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
clopidogrel,
telet drugs include
used antiplatelet drug. Examples of other oral antipla
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
:
.
1-Vitamin K antagonists: Inhibit the activation of the vitamin K-dependent
clotting factors. The degree of depression of clotting factors is dose-dependent. The
only vitamin K antagonist available in Hong Kong is warfarin
.
2-Direct thrombin inhibitors (DTIs): Bind with thrombin which is the central
effector of coagulation to inactivate thrombin. Example includes dabigatran
etexilate
.
3-Direct factor Xa inhibitors: Bind to clotting factor Xa specifically to block
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
:
1-COX-1 inhibitor: Potent antiplatelet which inhibits platelet cyclooxygenase
(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 antagonists
2
-
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
.
3-Phosphodiesterase inhibitors: Inhibit adenosine uptake and cyclic GMP
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
rs
Direct thrombin inhibito
-
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
headache
dizziness
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
.
5-P2Y12 receptor antagonists
Examles :-
(
i) Thienopyridine
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
(
ii) Adenosine triphosphate analogue
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
6-Phosphodiesterase inhibitors
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