Mohammed Fadel Abdel Mohsen

Babylon University \ College of Nursing \ evening study \ first stage

‫بسم هللا الرحمن الرحيم‬

Babylon University
College of Nursing
evening study first stage

Article: Biochemistry
Student preparation
Mohammed Fadel Abdel Mohsen
Supervision: Dr. Hiba Hussain fadel

Delivery date:3/7/2020

1 Article: Biochemistry \\ Title: Heparin

 Mohammed Fadel Abdel Mohsen
Babylon University \ College of Nursing \ evening study \ first stage

Heparin
What is heparin?
Heparin is a prescription drug. It comes as a self-injectable solution that you
inject under your skin. It also comes as a solution that a healthcare provider
injects intravenously (into one of your veins).

Why it's used:

Heparin is a blood thinner that’s used to treat and prevent blood clots. These
can include venous thrombosis, pulmonary embolism, and peripheral arterial
embolism.

Heparin acts as an anticoagulant, preventing the formation of clots and

extension of existing clots within the blood. While heparin does not break
down clots that have already formed (unlike tissue plasminogen activator), it
allows the body's natural clot lysis mechanisms to work normally to break
down clots that have formed. Heparin is generally used for anticoagulation for
the following conditions:
• Acute coronary syndrome, e.g., NSTEMI
• Atrial fibrillation
• Deep-vein thrombosis and pulmonary embolism
• Cardiopulmonary bypass for heart surgery
• ECMO circuit for extracorporeal life support
• Hemofiltration
• Indwelling central or peripheral venous cath

2 Article: Biochemistry \ \T itle: Heparin

 Mohammed Fadel Abdel Mohsen
Babylon University \ College of Nursing \ evening study \ first stage

How it works:
Heparin belongs to a class of drugs called anticoagulants. A class of drugs is
a group of medications that work in a similar way. These drugs are often used
to treat similar conditions.
Heparin works by disrupting the formation of blood clots in your veins. It can
prevent blood clots from forming, or stop clots that have already formed from
getting larger.
Heparin side effects:
Heparin injectable solution doesn’t cause drowsiness, but it can cause other
side effects.

More common side effects

The more common side effects of this drug include:
• Bruising more easily
• Bleeding that takes longer to stop
• Irritation, pain, redness, or sores at the injection site
• Allergic reactions, such as hives, chills, and fever
• Increased liver enzymes on liver function test results
Allergy warning:
Heparin can cause a severe allergic reaction. Symptoms can include:
• Skin tissue death at the injection site
• Chills
• Fever
• Rash
• Hives
• Itching
• Burning
• Shortness of breath
• Swelling of your face, lips, throat, or tongue
• eters
Pharmacology:
In nature, heparin is a polymer of varying chain size. Unfractionated
heparin (UFH) as a pharmaceutical is heparin that has not been
fractionated to sequester the fraction of molecules with low molecular

3 Article: Biochemistry \ \T itle: Heparin

 Mohammed Fadel Abdel Mohsen
Babylon University \ College of Nursing \ evening study \ first stage

weight. In contrast, low-molecular-weight heparin (LMWH) has

undergone fractionation for the purpose of making its
pharmacodynamics more predictable. Often either UFH or LMWH can
be used; in some situations one or the other is preferable.[35]
Mechanism of action
Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a
conformational change that results in its activation through an
increase in the flexibility of its reactive site loop.[36] The activated AT
then inactivates thrombin, factor Xa and other proteases. The rate of
inactivation of these proteases by AT can increase by up to 1000-fold
due to the binding of heparin.[37] Heparin binds to AT via a specific
pentasaccharide sulfation sequence contained within the heparin
polymer:
GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S)
The conformational change in AT on heparin-binding mediates its
inhibition of factor Xa. For thrombin inhibition, however, thrombin must
also bind to the heparin polymer at a site proximal to the
pentasaccharide. The highly negative charge density of heparin
contributes to its very strong electrostatic interaction with thrombin.[21]
The formation of a ternary complex between AT, thrombin, and
heparin results in the inactivation of thrombin. For this reason, heparin's
activity against thrombin is size-dependent, with the ternary complex
requiring at least 18 saccharide units for efficient formation.[38] In
contrast, antifactor Xa activity via AT requires only the
pentasaccharide-binding site.
Administration:

4 Article: Biochemistry \ \T itle: Heparin

 Mohammed Fadel Abdel Mohsen
Babylon University \ College of Nursing \ evening study \ first stage

Heparin is given parenterally because it is not absorbed from the gut,

due to its high negative charge and large size. It can be injected
intravenously or subcutaneously (under the skin); intramuscular
injections (into muscle) are avoided because of the potential for
forming hematomas. Because of its short biologic half-life of about one
hour, heparin must be given frequently or as a continuous infusion.
Unfractionated heparin has a half-life of about one to two hours after
infusion,[40] whereas LMWH has a half-life of four to five hours.[41] The
use of LMWH has allowed once-daily dosing, thus not requiring a
continuous infusion of the drug. If long-term anticoagulation is required,
heparin is often used only to commence anticoagulation therapy until
an oral anticoagulant e.g. warfarin takes effect.
The American College of Chest Physicians publishes clinical guidelines
on heparin dosing.[42
Natural degradation or clearance:
Unfractionated heparin has a half-life of about one to two hours after
infusion,[40] whereas low-molecular-weight heparin's half-life is about
four times longer. Lower doses of heparin have a much shorter half-life
than larger ones. Heparin binding to macrophage cells is internalized
and depolymerized by the macrophages. It also rapidly binds to
endothelial cells, which precludes the binding to antithrombin that
results in anticoagulant action. For higher doses of heparin, endothelial
cell binding will be saturated, such that clearance of heparin from the
bloodstream by the kidneys will be a slower process.[43]
Chemistry
Heparin structure

Ball-and-stick model of heparin

5 Article: Biochemistry \ \T itle: Heparin

 Mohammed Fadel Abdel Mohsen
Babylon University \ College of Nursing \ evening study \ first stage

Native heparin is a polymer with a molecular weight ranging from 3 to

30 kDa, although the average molecular weight of most commercial
heparin preparations is in the range of 12 to 15 kDa.[44] Heparin is a
member of the glycosaminoglycan family of carbohydrates (which
includes the closely related molecule heparin sulfate) and consists of a
variably sulfated repeating disaccharide unit.[45] The main
disaccharide units that occur in heparin are shown below. The most
common disaccharide unit is composed of a 2-O-sulfated iduronic
acid and 6-O-sulfated, N-sulfated glucosamine, IdoA(2S)-Glens'(6S). For
example, this makes up 85% of heparins from beef lung and about 75%
of those from porcine intestinal mucosa.[46]

Not shown below are the rare disaccharides containing a 3-O-sulfated

glucosamine (GlcNS(3S,6S)) or a free amine group (GlcNH3+). Under
physiological conditions, the ester and amide sulfate groups are
deprotonated and attract positively charged counterions to form a
heparin salt. Heparin is usually administered in this form as an
anticoagulant.

Sources:
https://www.healthline.com/health/heparin-injectable-solution
https://en.m.wikipedia.org/wiki/Heparin

6 Article: Biochemistry \ \T itle: Heparin