Anticoagulation and NOACs Flashcards by M K

PT (INR) measures Extrinsic pathway (FVII and then combined pathway X + V -> II). Causes of prolonged PT?

Factor VII deficiency
Warfarin
Oral Xa inhibitors
LAC
Mild factor X, V or II def

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aPTT measures intrinsic pathway (Factors XII, XI, IX and VIII and then combined X+V and II). Causes of prolonged aPTT?

Factors XII, XI, IX and VIII def
vWD
LAC
Mild X, V or II def

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What is the best predictor of perioperative bleeding?

The bleeding history

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How does Heparin affect the coag assay?

Prolong aPPT and TT

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What test confirms the presence of Heparin?

Reptilase time

Activates prothrombin, not inhibited by heparin

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What prolongs reptilase time?

Abnormal or reduced fibrinogen
Hypoalbuminaemia
Raised FDPs

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What causes a prolonged PT and APTT?

Vit K def
Warfarin anticog
Liver failure
Combined V and VIII def

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What causes a long PT, APTT, TT and normal or abnormal fibrinogen?

Heparin in large amounts
Liver disease
Finronogen def or disorder
Excess dabigatran and anticoagulation

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What causes a long PT, APTT, Normal TT and Normal or abnormal Fibrinogen and low platelet count?

Massive transfusion

Liver disease

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What causes a long PT, APTT, TT, low fibrinogen and low platelet count?

DIC

Acute liver disease

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Antithrombin deficiency. What, associations?

AD
Prevalence of symptomatic disease 0.01%

Antithrombin inhibits XIIa, Xia, IXa and Xa

Acquired casues are DIC, cirrhosis, nephrotic syndrome and L- asparaginase therapy

Associated with VTE from puberty in 55%
Recurrence of 60%

Very high risk of VTE in pregnancy = 50%
prophylactic anti-coagulation and antithrombin concentrates at delivery

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Protein C and S def.

What, prevalence, causes, associations?

AD
Prevalence of symptomatic disease is 0.1% or less

Acquired causes are liver disease, warfarin therapy, OCP and preg

Associations:
VTE from puberty, less risk than antithrombin. Spontaneous and associated with surgery, trauma, pregnancy etc.

Warfarin induced skin necrosis

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Role of activated protein C?

Protein C inactivates Factor V and FVIII with protein S as a cofactor

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What inherited clotting disorder is associated with venous, not arterial thrombosis?

Activated protein C resistance
- Mutation Factor V Leiden found

Moderate risk for venous thrombosis
Synergictic with OCP, preg, Sx

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Elevated Factor VIII.
Cause
Main risk association

Elevtaed levels are related to ABO blood group - Group O have lower FVIII
Inherited in some

FVIII levels may rise with infection, inflammation etc
Rise with age, esp post menopause

Elevated FVIII >150% (1.5 IU/L) is associated with a 4.8 fold risk of VTE!!!
Greater than activated protein C resistance (Factor V Leiden) etc

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Pregnancy associated VTE. Highest risk periods?

Highest risk post partum, 5 x higher
1st trimester higher risk than others.
Left LL more common = 85%

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Coagulation Tx for unprovoked VTE?

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3 months

With mild RF, 3 months then reassess

Coagulation Tx period for Recurrent idiopathic VTE?

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Long term warfarin

First idiopathic VTE. Tx period?

When do you consider long term warfarin?

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Tx for 3-6 months
Consider long term warfarin id
- life threatening 1st event
- unusual site esp if APLS
- incomplete recovery from primary event
- patient preference
- APLS
- high risk thrombophilia

HITTS Mx?

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Stop heparin
DO NOT GIVE PLATELETS
Start Danaparoid, argatroban or fondaprinux
Delay starting warfarin until platelet count recovers

What are the long distance guidelines for VTE prevention in pts with no RF for VTE vs. patients with RF?

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No RF:
Flight > 6 hrs
- avoid constrictive clothing around lower extrememties or waste
- avoid hydration
- do frequent calf muscle stretching

RF:
Above PLUS
- properly fitted below knee GCS providing 15-30 mmHg of pressure at the ankle (grade 2B) OR
Single dose LMWH injected prior to departure

No evidence for aspirin in VTE prevention associated with travel (grade 1B)

Prasugel. MOA. Indications. CI?

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Reversibly binds to P2Y12 receptor and inhibits platelet aggregation for the life of the platelet.

Indications:
ACS to be managed with PCI (with aspirin)

AE:
Common is bleeding
Rare - angioedema

CI:
Hx of stroke of TIA due to increased risk of bleeding

Which factors initiate coagulation?

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Factor VII and tissue factor (VIIa)

Which bleeding disorder can have a severe phenotype but normal APTT and PT?

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Factor XIII

Factor XIII crosslinks fibrin to stabilise the clot in the last step

How is vWBD most commonly inherited? | Which factor is vWB a carrier for?

AD Factor VIII therefore low in vWD and prolonged aPPT

The antithrombotic effect of warfarin is due to its inhibition of?

Factor II (Prothrombin) Antithrombotic effect is not present until the 5th day if therapy. Depends on clearance of prothrombin which has a half life of 50 hrs.

The anticoagulant activity of warfarin is dependent on?

The clearance of clotting factors from the systemic circulation after the 1st dose. The clearance is determined by the half lives. the changes are noted 24-36 hrs and due to clearance of Factor VII which is the clotting factor with the shortest half life.

What does prothrombinex contain?

Inactivated concentrate of II, IX and X with variable amounts of VII Activated prothrombinex used when pt has an inhibitor

Actions of antiphospholipid syndrome in vivo (inside living organism) vs. in vitro (test tube)?

In vivo = prothrombotic In vitro = prolong APTT If no AI features = primary APS Tx: Lifelone anticoagulation

Protein C activated by?

Thrombin

Greater risk of recurrent DVT/PE. Antithrombin III deficiency or Protein C deficiency?

Antithrombin deficiency portends the highest risk of VTE but is not a common genetic thrombophilia

What is the most common cause of acquired protein C resistance?

Factor V Leiden

What is the difference between Factor V Leiden and Protein C deficiency?

Factor V Leiden is the congenital form of Protein C resistance. Protein C def also affects the same pathway but does not cause resistance of FVL to APC - just less Activated protein C

MOA protein C?

Inactivate FVa (cleaves Xa to thrombin) and inactivates VIIIa

What is the better Tx for HITS in the prevention of thrombosis? LMWH or Direct thrombin inhibitor?

Direct thrombin inhibitor - danaparoid or fondaparinux. Warfarin can be commenced once the PLTs >= 150, 000/microL

How do you monitor Rivaroxiban?

Anti-Xa level specific for rivaroxiban Also anti-Xa levels specific for Apixaban present 30% renal excretion 70% liver (CYP3A4) Half life 9 hrs

How do you measure for Dabigatran?

Dilute thrombin clotting time assay (HEMOCLOT assay) Half life of dabigatran is 12-14h

MOA of thrombolysis?

Activation of plasminogen

What is the most common cause of bud chairi syndrome?

Polycythemia Rubra vera is themsot common cause overall. Myeloproliferative disease cause 50% ``` Other causes: PNH Pregnancy and OCP Drugs- azathioprine, adriamycin Cancer esp HCC, renal Hypercoagulable states e.g. FVL mutations, APLS, ATIII/PC/PS def Idiopathic 20% ```

Myeloproliferative disorder BCR-ABL +ve. Dx?

CML

Myelopriliferative disorder, BCR-ABL -ve, JAK-2 +ve. Dx?

PRV, > 90% 50% MF and ET

Myelopriliferative disorder, BCR-ABL -ve, JAK-2 -ve. Dx?

50% ET and MF Infrequent PRV

Anticoagulation and NOACs Flashcards

(42 cards)