Q2i / 24A20 / 18B20 / 17B05: UFH v LMWH

24A20: Exam Report

Outline the important similarities and differences between unfractionated heparin and enoxaparin using the following headings (20% of marks each):

  1. Mechanism of action

  2. Pharmacokinetics

  3. Adverse effects

  4. Dosing

  5. Monitoring and reversal

27% of candidates passed this question.

These are commonly used and important drugs in intensive care practice and a high level of detail was expected.

Unfractionated heparin and enoxaparin have specific differences that influence how we use them in practice and this information was required for full marks.

This question was answered well by providing the detail on each domain for both heparin and enoxaparin and then highlighting if this factors into how they are used.

18B20: Exam Report

Describe the pharmacology of heparin highlighting important differences between unfractionated and fractionated (low molecular weight) heparin.

71% of candidates passed this question.

Better answers were tabulated and included sections on pharmaceutics, indications and an explanation on how the difference in molecular weight influenced pharmacodynamics and pharmacokinetics. Knowledge of adverse effects was limited to bleeding and HITTS, often without consideration of relative risk from LMWH. Many candidates did not know the t1/2 of UFH or LMWH.

17B05: Exam Report

Compare and contrast unfractionated heparin with low molecular weight heparin.

68% of candidates passed this question.

This question was generally well answered and lent itself well to a tabular format. Expected information included an approximation of the molecular weights / significance of the differences in size and therefore its mechanism of action.
Other pertinent areas to mention included pharmacokinetic differences and its use in renal failure, side effect profiles, monitoring, predictability of response and reversibility for the two agents.

Q2i / 24A20 / 18B20 / 17B05: Describe the pharmacology of heparin highlighting the important differences between unfractionated and fractionated heparin

Thrombin

UFH

Inactivates

Long chain bridging when on ATIII

But does not affect Thrombin bound to Fibrin; already enzymatically active & protected from inactivation

LMWH

Indirect effect

By binding ATIII inhibits Xa activity

So reduced formation of Thrombin

Xa

UFH

Inactivates

LMWH

Inactivates

Xa:IIa activity ratio

UFH

1:1

LMWH

2:1 or 4:1

AT III

UFH

Mediates effect

LMWH

Mediates effect

Platelets

UFH

Via thrombin inhibition

LMWH

Moderate plat inhibition

Fibrin

UFH

Prevents cross-linking due to Thrombin inhibition

LMWH

Inhibits formation of Fibrin Stabilising Factor

Factor V, VIII, XI, XIII

UFH

Via Thrombin inhibition

LMWH

Time to peak effect

UFH

IV ~1min

SC ~45min

LMWH

~4hrs

Time to normal hemostasis on cessation

UFH

4-6h

LMWH

>12hrs

Predictability of effect

UFH

unpredicatable

LMWH

Predictable

(remember it is like a refined selection of the heparins)

PK

UFH

LMWH

D

UFH

High PPB

Binds many proteins \large interpatient variability

LMWH

Much less PPB

Great 100% bioavailability after sc injection

M

UFH

Heparinases of liver, kidney, RES

LMWH

Desulfation +/- depolymerisation in liver

E

UFH

Metabolites excreted renally

(no dose adj w renal impair)

LMWH

Majority of dose renally cleared as active/inactive metabolites

Needs dose adjustment in renal impairment

Monitoring

UFH

APTT

ACT (high dose)

LMWH

Anti-Xa-levels

Reversal

UFH

Protamine

LMWH

Protamine

But variable, up to 60% of dose

May rebound due to cont subcut depot after protamine dose

Comparison

UFH

SC injection twice daily

LMWH

Excellent bioavailability -> predictable dosing od

Daily monitoring for Tx dose

Predictable, no monitoring for prophylactic/Tx dose

Not easily used for outpatients

Outpatients can use much easier

Plat dysfn; reduce count or HITS

Lower incidence of HITS

Risk of bleeding

Less risk of bleeding

Osteoporosis

Less risk of osteoporosis

Fully reversible w Protamine

Up to 60% reversibility w Protamine

Can be used in renal impairment

Accumulates in renal impairment

Rapid onset & clearance

Delayed Clearance – need to wait 12-24h post dose for CNB