Coagulation

Question 1

Unfractionated heparin: mechanism and half-life

Answer 1

Mechanism: accelerates inhibition of factors Xa, IXa, and thrombin by up to 10,000x

T1/2 = 1-2 hrs

Question 2

Goal ACT for CPB

Answer 2

> 400-480 sec

Question 3

Causes of heparin resistance

Answer 3

• AT deficiency (congenital or acquired due to consumption)
• Nonspecific protein binding (in inflammation or infection)
• Elevated Factor VIII (acute phase reactant)
• Andexanet alfa administration (anticoagulation reversal agent)

Question 4

HIT frequency and cause

Answer 4

• Occurs in up to 5% of patients exposed to heparin
• Autoantibodies to platelet factor 4 (PF4) complexed with heparin
• The antibodies activate platelets leading to thrombosis and consumptive thrombocytopenia

Question 5

Warfarin mechanism of action and reversal agents

Answer 5

Mechanism: inhibits recycling of vitamin K = deficiency of vitmain K-dependent clotting factors

Reversal:
- 4-factor prothrombin complex concentrate: immediate onset, replaces missing factors (low volume)
- FFP: immediate onset, replaces missing factors (but high volume)
- Vitamin K: allows liver to synthesize missing factors (onset 4-24 hrs)

Question 5

HIT diagnosis

Answer 5

Presence of anti-heparin-PF4 antibodies AND a positive functional (platelet activation) test

• anti-heparin-PF4 ELISA (note: not all anti-heparin-PF4 antibodies are activating so a positive ELISA does not equal HIT)
• Platelet activation tests: serotonin release assay or heparin-induced platelet activation tests

Question 6

What are the direct factor Xa inhibitors?

Answer 6

• Apixaban
• Rivaroxaban
• Edoxaban

Question 7

Direct factor Xa inhibitor mechanism and reversal

Answer 7

Mechanism: noncompetitive inhibition of coagulation factor xa

Reversal:
- Andexanet alfa: “decoy” enzyme that binds the inhibitor. Immediate reversal, causes severe heparin resistance.
- 4-factor PCC: unknown mechanism

Question 8

Direct thrombin inhibitors

Answer 8

• Dabigatran
• Argatroban
• Bivalrudin

Question 9

Direct thrombin inhibitor mechanisms and reversal

Answer 9

Mechanism: noncompetitive inhibitor of thrombin

Reversal:
- idarucizumab (Praxbind) Fab binds and sequesters dabigatran. Immediate effect.
- No FDA-approved reversal agents for argatroban or bivalrudin (but both of these have a short half-life of 25-60 mins; prolonged to 3-4 hrs in renal dyfunction for argatroban and in liver dysfunction for bivalrudin)
- Argatrovan and bivalrudin can be cleared with dialysis

Question 10

LMWH mechanism and reversal

Answer 10

Mechanism: potentiates antithrombin to cause rapid inhibition of FXa and FIXa (but not thrombin)

Reversal: None

Question 11

What are the LMWH agents?

Answer 11

• Enoxaparin
• Dalteparin
• Tinzaparin
• Fondaparinux

Question 12

What does the standard citrated kaolin-activated TEG measure?

Answer 12

• Measures maximum platelet AND fibrin component of the clot
• Uses kaolin to activate the clotting cascade by activating factor XII and XIIa (contact pathway)

Question 13

Based on coagulation testing, when should protamine be given?

Answer 13

TEG R > hTEG R x1.25

INTEM CT >240 and hepTEM CT < 0.9 INTEM CT

Question 14

Based on coagulation testing, when should platelets be given?

Answer 14

MA < 40 and functional fibrinogen >8

FIBTEM A10 > 10 and EXTEM A10 < 40

Question 15

Based on coagulation testing, when should cryo/fibrinogen concentrate be given?

Answer 15

MA < 40 and functional fibrinogen < 8

FIBTEM A10 < 10 and EXTEM A10 < 40

Question 16

Based on coagulation testing, when should FFP or PCCs be given?

Answer 16

hTEG R >12

EXTEM CT >100

Question 17

Based on coagulation testing, when should antifibrinolytics be given?

Answer 17

LY30 > 7.5%

INTEM or EXTEM ML > 7% at 30 min or ML >15% at 60 min