Heparin Anticoagulants Flashcards

1
Q

What kinds of cell is heparin found in?

A

Mast cells (along with histamine and serotonin)

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2
Q

Heparin

Acidic or Basic? Is it a protein, lipid, sugar?

A

Strongly acidic

Mucopolysaccharide with repeating units of glucoronic acid and sulfated glucosamine

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3
Q

What is the average size of heparin?

A

12 kDa, but can range from 2-40 kDa

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4
Q

What animal do we mainly get our heparin from?

A

Pigs!

Different species produce slightly different heparin.

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5
Q

How do we standardize heparin acquired from different pigs?

A

Anti-Xa and Anti-IIa methods

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6
Q

Heparin is dosed in units, not grams. I mg of heparin is about equal to…

A

120 USP units

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7
Q

Heparin

Mechanism of Action

A

Inhibits action of activated Factor Xa and Factor IIa
Also interacts with XIIa and XIa
Inhibits aggregation of platelets (at high concs)

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8
Q

What does heparin bind in its normal MOA and how does that bring about anti coagulability?

A

Binds antithrombin III (ATIII)

Causes a conformation change in ATIII, making it more likely to block thrombin and other coag factors

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9
Q

What is the plasma clearing effect of heparin?

A

Releases lipoprotein lipase from blood vessels to break down fat chylomicrons

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10
Q

Heparin causes release of TFPI. What does this accomplish?

A

Inhibits tissue factor/VIIa complex, which would normally activate the extrinsic system

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11
Q

Heparin Administration

A

Only IV and Subcutaneous

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12
Q

Therapeutic Monitoring of Heparin

What test do you use? What is the therapeutic range?

A

Use the APTT (activated partial thromboplastin time) for monitoring

Therapeutic range is 2-2.5x baseline APTT

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13
Q

Heparin Elimination

A

Renal or metabolic (through liver heparinase enzymes)

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14
Q

Heparin

Duration of Action

A
Rapid onset (5-10 min)
1-3 hour half life

Higher dose –> longer half life

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15
Q

What are some endogenous modulators of heparin?

A

Antithrombin III (ATIII)
Heparin cofactor II
TFPI
Platelet Factor 4

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16
Q

Side Effects of Heparin

A

Hemorrhage (adrenals, gut)
Heparin induced thrombocytopenia (HIT), leading to thrombosis of superficial veins and gangrene
Osteoporosis
Alopecia (long term)

17
Q

Clinical Uses of Heparin

A
  • Therapeutic anticoagulation
  • Surgical anticoagulation
  • Prophylactic anticoagulation
  • Unstable angina and related coronary syndromes
  • Adjunct therapy with thrombolytic drugs
  • Thrombotic and ischemic stroke
18
Q

What drug is used as a heparin antagonist?

A

Protamine sulfate

19
Q

Protamine Sulfate

Mechanism of Action

A

Protamine Sulfate is strongly basic. Combines with the acidic heparin and causes loss of anticoagulant activity

20
Q

Protamine Sulfate

Dosage – how much Protamine sulfate is required to neutralize one USP unit heparin?

A

One USP unit heparin neutralized by 10 ug protamine sulfate

21
Q

Protamine Sulfate is given IV. What can this cause?

A

Hypotension
Bradycardia

Give Protamine sulfate by slow infusion to prevent these

22
Q

Low MW Heparins

How are they prepared?

A

Chemical and enzymatic degradation of heparin to make it more homogenous.

23
Q

What does synthetic heparin pentasaccharide mimic?

A

The sequence of heparin that binds ATIII

24
Q

Where are low MW heparins and synthetic heparin pentasaccharides commonly used?

A

Outpatient settings
Prophylaxis for certain surgeries (like knee or hip)
Prophylaxis and treatment of DVT

25
Q

Low MW Heparin

Advantages over heparin

A

Better bioavailability (100%)
Longer duration of action
Less bleeding
Less thrombocytopenia

26
Q

Antithrombin Concentrates

Clinical Uses

A

Patients with acquired or congenital antithrombin deficiency
Sepsis
DIC

27
Q

Hirudin
Mechanism of Action
Clinical Uses

A

Thrombin inhibitor found in leech saliva.
Refludan is used clinically.

Used in management of HIT.

28
Q

Argatroban
Mechanism of Action
Clinical Uses

A

Synthetic anti-thrombin agent used for HIT

29
Q

Bivalirudin

Mechanism of Action

A

Synthetic anti-thrombin agent used for PTCA anticoagulation.
Also has anti-platelet effects.