Flashcards in Heparin-Induced Thrombocytopenia Test 3/3 Deck (31)
In the Coagulation Cascade A portion of protein is cleaved off to form an active enzyme ?
(a serine protease)
Heparin binds to a lysine site on AT, inducing a conformational change at the ?
This converts AT from a slow, progressive clotting factor inhibitor to ?
clotting factor binding site
a very rapid inhibitor of thrombin and factor Xa
What molecules are most responsive to inhibition by the the binding of ATIII to heparin ?
Thrombin X10 fold and factor Xa
Other heparin mechanisms of action include binding directly to
platelets and binding cofactor II
Multiple causes of Heparin Resistance
-Increased heparin clearance,
-Elevations in heparin binding proteins, such as:
-platelet factor 4 (PF4)
There are some Reports of heparin resistance induced by ?
aprotinin and nitroglycerin
Heparin Clearance involves a combination of:
1.) Rapid, saturable phase through binding to receptors on endothelial cells and macrophages that leads to metabolism in the
2.) Slower first-order __ ___
1.) reticuloendothelial system - (main mechanism of clearance of therapeutic doses.
2.) renal elimination
Heparin Dose vs. Half Life ?
4 Protamine – Adverse Reactions ?
Protamine Adverse Reaction of Pulmonary vasoconstriction can lead to what ?
-Rt ventricular failure,
Ag/Ab complexes interact with platelets and endothelial cells, resulting in release of ?
-massive thrombin generation
Thrombosis typically characterized by presence of white clots rich in platelets, AKA ?
(white clot syndrome)
HIT should be suspected in any patient who develops what ?
50% reduction of platelet count while on heparin treatment
Laboratory that detects binding of antibody to heparin/PF 4 complexes /
Functional Assays –
similar sensitivity to ELISA with improved ?
Should be avoided during acute HIT
Depletion of protein C anticoagulant can lead to limb necrosis resulting from microvascular thrombosis – usually seen when INR rises above
-Synthetic L-arginine derivative
-Exerts its anticoagulant effects by competitively and reversibly inhibiting thrombin
-Binds directly to the catalytic site of thrombin, independently of AT III.
Monitor with PTT & PT
- a 65-amino acid polypeptide secreted by the salivary glands of the medicinal leech.
-Most potent natural thrombin inhibitor known
-Binds to and inhibits both soluble and clot-bound thrombin.
-No antidote is available
monitored with PTT (goal 2.5x normal)
High risk of bleeding with supratherapeutic levels of Lepirudin.
In cases of severe bleeding what can we do ?
-hemodialysis have been used to reduce lepirudin concentrations
-A synthetic 20-amino acid peptide of two short hirudin peptide fragments connected by a tetraglycine spacer
-Neutralizes the fibrinogen binding site and catalytic site of thrombin
-Lower rate of hemorrhage than lepirudin
-Reversible thrombin inhibitor
HIT antibodies are transient – usually decline to nondetectable levels by
100 days (median 50 days)
If urgent surgery and > 100 days since heparin exposure, it is considered ?
safe to proceed with heparin
After surgery, nonheparin anticoagulants should be used if antithrombotic prophylaxis is needed you should use the following?
danaparoid 750 U SQ bid-tid, lepirudin 15 mg SQ bid
Eliminated primarily by hepatic mechanisms, and may be useful for patients with renal failure describes what drug ?
A snake venom prothrombin activator-based assay
Ecarin Clotting Time (ECT)
Target CPB lepirudin levels are between ?
Lepirudin Levels >4.0 are associated with ?
increased post-op bleeding