BULLETIN

25th July 2014

Heparin vs Enoxaparin vs Fondaparinux

In Post Delivery
Background:
For many years, unfractionated heparin (UFH) was the mainstay of anti-coagulation therapy for treatment and prevention of thrombosis. Newer agents with more predictable pharmacokinetics profiles
such as the low molecular weight heparins ( LMWHs ) and fondaparinux, have proven to be just as effective for the same indications as heparin. Currently has two LMWHs formulary, Dalteparin and Enoxaparin. Although these agents share similarities, differences in their mechanism of action, pharmacokinetic
profiles, contraindications.

Mechanism of Action
Heparin:
Binds to and potentiates the actions of anti-thrombin (AT) to inactivate
factor Xa and prevent the conversion of prothrombin to thrombin, as well
as prevent the conversion of fibrinogen to fibrin. Binds to and potentiates
the actions of anti-thrombin (AT) to inactivate factor Xa and prevent the
conversion of prothrombin to thrombin, as well as prevent the conversion
of fibrinogen to fibrin.

LMWHs ( Dalteparin and Enoxaparin )

Fondaparinux

LMWHs bind and accelerate the activity of

AT, but with a preferential, and longer lasting
effect on factor Xa. When compared to heparin, LMWHs are less able to inhibit the production of thrombin and bind to plasma proteins and endothelial cell less due to their
decreased sized. This accounts for an 85-99%
bioavailability when administered subcutaneous, more predictable anti-coagulant response, less inter-patient variability, and
longer duration of action than heparin.

Fondaparinux binds and enhances the antiXa activity of AT by 300 fold. AT specificity
does not allow binding to other plasma proteins. It has no direct effect on thrombin,
has excellent bioavailability after subcutaneous administration and a long half-life.

Comparison of Pharmacokinetic Parameters, and Indications

for
Heparin, Enoxaparin, & Fondaparinux
Heparin

Enoxaparin

Fondaparinux

Mechanism

Enhances AT effects
on Factor Xa and
thrombin.
Binds non-specifically
to plasma protein
and cause unpredictable dose response.

Enhances AT effects
more selectively on
Factor Xa than on
thrombin.
Less binding to plasma protein, so more
predictable dose response, less interpatient variability.

Enhances anti-Xa activity of AT

Specificity for AT so no
binding to other plasma
proteins, good predictability

Half-Life

1-2 hours

4.5 7 hours

17 - 21 hours

Clearance

Hepatic and Reticulo- Renal

endothelial system
Adjust for CrCl < 30
No renal adjustments mL/min

Renal
Contraindicated in CrCl
< 30 mL/min

Pregnancy

OK

OK

CI Insufficient data
Case reports available

Breast Feeding

OK ( does not pass

into breast milk )

Unknown if excreted
in breast milk

Ability to
cause HIT

YES

OK (Low bioavailability when ingested

orally )
YES

Use in HIT
treatment

NO

NO

Yes

Images

No in vitro cross reactivity to anti-PF4/

heparin antibodies
Case reports

Why Heparin is Needed for Pregnant Women?

Pregnancy requires special consideration with respect to the prevention and treatment of blood clots. Pregnancy does not cause blood
clots, but increases the chance that a blood clot will develop by fourto five-fold.
Pregnancys tendency to form clots is an evolutionary response to
protect women against the bleeding challenges of miscarriage and
childbirth.

In general:

Women who have had a blood clot in the past and are on anticoagulation
will need to continue their anticoagulation during pregnancy.
Most women who have had a blood clot in the past, but are not currently
on anticoagulation, will need to be restarted on anticoagulation during
pregnancy.
Women who develop a blood clot during pregnancy will need to be started on anticoagulation.

Warfarin,

the most commonly prescribed anticoagulant, or the new oral anticoagulants

(dabigatran, rivaroxaban and apixaban), are convenient to take because they do not have to
be injected, but they are not considered safe for unborn babies.
Heparin LMWH are safe in pregnancy because they do not cross the placenta and, therefore,
do not enter the blood stream of unborn babies. In fact, in women who have thrombophilia,
heparin or LMWH may actually improve the outcome of pregnancy in women who have had a
previous pregnancy that was complicated by severe high blood pressure of pregnancy
(severe preeclampsia).
Heparin and LMWH have been used in pregnancy by thousands of women with no birth defects
or bleeding problems in their unborn babies. Whether women are treated with heparin, or
LMWH, they will ultimately need to receive once or twice-daily injections until at least 6 weeks
after delivery of the baby.

Why heparin is taken twice a day?

For most of the patients after delivery, one shot daily of heparin injection is more convenient for them as they are preferred to lay down and rest. But twice shots of daily
heparin injection will increase the efficiency of the heparin in anticoagulant properties.
Twice shots of heparin do reduce the thrombus size in Vein Thromoembolism (VTE) patients.

Managements

During heparin management, patients delivery should beware of any bleeding occur.
Occurrence of bleeding may indicates excessive in taking heparin, which will cause blood become
thinner and promotes bleeding. Patients are advised to go to hospital to treat the bleeding.
During heparin treatment, patients will have fatigue feel and muscles numbness. Patients are also
has tremors. These are causes by low potassium level in the blood. Heparin will lower the potassium level in the blood, which will lead to hypokalemia. Hence, patients after delivery who receiving
heparin treatment should have accompany by a person to aids in their daily activities.
Patients should be monitored to ensure allergic response occurs on the patients after delivery. If
allergic response does occur, replacement of heparin should be considered with other anticoagulants, such as Warfarin.

Missed Dose of Heparin Injection

Reasons of patients after delivery to miss heparin injection may included:
Patients start to work and missed a dose of injection.
Patients are resting or sleep and forget to have following heparin injection.
Patients feel not convenient to go to nearby health facilities for follow-up heparin injection.
Patients are not compliance due to irritating feel of injection, hence reject injection.

PS: If patients are missed a dose of injection in twice shot of daily heparin treatment,
take the injection immediately. If the time is near the time to take second dose, skip the
dose and take the second dose of heparin injection.

Interactions

Complications

Taking of certain medicines will increase the risk of

bleeding, which are:

1. Hemorrhage

Non-steroidal anti-inflammatory (NASIDs), eg:

Ibuprofen, Aspirin, Diclofenac

Anticoagulant, eg: Warfarin, Low Molecular

Weight Heparin

Excessive in taking heparin injection will leads to hemorrhagic event. Bleeding will occurs in patients after delivery who taking heparin injection. Symptoms will appear
in hemorrhagic effect are nose bleeding, appearance of
hematoma and prolonged bleeding from wounds.

While certain drugs may decrease the efficiency of

the heparin, which are:

If such hemorrhagic event occurs, patients should stop

heparin injection immediately and visit doctors for antocoagulating treatment.

Nicotine (smoking)

2. Hypersensitivity

Benzodiazepine, eg: clonazepam, diazepam

It is rare, but hypersensitivity response will appear on

certain patients after delivery who allergic to the heparin. Symptoms will appear such as rashes, headache, rhinitis and nausea. In severe condition, shock will be occurred.

Digitalis, eg: digitoxin, digoxin

Stop the heparin injection and visit doctor for alternative

treatment.

References
Article:
1. Formulary Flash, Volume 09, Issue 1, Heparine vs LMWH vs Fondaparinux, What is the difference?,
February 12, 2009.
2. Once versus twice daily heparin for initial treatment of venous thromboembolism, written by Peng
Wong, 07/2013

Website:
1. http://www.rcog.org.uk/womens-health/clinical-guidance/venous-thrombosis-pregnancy-and-afterbirth
2. http://www.drugs.com/cons/heparin-intravenous-subcutaneous.html
Heparin (Intravenous route, Subcutaneous route)
3. http://www.netdoctor.co.uk/heart-and-blood/medicines/heparin-injection.html
Heparin Injection, 7/2/2007