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LAMP > Coagulation 2 > Flashcards

Coagulation 2 Flashcards

1
Q

What are antiphospholipid antibodies?

A

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

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2
Q

What detects antiphospholipid antibodies?

A
  1. Activity tests for lupus anticoagulants

2. Measuring antibodies by ELISA tests (anticardolipin ab, antibeta 2 glycoprotein Ab)

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3
Q

How do you make a laboratory diagnosis of Lupus anticoagulants?

A
  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
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4
Q

How do you diagnosis antiphospholipid syndrome?

A

need at least 1 clinical and 1 lab criteria

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5
Q

What are hte clinical criteria for antiphospholipid syndrome?

A

– Occurrence of thrombotic event – venous or arterial

– Recurrent miscarriage, fetal death, premature birth

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6
Q

What are the lab criteria for antiphosphlipid syndrome?

A

– 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

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7
Q

What factors and inhibitors are vitamin K dependent?

A

II, VII, IX, X

Protein C and S

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8
Q

Describe the structure of vitamin K dependent factors and inhibitors? What are the reaction dependent on?

A

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)

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9
Q

What is the mechanism of action of warfarin?

A

it inhibits vit K1,2,3 expoxide reductase

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10
Q

What does warfarin do?

A

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

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11
Q

What vit K dependent factors have the shortest half life?

A

VII, Protein C

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12
Q

How do you monitor warfarin?

A

PT/INR

Or measure a vit K dependent factor, like X

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13
Q

What is the mechanism of heparin?

A

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

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14
Q

What factors does heparin inhibit?

A

IIa, IXa, Xa, XIa, XIIa

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15
Q

How does HIT occur?

A

antibody causes platelet activation that leads to thrombosis and thrombocytopenia

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16
Q

How do you monitor heparin?

A
  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
Q

What is too sensitive to use for monitoring of heparin?

A

thrombin time

18
Q

enoxaparin, dalteparin, tinzaparin

A

LMWH

fractionated forms of heparin

19
Q

How does LMWH differ from heparin?

A
  • fractionated
  • Less plasma protein binding
  • 2-4 fold increase in factor Xa inhibition and less thrombin inhibition
20
Q

How do you monitor LMWH?

A

anti-XA assay (NOT aPTT)

4 hours after dose

21
Q

What are indirect Xa inhibitors?

A

fondaparinux

22
Q

What are direct Xa inhibitors?

A

– Rivaroxaban
– Apixaban
– Edoxaban

23
Q

What is the mechanism of fondaparinux?

A

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
Q

How is fondaparinux given? How is it monitored?

A

subcutaneously

Modified anti-Xa assays

25
Q

What is the mechanism of direct factor Xa inhibiotrs?

A

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

26
Q

What do direct Xa inhibotrs inhibit?

A

– Free Factor Xa
– Factor Xa in the prothrombinase complex
• This Factor Xa is protected from inhibition by antithrombin
– Clot associated Factor Xa

27
Q

do direct Xa inhibitors need to be monitored?

A

NO!

28
Q

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

A

heparin

29
Q

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

A

bivalent DTI: bivalirudin, lepirudin

30
Q

What thrombin inhibotrs just bind to the active site?

A

argatroban

dabigatran

31
Q

How do you monitor direct thrombin inhibitors?

A

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

32
Q

Why monitor an anticoagulant?

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

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