Haematology drugs

Drugs in medical terms refer to as ‘medicines’-substances that can cure

or arrest a disease, relieve symptoms, ease pain, and provide other
benefits. This definition includes any vitamins and minerals that maybe
given to correct deficiency disease. Powerful drugs often have marked
adverse effects. Drugs are classified as specific names for example, the
generic, brand and chemical names. Brand names are usually chosen
by the manufacturers, generic name is mainly based on active
substances in it and the chemical name is mainly the technical
description of the drug. Drugs with less potential to cause harm are sold
over the counter pharmacies but more powerful drugs according to the
MHRA (medicines and healthcare products regulatory agency) has ruled
cannot be used without medical supervision meaning it requires the
doctor’s prescription. Haematological drugs act on blood and blood
forming organs and those that effect the homeostatic system. The main
five haematological drugs are as follow:
Heparin: Its brand names are Calciparin, Monoparin, Multiparin; low
molecular weight heparins [LMWH] Clexane, Clivarine, Fragmin,
Innohep, Zibor.
Heparin is an anticoagulant drug used to prevent the formation of and
aid in the dispersion of blood clots. This drug acts very quickly and is
particularly useful in emergencies to prevent further clotting when the
clot has already reached the lungs or the brain. People with open heart
surgeries and kidney dialysis are also given heparin. A low does is
sometimes given following surgery to prevent developing (DVT) deep
vein thrombosis (clots in the leg veins). Heparin is often given in
conjunction with other slower acting anticoagulants, such as Warfarin. It
is also used to treat angina.
Complications: The most serious side effect, as with all the
anticoagulants is excessive bleeding, so blood clotting ability is watched
very carefully. Bruising may occur around the injection site. Its prolonged
use may develop osteoporosis and hair loss may occur as well. It’s very
rare but tolerance to heparin may develop as well. (O’Shaughnessy
2011).
Image 1 by O’Shaughnessy (2011).
Monitoring: As monitoring is required after the use or while taking
heparin, blood test and liver function test will be required. Its overdose
rate is very high.
Administration: It’s administered via injection. Its dosage range is
determined by the nature of the condition being treated or prevented.
The frequency and timings of the doses is every 8-10 hours or
continuous intravenous infusion: once daily. Its onset of effect is within
15 minutes. The duration of its action stays for 4-12 hours after the
treatment is stopped and 24 hours after the end of the treatment.
Warfarin: Warfarin has anticoagulant effects due to being an
oral vitamin K antagonist. Warfarin is the anticoagulant of choice for the
prevention of thromboembolic events in patients with mechanical heart
valves and valvular atrial fibrillation, as well as in patients with end-
stage renal failure. Several brands of warfarin exist including Coumadin,
Marevan, and many more internationally. (Geeky medics)

Mechanism of action: Warfarin exerts its effect through antagonising

vitamin K, which is responsible for synthesising vitamin K-dependent
clotting factors II, VII, IX and X, as well as proteins C and S.
The mnemonic “2 + 7 = 9, not 10” can be used to remember the vitamin
K-dependent clotting factors.

DOACs, by contrast, directly inhibit a single blood clotting factor:

 Dabigatraninhibits thrombin
 Rivaroxaban, apixaban and edoxaban inhibit activated factor Xa
(Geeky medics)
Indications & contraindications
Indications for warfarin include:

 Treatment of venous thromboembolism (deep vein thrombosis and

pulmonary embolism)
 Atrial fibrillation: if anticoagulation is indicated for prophylaxis of
systemic embolisation
 Rheumatic heart disease: for prophylaxis of systemic embolisation
 Mechanical heart valves: for prophylaxis of systemic embolisation
and valve thrombosis
 Mitral valve disease, irrespective of valve replacement, for
prophylaxis of systemic embolisation
 Inherited, symptomatic thrombophilia
Contraindications for warfarin include:

 Malignancy (heparin or a DOAC must be used in this instance)

 Known hypersensitivity to warfarin or its ingredients
 Haemorrhagic stroke
 Clinically significant bleeding
 Potential bleeding lesions (e.g. active peptic ulcer, oesophageal
varices)
 Uncorrected major bleeding diathesis (e.g. haemophilia, chronic
kidney disease)
 Pregnancy, due to the risk of congenital malformations and fetal
death (breastfeeding is allowed)
 Within 72 hours of major surgery with the risk of severe bleeding
 Within 48 hours postpartum
 Uncontrolled severe hypertension
 Patient factors (e.g. uncooperative, unreliable and/or high risk of
repeated falls)
 Drugs with which there is a significantly increased risk of bleeding
(e.g. antiplatelet drugs*, non-steroidal anti-inflammatory drugs,
and enzyme inhibitors)
*Concomitant use of aspirin and other antiplatelets with warfarin may be
indicated in a small selection of patients, after careful instruction by their
specialists with haematology input as appropriate (e.g. <12 months post-
acute coronary syndrome after the insertion of a drug-eluting
stent). However, in most other circumstances, if warfarin therapy is
indicated, aspirin is discontinued.

Side effects: The most common side effect of warfarin is haemorrhage.

This may manifest as easy bruising, epistaxis and bleeding for longer
than expected with simple wounds. Life-threatening bleeding can occur
including prolonged epistaxis, haematemesis, haematochezia, melaena,
haemoptysis, haematuria, and menorrhagia. Additionally, intracranial
haemorrhage must be excluded following a head injury. Other side
effects include hypersensitivity, rash, and alopecia.

Fondaparinux:
Drug Action: Fondaparinux sodium is a synthetic pentasaccharide that
inhibits activated factor X.

Indications and dose: Prophylaxis of venous thromboembolism in

patients after undergoing major orthopaedic surgery of the hip or leg, or
abdominal surgery

By subcutaneous injection
 For Adult 
Initially 2.5 mg, dose to be given 6 hours after surgery, then 2.5 mg
once daily. Prophylaxis of venous thromboembolism in medical
patients immobilised because of acute illness
 2.5 mg once daily. Treatment of superficial-vein thrombosis

By subcutaneous injection
 For Adult (body-weight 50 kg and above) 
2.5 mg once daily for at least 30 days (max. 45 days if high risk of
thromboembolic complications), treatment should be stopped 24
 hours before surgery and restarted at least 6 hours post
operatively.
Treatment of unstable angina and non-ST-segment elevation myocardial
infarction

By subcutaneous injection
 For Adult 
2.5 mg once daily for up to 8 days (or until hospital discharge if
sooner), treatment should be stopped 24 hours before coronary
artery bypass graft surgery (where possible) and restarted 48
hours post operatively.
Treatment of ST-segment elevation myocardial infarction

Initially by intravenous injection, or by intravenous infusion

 For Adult 
Initially 2.5 mg daily for the first day, then (by subcutaneous
injection) 2.5 mg once daily for up to 8 days (or until hospital
discharge if sooner), treatment should be stopped 24 hours before
coronary artery bypass graft surgery (where possible) and
restarted 48 hours post operatively.
Treatment of deep-vein thrombosis and pulmonary embolism

By subcutaneous injection
 For Adult (body-weight up to 50 kg) 
5 mg every 24 hours, an oral anticoagulant (usually warfarin) is
started at the same time as fondaparinux (fondaparinux should be
continued for at least 5 days and until INR ≥ 2 for at least 24
hours).
 For Adult (body-weight 50–100 kg) 
7.5 mg every 24 hours, an oral anticoagulant (usually warfarin) is
started at the same time as fondaparinux (fondaparinux should be
continued for at least 5 days and until INR ≥ 2 for at least 24
hours).
  For Adult (body-weight 101 kg and above) 
10 mg every 24 hours, an oral anticoagulant (usually warfarin) is
started at the same time as fondaparinux (fondaparinux should be
continued for at least 5 days and until INR ≥ 2 for at least 24
hours).
Contraindications: Active bleeding; bacterial endocarditis
Caution: Active gastro-intestinal ulcer disease; bleeding disorders; brain
surgery; elderly patients; low body weight; ophthalmic surgery; recent
intracranial haemorrhage; risk of catheter thrombus during percutaneous
coronary intervention; spinal or epidural anaesthesia (risk of spinal
haematoma—avoid if using treatment doses for venous
thromboembolism); spinal surgery
Interactions:
Individual interactants:
Fondaparinux 
 https://bnf.nice.org.uk/interaction/fondaparinux.html
Side effects:
Common or very common: Anaemia; haemorrhage
Uncommon: Chest pain; coagulation disorder; dyspnoea; fever; hepatic
function abnormal; nausea; oedema; platelet abnormalities; skin
reactions; thrombocytopenia; vomiting; wound secretion.
Rare or very rare:
Anxiety; confusion; constipation; cough; diarrhoea; dizziness; drowsines
s; fatigue; gastritis; gastrointestinal discomfort; genital
oedema; headache; hyperbilirubinaemia; hypersensitivity; hypokalaemia; 
hypotension; leg pain; post procedural
infection; syncope; vasodilation; vertigo
Pregnancy: Manufacturer advises avoid unless potential benefit
outweighs possible risk—no information available. Present in milk
in animal studies—manufacturer advises avoid.
Hepatic impairment:
 When used for Venous thromboembolism, unstable angina, non-
ST-segment elevation myocardial infarction and ST-segment
elevation myocardial infarction, manufacturer advises caution in
severe impairment (increased risk of bleeding complications).
  When used for Superficial-vein thrombosis, manufacturer advises
avoid in severe impairment (no information available).
Renal impairment: Increased risk of bleeding in renal impairment.
 When used for treatment of acute coronary
syndromes or prophylaxis of venous thromboembolism and
treatment of superficial-vein thrombosis-Avoid if creatinine
clearance less than 20 mL/minute.
 When used for treatment of venous thromboembolism-Use with
caution if creatinine clearance 30–50 mL/minute; avoid if creatinine
clearance less than 30 mL/minute.
Dose Adjustment: When used for prophylaxis of venous
thromboembolism and treatment of superficial-vein thrombosis, reduce
dose to 1.5 mg daily if creatinine clearance 20–50 mL/minute.
Direction of Administration: For intravenous infusion (Arixtra®), give
intermittently in Sodium chloride 0.9%. For ST-segment elevation
myocardial infarction, add requisite dose to 25-50 mL infusion fluid and
give over 1-2 minutes.
(NICE)

Iron:

The role of iron in the body: Iron is essential for a wide range of
functions in the human body including

 Transport of oxygen in red blood cells (as part of haemoglobin)

 Providing oxygen to muscles, especially skeletal and cardiac
muscle (as part of myoglobin)
 Acting as a co-factor for important enzymes
 Playing a role in immune response
When to take iron supplements:  iron is absorbed best if taken an hour
before a meal, however, iron can irritate the stomach of some people,
causing them to feel nauseated, in which case iron may be best taken
just after a meal.
How to take iron supplement: iron supplement regimen to the patient,
which will differ depending on the indication for supplementation and
the form of iron. The most common form of oral iron supplement
is ferrous fumarate.
Prophylactic supplementation: Prophylactic iron
supplementation may be indicated for patients with borderline iron
levels who have risk factors for iron deficiency such as poor dietary
intake or malabsorption. This typically involves taking an iron
supplement once a day.
Treatment dose supplementation: Typically, treatment dose iron
supplementation is prescribed for three to six months and iron levels are
then re-assessed to decide if long term prophylaxis is required (due to
ongoing risk factors) or if treatment can be stopped completely (e.g. if a
patient had a single episode of blood loss which has now been
treated/resolved).

Alternative routes of administration: Intravenous iron administration is

only indicated in cases of severe iron deficiency where the oral route
is unlikely to be tolerated or would take too long to replenish iron stores.7

 Monofer (iron isomaltoside) is a form of iron that can be

administered via intravenous infusion. The dose depends on the
patient’s weight. 

 IV iron administration (iron dextran) is associated with a risk

of anaphylaxis, so all patients need to be monitored during an
infusion in a setting with adequate resuscitation facilities.

Side effects of oral iron: Side effects reduce with time. Common side
effects of taking oral iron can include:

 Nausea
 Constipation
 Diarrhoea
 Dark-coloured stools
 Metallic taste
Vitamin:
Image 2 by O’Shaughnessy K.M. (2011).
Vitamins are complex chemicals that are essential for a variety of body
functions as seen above in image 2. Except for vitamin D which is
produced in the body when the skin is exposed to sunlight, our body
manufacture these substances itself, therefore we need to include them
in our diet. There are 13 major vitamins: A, C, D, E, K, and B complex
vitamins- thiamine B1, Riboflavin B2, niacin B3, pantothenic acid B5,
pyridoxine B6, cobalamin B12, folic acid and biotin.
Vitamin A and D indications and dose: Prevention of vitamin A and D
deficiency (using 4500 units vitamin A/450 units vitamin D 3capsules)

By mouth
 For Child 7–17 years 
1 capsule daily, increased if necessary to 2 capsules daily, dose
increase to be guided by serum values.
 For Adult 
 1 capsule daily, increased if necessary to 2 capsules daily, dose
increase to be guided by serum values.
Prevention of vitamin A and D deficiency (using 4000 units vitamin
A/400 units vitamin D capsules)

By mouth
 For Child 1–17 years 
1 capsule daily.
 For Adult 
(consult product literature or local protocols).
Dose equivalence and conversion

Each 4500 units vitamin A/450 units vitamin D3 capsule contains the

equivalent of 11 micrograms vitamin D3.
Each 4000 units vitamin A/400 units vitamin D capsule (vitamins A and D
capsules BPC 1973) contains the equivalent of 10 micrograms vitamin
D.
Interactions

Individual interactants:

 Colecalciferol 
 Vitamin A 

Overdose: Prolonged excessive ingestion of vitamins A and D can lead

to hypervitaminosis.
Breast feeding: Manufacturer advises avoid—present in milk.

Prescribing and dispensing information: This drug contains vitamin

D; consult individual vitamin D monographs.

Vitamin A, C and D Indications and dos: Prevention of vitamin

deficiency
By mouth
 For Child 1 month–4 years 
5 drops daily, 5 drops contain vitamin A approx. 700 units, vitamin
D approx. 300 units (7.5 micrograms), ascorbic acid approx. 20 mg.
Interactions

Individual interactants:

Ascorbic acid 
 Vitamin A
Vitamin B Complex Indications and dose:Treatment of deficiency

By mouth using tablets

 For Adult 
1–2 tablets 3 times a day, this dose is for vitamin B
compound strong tablets.

Prophylaxis of deficiency

By mouth using tablets

 For Adult 
1–3 tablets daily, this dose is for vitamin B compound tablets.

COLECALCIFEROL indications and dose: Prevention of vitamin D

deficiency

By mouth
 For Adult 
400 units daily.
Treatment of vitamin D deficiency

By mouth
 For Adult 
800 units daily, higher doses may be necessary for severe
deficiency.

Contra-indications

For all VITAMIN D AND ANALOGUES (SYSTEMIC)

Hypercalcaemia; metastatic calcification

Cautions

Sarcoidosis
Interactions

Individual interactants:

Colecalciferol 
Side-effects
For all VITAMIN D AND ANALOGUES (SYSTEMIC)

Common or very common: Abdominal

pain; headache; hypercalcaemia; hypercalciuria; nausea; skin reactions

Uncommon: Appetite decreased; arrhythmia (frequency not known in

children); asthenia; constipation; diarrhoea; myalgia; vomiting; weight
decreased (frequency not known in children)

Overdose: Symptoms of overdosage include anorexia, lassitude,

nausea and vomiting, diarrhoea, constipation, weight loss, polyuria,
sweating, headache, thirst, vertigo, and raised concentrations of calcium
and phosphate in plasma and urine.

Pregnancy

For all VITAMIN D AND ANALOGUES (SYSTEMIC)

High doses teratogenic in animals but therapeutic doses unlikely to be

harmful.

Breast feeding

For all VITAMIN D AND ANALOGUES (SYSTEMIC)

Caution with high doses; may cause hypercalcaemia in infant—monitor

serum-calcium concentration.
Renal impairment

Monitoring

Monitor plasma-calcium concentration in renal impairment.

Monitoring requirements
For all VITAMIN D AND ANALOGUES (SYSTEMIC)

Monitoring of patient parameters

Important: all patients receiving pharmacological doses of vitamin D

should have their plasma-calcium concentration checked at intervals
(initially once or twice weekly) and whenever nausea or vomiting occur.
For COLECALCIFEROL

Monitoring of patient parameters

Monitor plasma-calcium concentration in patients receiving high doses.

Directions for administration

For InVita D3® oral solution

With oral use
Manufacturer advises may be mixed with a small amount of cold or
lukewarm food immediately before administration.

ERGOCALCIFEROL Indications and dose: Vitamin D deficiency

caused by intestinal malabsorption or chronic liver disease

By mouth
 For Adult 
Up to 40 000 units daily.
Hypocalcaemia of hypoparathyroidism to achieve normocalcaemia

By mouth
 For Adult 
Up to 100 000 units daily.
Prevention of vitamin D deficiency

By mouth
 For Adult 
400 units daily.

Treatment of vitamin D deficiency

By mouth
 For Adult 
800 units daily, higher doses may be necessary for severe
deficiency.

Contra-indications for all VITAMIN D AND ANALOGUES (SYSTEMIC).

Hypercalcaemia; metastatic calcification

Side-effects

For all VITAMIN D AND ANALOGUES (SYSTEMIC)

Common or very common: Abdominal

pain; headache; hypercalcaemia; hypercalciuria; nausea; skin reactions

Uncommon: Appetite decreased; arrhythmia (frequency not known in

children); asthenia; constipation; diarrhoea; myalgia; vomiting; weight
decreased (frequency not known in children)

Overdose: Symptoms of overdosage include anorexia, lassitude,

nausea and vomiting, diarrhoea, constipation, weight loss, polyuria,
sweating, headache, thirst, vertigo, and raised concentrations of calcium
and phosphate in plasma and urine.

Pregnancy: High doses teratogenic in animals but therapeutic doses

unlikely to be harmful.
Breast feeding: Caution with high doses; may cause hypercalcaemia in
infant—monitor serum-calcium concentration.

Renal impairment: Monitor plasma-calcium concentration in renal

impairment.

Monitoring of patient parameters: Important: all patients receiving

pharmacological doses of vitamin D should have their plasma-calcium
concentration checked at intervals (initially once or twice weekly) and
whenever nausea or vomiting occur.

For ERGOCALCIFEROL

Monitoring of patient parameters: Monitor plasma-calcium

concentration in patients receiving high doses.

References:

O’Shaughnessy K.M. (2011). British Medical association. New guide to

medicine and drugs. Heparin. 8th edition. Pg. 268

Image 1: O’Shaughnessy K.M. (2011). British Medical association. New

guide to medicine and drugs. Heparin. 8th edition. Pg. 268

Image 2: O’Shaughnessy K.M. (2011). British Medical association. New

guide to medicine and drugs. vitamins. 8th edition. Pg. 107

https://geekymedics.com/iron-supplementation-counselling-osce-guide/

https://bnf.nice.org.uk/drug/fondaparinux-sodium.html#drugAction

https://geekymedics.com/warfarin-prescribing/