dis heparin
DESCRIPTION
hTRANSCRIPT
25th July 2014
BULLETIN
Heparin vs Enoxaparin vs Fondaparinux
In Post Delivery
Background:
For many years, unfractionated heparin (UFH) was the mainstay of anti-coagulation therapy for treat-
ment 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 effec-
tive for the same indications as heparin. Currently has two LMWHs formulary, Dalteparin and Enoxapa-
rin. 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 )
LMWHs bind and accelerate the activity of
AT, but with a preferential, and longer lasting
effect on factor Xa. When compared to hepa-
rin, LMWHs are less able to inhibit the pro-
duction of thrombin and bind to plasma pro-
teins and endothelial cell less due to their
decreased sized. This accounts for an 85-99%
bioavailability when administered subcuta-
neous, more predictable anti-coagulant re-
sponse, less inter-patient variability, and
longer duration of action than heparin.
Fondaparinux
Fondaparinux binds and enhances the anti-
Xa activity of AT by 300 fold. AT specificity
does not allow binding to other plasma pro-
teins. It has no direct effect on thrombin,
has excellent bioavailability after subcuta-
neous administration and a long half-life.
Comparison of Pharmacokinetic Parameters, and Indications
for
Heparin, Enoxaparin, & Fondaparinux
Heparin Enoxaparin Fondaparinux
Images
Mechanism Enhances AT effects on Factor Xa and thrombin. Binds non-specifically to plasma protein and cause unpredict-able dose response.
Enhances AT effects more selectively on Factor Xa than on thrombin. Less binding to plas-ma protein, so more predictable dose re-sponse, less inter-patient variability.
Enhances anti-Xa ac-tivity of AT
Specificity for AT so no binding to other plas-ma
proteins, good predict-ability
Half-Life 1-2 hours 4.5 – 7 hours
17 - 21 hours
Clearance Hepatic and Reticulo-endothelial system
No renal adjustments
Renal Adjust for CrCl < 30 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 )
OK (Low bioavailabil-ity when ingested orally )
Unknown if excreted in breast milk
Ability to cause HIT
YES YES No in vitro cross reac-tivity to anti-PF4/heparin antibodies
Case reports
Use in HIT treatment
NO NO Yes
Why Heparin is Needed for Pregnant Women?
Pregnancy requires special consideration with respect to the preven-
tion and treatment of blood clots. Pregnancy does not cause blood
clots, but increases the chance that a blood clot will develop by four-
to five-fold.
Pregnancy’s 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 start-
ed 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.
For most of the patients after delivery, one shot daily of heparin injection is more con-venient 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) pa-tients.
Why heparin is taken twice a day?
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 potassi-um 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 anticoagu-
lants, such as Warfarin.
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
Taking of certain medicines will increase the risk of bleeding, which are:
Non-steroidal anti-inflammatory (NASIDs), eg:
Ibuprofen, Aspirin, Diclofenac
Anticoagulant, eg: Warfarin, Low Molecular
Weight Heparin
While certain drugs may decrease the efficiency of the heparin, which are:
Nicotine (smoking)
Benzodiazepine, eg: clonazepam, diazepam
Digitalis, eg: digitoxin, digoxin
Complications
1. Hemorrhage
Excessive in taking heparin injection will leads to hemor-rhagic event. Bleeding will occurs in patients after deliv-ery who taking heparin injection. Symptoms will appear in hemorrhagic effect are nose bleeding, appearance of hematoma and prolonged bleeding from wounds.
If such hemorrhagic event occurs, patients should stop
heparin injection immediately and visit doctors for anto-
coagulating treatment.
2. Hypersensitivity
It is rare, but hypersensitivity response will appear on certain patients after delivery who allergic to the hepa-rin. Symptoms will appear such as rashes, headache, rhi-nitis and nausea. In severe condition, shock will be oc-curred.
Stop the heparin injection and visit doctor for alternative
treatment.
Man
age
me
nts
Missed Dose of Heparin Injection
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-after-
birth 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
References