Thrombophilia Flashcards
What is Venous thromboembolism (VTE)?
A disease that includes Deep Vein Thrombosis (DVT) and/or Pulmonary Embolism (PE)
What are risk factors for VTE?
Male, over 55, recently hospitalized
What are the three risk factors for thrombosis (Virchow’s Triad)?
Circulatory Stasis (Disruption in Blood Flow), Endothelial Injury, Hypercoagulable State
What are disruptions in normal blood flow?
Stasis (activation of the coag cascade) or turbulence of blood flow increases risk for thrombosis
What are examples that may cause stasis or turbulence of the blood flow?
Immobilization, Cardiac wall dysfunction (Dilated atrium), Aneurysm
Why does endothelial damage increase risk for thrombosis?
Disrupts protective function of enothelial cells, it does many things to prohibit the coagulation cascade
How is blood flow in the body described?
Laminar flow
What sites are most commonly affected by enothelial injury due to high flow rates?
Arterial/cardiac sites
What happen when laminar flow is disrupted via stasis and turbulence?
Allows platelets to interaxct with endothelium, activates endothelium, prolongs exposure of activated clotting factors
What are features of heritable thrombophilia?
Early age thrombosis (younger than 40), Unprovoked thrombosis, family history of thrombosis, thrombosis at unusal site
What two inherited conditions of hypercoagulability that can be measured by genetic testing?
Factor II hyperprothrombinemia, Factor V Leiden
What conditions are procoagulant gains of function and have a weaker risk for VTE but are more common?
Factor V Leiden, Factor II hyperprothrombinemia
What is the recurrence risk for Factor V Leiden?
Negligible recurrence risk
What blood types are more at risk for Factor V Leiden?
non-O blood types because they have higher levels of factor 8
What does the single point mutation (arginine to glutatmine) in Factor V Leiden do?
Activates protein C (APC) resistance - makes factor 5 less susceptible to the actions of Protein C, this causes Favtor Va to be inactivated at a 10-fold slower rate, allowing increased thrombin generation which leads to increased clotting
What is the recurrence risk for Factor II hyperprothrombinemia?
Negligible recurrence risk
What does the gain of fuction mutation in the Factor II hyperprothrombinemia do?
Gain of function mutation in the 3’ untranslated region of the prothrombin gene causes increased plasma prothrombin levels by 25%
What is the risk of VTE with anticogulant deficiencies?
More rare but stronger risk of VTE than mutations in Factor V, Factor II
What is the is the inheritnace pattern for inherited conditions of hypercoagulability?
Autosomal dominant
When a homozygous individual with a Protein C deficiency comes to term what skin finding will occur?
Purpura fulminans, also seen in homozygous Protein S deficiency
What other time could an individual experience a Protein S deficiency?
Pregnancy (Protein S goes down)
What conditions are at risk of warfarin skin necrosis?
Protein C and Protein S deficiency
Antithrombin deficiency can be acquired in what syndrome?
Nephrotic syndrome
Who has the highest risk for heparin-induced thrombocytopenia?
Highest risk in patients receiving unfractioned heparin for 7-10 days
