Drugs used in haematological disorders - Nursing

1. Drugs used in haematological disorders
(Aneamia, Thrombocytopenia, Disseminated
Intravascular Coagulation [DIVC])
S. Parasuraman, M.Pharm., Ph.D.,
Associate Professor,
Faculty of Pharmacy, AIMST University

2. Haematinics and Erythropoietin

3. Haematinics
• Haematinics are substances required in the
formation of blood and are used for treatment of
anaemias.
• Anaemia occurs when the balance between
production and destruction of RBCs is disturbed by:
• Blood loss (acute or chronic)
• Impaired red cell formation due to
• deficiency of essential factors (iron, vitamin B12, folic acid)
• bone marrow depression (hypoplastic anaemia)
• erythropoietin deficiency.
• Increased destruction of RBCs (haemolytic anaemia).

4. Haematinics

5. Haematinics
• Iron
• Iron is an essential body constituent Total body iron
in an adult is 2.5–5 g (average 3.5 g). It is more in
men (50 mg/kg) than in women (38 mg/kg).
• It is distributed into:
• Haemoglobin (Hb) : 62%
• Iron stores as ferritin and : 25%
• Haemosiderin Myoglobin (in muscles) : 7%
• Parenchymal iron (in enzymes, etc.) : 6%

6. Haematinics
• Iron - Daily requirement
• Adult male : 0.5–1 mg (13 μg/kg)
• Adult female : 1–2 mg (21 μg/kg)
• Infants : 60 μg/kg
• Children : 25 μg/kg
• Pregnancy : 3–5 mg (80 μg/kg) (last 2 trimesters)
• Dietary sources of iron
• Rich : Liver, egg yolk, oyster, dry beans, dry fruits, wheat
germ, yeast.
• Medium : Meat, chicken, fish, spinach, banana, apple.
• Poor : Milk and its products, root vegetables

7. Haematinics
• Iron deficiency
• Iron deficiency is the most common nutritional
cause of anemia in humans. It can result from
inadequate iron intake, malabsorption, blood loss,
or an increased requirement, as with pregnancy.
When severe, it results in a characteristic
microcytic, hypochromic anemia.
• Iron deficiency can affect metabolism in muscle
independently of the effect of anemia on O2
delivery.

8. Haematinics
• Treatment of Iron Deficiency: Orally administered
ferrous sulfate is the treatment of choice for iron
deficiency.
• Side effects: Oral iron preparations include heartburn,
nausea, upper gastric discomfort, and diarrhea or
constipation. A good policy is to initiate therapy at a
small dosage and then gradually to increase the dosage
to that desired.
• Parenteral Iron: When oral iron therapy fails,
parenteral iron administration may be an effective
alternative.
• Iron Dextran – IV or IM - test dose of 0.5 mL (25 mg of iron); > 500 mg
/ iv
• Sodium Ferric Gluconate – IV
• Iron Sucrose – IV
• Ferric Carboxymaltose – IV

9. Haematinics
• Acute iron poisoning:
• It occurs mostly in infants and children.
• Manifestations are vomiting, abdominal pain,
haematemesis, diarrhoea, lethargy, cyanosis,
dehydration, acidosis, convulsions; finally shock,
cardiovascular collapse and death.
• In few cases death occurs early (within 6 hours), but is
typically delayed to 12–36 hours, with apparent
improvement in the intervening period.
• Treatment:
• To prevent further absorption of iron from gut.
• Induce vomiting or perform gastric lavage with sodium
bicarbonate solution—to render iron insoluble.
• Give egg yolk and milk orally: to complex iron. Activated charcoal
does not adsorb iron.
• To bind and remove iron already absorbed: Desferrioxamine.
Alternatively, diethylenetriaminepentaacetic acid (DTPA) or
calcium edetate

10. Haematinics
• Copper , Pyridoxine, and Riboflavin:
• Copper has redox properties similar to those of
iron, which simultaneously are essential and
potentially toxic to the cell.
• Pyridoxine responsive anaemia is a rare entity. It is
due to inherent abnormality in haeme synthesis.
Sideroblastic anaemia associated with isoniazid and
pyrazinamide therapy needs to be treated with
pyridoxine.
• Riboflavin - red cell aplasia due to riboflavin
deficiency

11. Haematinics
• Vitamin B12: Cyanocobalamin and
hydroxocobalamin are complex cobalt containing
compounds present in the diet and referred to as
vit B12.
• Daily requirement: 1–3 μg, pregnancy and
lactation 3–5 μg.
• Vit B12 Therapy:
• Oral liquids, multivitamin supplements
• Vit B12 should be given prophylactically only when there
is a reasonable probability that a deficiency exists or will
exist.
• Long-term therapy with vitamin B12 must be evaluated
at intervals of 6–12 months in patients who are
otherwise well.

12. Haematinics
• Folic Acid:
• Folic acid is used for preventing and treating low
blood levels of folate (folate deficiency) and high
blood levels of homocysteine
(hyperhomocysteinemia).
• Dietary sources Liver, green leafy vegetables
(spinach), egg, meat, yeast. It is synthesized by gut
flora, but this is largely unavailable for absorption.
• Daily requirement:
• Adult is < 0.1 mg (but dietary allowance of 0.2 mg/day is
recommended).
• During pregnancy, lactation: 0.8 mg/day

13. Haematinics
• Folic Acid:
• Folate deficiency occurs due to:
• Inadequate dietary intake
• Malabsorption
• Biliary fistula
• Chronic alcoholism
• Increased demand
• Drug induced: prolonged therapy with anticonvulsants and
oral contraceptives.
• Uses
• Treatment of megaloblastic anaemias
• Prophylaxis
• Management of methotrexate toxicity
• To enhance anticancer efficacy of
• 5-fluorouracil
• Adverse effects: Oral folic acid is entirely nontoxic. Injections
rarely cause sensitivity reactions.

14. Erythropoietin
• Erythropoietin (EPO) is a glycoprotein hormone, naturally
produced by the peritubular cells of the kidney, that stimulates
red blood cell production.
• Epoetin α and β: It is recombinant human erythropoietin. It is
administered by i.v. or s.c. injection and has a plasma t½ of 6–10
hr, but action lasts several days.
• Use:
• The primary indication for epoetin is anaemia of chronic renal failure
which is due to low levels of EPO.
• Other uses:
• Anaemia in AIDS
• Cancer chemotherapy induced anaemia
• Preoperative increased blood production forautologous transfusion during
surgery
• Adverse effects: Epoetin is nonimmunogenic. sudden increase
in haematocrit, blood viscosity and peripheral vascular
resistance.
• Darbepoetin α: This is a hyperglycosylated modified preparation
of EPO that has a t½ of 24–36 hours. Indications, efficacy and
adverse effects are similar to epoetin.

16. Thrombocytopenia
• Thrombocytopaenia (low platelet count) can be due to either a failure of
platelet production or a shortened platelet lifespan.
• Thrombopoietin (TPO), produced mainly in the liver but also in the
kidneys, is a key regulator of platelet production. TPO is removed from
the circulation by platelets via the c-MPL receptor.
• A normal platelet count ranges between 150 and 400 x 109/litre.
• Platelets Lifespan: 7 - 10 days.
• Pathophysiology thrombocytopaenia:
• Anti-platelet antibody production
• Abnormalities of T-helper cells, regulatory T-cells and cytotoxic T-cells.
Ref: Radia D. Thrombocytopenia. Medicine. 2013;41(4):225-7. doi: 10.1016/j.mpmed.2013.01.017

17. Causes of thrombocytopenia
Ref: https://www.aafp.org/pubs/afp/issues/2022/0900/thrombocytopenia.html

18. Thrombocytopenia/ immune thrombocytopenia
(ITP) – Management
• Steroids: Dexamethasone, Methylprednisolone, Prednisolone
• Immune globulin: Intravenous immune globulin (IVIG)
• Drugs that boost platelet production: Avatrombopag,
Eltrombopag, Romiplostim (stimulate the bone marrow to produce more platelets)
• Other drugs: Rituximab helps to increase platelet count by
reducing the immune system response that's damaging platelets.
• Surgery: Splenectomy (only useful in cases of autoimmune thrombocytopenia)
• Emergency treatment: Transfusions of platelet concentrates

19. Disseminated
Intravascular
Coagulation
[DIVC/ DIC]
Scanning electron micrograph of platelets

20. DIVC
• Disseminated intravascular coagulation (DIC) is a serious disorder in
which the proteins that control blood clotting become overactive.
• Causes: Usually caused by inflammation from an infection, injury, or
illness.
• Risk factors
• Blood transfusion reaction
• Cancer, especially certain types of leukemia
• Inflammation of the pancreas
• Infection in the blood, especially by bacteria or fungus
• Liver disease
• Pregnancy complications Recent surgery or anesthesia
• Severe tissue injury
• Large hemangioma
Ref: https://medlineplus.gov/ency/article/000573.htm

21. DIVC
• Treatment: There is no specific treatment for DIC. The goal
is to determine and treat the underlying cause of DIC.
• Supportive treatments may include:
• Plasma transfusions to replace blood clotting factors if a
large amount of bleeding is occurring.
• Blood thinner medicine/ anticoagulants (heparin) to
prevent blood clotting if a large amount of clotting is
occurring.
Ref: https://medlineplus.gov/ency/article/000573.htm
https://www.nhlbi.nih.gov/health/disseminated-intravascular-coagulation

22. Anticoagulants

23. Anticoagulant
• The anticoagulant drugs inhibit either the action of the
coagulation factors (heparin) or interfere with the
synthesis of the coagulation factors (warfarin).

24. Anticoagulant - Heparin
• Heparin or Unfractionated heparin (UFH) is a
heterogeneous mixture of sulfated
mucopolysaccharides with MW 10,000 to 20,000
g/mol. Its biologic activity is dependent upon the
endogenous anticoagulant antithrombin.

25. Anticoagulant - Heparin
• The shorter-chain, low-molecular-weight (LMW)
fractions of heparin (enoxaparin, dalteparin, and
tinzaparin) inhibit activated factor X but have less
effect on thrombin than the high-molecular-weight
(HMW) species.
• Monitoring of Heparin Effect: Close monitoring of the
activated partial thromboplastin time (aPTT or PTT) is
necessary in patients receiving UFH. Levels of UFH may
also be determined by protamine titration (therapeutic
levels 0.2–0.4 unit/mL) or anti-Xa units (therapeutic
levels 0.3–0.7 unit/mL).

26. Anticoagulant - Heparin
• Toxicity: Bleeding, loss of hair and reversible alopecia,
heparin-Induced thrombocytopenia.
• Contraindications: Heparin should be avoided in
patients who have recently had surgery of the brain,
spinal cord, or eye; and in patients who are undergoing
lumbar puncture or regional anesthetic block.
• Reversal of Heparin Action: Protamine antagonize the
heparin. Intravenous injection of protamine neutralises
heparin weight for weight, i.e. 1 mg is needed for every
100 U of heparin.

27. Use of anticoagulant
• The aim of using anticoagulants is to prevent thrombus
extension and embolic complications by reducing the
rate of fibrin formation.
• Deep vein thrombosis and pulmonary embolism
• Myocardial infarction
• Unstable angina
• Rheumatic heart disease; Atrial fibrillation
• Cerebrovascular disease
• Vascular surgery, prosthetic heart valves, retinal vessel
thrombosis, extracorporeal circulation, haemodialysis
• Defibrination syndrome

28. Direct factor Xa inhibitors
• Rivaroxaban: It is an orally active direct inhibitor of
activated factor Xa which has become available for
prophylaxis and treatment of Deep Vein Thrombosis
(DVT).
• Apixaban: Indications similar to rivaroxaban.
Oral direct thrombin inhibitor
• Dabigatran etexilate: It is a prodrug which after oral
administration is rapidly hydrolysed to dabigatran, a
direct thrombin inhibitor. Dabigatran reversibly blocks
the catalytic site of thrombin and produces a rapid
anticoagulant action.

29. Choice of anticoagulants for various clinical
indications
Ref: K.D. Tripathi. Essentials of medical pharmacology. 8th ed.

31. FIBRINOLYTICS
(Thrombolytics)

32. Thrombolytics
• These are drugs used to lyse thrombi/clot to recanalize
occluded blood vessels (mainly coronary artery). They
are therapeutic rather than prophylactic and work by
activating the natural fibrinolytic system.
Drugs: Streptokinase, Urokinase, Alteplase (rt-PA),
Reteplase, Tenecteplase.

33. Thrombolytics
• Streptokinase is a protein synthesized by Streptococci
that combines with the proactivator plasminogen.
• Urokinase is a human enzyme synthesized by the
kidney that directly converts plasminogen to active
plasmin.
• Alteplase is recombinant tissue plasminogen activator
(rt-PA)
• Reteplase
• Tenecteplase

34. Thrombolytics
• Uses of fibrinolytics:
• Administration of fibrinolytic drugs by the i.v. route is
indicated in cases of pulmonary embolism with
hemodynamic instability, severe deep venous
thrombosis such as the superior vena caval syndrome,
and ascending thrombophlebitis of the iliofemoral
vein with severe lower extremity edema.
• These drugs are also given intra-arterially, especially
for peripheral vascular disease.

35. Platelet aggregation inhibitors
Image source: Jackson SP. The growing complexity of platelet aggregation. Blood. 2007;109(12):5087-95.

36. Platelet aggregation inhibitors
Aspirin:
• Platelet aggregation inhibitors decrease the formation
of a platelet-rich clot or decrease the action of
chemical signals that promote platelet aggregation.
• The platelet aggregation inhibitors described below
inhibit cyclooxygenase-1 (COX-1) or block GP IIb/IIIa or
ADP receptors, thereby interfering with the signals that
promote platelet aggregation.
• Use: Aspirin is used in the prophylactic treatment of
transient cerebral ischemia.

37. Platelet aggregation inhibitors
Ticlopidine, clopidogrel, prasugrel, and ticagrelor:
• These drugs inhibit the binding of ADP to its receptors
on platelets and, thereby, inhibit the activation of the
GP IIb/IIIa receptors required for platelets to bind to
fibrinogen and to each other. Ticagrelor binds to the
P2Y12 ADP receptor in a reversible manner.
• Use: Clopidogrel is approved for prevention of
atherosclerotic events in patients with a recent MI or
stroke and for prophylaxis of thrombotic events in
acute coronary syndromes.

38. Platelet aggregation inhibitors
Ticlopidine, clopidogrel, prasugrel, and ticagrelor:
• Use: Ticlopidine is indicated for the prevention of
transient ischemic attacks and strokes in patients with
a prior cerebral thrombotic event. It is generally
reserved for patients who are intolerant to other
therapies.
• Prasugrel is approved to decrease thrombotic
cardiovascular events in patients with acute coronary
syndromes.
• Ticagrelor is approved for the prevention of arterial
thromboembolism in patients with unstable angina
and acute MI.

39. Platelet aggregation inhibitors
Abciximab, eptifibatide, and tirofiban:
• A chimeric monoclonal antibody, abciximab,
eptifibatide inhibits the glycoprotein IIb/IIIa receptor
complex.
• Use: These agents are given intravenously, along with
heparin and aspirin, as an adjunct to percutaneous
coronary intervention (PCI) for the prevention of
cardiac ischemic complications.

40. Thank you