Flashcards in Coagulation 2 Deck (32):
What are antiphospholipid antibodies?
IgG, IgM or IgA antibodies directed against proteins that bind to phospholipids
What detects antiphospholipid antibodies?
1. Activity tests for lupus anticoagulants
2. Measuring antibodies by ELISA tests (anticardolipin ab, antibeta 2 glycoprotein Ab)
How do you make a laboratory diagnosis of Lupus anticoagulants?
1. Prolongation of a phospholipid dependent clotting assay (PTT, DRVVT)
2. Evidence of inhibitor shown by mixing studies
3. evidence of phospholipid dependence
4. lack of specific inhibition on any one coagulation factor
How do you diagnosis antiphospholipid syndrome?
need at least 1 clinical and 1 lab criteria
What are hte clinical criteria for antiphospholipid syndrome?
– Occurrence of thrombotic event – venous or arterial
– Recurrent miscarriage, fetal death, premature birth
What are the lab criteria for antiphosphlipid syndrome?
– Lupus anticoagulant (LAC)
– Anti-cardiolipin (IgG or IgM)
– Anti-Beta 2 glycoprotein (IgG or IgM)
– Perform testing on two or more occasions, 12 weeks apart
What factors and inhibitors are vitamin K dependent?
II, VII, IX, X
Protein C and S
Describe the structure of vitamin K dependent factors and inhibitors? What are the reaction dependent on?
contain 9-11 glutamic acids
- form gamma- carboxyglutamic acid tail
- bind factors to phospholpid surfaces through Ca
Vit K (warfarin blocks recycling of vitamin K)
What is the mechanism of action of warfarin?
it inhibits vit K1,2,3 expoxide reductase
What does warfarin do?
reduces vitamin K dependent factor activity (II, VII, IX, X, C and S)
What vit K dependent factors have the shortest half life?
VII, Protein C
How do you monitor warfarin?
(Or measure a vit K dependent factor, like X)
What is the mechanism of heparin?
Antithrombin binds to a pentasaccharide structure on heparin resulting in a conformational changes which enhances antithrombin activity
– for thrombin inhibition needs an additional site on heparin
What factors does heparin inhibit?
IIa, IXa, Xa, XIa, XIIa
How does HIT occur?
antibody causes platelet activation that leads to thrombosis and thrombocytopenia
How do you monitor heparin?
2. anti-XA heparin level assay (chromogenic assay)
3. Activated clotted time
NOT a Factor X level
• Free AT + HeparinAT-HepAT-Hep + FXa (reagent)AT-Hep-Fxa + excess Fxa Residual FXa + substratechromogenic signal
What is too sensitive to use for monitoring of heparin?
enoxaparin, dalteparin, tinzaparin
fractionated forms of heparin
How does LMWH differ from heparin?
- Less plasma protein binding
- 2-4 fold increase in factor Xa inhibition and less thrombin inhibition
How do you monitor LMWH?
anti-XA assay (NOT aPTT)
4 hours after dose
What are indirect Xa inhibitors?
What are direct Xa inhibitors?
What is the mechanism of fondaparinux?
Selective inhibition of activated Factor X
• Synthetic pentasaccharide sequence required to promote the binding of antithrombin to Factor Xa
• Induces conformational change in ANTITHROMBIN increases its affinity for Factor Xainhibition of Factor Xa decreased thrombin generation and thrombus development
How is fondaparinux given? How is it monitored?
Modified anti-Xa assays
What is the mechanism of direct factor Xa inhibiotrs?
directly inhibit the active site of Xa (small molecules that do not require a cofactor)
What do direct Xa inhibotrs inhibit?
– Free Factor Xa
– Factor Xa in the prothrombinase complex
• This Factor Xa is protected from inhibition by antithrombin
– Clot associated Factor Xa
do direct Xa inhibitors need to be monitored?
What anticoagulant binds to the active site and exosite 2 of thrombin?
What anticoagulant binds to the active site and exosite 1 of thrombin?
bivalent DTI: bivalirudin, lepirudin
What thrombin inhibotrs just bind to the active site?
How do you monitor direct thrombin inhibitors?
– Other assays = ecarin clot time, dilute
thrombin time, hemoclot assay, chromogenic assays