS13 protein indicates TTP
  • ADAMTS13 is the enzyme that cleaves these large vWF complexes
• A simple transfusion may exacerbate the problem. Patients require an exchange transfusion.

DIC – Disseminated Intravascular Coagulation

• DIC results from a dysregulation of the clotting system resulting in clots forming throughout the vascular system.
• With this significant amount of clot formation through the body the clotting factors are used up.
• With all of this clot formation the clotting breakdown system goes into overdrive activating powerful anticoagulants leading to hemorrhage.
• DIC often occurs in the face of severe disease
  • Sepsis is the most common predisposing condition
  • Cancer
  • Pre-eclampsia
  • Placental abruption
  • Massive tissue injury
• PT and PTT are very prolonged in the acute phase
• Thrombocytopenia
• Low fibrinogen concentration
• Increased levels of fibrin degradation products like D-dimer
• Platelet transfusion
• Fresh frozen plasma
• 10-50% of patients will not survive