Coagulation

Question 1

How does heparin work?

Answer 1

Potentiates the plasma coagulation inhibitor ATIII (by 10,000 fold)

Question 2

How does ATIII work?

Answer 2

Irreversibly inhibits procoagulant coagulation factors IXa, Xa and thrombin (IIa)

Question 3

What is the half-life of untractionated heparin?

Answer 3

1-2 hours

Question 4

How does an activated clotting time (ACT) work?

Answer 4

Uses an initiator of the contact/intrinsic pathway to measure the clotting time of a whole blood sample

Question 5

What are causes of heparin resistance?

Answer 5

AT deficiency (congenital or acquired from consumption - prolonged heparin infusion or mechanical circulatory support devices) + nonspecific protein binding (infection/inflammation) + elevated factor VIII levels (acute phase reactant) + anticoagulant reversal agent andexanet alfa

Question 6

How often does Heparin-Induced Thrombocytopenia occur?

Answer 6

Up to 5% of patients exposed to UFH

Question 7

What is the cause of HIT?

Answer 7

Autoantibodies to platelet factor 4 (PF4) in complex with heparin; can cause arterial thrombosis and consumptive thrombocytopenia

Question 8

How do you diagnose HIT?

Answer 8

Presence of anti-PF4 antibodies + a positive functional test (i.e. serotonin release assay SRA or heparin-induced platelet activiation HIPA)

Question 9

When does a positive anti-heparin-PF4 ELISA not necessary mean a positive HIT diagnosis?

Answer 9

There are many anti-heparin-PF4 antibodies that are not activating

Question 10

When should you avoid heparin in patients with HIT?

Answer 10

Patients with acute or subacute HIT since they have activated antibodies; either delay surgery or use a direct thrombin inhibitor (bivalirduin or argatroban)

Question 11

When can you use heparin in patients with HIT?

Answer 11

Patients with subacute HIT B and remote HIT; they can receive a single brief period of heparin exposure; they might develop antibodies after but the antigen will be gone by then

Question 12

What is acute HIT vs subacute HIT A vs subacute HIT B vs remote HIT?

Answer 12

Acute HIT: PF4+ (high concentration) and SRA+, Subacute HIT A: PF4+ (lower conc) and SRA+, Subacute HIT B: PF4+ (even lower conc) and SRA negative, Remote HIT: PF4+ (low) and SRA negative

Question 13

How does warfarin work and how do you reverse it?

Answer 13

Inhibits recycling of Vit K which depletes Vit K dependent clotting factors; Reversal = 4-PCC, FFP, Vit K

Question 14

What are examples of direct factor Xa inhibitors and how do you reverse it?

Answer 14

Apixaban, rivaroxaban, edoxaban; Reversal = Andexanet alfa, 4-PCC

Question 15

What are examples of a direct thrombin inhibitor and how do you reverse it?

Answer 15

Dabigatran, Argatroban, Bivalrudin; Reversal = Idarucizumab, dialysis

Question 16

How does LMWH work and how do you reverse it?

Answer 16

Potentiates antithrombin to cause rapid inhibition of Factor IXa and Xa (not thrombin like heparin does); Reversal = none

Question 17

What should you worry about in patients with liver or kidney dysfunction with direct thrombin inhibitors?

Answer 17

Bivalirudin: prolonged half-life (usually 25-35min) with renal dysfunction; Argatroban: prolonged half-life (usually 30-40min) with hepatic dysfunction

Question 18

What does kaolin do to coagulation?

Answer 18

Activates Factor XII and XIIa in the contact/intrinsic pathway

Question 19

How does platelet mapping work with TEG?

Answer 19

Standard TEG is done to calculate MA; then a second TEG is done with reptilase (direct fibrinogen activator) and with heparin (MA fibrin); then a third TEG is done with arachadonic acid (for ASA) or ADP (P2Y12); MA - MA fibrin = platelet component of clot

Question 20

What TEG/ROTEM tests are available for measuring the intrinsic pathway? Extrinsic pathway? Heparin anticoagulation? Fibrin clot quality? Fibrinolysis?

Answer 20

Intrinsic = KaoTEG (adds kaolin) or INTEM (adds ellagic acid); Extrinsic = rapidTEG (adds tissue factor) or EXTEM (adds tissue factor); Heparin = HTEG or HEPTEM (both add heparinase); Fibrin clot = functional fibrinogen (adds abciximab) or FIBTEM (adds cytochalasin D); Fibrinolysis = APTEM (adds aprotinin)

Question 21

What are the TEG parameters?

Answer 21

R time, K time, alpha angle, A30/A60, MA, LY30/LY60

Question 22

What are the ROTEM parameters?

Answer 22

CT, CFT, alpha angle, A5/A10/A15/A20, MCF, CL30/CL60

Question 23

What is Shear modulus for Quantra?

Answer 23

Measure of clot strength; resistance to deformation from stress parallel to its surface

Question 24

What is shear modulus better at than traditional TEG or ROTEM?

Answer 24

More accurately reflects the force with which blood resists oscillation + more accurate indicator of platelet contribution to the developing clot

Question 25

What are the Quantra parameters?

Answer 25

CT (kaolin), CTH (heparinase), CTR (ratio), CS (clott stiffness), FCS (fibrinogen contribution to clot stiffness) and PCS (platelet contribution fo clot stiffness)