List of Anticoagulants

Oct 10, 2009 | By Leigh A. Zaykoski Photo Credit Thinkstock Images/Comstock/Getty Images
Anticoagulants, commonly known as blood thinners, prevent or treat blood clot formation. These drugs can be administered to prevent strokes
and heart attacks caused by blood clots, or they can be used to treat deep vein thrombosis or pulmonary embolism (blood clot in the lungs). These
drugs can cause serious side effects, so it's important to follow all instructions and read the package labels carefully for warnings and important
information.
Warfarin
Warfarin reduces blood clot formation by blocking clotting factors from forming in the blood. This drug is used to prevent strokes, heart attacks
and blood clot formation in the lungs, arteries and veins. Pregnant women should not take warfarin. According to Cerner Multum, the drug is
known to cause birth defects, miscarriages, stillbirths and fetal bleeding. Possible side effects of warfarin include hair loss, vomiting, nausea,
stomach pain, bloating and gas. Seek immediate medical attention for bleeding that will not stop, easy bruising or signs of internal bleeding, such
as black, tarry stools or blood in the urine.
Heparin
Heparin reduces the blood's ability to clot so that clots cannot form in the veins, arteries or lungs. This drug can be used during surgical
procedures that create a high risk of blood clot formation. It can also be used to treat heart, lung and blood vessels conditions that increase the
likelihood of dangerous clots. Patients taking heparin should not take drugs that contain aspirin or ibuprofen, as these drugs can change the way
heparin works and cause serious side effects. Easy bruising and bleeding are the most common side effects of this drug. According to the Mayo
Clinic, heparin can also cause abdominal pain, bleeding from the gums, constipation, dizziness, headaches, joint pain, unexplained nosebleeds
and heavy menstrual periods. If bleeding cannot be controlled or if there is blood in the urine or stool, seek immediate medical treatment.
Clopidogrel
Clopidogrel is used in the prevention or management of strokes and heart attacks. This drug is an anti-platelet drug, which means that it prevents
platelets from sticking together and forming blood clots that can lead to strokes and heart attacks. People with bleeding ulcers, brain bleeds or
other bleeding conditions may not be able to take this drug. According to the National Institutes of Health, clopidogrel can cause headache,
dizziness, stomach pain, nosebleed, diarrhea, nausea and excessive tiredness. Seek immediate medical attention for allergic reactions to
clopidogrel, uncontrollable bleeding or signs of internal bleeding, such as bleeding under the skin or blood in the urine or stool.
Ticlopidine
Ticlopidine is a medication used to prevent strokes by preventing excessive blood clotting. This drug should be used with caution in people who
have liver disease, low blood cell counts, high cholesterol, kidney disease, high triglycerides and bleeding disorders. Patients should inform their
doctors about all prescription and over-the-counter medications they are taking, as well as any vitamins or supplements. Possible side effects of
this drug include diarrhea, stomach pain, gas, itching, upset stomach, vomiting, loss of appetite and headache. Seek immediate medical attention
for unusual bleeding and bruising, skin rash, light-colored stools and signs of infection.
Enoxaparin
Enoxaparin is an anticoagulant used to prevent blood clots in people who are immobile because of major surgery or the need for bed rest. It can
also be used with aspirin to prevent heart attacks or with warfarin to treat the formation of blood clots in the legs. This drug should be used with
caution in people who have or have had heart infections, bleeding disorders, kidney disease, strokes, low platelet counts or ulcers. Enoxaparin
may cause side effects, such as upset stomach, fever and burning or irritation at the injection site. Seek immediate medical attention for black or
bloody bowel movements, unusual bruising, swollen feet and ankles, blood in the urine or unusual bleeding.
Types of Anticoagulants

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An anticoagulant is a substance or agent that interferes, suppresses and/or prevents blood from clotting. The parenteral
anticoagulants commonly prescribed and administered in a hospital setting include heparin and the most frequently prescribed
oral anticoagulant is coumadin.

Anticoagulation medications don't dissolve any blood clots present. But they do stop the enlargement of existing clots and prevent
the development of new ones. These agents exert their effects by interfering with some of the steps involved in the clotting cascade.
Heparin and Its Indications
o Unfractionated heparin is a parenteral anticoagulant that prevents a stable fibrin blood clot from forming, by inactivating thrombin.
It is used for treatment of venous thrombosis and its extension, pulmonary embolism, thromboembolic complications associated
with atrial fibrillation and cardiac valve replacement and arterial thrombosis.
It is also used post MI, to reduce risk of death, recurrent MI and thromboembolic (clotting) events, such as stroke or systemic
embolization (moving clot).
Furthermore, it is use for prevention of clotting during cardiac surgery and in dialysis procedures too.
2. Heparin Counterindications
o Contraindications to heparin therapy include bleeding/hemorrhage, heparin allergy, thrombocytopenia, allergy to beef or pork,
purpura (bruising), intracranial hemorrhage, gastrointestinal bleeding and shock. Also, assessment for adverse reactions should
include bleeding, thrombocytopenia (low platelet count), chills, fever and hives that could be due to a hypersensitivity reaction. In
addition, shock may occur.
3. Reversal of Heparin (Antidote)
o Protamine sulfate, a heparin antidote, will neutralize the effects of heparin if a heparin overdose is suspected. Approximately 1 mg of
protamine will neutralize approximately 100 units of heparin. This medication must be administered via IV very slowly, and the dose
should not exceed 50 mg in a 10-minute period.
Coumadin and Its Indications
o Coumadin is the approved oral anticoagulant and the mechanism of action includes direct inhibition of viatmin K dependent
synthesis. It is used for the prophylaxis and or treatment of venous thrombosis, pulmonary embolism and atrial fibrillation. It is also
used post MI to reduce death risk and further clotting events. It also helps reduce the risks associated with peripheral vascular
disease.
Counterindications of Coumadin
o Coumadin is contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and
may cause fatal hemorrhage to the fetus in utero.
Coumadin Antidote
o Vitamin K laden foods (generally leafy green vegetables) and diuretics (increase clotting factor concentration) reduce the
anticoagulant effect and hypothyroidism decreases anticoagulation effect.
FFP or fresh frozen plasma is indicated for the bleeding patient who cannot wait for the vitamin K to take effect. It should only be
used in emergencies as there are risks associated


Heparin is frequently used in order to prevent life-threatening clotting in many patients, especially those which have had
stent implants on their heart. Unlike some other coagulants, Heparin is a biological substance. Although there are many forms of
production, it is usually made from pig intestines. The mechanism of function is rather simple; it activates antithrombin III,
a substance in our body that blocks thrombin from clotting blood.
Heparin can be administrated by injection or in vitro to prevent blood or plasma clotting in or on medical devices. There are several
forms of Heparin and the most commonly used is called low molecular weight heparin.

Vitamin K antagonists

Also called the common oral anticoagulants, these represent a form of anticoagulants which act by blocking the effects of vitamin K
(which promotes coagulation). They take 48-72 hours to develop to full effect, which is why they shouldnt be used when immediate
effect is required. In these cases, its best to use heparin. Most common indications for this type of anticoagulants are deep-vein
thrombosis (DVT), pulmonary embolism, atrial fibrillation, and mechanical prosthetic heart valves such as stents and different
dilatators!
The most common complication is of course unstoppable bleeding, especially in patients aged 80 or more.

Oral Coagulants

The most important oral anticoagulants are: Warfarin (Coumadin ), Acenocoumarol, Phenprocoumon, and Phenindione.

Direct thrombin inhibitors

Some of the most commonly used medications from this group are Argatroban, Lepirudin, and Bivalirudin.
There was a minor affair with one medication from this group an oral direct thrombin inhibitor called Ximelagatran (Exanta). It
has been proven that it can cause severe liver damage and heart attacks. It was denied approval by the FDA in September 2004.


Cofactors
Various different substances are required for the proper functioning of the coagulation cascade. They are usually called cofactors,
and the most important are Vitamin K, Calcium and phospholipid!

Calcium and phospholipids are required for several complexes to function, especially tenase and prothrombinase. Not only that
calcium is also required at other points in the coagulation cascade.

Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase, an especially important liver enzyme which adds a
carboxyl group to residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z.

Anticoagulants Outside The Body
Our blood is normally filled with anticoagulants but are there any outside of the body? Although we dont think about it, all
laboratory instruments, test tubes, blood transfusion bags, and medical and surgical equipment is covered with anticoagulants. If
there was no anticoagulant on them, they would get clogged up and become non-operational.

Beside heparin, most commonly used anticoagulants are:

EDTA - one of the most commonly used types; it can be normally found on purple caps on Vacutainer brand test tubes. It
works by binding Ca-ions.
Citrate: This anticoagulant is also normally found on blue Vacutainer tubes. It exists in liquid form, which makes it suitable for
coagulation tests.
Ethylene diamine Tetra-acetic Acid (EDTA)
This is the anticoagulant of choice for the FBC. di-Na and di-K salts are solids and tri-Na is the liquid form.
Mode of Action
EDTA chelates calcium ions to form a soluble complex
Uses
Haematology Profile
EDTA blood smears
Concentration
1.5mg/mL +/- 0.35mg/mL
If less blood is collected than fills the complete tube containing the anticoagulant shrinkage of the RBCs and
degenerative changes (eg. swelling of the Plts) will occur - this will affect MCV and Hct etc.
Stability
Blood smears should be made within 3hrs of collection (to avoid changes in morphology)
Disadvantages
EDTA cannot be used for coagulation studies (as it chelates calcium)
Platelets can sometimes be seen to satellite neutrophils
EDTA effects the function of fibrinogen (can sometimes be seen as stranding of fibrin on a blood smear)
Sodium Citrate
This is a liquid anticoagulant.

Mode of Action
Removes calcium ions by forming a soluble calcium citrate complex.

Uses
Coagulation studies 9:1 - blood:citrate
ESR 4:1 - blood:citrate
Reticulocyte count
Heinz body detection
Acts as both a diluent and an anticoagulant
Concentration
0.109mg/mL
Disadvantages
Cannot use for FBC because of the dilution factor
Heparin
This anticoagulant is an acid mucopolysaccharide which is considered to be the anticoagulant of reference for red
cell morphology.

Mode of Action
Stops the formation of thrombin from prothrombin therefore stopping formation of fibrin from fibrinogen

Uses
Enzyme studies
Cell cultures
Osmotic fragility testing
Concentration
15IU/mL +/- 2.5IU/mL

Disadvantages
Relatively Expensive
Can give a blue background to blood films
Platelet aggregation
Glossary
Hb
Haemoglobin. This abbreviation is comonly used to represent the concentration of haemoglobin in the
blood.
Hct
Haematocrit. The Hct is the volume of packed red cells in whole blood, in relation to the total volume of
the whole blood specimen (L/L).
MCV
Mean Cell Volume. The MCV indicates the average cell volume of red cells in femtolitres (fl).
haematocrit (L/L)
MCV (fL) = ------------------
RCC (x 10
12
)
Plt
Platelets. Discoid-shaped, anuclear bodies which are necessary for maintaining the haemostatic
mechanism.
RCC
Red Cell Count. This abbreviation usually refers to the total number of red cells (erythrocytes) in whole
blood (million/mL)

Pharmacology (from Greek , pharmakon, "poison" in classic Greek; "drug" in modern Greek;
and -, -logia "study of", "knowledge of") is the branch of medicine and biologyconcerned with the
study of drug action,
[2]
where a drug can be broadly defined as any man-made, natural, or endogenous
(within the body) molecule which exerts a biochemical and/or physiological effect on the cell, tissue,
organ, or organism. More specifically, it is the study of the interactions that occur between a living
organism and chemicals that affect normal or abnormal biochemical function. If substances
have medicinal properties, they are considered pharmaceuticals.
The field encompasses drug composition and properties, synthesis and drug design, molecular and
cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular
diagnostics, interactions, toxicology, chemical biology, therapy, and medical applications and
antipathogenic capabilities. The two main areas of pharmacology
arepharmacodynamics and pharmacokinetics. The former studies the effects of the drug on biological
systems, and the latter the effects of biological systems on the drug. In broad terms, pharmacodynamics
discusses the chemicals with biological receptors, and pharmacokinetics discusses the absorption,
distribution, metabolism, and excretion (ADME) of chemicals from the biological systems. Pharmacology
is not synonymous with pharmacy and the two terms are frequently confused. Pharmacology, a
biomedical science, deals with the research, discovery, and characterization of chemicals which show
biological effects and the elucidation of cellular and organismal function in relation to these chemicals. In
contrast, pharmacy, a health services profession, is concerned with application of the principles learned
from pharmacology in its clinical settings; whether it be in a dispensing or clinical care role. In either field,
the primary contrast between the two are their distinctions between direct-patient care, for pharmacy
practice, and the science-oriented research field, driven by pharmacology.
Dioscorides' De Materia Medica is often said to be the oldest and most valuable work in the history of
pharmacology.
[3]
The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The
Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the
Antedotary of Nicholas.
[4]
Clinical pharmacology owes much of its foundation to the work of William
Withering.
[5]
Pharmacology as a scientific discipline did not further advance until the mid-19th century
amid the great biomedical resurgence of that period.
[6]
Before the second half of the nineteenth century,
the remarkable potency and specificity of the actions of drugs such
as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical
powers and affinities to certain organs or tissues.
[7]
The first pharmacology department was set up
by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons
produced their effects.
[6]

Early pharmacologists focused on natural substances, mainly plant extracts. Pharmacology developed in
the 19th century as a biomedical science that applied the principles of scientific experimentation to
therapeutic contexts.
[8]
Today Pharmacologists harness the power of genetics, molecular biology,
chemistry, and other advanced tools to transform information about molecular mechanisms and targets
into therapies directed against disease, defects or pathogens, and create methods for preventative care,
diagnostics, and ultimately personalized medicine.


Introduction
In order to analyze the work and development of the wearable artificial kidney and bio-artificial
kidney, it is important to understand the physiology that the organ replacement therapies intend
to replace. This section describes the important aspects of the anatomy, functions, and failure of
the kidney that will help you in analyzing the present and future research endeavors presented in
this site.

Anatomy
The kidneys are a pair of fist sized organs located in the small of the back behind the peritoneum.
Each kidney weighs about 115g-170g and have the following approximate dimensions: 11 cm in
length, 6 cm in width, and 3 cm thick - about the size of a deodorant stick.[3]




Source: Fox S.I., Human Physiology 6th edition, pg. 528
Each kidney is perfused at a rate of 600 ml/min by way of the renal artery [3]. Each renal artery
branches into interlobar arteries, arcuate arteries, interlobular arteries, and then into 1.2 million
afferent arterioles that each feed each nephron, the functional unit of the kidney. After blood has
been filtered through the glomerulus and transported through the nephron's vasculature it passes
through the interlobular, arcuate, and interlobar that merge into the renal vein and back in to
systemic circulation. [2]


The kidney is composed of two regions, the renal cortex and medulla. The cortex is where the
renal corpuscles reside, proximal tubules, and distal tubules are found. The medulla is home to
the loop of Henle, vasa recta, and collecting tubules. Urine from the various collecting ducts
drains into the renal pelvis, ureter, and bladder.

Major functions
The kidneys are often thought of as the body's filters, removing toxins and metabolic waste
products from the body. The kidneys certainly perform this task; however they have a few more
responsibilities, without which we would not be able to survive.


Ultrafiltration
Of the renal blood flow, 125 ml/min is filtered by glomerulus. In one day, the kidney filters
approximately 180 liters of blood and produces 1.5 liters of urine. Thus, it is evident that the
kidneys possess extraordinary mechanisms to reabsorb water while removing metabolic waste by-
products and toxins. [3] Kidney function is measured by the glomerular filtration rate (ml/min)
which is defined as the filtration of a solute that is not reabsorbed nor secreted. The clearance
(mass removal of a solute/concentration of solute) of a solute can also be used to quantify renal
function.

Source: Fox S.I., Human Physiology, 6th edition, pg. 544.


Endocrine Function
The kidneys secrete the following hormones to initiate processes that occur in other parts of the
body:
1. Erythropoietin to stimulate erythrocyte production in bone marrow.
2. The active form of Vitamin D, 1,25-dihydroxyvitamin D3, to aid in gut absorption of calcium for
bone deposition.
3. Renin to help regulate blood volume and potassium balance (described in Volume Regulation).


Osmolarity Regulation
Antidiuretic hormone (ADH or vasopressin) is synthesized in the hypothalamus and released in the
posterior pituitary in response to an increase in osmolarity as sensed by osmoreceptors in the
anterior hypothalamus. The presence of ADH increases the water permeability of the collecting
tubule permitting water reabsorption and a shift towards normal plasma osmolarity. In the
process, concentrated urine is formed. In the absence of ADH, the water permeability of the
collecting tubules is low, more water is excreted in diluted urine, and blood osmolarity returns to
normal.


Volume Regulation
In addition to the kidney being anatomically designed to create concentrated urine in order to
conserve fluid volume, the kidney is also designed to regulate extracellular fluid volume through
the Renin-Angiotensin-Aldosterone (RAA) pathway and Atrial Natriuretic Factor (ANF).
The kidneys initiate the RAA pathway by secreting renin within the lumen of the afferent
arteriole. Renin initiates the cascade of reactions that releases aldosterone from adrenal cortex;
thereby stimulating the reabsorption of Na+ in the collecting tubule lumen. Since sodium is
primarily an extracellular solute, a change in its concentration will lead to a change in
extracellular volume (plasma and interstitial volume).
Atrial Natriuretic Factor (ANF) is secreted by cells in the atria of the heart to inhibit Na+
reabsorption in the kidneys when there is an excess of Na+ and fluid in plasma. It also inhibits
secretion of aldosterone, which also inhibits Na+ reabsorption.


Acid-Base Regulation
Everyday metabolism of proteins and phospholipids generates sulfuric and phosphoric acids,
respectively. In order to maintain a normal physiologic pH, the body maintains a buffer reserve of
bicarbonate ions. The kidneys regenerate this buffer reserve and excrete the acidic metabolic
waste products.