Heparin Alternatives And Thrombolytic Therapy

Front 1

Heparin Induced Thrombocytopenia (HIT)

Back 1

Clotting disorder intiated by Ab/heparin/PF4 complexes
Complexes cause platelet activation, endothelial cell activation, coag cascade activation, monocyte activation
More Heparin of more platelets incr risk! Risk UFH>LMWH
Occurs 4-14 days after initiation or immediately if previous HIT

Front 2

HIT management

Back 2

1) Stop all forms of heparin and monitor platelets at first clinical suspicion
2) Strongly consider & do not delay DTI Tx
3) Confirmatory Tests

Front 3

Direct Thrombin Inibitors

Back 3

YAY: AT independent, inhibits clot bound thrombin, no HIT Ab rxn, dose response curve, short t1/2, rapid effect, easily monitored
BOO: no reversal, doesn't effect thrombin generation, rebound coag?, small therapeutic window, difficult to convert to Warfarin, $$$
Lepirudin - recombinant Hirudin (leech saliva), bivalet, RENALLY CLEARED
Agratroban - L-arginine derivative, univalent, HEPATICALLY CLEARED
Bivalirudin - not FDA for HIT (bypass), bivalent, hepatic met, renal clear

Front 4

Heparin in previous HIT pt?

Back 4

sure, if they are Ab negative with a remote hx of HIT w/o alternative tx and predicted limited exposure

Front 5

Fibrinolysis

Back 5

uPA or tPA convert plasminogen to plasmin
Plasmin degrades cross linked fibrin (creates D-Dimers)

Front 6

Fibrinolysis Inhibition

Back 6

Plasminogen Activator Inhibitor 1 (PAI-1)
Antiplasmin
Thrombin-activatable fibrinolysis inhitibory (TAFI)

Front 7

Thrombolytic Therapy

Back 7

tPA (Alteplase, Reteplase) or uPA (Urokinase) given for life or limb threatening thrombosis
Streptokinase - forms complex w/ plasminogen resulting in free plasmin (NO LONGER USED)
Follow up w/ antiplatelet or anticoag therapy
Contra in bleeding risk pts.