Heparin-Induced Thrombocytopenia Test 3/3

Question 1

In the Coagulation Cascade A portion of protein is cleaved off to form an active enzyme ?

Answer 1

(a serine protease)

Question 2

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 ?

Answer 2

clotting factor binding site

a very rapid inhibitor of thrombin and factor Xa

Question 3

What molecules are most responsive to inhibition by the the binding of ATIII to heparin ?

Answer 3

Thrombin X10 fold and factor Xa

Question 4

Other heparin mechanisms of action include binding directly to

Answer 4

platelets and binding cofactor II

Question 5

Multiple causes of Heparin Resistance

Answer 5

• AT deficiency,
• Increased heparin clearance,
• Elevations in heparin binding proteins, such as:
• factor VIII,
• fibrinogen, and
• platelet factor 4 (PF4)

Question 6

There are some Reports of heparin resistance induced by ?

Answer 6

aprotinin and nitroglycerin

Question 7

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 __ ___

Answer 7

1. ) reticuloendothelial system - (main mechanism of clearance of therapeutic doses.
2. ) renal elimination

Question 8

Heparin Dose vs. Half Life ?
25 U/kg
100 U/kg
400 U/kg

Answer 8

30 min
60 min
150 min

Question 9

4 Protamine – Adverse Reactions ?

Answer 9

Hypotension
Anaphylactic
Anaphylactoid
Pulmonary vasoconstriction

Question 10

Protamine Adverse Reaction of Pulmonary vasoconstriction can lead to what ?

Answer 10

• Rt ventricular failure,
• decreased CO,
• systemic hypotension

Question 11

Ag/Ab complexes interact with platelets and endothelial cells, resulting in release of ?

Answer 11

• platelet microparticles,
• thromboxane, and
• massive thrombin generation

Question 12

Thrombosis typically characterized by presence of white clots rich in platelets, AKA ?

Answer 12

(white clot syndrome)

Question 13

HIT should be suspected in any patient who develops what ?

Answer 13

50% reduction of platelet count while on heparin treatment

Question 14

Laboratory that detects binding of antibody to heparin/PF 4 complexes /

Answer 14

ELISA

Question 15

Functional Assays –

similar sensitivity to ELISA with improved ?

Answer 15

specificity

Question 16

Should be avoided during acute HIT

Answer 16

Warfarin

Question 17

Depletion of protein C anticoagulant can lead to limb necrosis resulting from microvascular thrombosis – usually seen when INR rises above

Answer 17

3.5

Question 18

Thrombin inhibitors

Answer 18

Argatroban
Lepirudin
Bivalirudin

Question 19

• 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.

Answer 19

Argatroban

Monitor with PTT & PT

Question 20

• 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

Answer 20

Lepirudin

monitored with PTT (goal 2.5x normal)

Question 21

High risk of bleeding with supratherapeutic levels of Lepirudin.
In cases of severe bleeding what can we do ?

Answer 21

• modified ultrafiltration,
• hemofiltration, and
• hemodialysis have been used to reduce lepirudin concentrations

Question 22

• 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

Answer 22

Bivalirudin

Question 23

HIT antibodies are transient – usually decline to nondetectable levels by

Answer 23

100 days (median 50 days)

Question 24

If urgent surgery and > 100 days since heparin exposure, it is considered ?

Answer 24

safe to proceed with heparin

Question 25

After surgery, nonheparin anticoagulants should be used if antithrombotic prophylaxis is needed you should use the following?

Answer 25

Warfarin,

danaparoid 750 U SQ bid-tid, lepirudin 15 mg SQ bid

Question 26

Eliminated primarily by hepatic mechanisms, and may be useful for patients with renal failure describes what drug ?

Answer 26

Argatroban

Question 27

A snake venom prothrombin activator-based assay

Answer 27

Ecarin Clotting Time (ECT)

Question 28

Target CPB lepirudin levels are between ?

Answer 28

3.5-4.0 mcg/mL

Question 29

Lepirudin Levels >4.0 are associated with ?

Answer 29

increased post-op bleeding

Question 30

Lepirudin Levels

Answer 30

clotting in the CPB circuit

Question 31

What percentage of lepirudin distributes in the extravascular space?

Answer 31

80%