Anticoagulation and NOACs Flashcards
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
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
What is the best predictor of perioperative bleeding?
The bleeding history
How does Heparin affect the coag assay?
Prolong aPPT and TT
What test confirms the presence of Heparin?
Reptilase time
Activates prothrombin, not inhibited by heparin
What prolongs reptilase time?
Abnormal or reduced fibrinogen
Hypoalbuminaemia
Raised FDPs
What causes a prolonged PT and APTT?
Vit K def
Warfarin anticog
Liver failure
Combined V and VIII def
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
What causes a long PT, APTT, Normal TT and Normal or abnormal Fibrinogen and low platelet count?
Massive transfusion
Liver disease
What causes a long PT, APTT, TT, low fibrinogen and low platelet count?
DIC
Acute liver disease
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
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
Role of activated protein C?
Protein C inactivates Factor V and FVIII with protein S as a cofactor
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
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
Pregnancy associated VTE. Highest risk periods?
Highest risk post partum, 5 x higher
1st trimester higher risk than others.
Left LL more common = 85%
Coagulation Tx for unprovoked VTE?
3 months
With mild RF, 3 months then reassess
Coagulation Tx period for Recurrent idiopathic VTE?
Long term warfarin
First idiopathic VTE. Tx period?
When do you consider long term warfarin?
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?
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?
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?
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?
Factor VII and tissue factor (VIIa)
Which bleeding disorder can have a severe phenotype but normal APTT and PT?
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
