Heparin-Induced Thrombocytopenia Test 3/3 Flashcards Preview

CVPR 330 Blood > Heparin-Induced Thrombocytopenia Test 3/3 > Flashcards

Flashcards in Heparin-Induced Thrombocytopenia Test 3/3 Deck (31):
1

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

(a serine protease)

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 ?

clotting factor binding site


a very rapid inhibitor of thrombin and factor Xa

3

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

Thrombin X10 fold and factor Xa

4

Other heparin mechanisms of action include binding directly to

platelets and binding cofactor II

5

Multiple causes of Heparin Resistance

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

6

There are some Reports of heparin resistance induced by ?

aprotinin and nitroglycerin

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 __ ___

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


2.) renal elimination

8

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

30 min
60 min
150 min

9

4 Protamine – Adverse Reactions ?

Hypotension
Anaphylactic
Anaphylactoid
Pulmonary vasoconstriction

10

Protamine Adverse Reaction of Pulmonary vasoconstriction can lead to what ?

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

11

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

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

12

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

(white clot syndrome)

13

HIT should be suspected in any patient who develops what ?

50% reduction of platelet count while on heparin treatment

14

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

ELISA

15

Functional Assays –
similar sensitivity to ELISA with improved ?

specificity

16

Should be avoided during acute HIT

Warfarin

17

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

3.5

18

Thrombin inhibitors

Argatroban
Lepirudin
Bivalirudin

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.

Argatroban

Monitor with PTT & PT

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


Lepirudin

monitored with PTT (goal 2.5x normal)

21

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

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

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

Bivalirudin

23

HIT antibodies are transient – usually decline to nondetectable levels by

100 days (median 50 days)

24

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

safe to proceed with heparin

25

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

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

26

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

Argatroban

27

A snake venom prothrombin activator-based assay

Ecarin Clotting Time (ECT)

28

Target CPB lepirudin levels are between ?

3.5-4.0 mcg/mL

29

Lepirudin Levels >4.0 are associated with ?

increased post-op bleeding

30

Lepirudin Levels

clotting in the CPB circuit

31

What percentage of lepirudin distributes in the extravascular space?

80%