Coagulation Flashcards
How does heparin work?
Potentiates the plasma coagulation inhibitor ATIII (by 10,000 fold)
How does ATIII work?
Irreversibly inhibits procoagulant coagulation factors IXa, Xa and thrombin (IIa)
What is the half-life of untractionated heparin?
1-2 hours
How does an activated clotting time (ACT) work?
Uses an initiator of the contact/intrinsic pathway to measure the clotting time of a whole blood sample
What are causes of heparin resistance?
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
How often does Heparin-Induced Thrombocytopenia occur?
Up to 5% of patients exposed to UFH
What is the cause of HIT?
Autoantibodies to platelet factor 4 (PF4) in complex with heparin; can cause arterial thrombosis and consumptive thrombocytopenia
How do you diagnose HIT?
Presence of anti-PF4 antibodies + a positive functional test (i.e. serotonin release assay SRA or heparin-induced platelet activiation HIPA)
When does a positive anti-heparin-PF4 ELISA not necessary mean a positive HIT diagnosis?
There are many anti-heparin-PF4 antibodies that are not activating
When should you avoid heparin in patients with HIT?
Patients with acute or subacute HIT since they have activated antibodies; either delay surgery or use a direct thrombin inhibitor (bivalirduin or argatroban)
When can you use heparin in patients with HIT?
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
What is acute HIT vs subacute HIT A vs subacute HIT B vs remote HIT?
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
How does warfarin work and how do you reverse it?
Inhibits recycling of Vit K which depletes Vit K dependent clotting factors; Reversal = 4-PCC, FFP, Vit K
What are examples of direct factor Xa inhibitors and how do you reverse it?
Apixaban, rivaroxaban, edoxaban; Reversal = Andexanet alfa, 4-PCC
What are examples of a direct thrombin inhibitor and how do you reverse it?
Dabigatran, Argatroban, Bivalrudin; Reversal = Idarucizumab, dialysis
How does LMWH work and how do you reverse it?
Potentiates antithrombin to cause rapid inhibition of Factor IXa and Xa (not thrombin like heparin does); Reversal = none
What should you worry about in patients with liver or kidney dysfunction with direct thrombin inhibitors?
Bivalirudin: prolonged half-life (usually 25-35min) with renal dysfunction; Argatroban: prolonged half-life (usually 30-40min) with hepatic dysfunction
What does kaolin do to coagulation?
Activates Factor XII and XIIa in the contact/intrinsic pathway
How does platelet mapping work with TEG?
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
What TEG/ROTEM tests are available for measuring the intrinsic pathway? Extrinsic pathway? Heparin anticoagulation? Fibrin clot quality? Fibrinolysis?
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)
What are the TEG parameters?
R time, K time, alpha angle, A30/A60, MA, LY30/LY60
What are the ROTEM parameters?
CT, CFT, alpha angle, A5/A10/A15/A20, MCF, CL30/CL60
What is Shear modulus for Quantra?
Measure of clot strength; resistance to deformation from stress parallel to its surface
What is shear modulus better at than traditional TEG or ROTEM?
More accurately reflects the force with which blood resists oscillation + more accurate indicator of platelet contribution to the developing clot
What are the Quantra parameters?
CT (kaolin), CTH (heparinase), CTR (ratio), CS (clott stiffness), FCS (fibrinogen contribution to clot stiffness) and PCS (platelet contribution fo clot stiffness)
