Heparin-Induced Thrombocytopenia Test 3/3 Flashcards

1
Q

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

A

(a serine protease)

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2
Q

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 ?

A

clotting factor binding site

a very rapid inhibitor of thrombin and factor Xa

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3
Q

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

A

Thrombin X10 fold and factor Xa

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4
Q

Other heparin mechanisms of action include binding directly to

A

platelets and binding cofactor II

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5
Q

Multiple causes of Heparin Resistance

A
  • AT deficiency,
  • Increased heparin clearance,
  • Elevations in heparin binding proteins, such as:
  • factor VIII,
  • fibrinogen, and
  • platelet factor 4 (PF4)
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6
Q

There are some Reports of heparin resistance induced by ?

A

aprotinin and nitroglycerin

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7
Q

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 __ ___
A
  1. ) reticuloendothelial system - (main mechanism of clearance of therapeutic doses.
  2. ) renal elimination
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8
Q

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

A

30 min
60 min
150 min

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9
Q

4 Protamine – Adverse Reactions ?

A

Hypotension
Anaphylactic
Anaphylactoid
Pulmonary vasoconstriction

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10
Q

Protamine Adverse Reaction of Pulmonary vasoconstriction can lead to what ?

A
  • Rt ventricular failure,
  • decreased CO,
  • systemic hypotension
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11
Q

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

A
  • platelet microparticles,
  • thromboxane, and
  • massive thrombin generation
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12
Q

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

A

(white clot syndrome)

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13
Q

HIT should be suspected in any patient who develops what ?

A

50% reduction of platelet count while on heparin treatment

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14
Q

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

A

ELISA

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15
Q

Functional Assays –

similar sensitivity to ELISA with improved ?

A

specificity

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16
Q

Should be avoided during acute HIT

A

Warfarin

17
Q

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

A

3.5

18
Q

Thrombin inhibitors

A

Argatroban
Lepirudin
Bivalirudin

19
Q
  • 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.
A

Argatroban

Monitor with PTT & PT

20
Q
  • 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
A

Lepirudin

monitored with PTT (goal 2.5x normal)

21
Q

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

A
  • modified ultrafiltration,
  • hemofiltration, and
  • hemodialysis have been used to reduce lepirudin concentrations
22
Q
  • 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
A

Bivalirudin

23
Q

HIT antibodies are transient – usually decline to nondetectable levels by

A

100 days (median 50 days)

24
Q

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

A

safe to proceed with heparin

25
Q

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

A

Warfarin,

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

26
Q

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

A

Argatroban

27
Q

A snake venom prothrombin activator-based assay

A

Ecarin Clotting Time (ECT)

28
Q

Target CPB lepirudin levels are between ?

A

3.5-4.0 mcg/mL

29
Q

Lepirudin Levels >4.0 are associated with ?

A

increased post-op bleeding

30
Q

Lepirudin Levels

A

clotting in the CPB circuit

31
Q

What percentage of lepirudin distributes in the extravascular space?

A

80%