MT2 Hemostatic Abnormalities (Dustin) Flashcards
What is the most frequently inherited hemophilia? Which factor is affected by a mutation?
Hemophilia A (1 / 10,000 males) Deficiency of factor VIII
What factor is deficient in hemophilia B? and for C?
B: factor IX
C: factor XI
What is the difference between primary and secondary hemophilias?
(the difference between “primary” and “secondary” applies to thrombophilias too)
Primary hemophilias are usually caused by a genetic defect, secondary hemophilias are caused by some other medical problem where hemophilia is just one of many problems (like liver failure)
What are some causes of secondary hemophilias?
- Vitamin K deficiency (rare, may be caused by obstruction of bile duct)
- Vitamin K antagonist poisoning (either from warfarin or from toxic plants)
- Chronic liver failure (thrombophilia can also happen though!)
What are 3 major pathologies that result from thrombophilia?
Myocardial infarction, stroke (CVA), deep vein thrombosis (DVT)
What is the most common primary thrombophilia?
APC resistance, and of these usually it is the Leiden mutation: a single nucleotide polymorphism (SNP) missense mutation on Arg 506 (R506 replaced by Glu) in Factor V that prevents free Factor Va from being inactivated by Protein C
How do you test for APC resistance? How do you confirm Leiden mutation?
APC resistance is tested with an Activated Partial Thromboplastin Time (APTT) test, which first comes out normal, but you also do another APTT test where you add APC to the sample. In a person with APC resistance, the sample containing APC will take a much shorter time to clot than in a normal person.
Leiden mutation is confirmed by PCR / DNA sequencing.
What is the most common acquired thrombophilia?
Antiphospholipid syndrome (APS), which has a similar prevalence to APC resistance (~5% of the population).
This is an autoimmune disease attacking phospholipids of platelets, but surprisingly causes more thrombosis than hemophilia because it affects anticoagulants more than procoagulants. Usually this occurs during a larger autoimmune disease like Lupus
Which substances related to clotting are reduced in concentration as a result of Vitamin K Antagonists?
Everything with Gla domains: Factors II, VII, IX, X, as well as the anticoagulants Protein C, S, and Z
Why is Heparin normally given at the start of Vitamin K Antagonist treatment?
Heparin begins anticoagulant effects immediately, whereas VKA’s first cause a procoagulant effect (surprisingly) because PC, PS, and PZ have shorter half-lives than clotting factors II, VII, IX, and X, and thus it takes longer to clear the clotting factors from the system than the anticoagulant factors. After a few days on VKA’s, the more powerful effect is reduction of clotting factors.
Heparin has to be injected and has too many side effects to be given for a long period of time.
Where is someone with Leiden mutation most likely to have a clot?
In the veins, so usually come to the hospital with deep vein thrombosis (DVT)
Which clotting pathway does the Activated Partial Thromboplastin Time test check?
What about the Prothrombin Time?
APTT checks the Intrinsic Pathway (use glass tubes and other negative charges to activate Factor XII)
Prothrombin Time tests the Extrinsic Pathway (uses hydrophobic plastic tubes to prevent activation of factor XII, while substituting phospholipid membrane and Tissue Factor / Thromboplastin to activate the extrinsic pathway)
What reason might a person be treated with Hirudin?
Hirudin is a powerful anticoagulant that directly inhibits thrombin. It is uses in the case where a person lacks antithrombin III, and thus taking heparin (catalyst for antithrombin) is ineffective
What are the anticoagulant effects of Aspirin (acetylsalicylic acid)
Inhibition of COX leads to inhibition of platelet aggregation by preventing TXA2 production.
Only need a small dose of ASA to be effective here, so side effects of daily use are minimized.
What are some lifestyle/hormonal factors that increase risk of thrombosis?
Smoking, hormonal contraceptives, poor diet (cholesterol, atherosclerosis), stress
Post-menopause there is an increase in gestagens which also increase risk of clotting
