Oral Anticoagulants and Antiplatelet Drugs

Blood clotting, or coagulation, is an important process that prevents excessive

bleeding when a blood vessel is injured. Platelets and protein (clotting factors) in your
plasma work together to stop the bleeding by forming a clot over the wound.
Sometimes, however, clots form on the inside of vessels without an obvious injury or
do not dissolve naturally. These situations can be dangerous and require accurate
.diagnosis and appropriate treatment including the use of a blood thinner

If you have some kinds of heart or blood vessel disease, or if you have poor blood
flow to your brain, your doctor may recommend that you take a blood thinner. Blood
thinners reduce the risk of heart attack and stroke by reducing the formation of blood
clots in your arteries and veins. You may also take a blood thinner if you have an
abnormal heart rhythm called atrial fibrillation, heart valve disease, or congenital
.heart defects

:Treatment with blood thinners

There are two types of blood thinners – anticoagulants and antiplatelet drugs.
Anticoagulants work by interfering with blood protein to lengthen the time it takes to
form a blood clot. Antiplatelet drugs prevent blood cells called platelets from
clumping together to form a clot. Both types of drugs are effective in keeping a clot
..from forming or stopping the growth of a clot

All registered anticoagulants in Hong Kong are prescription-only medicines and

should be administered strictly under doctor’s instruction and recommendation. Some
are available in oral dosage forms such as tablets and capsules, while others are only
available in injectable forms. There are four oral anticoagulants available in Hong
Kong, including the traditional drug warfarin, and the newer drugs dabigatran
..etexilate, apixaban, and rivaroxaban

Anticoagulants are considered more aggressive drugs than antiplatelet drugs. They are
recommended primarily for people with a high risk of stroke and people with atrial
fibrillation (a heart condition that causes a irregular heart rate). Other people with
blood that clots easily, such as those who have deep vein thrombosis (blood clots in
the deep veins of the legs) or pulmonary embolism (a blood clot in the lungs), may
.also benefit from anticoagulant therapy
All registered antiplatelet drugs in Hong Kong are prescription-only medicines except
aspirin. Some are available in oral dosage forms such as tablets and capsules, while
others are only available in injectable forms. Low-dose aspirin is the most commonly
used antiplatelet drug. Examples of other oral antiplatelet drugs include clopidogrel,
.ticlopidine, dipyridamole, prasugrel, and ticagrelor

Low-dose aspirin is highly recommended for preventing a first stroke, but it and other
antiplatelet drugs also have an important role in preventing recurrent strokes.
Antiplatelet drugs may also be given if you have had acute coronary syndrome (heart
.attack or unstable angina) or a coronary stent

Classification of blood thinners

Anticoagulants and antiplatelet drugs can be classified according to their mechanism
. of action Anticoagulants

Anticoagulants interfere with various clotting factors in the coagulation process to

:slow down the process. Oral anticoagulants can be classified as follows

Vitamin K antagonists: Inhibit the activation of the vitamin K-dependent -1 .

clotting factors. The degree of depression of clotting factors is dose-dependent. The
.only vitamin K antagonist available in Hong Kong is warfarin

Direct thrombin inhibitors (DTIs): Bind with thrombin which is the central -2
effector of coagulation to inactivate thrombin. Example includes dabigatran
.etexilate

Direct factor Xa inhibitors: Bind to clotting factor Xa specifically to block -3

.its activity. Examples include apixaban and rivaroxaban

:Antiplatelet Drugs
Antiplatelet drugs describe agents which decrease platelet aggregation and inhibit
thrombus (clot) formation. Platelet activation process involves the production of
several platelet activation agonists including thrombin, thromboxane A2 (TXA2) and
adenosine diphosphate (ADP), which amplify the platelet response and stimulate
:platelet aggregation. Oral antiplatelet drugs can be classified as follows
COX-1 inhibitor: Potent antiplatelet which inhibits platelet cyclooxygenase -1
(COX), a key enzyme in the generation of TXA2 which is responsible for platelet
.activation and aggregation. The main member of this class is aspirin

P2Y12 receptor antagonists2-2

A-Thienopyridine: Act by inhibiting the ADP-dependent pathway of platelet

.activation. Examples include ticlopidine, clopidogrel and prasugrel

B-Adenosine triphosphate analogue: Reversibly interact with the P2Y12

receptor to inhibit the receptor to prevent ADP-induced platelet aggregation. Example
.includes ticagrelor

Phosphodiesterase inhibitors: Inhibit adenosine uptake and cyclic GMP -3

phosphodiesterase activity, thus decreases platelet aggregability. Phosphodiesterase
inhibitor alone has little antiplatelet effect and is currently used in combination with
.other drugs. Example includes dipyridamole

Common side effects and precautions of Anticoagulants

Vitamin K antagonist-1

Hemorrhages, nausea and vomiting, diarrhea, jaundice, hepatic dysfunction

.pancreatitis, pyrexia, alopecia, rash

Use with caution in mild to moderate renal impairment. Monitor INR more *
frequently in severe impairment

Not recommended for patients with severe hepatic impairment, or in first trimester *
of pregnancy

Regular blood test to check how long it takes for your blood to clot (INR test) and *
dose may need to be adjusted

Direct thrombin inhibitors-2

hemorrhages, nausea, diarrhoea , dyspepsia, abdominal pain, anaemia

Use with caution in the elderly and in patients with low body weight

Use with caution in patients with bleeding disorders, thrombocytopenia, recent biopsy
or major trauma, oesophagitis, gastritis and oesophageal reflux
Use with caution in patients taking concomitant drugs that increase risk of bleeding

Not recommended for patients with active bleeding, or at significant risk of major
bleeding, or with severe hepatic and renal impairment

Not recommended in pregnancy or breastfeeding

Direct factor Xa inhibitors-3

hemorrhages nausea bruising anaemia Example:- Apixaban:-causing

-:Rivaroxaban

Dyspepsia constipation diarrhoea nausea and vomiting hemorrhage abdominal pain

headachedizziness

Use with caution in patients at risk of bleeding, or taking concomitant drugs

that increase risk of bleeding

Not recommended for patients with active bleeding, or at significant risk of major
bleeding, or with severe renal or hepatic impairment

Not recommended in pregnancy or breastfeeding

-Antiplatelet Drugs 4

Example:-COX-1 inhibitor

bronchospasm

gastro-intestinal irriation such as nausea

gastro-intestinal haemorrhage

other haemorrhage (e.g. subconjunctival)

Use with caution in patients with renal impairment, and during third trimester of
pregnancy

Use with caution in patients with asthma, uncontrolled hypertension, previous peptic
ulceration, concomitant use of drugs that increase risk of bleeding, G6PD deficiency,
dehydration and elderly patients

Not recommended for patients with severe hepatic or renal impairment, with active
peptic ulceration, haemophilia and other bleeding disorders, or with previous history
of hypersensitivity to aspirin or other non-steroidal anti-inflammatory drugs (NSAID)

Not recommended in breastfeeding

P2Y12 receptor antagonists-5 .

-: Examles

Thienopyridine )i(

Haemorrhage, rash gastrointestinal disturbances, such as dyspepsia,

abdominal pain, diarrhea (common for ticlopidine and more frequent for geriatric
patients)

blood dyscrasia (most common for ticlopidine)

Use with caution in patients with renal or hepatic impairment; avoid use in those with
severe hepatic impairment

Use with caution in patients at increased risk of bleeding, or with concomitant use of
drugs that increase risk of bleeding

Not recommended for patients with active bleeding

Not recommended in pregnancy and breastfeeding

Regular blood test for ticlopidine therapy for signs of blood dyscrasia

Adenosine triphosphate analogue )ii(

haemorrhage

dyspnoea

bruising

Use with caution in patients at increased risk of bleeding, or with concomitant use of
drugs that increase risk of bleeding, with cardiac conduction problem, asthma, chronic
obstructive pulmonary disease

Not recommended for patients with active bleeding or history of intracranial

haemorrhage

Not recommended in pregnancy or breastfeeding

Monitor renal function 1 month after initiation

Phosphodiesterase inhibitors-6

gastrointestinal effects dizziness myalgia throbbing headache hypotension rash

severe bronchospasm and angioedema increased bleeding during or after surgery

Use with caution in rapid worsening of angina, aortic stenosis, recent myocardial
infarction, heart failure
Use with caution in patients with concomitant use of drugs that increase risk of
bleeding

Use with caution in pregnancy or breastfeeding

General advice

Take warfarin once a day at the same time each day as prescribed, usually in the
.evening

If you accidentally miss a dose of warfarin, never take a double dose to catch up
.(unless specifically advised by a doctor)

If you forgot to take your dose of antiplatelet drug, take the dose as soon as you
remember, then continue to take your course as normal. Never double dose to make
.up for a missed dose

.Take antiplatelet drugs with or after food to help reduce irritation to the stomach

,When you are taking warfarin

Avoid binge drinking or getting drunk as doing this can increase the effect of warfarin
.and so increase the risk of bleeding

Maximum daily limit is three units of alcohol a day for man and two units a day for
woman. One unit is roughly equivalent to half a pint of beer or a single measure
.(25ml) of a spirit such as vodka

Avoid situations that increase your risk of injury (e.g. sports that involve physical
.contact with other people)

Seek immediate medical attention if you are bleeding a lot or it takes a long time for
.bleeding to stop

Get medical help if you have a hard blow to the head as you may have bleeding inside
.without knowing it

Communication with your doctor

When you start taking warfarin as prescribed, tell your doctor about any medications
or supplements that you are taking. Lots of herbal medicines and supplements can
interact with warfarin. Do not start taking any new herbal medicines or supplements
without checking with your doctor. Examples of such herbal medicines and
supplements include dong quai, glucosamine, ginkgo biloba, ginseng, St. John’s wort,
.evening primrose oil, etc

If you receive new prescriptions from someone other than your usual medical
provider, make sure you remind him that you are taking an anticoagulant or
.antiplatelet drug as the drugs may interact with each other

Consult your doctor before making any major changes to your diet. Some foods
contain large amounts of vitamin K and can interact with the effect of warfarin if
eaten in large amounts. Examples include liver, green leafy vegetables such as
.broccoli and spinach, cranberry juice, garlic, black licorice and soybean

Tell your healthcare provider you are taking warfarin before you have any medical or
.dental procedures. Warfarin should usually be stopped 5 days before elective surgery

Seek advice promptly if you become pregnant or are planning a pregnancy as warfarin
can be harmful to a baby, especially in the first trimester of pregnancy; aspirin
increases the risk of bleeding during the third trimester of pregnancy; and some drugs
.should be altogether avoided in pregnancy

Tell your doctor if you are breastfeeding as some antiplatelet drugs are not
.recommended for use in breastfeeding women

Inform your doctor of your medical history as special precautionary measures may be
.warranted if you have certain diseases

Watch out for any unusual and serious side effects that develop. If you experience any
.such symptoms, contact your doctor immediately

Communicate with your doctor for the best treatment option. Your doctor will
prescribe the most appropriate drugs for you after considering your condition and
.your response to the drugs
Storage of anticoagulants and antiplatelet drugs

Anticoagulants and antiplatelet drugs should be kept in a cool and dry place. Unless
specified on the label, medicines should not be stored in refrigerators. Furthermore,
drugs should be kept properly in places unreachable by children to prevent accidental
ingestion