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Flashcards in Coagulation 2 Deck (32):
1

What are antiphospholipid antibodies?

IgG, IgM or IgA antibodies directed against proteins that bind to phospholipids

2

What detects antiphospholipid antibodies?

1. Activity tests for lupus anticoagulants
2. Measuring antibodies by ELISA tests (anticardolipin ab, antibeta 2 glycoprotein Ab)

3

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

4

How do you diagnosis antiphospholipid syndrome?

need at least 1 clinical and 1 lab criteria

5

What are hte clinical criteria for antiphospholipid syndrome?

– Occurrence of thrombotic event – venous or arterial
– Recurrent miscarriage, fetal death, premature birth

6

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

7

What factors and inhibitors are vitamin K dependent?

II, VII, IX, X
Protein C and S

8

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)

9

What is the mechanism of action of warfarin?

it inhibits vit K1,2,3 expoxide reductase

10

What does warfarin do?

reduces vitamin K dependent factor activity (II, VII, IX, X, C and S)

11

What vit K dependent factors have the shortest half life?

VII, Protein C

12

How do you monitor warfarin?

PT/INR

(Or measure a vit K dependent factor, like X)

13

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

14

What factors does heparin inhibit?

IIa, IXa, Xa, XIa, XIIa

15

How does HIT occur?

antibody causes platelet activation that leads to thrombosis and thrombocytopenia

16

How do you monitor heparin?

1. aPTT
2. anti-XA heparin level assay (chromogenic assay)
3. Activated clotted time

NOT a Factor X level
Heparin
• Free AT + HeparinAT-HepAT-Hep + FXa (reagent)AT-Hep-Fxa + excess Fxa Residual FXa + substratechromogenic signal

17

What is too sensitive to use for monitoring of heparin?

thrombin time

18

enoxaparin, dalteparin, tinzaparin

LMWH

fractionated forms of heparin

19

How does LMWH differ from heparin?

- fractionated
- Less plasma protein binding
- 2-4 fold increase in factor Xa inhibition and less thrombin inhibition

20

How do you monitor LMWH?

anti-XA assay (NOT aPTT)

4 hours after dose

21

What are indirect Xa inhibitors?

fondaparinux

22

What are direct Xa inhibitors?

– Rivaroxaban
– Apixaban
– Edoxaban

23

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 Xainhibition of Factor Xa decreased thrombin generation and thrombus development

24

How is fondaparinux given? How is it monitored?

subcutaneously
Modified anti-Xa assays

25

What is the mechanism of direct factor Xa inhibiotrs?

directly inhibit the active site of Xa (small molecules that do not require a cofactor)

26

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

27

do direct Xa inhibitors need to be monitored?

NO!

28

What anticoagulant binds to the active site and exosite 2 of thrombin?

heparin

29

What anticoagulant binds to the active site and exosite 1 of thrombin?

bivalent DTI: bivalirudin, lepirudin

30

What thrombin inhibotrs just bind to the active site?

argatroban
dabigatran

31

How do you monitor direct thrombin inhibitors?

– APTT
– ACT
– Other assays = ecarin clot time, dilute
thrombin time, hemoclot assay, chromogenic assays

32

Why monitor an anticoagulant?

• Variable pharmacokinetics
• Patient compliance
• Emergency settings
• Changes in renal or hepatic function • Interacting medications