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1. DRUG INDUCED BONE MARROW
SUPPRESSION
Dr. Ayush Gupta
1st year PG Resident
Department Of Pharmacology
AIIMS Bhopal

2. OUTLINE
 INTRODUCTION
• BONE MARROW
• BONE MARROW BLOODVASCULATURE
• NORMAL HEMATOPOIESIS
 MYELOSUPPRESSION
CATEGORIES OF DRUG INDUCED MYELOSUPPRESSION
MECHANISM OF DRUG INDUCED MYELOSUPPRESSION
 TIMING AND EXTENT OF CHEMOTHERAPY INDUCED
MYELOSUPPRESSION
 PATHOPHYSIOLOGY
 DIAGNOSIS OF DRUG INDUCED MYELOSUPPRESSION
 CONCLUSION

3. BONE MARROW
 Bone marrow is highly cellular, spongy or viscous tissue that fills the inside of your bones.
Two types of bone marrow :
Red bone marrow &Yellow bone marrow
 Pattern of distribution
 Human marrow produces approximately 500 billion
blood cells per day in adults
 On average, bone marrow comprises approximately
5% of total body weight

4. BLOODVASCULATURE
• Bone receive up to about 10% of cardiac
output
• The blood supply of bone is delivered to
endosteal cavity by
• The marrow cavity afford a range of
vascular niches that regulate the growth
and differentiation of hematopoietic and
stromal cells
• Metaphyseal and Epiphyseal flow
• The blood vessels between the
haematopoietic compartment and the
circulation form a barrier, referred to as
the marrow-blood barrier (MBB)

5. NORMAL HEMATOPOIESIS
 Normal haematopoiesis
involves the development of
various cell lineages –
mediated by various growth
and cytokines in the marrow
environment
 multipotent progenitor
cells become differentiated
and committed to specific
developmental pathway
best known CSF are IL-3,
GM-CSF, G-CSF,
erythropoietin and M-CSF.
IL-3 is active throughout
the hemopoietic
cascade

6. Myelosuppression
 Myelosuppression is caused by the destruction of the proliferating progenitor cells that
produce the mature red and white blood cells and platelets found in the peripheral
circulation
Myelosuppression is a common and anticipated adverse effect of cytotoxic chemotherapy
 It is a potential but rare idiosyncratic effect with any other drug
there is a recognised association with a number of higher-risk agents which justify
additional vigilance
Genetic risk factors are being identified which may predispose individuals to this reaction
with particular drugs – e:g- mercaptopurine

7. Contin..
• Myelosuppression is potentially life threatening because of the infection and
bleeding complications of neutropenia and thrombocytopenia
• Immediate concern for patients undergoing cancer therapy, its management has
been improved significantly in recent years by the use of various hematopoietic
growth factors
• However, many patients receiving chemotherapy and/or ionizing radiation (IR) also
develop residual (or long-term) BM injury (a sustained decrease in HSC reserves due
to an impairment in HSC self-renewal) after the recovery from acute
myelosuppression

8. CATEGORIES OF DRUG INDUCED
MYELOSUPPRESSION
ONTHE BASIS OF MARROW CELLULARITY ONTHE BASIS OF PERIPHERAL CELL DISTRUCTION
 Reducing the cellularity of marrow
 bi or tricytopenia due to hypoplasia/aplasia of the bone
marrow :
AplasticAnaemia
 Selective marrow hypoplasia/ aplasia :
1. pure red cell aplasia
2. drug induced neutropenia/Agranulocytosis
3. drug induced non immune thrombocytopenia
 Without reducing the cellularity of marrow
( interfering with marrow cell maturation)
 MegaloblasticAnaemia
 SideroblasticAnaemia
 Drug induced Haemolytic Anaemia
 drug induced oxidative haemolytic anaemia
 drug induced immune mediated haemolytic anaemia
 drug induced immune thrombocytopenia

9. MECHANISMS OF DRUG INDUCED BONE MARROW
SUPPRESSION
TYPE A, DIRECT DOSE RELATEDTOXICITY
1. Acute
myelosuppression
2. Residual bone
marrow injury
TYPE B, IDIOSYNCRATIC MEDIATED
1. Metabolite driven
toxicity
2. Genetic
polymorphisms
IMMUNE MEDIATED TOXICITY
1. Hapten mechanism(drug
adsorption mechanism)
2. Immune complex
mechanism(innocent
bystander mechanism)
3. Autoimmune mechanism

10. PATHOPHYSIOLOGY OF CYTOTOXIC DRUG
 Stem cells have two cardinal functions: self-renewal
and differentiation
 HSCs serve as reserves to protect the hematopoietic
system from exhaustion under various stress
conditions
HPCs are rapidly proliferating cells with limited self-
renewal ability.
HSCs can undergo self-renewing proliferation and
differentiation

11. PREDICTING MYELOSUPPRESSION
Three main factors will determine when and how much myelosuppression will occur for any
patient about to embark on a course of chemotherapy
 Factor 1 : Blood cell life cycle
primary responsible for the timing of myelosuppression
• This is a static factor, applies to all patients, and will be the same no matter which drug is
being used
• Differences in the length and kinetics of the life cycle of particular blood cells account for the
frequency of granulocytopenia, thrombocytopenia and anaemia
E:g. difference in half lives of red blood cell and neutrophils
WBC – 6-8 hours circulating in blood and 2-3 days in tissues
lymphocyte- 100-300+ days
RBC- 120 days Platelets- 5-10 days

12. Contin…
 Factor 2 : Drug Characteristics
A) Pharmacokinetics factor
ADME of anticancer drugs is important and have to
be considered.
Drug administration-
The anti tumour effect of 5 – fluorouracil can be
enhanced when treating liver metastasis by direct
infusion through an arterial catheter into the liver ,
Much larger doses can be administered.
•

13. Drug Distribution –
The blood brain barrier can lead to a “ sanctuary effect” where the majority of lipid
soluble antineoplastic agents are unable to effectively reach target malignant cells
despite drug doses that produce life threatening toxicity.
Excretion –
e.g. Methotrexate is primarily excreted by kidneys , can cause major
myelosuppression when administered to a patient with elevated serum creatinine.

14. B) Phase specificity- cell cycle specific and cell cycle non specific
• Drug that are phase specific lead to a fairly rapid
cytopenia (mostly granulocytopenia followed by
thrombocytopenia).
• Recovery- quicker, especially from drugs that are
active in the S and M phase
• Non specific drug – leads to delayed, prolonged
and cumulative myelosuppression

15. Timing and Extent of Chemotherapy induced Myelosuppression
WBC Nadir (Days) WBC Recovery
(Days)
Platelet Nadir (Days)
Comment
Asparaginase 4-7 10-14 5-10
Myelosuppression is rarely a problem
Hydroxyurea
5-Fluorouracil
Cytarabine
7
7-14
12-14
14-21
20-30
22-24
NA
7-17
22-24 Somewhat platelet sparing
6-Mercaptopurine 7-14 14-21 10-14
Methotrexate 7-14 14-21 5-12
Bleomycin
Etoposide
NS
7-14
NS
21
NS
9-16
Vinblastine
Vincristine
Vindesine
5-9
3-5
7
14-21
7
14
4-10
NA- marrow sparing
7- platelet sparing

16. WBC Nadir
(Days)
WBC Recovery
(Days)
Platelet Nadir
(Days) Comment
Busulfan
Carboplatin
Cisplatin
Cyclophosphamide
Procarbazine
7-10
21
18-23
8-14
25-36
24-25
28
29
18-25
35-50+
10-30
21
14
10-25
21
Dose limiting toxicity: thrombocytopenia can be severe
Anaemia can be severe
Platelet sparing
Prolonged, delayed myelosuppression
Dactinomycin
Daunorubicin
Doxorubicin
Mitomycin
14-21
8-10
10-14
21-25
22-25
21
22
28-42
10-14
10-14
14
30
Profound myelosuppression
Cumulative, prolonged myelosuppression
Carmustine
Losmustine
35-42
42
42-56
60
28-35
28
Cumulative, delayed and prolonged myelosuppression
Thrombocytopenia more common than leukopenia
Dacarbazine 10-14 24 14-28

17.  Factor 3: Characteristics of the patient
The degree of myelosuppression expected from a specific treatment will be influenced by:
• Patient’s age- older patients have a less cellular marrow with more fat space, and possible
aplasia
• Patient’s Health- debilitation may increase the severity and unpredictability of
myelosuppression
• Nutritional status- the greater the negative nitrogen balance and weight loss, the less
tolerant the patient will be to the drug’s toxic effect on the marrow because there are less
nutritional resources for building new blood cells.

18. Contin..
• Degree of bone marrow reserve- cisplatin, carmustine and busulfan
• Adequacy of liver and kidney function- methotrexate , primarily excreted by kidney,
can cause major myelosuppression
• Fibrosis due to prior radiation therapy decreases bone marrow reserves
• Ascites and pleural effusion create a third space which can prolong drug toxicity.

19. DRUGS ASSOCIATEDWITH IDIOSYNCRATIC(TYPE B)
MYELOSUPPRESSIOM
• Drug reactions that occur rarely and unpredictably amongst the population
• They frequently occur with exposure to new drugs, as they have not been fully tested and the full
range of possible side-effects have not been discovered
• Idiosyncratic drug reactions appear to not be concentration dependent

20. • The proposed mechanism of most idiosyncratic drug reactions is immune-mediated
toxicity and reactive metabolites of the offending drugs
• There is new evidence that drugs that cause IDRs including IDIAG can activate
inflammasome
 Genetic polymorphism
• mercaptopurine – inactivated by enzyme thiopurine methyltransferase(TPMT) –
genetically variation inTPMT activity associated with myelosuppression
• mutation in methylenetetrahydrofolate reductase(MTHFR) gene

22. DRUG INDUCED APLASTIC ANAEMIA
Definition:
“Condition, in which body is unable to produce enough new blood cells”
 Characterized by a bi- or tricytopenia (thrombocytopenia, anaemia
and granulocytopenia) due to hypoplasia or aplasia of the bone marrow
 It was initially reported in the 1930 associated with arsenicals and
aminopyrines.
 Bimodal risk distribution when it comes to age
peak incidence between 10-25 years and age >60 years
 It is the most serious acquired blood dyscrasia because of its associated high mortality which
averages about 50%

23. PATHOPHYSIOLOGY
• The cause of drug-induced aplastic anaemia is damage to the pluripotential
hematopoietic stem cells before their differentiation to committed stem
cells.
• There are three major etiologies of acquired aplastic anaemia
i. Direct, dose-related drug toxicity
ii. Idiosyncratic mechanisms
iii. Drug-induced autoimmune aplastic anaemia

24. i. DIRECT, DOSE RELATEDTOXICITY :
The majority of chemotherapeutic agents can cause myelosuppression in a dose-
dependent manner.
Among these compounds, alkylating agents, pyrimidine analogues,
methotrexate, hydroxyurea and mitomycin C are highly cytotoxic to BM
Example: Among women with breast cancer, patients receiving CMF regimens and CAF
regimen, were strongly associated with risk of aplastic anaemia
ACUTE MYELOSUPPRESSION (< 3 month) RESIDUAL BONE MARROW INJURY ( >3 months)
• Due to depletion of HPCs • Impaired self-renewal ability of HSCs

25. • The main effect of cyclophosphamide
is due to its active metabolite
• alcohol, rifampicin and phenytoin
• corticosteroids, allopurinol

26. Methotrexate induced Myelosuppression
• Methotrexate has higher affinity than DHF
for DHFR
• The frequency of pancytopenia may
increase if other drugs, such as NSAIDS,
PPI and antidiabetics are co-administered
• Polymorphism in the MTHFR gene have
been associated with toxicity of mtx in RA
pt

28. TREATMENT
 Rapid diagnosis and immediate therapy initiation is important because of the high mortality
rate associated with severe and very SAA.
• First step is to remove the suspected offending agent
• Supportive care
• Recombinant human erythropoietin and granulocyte colony-stimulating factor (G-CSF) has not
been shown to improve outcome
• Current treatment guidelines for aplastic anaemia recommend the use of prophylactic
antibiotic and antifungal agents when neutrophil counts are below 500
• The two major treatment options for patients with drug-induced aplastic anaemia are
allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy
a). For age ≤45 years-TOC allogeneic HSCT
b). For age >45 years-TOC IST- antithymocyte globulin and cyclosposrine

29. • Current treatment guidelines for aplastic anaemia recommend the use of prophylactic
antibiotic and antifungal agents when neutrophil counts are below 500
• The two major treatment options for patients with drug-induced aplastic anaemia are
allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppressive
therapy
• a). For age ≤45 years-TOC allogeneic HSCT
• b). For age >45 years-TOC IST- antithymocyte globulin and cyclosposrine

30. Drug Induced Neutropenia/Agranulocytosis
• Many drugs can cause agranulocytosis and neutropenia by bone marrow suppression
• Agranulocytosis is used to describe a more severe subcategory of neutropenia, applied to cases
in which the ANC is lower than 500/ml
• older patients –greater risk
• women>men
• The highest risk drug groups are antithyroid drugs, macrolides , and procainamides

31. MECHANISMS
The cause of drug induced agranulocytosis by two mechanism
• a). Direct toxicity to myeloid cells, particularly neutrophils
The toxicity may be due to either parent drug or a toxic metabolites
• b). Immune mediated reaction
i. Hapten mechanism
ii. Immune complex mechanism
iii. Complement mediated mechanism(Innocent bystander mechanism)

32. CLOZAPINE INDUCED AGRANULOCYTOSIS
• The mechanism of CIAG is dose independent, with a significant genetic predisposition
without well established pathological background (so-called idiosyncratic)
• Annually, the incidence of drug-induced agranulocytosis, excluding cytotoxic agents, is
estimated to be approximately seven cases per one million people
• The mortality rate from drug-induced agranulocytosis is approximately 5 to 10 percent but
decreases with early identification and treatment
• Clozapine can induce two clinically distinct types of neutropenia
1st- mild to moderate- neutrophils count between 500-1500, which occurs in 1.8% of
treated patients.
2nd- severe- neutrophil count <500, which occurs in 0.78% of treated patients.
• There is an age-related increase in risk of 53% per decade

33. • The pathogenesis, despite multiple
experiment , is not fully cleared
• The current theory suggests reactive oxygen
species- nitrenium ion as an important factor
for CIAG
.
• This metabolite covalently binds to cellular
proteins, run down intracellular glutathione
and leads to cell toxicity.
• Co treatment with CYP1A2 inhibitors
• Specific allele of HLA-38/B39/B67 and HLA
DQB1 showed significant association with
CIAG

34. HAPTEN MECHANISM
IMMUNE COMPLEX AND
INNOCENT BYSTANDER
MECHANISM

35. CONT…..
Class of drugs having higher risk of agranulocytosis are-
• Antithyroid, ticlopidine, clozapine, phenothiazine, chlorpromazine,
sulfasalazine and beta lactam antibiotics.
• Iron chelator – deferiprone
The most serious adverse reaction reported in clinical trial with
FERRIPROX was agranulocytosis
Significant risk of:
Neutropenia- 8.5%
Agranulocytosis- 0.5%

36. TREATMENT
 Withdrawal of offending dug- with WBC returning to normal within 2-3 weeks
 Granulocyte colony-stimulating factor
• Sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]) and
filgrastim (G-CSF) have been shown to shorten the duration of neutropenia, length of
antibiotic therapy, and hospital length of stay
• Drug-induced agranulocytosis usually resolves over time with supportive care and
management of infection
• Restarting the drug is not usually recommended.
• In the case of penicillin-induced agranulocytosis, the patient can often begin taking
penicillin again, at a lower dosage, after the neutropenia has resolved without any
recurrence of drug-induced agranulocytosis.

37. DRUG INDUCED MEGALOBLASTIC ANAEMIA
 More than 50 years ago,Victor Herbert first described the concept that defective nucleoprotein
synthesis, attributable to various causes, results in the development of megaloblastic anaemia
Definition:
“Condition, in which there is abnormal development of RBC precursors(Megaloblasts), in bone
marrow”.
 These abnormal megaloblasts, were first described by Paul Ehrlich in 1880.
 Drugs cause megaloblastic anaemia by impairing the cellular availability or use of folic acid or
vitamin B12 and by directly affecting the DNA synthesis

38. Drug that interfere with absorption of
folic acid
• Both folic acid and vitamin B12 play a
critical role as cofactors in the pathway
that leads to the synthesis of thymidylate
• methyl group is added to 5 carbon of
uridylate to form thymidylate
• Accumulation of one of the metabolites of
the vitamin in an unusable form, giving
rise to a megaloblastic anaemia
• Many drugs interfere with the absorption
or proper distribution of folic acid.These
include alcohol, antiepileptic agents,
contraceptive drugs, and antibiotics
5-FU
Mtx

39. Drug that decrease the absorption of vitamin B12
Cycloserine, Isoniazid, Metformin, Colchicine, Proton-pump inhibitors, H2 blockers
Increases excretion of vitamin B12
Sodium nitroprusside
Destroys vitamin B12
Nitric oxide

40. TREATMENT
 When drug-induced megaloblastic anaemia occurs following chemotherapy, the
anaemia is considered an accepted side effect of therapy.
• Results from cotrimoxazole- folinic acid, 5 to 10 mg up to four times a day,
correct the anaemia.
•
• Folic acid supplementation of 1 mg daily often corrects the drug-induced
megaloblastic anaemia produced by either phenytoin or phenobarbital

41. DRUG INDUCED HEMOLYTIC ANAEMIA
• After their release from the bone marrow, normal RBCs survive for about 120 days before
they are removed by phagocytic cells of the spleen and liver.
• The process of premature RBC destruction is referred to as haemolysis, which can occur
because of either defective RBCs or abnormal changes in the intravascular environment.
• Drugs can promote haemolysis by both processes
• The incidence of drug induced haemolytic anaemia is estimated to be about one in 1 to 2
million individuals

42.  The causes of drug-induced haemolytic anaemia divided into two categories
1). Immune mediated
2). Induction of haemolysis by metabolic abnormalities in the RBCs
Patients with drug-induced haemolytic anaemia can present with signs of intravascular or
extravascular haemolysis.

43. Drug induced immune haemolytic anaemia
• Drug-induced immune haemolytic anaemia has been estimated to occur in
approximately 1-4/ million/year
• It is a rare complication of drugs in which immunoglobulin M (IgM) or IgG binds to the
surface of RBCs and initiates haemolysis through mononuclear phagocytic cells or the
complement system
• > 130 drugs are associated with the development of drug-induced immune haemolytic
anaemia
• The most common classes are platinum based chemotherapies and the second and
third generation cephalosporins
• it involves the formation of antibodies directly against RBC.
• drug dependent antibodies and drug independent antibodies

44. Mechanism of drug induced immune haemolytic anaemia
• Hapten mechanism of drug-induced immune
haemolytic anaemia has been reported in
patients who received high doses of penicillin
and cephalosporin derivatives.
• Streptomycin and minocycline tolbutamide
• The anti-hypertensive drug methyldopa was the
first known drug associated with production of
true autoantibodies attacking RBCs and causing
hemolysis
• Cladribine and fludarabine

45. Drug induced oxidative haemolytic anaemia
 A hereditary condition
 drug induced oxidative haemolytic anaemia, most often accompanies a
glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)
• HMP shunt- responsible for NADPH IN RBC- glutathione in reduced state-
glutathione peroxidase - protecting from oxidative stress
• oxidative drugs can oxidize the sulfhydryl group of haemoglobin- removing
them from circulation
Drug – Dapsone, metformin, nitrofurantoin

46. TREATMENT
 immediate removal of the offending agent and supportive care
 Immune haemolytic anaemia immune complex mediated
and auto immune mediated
mild to moderate in severity severe haemolysis
 Indications for transfusions - given for severe, symptomatic anaemia or anaemia that is rapidly
progressing
 Therapies for drug induced AIHA- glucocorticoids and/or intravenous immune globulin
 Ascorbic acid – Ascorbic acid (vitamin C) is an alternative treatment for symptomatic
methemoglobinemia; this is the treatment of choice in individuals with G6PD deficiency.

47. DRUG INDUCEDTHROMBOCYTOPENIA
• Thrombocytopenia is usually defined as a platelet count below 100,000/ml or greater
than 50% reduction from baseline values.
• The annual incidence of drug-induced thrombocytopenia is about 10 cases per
1,000,000 population (excluding cases associated with heparin)
• Drug-induced thrombocytopenia typically presents 1 to 2 weeks after a new drug is
initiated
• but may present immediately after a dose when an agent has been used
intermittently in the past
• Rapid onset may also occur with the GPIIb/IIIa inhibitor class of drugs

48. Cause of drug induced thrombocytopenia
 There are two types of drug-induced thrombocytopenia:
immune and nonimmune
• If a medicine causes your body to produce antibodies, which seek and destroy your platelets, the
condition is called drug-induced immune thrombocytopenia. Heparin, a blood thinner, is the most
common cause of drug-induced immune thrombocytopenia.
• If a medicine prevents your bone marrow from making enough platelets, the condition is called
drug-induced nonimmune thrombocytopenia. Chemotherapy drugs and valproic acid may lead to
this problem.

49. Nonimmune-mediated mechanisms
• Nonimmune-mediated mechanisms, such as direct-toxicity-type reactions, are
associated with medications that cause bone marrow suppression
• This results in suppressed thrombopoiesis and a decreased number of megakaryocytes.
• This type of reaction is dose-dependent and takes weeks to manifest.

50. Immune mediated drug induced thrombocytopenia
 Several mechanism have been proposed for the development of immune mediated
1). Hapten Mechanism- drug + certain platelet GPs – abs are generated + these drug bound GPs
lysis occur through complement activation or through clearance from the
circulation by macrophages
• Hapten mediated immune thrombocytopenia usually occurs at least 7 days after the initiation
of the drugs
• it can occur sooner if the exposure is actually a reexposure t0 a previous administered drugs
Example : penicillin's and cephalosporins

51. Conti…
2). Drug dependent antibody mechanism
Quinine, anticonvulsants and NSAIDS
3). Immune complex induced thrombocytopenia
example- Heparin induced thrombocytopenia type II
• two types of HIT have been identified.
Type I- occur in 10-20% of patients – it is mild, reversible, nonimmune-mediated reaction
occurs within the first 2 days of therapy
Type II- less common but more severe- 1-5% of patients receiving UFH
0.8% of patients receiving LMWH
platelet declines 5-10 days after therapy
if recently received- decline occurs within an hour of receiving heparin

52. Other medicines that cause drug-induced thrombocytopenia include:
• Furosemide
• Gold, used to treat arthritis
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Penicillin
• Quinidine
• Quinine
• Ranitidine
• Sulfonamides
• Linezolid and other antibiotics platelet transfusions
• Statins

53. TREATMENT
 Drug discontinuation
 Decision to hospitalize- no bleeding or only minor purpura
bleeding more than minor purpura (eg, if there is epistaxis, heavy
menstrual bleeding, or other bleeding),
 Steroids are often given because the distinction of DITP from ITP is often initially unclear.
 Treatment of bleeding/severe thrombocytopenia
 DITP due to a GP IIb/IIIa inhibitor who have severe bleeding- platelet transfusions
 no evidence for the efficacy of immunosuppression in treating DITP

54. Drug Induced Sideroblastic Anaemia
 Accumulation of perinuclear siderotic granules in the mitochondria of nucleated red cells,
producing ‘ring sideroblasts’
• Drugs causing Sideroblastic Anaemia by :
Inhibiting amino levulinate synthase – depletion of haem synthesis
Pyridoxine act as cofactor for synthesis of amino levulinate
Example chloramphenicol and cycloserine, alcohol, isoniazid and linezolid

55. Treatment
 In drug-induced sideroblastic anaemia, the anaemia are reversible and disappear
upon drug withdrawal.
 isoniazid - anaemia can also be reversed by administering large doses of vitamin B6
(up to 200 mg/day orally) while continuing the drug, if needed.

56. Few examples of drugs associated with a variety of toxic effects and
their likely mechanism of action
Drug Effect Mechanism of action
Chloramphenicol, benzene,
sulfonamide, diclofenac
Bone marrow aplasia
Trimethoprim-sulfadiazine,
cephalosporin, phenobarbital
Pancytopenia Possibly immune-mediated destruction
of stem cells
Benzene idiosyncratic marrow aplasia Stem cell defect
Estrogen Anaemia; bone marrow suppression Stem cell damage and decreased EPO
Amphotericin B, insulin, isoniazid,
cisplatin, rifampicin, naproxen,
sulfonamide
Immune-mediated hemolytic
anaemia (IMHA)
Antibody-mediated destruction of
erythrocytes
Heparin, gentamycin, aspirin,
acetazolamide, cephalexin, gold salts
Thrombocytopenia Immune-mediated platelet destruction

57. DIAGNOSIS OF DRUG INDUCED MYELOSUPPRESSION
1. Recognition and confirmation of consequent peripheral blood cytopenia
2. whether it is due to a reduction in output of cells from the bone marrow or to a
shortened survival of the affected cell types in peripheral blood.
3. Important cause for shortened survival include haemolysis, immune neutropenia,
immune thrombocytopenia or platelet consumption
4. If myelosuppression is suspected, a drug induced aetiology must be differentiated
from other marrow pathology or marrow infiltration with secondaries

58. Contin…
Diagnostic pathway
involved
Clinical history &
examination
Blood count
Bone marrow
aspiration
Peripheral blood
examination

59. Bone marrow biopsy in aplastic anaemia.
no hematopoietic cells, and the marrow
space consists of fat and stroma.
Normal bone marrow biopsy at
low power

60. Non Chemotherapy Drug Associated with Myelosuppression

61. Conclusion
• Strategies for monitoring, early detection, diagnostic confirmation and appropriate
supportive care are well developed for cytotoxic therapy.
• Developments in antimicrobial chemotherapy, blood product transfusion support and
growth factor therapy have improved outcomes.These advances are largely applicable to
idiosyncratic drug-induced myelosuppression, reinforcing the importance of early
recognition and referral to appropriate expertise
• Because of the seriousness of drug-induced hematologic disorders, it is necessary to track
the development of these disorders to predict their occurrence and to estimate their
incidence.

62. Conti..
• Reporting during post marketing surveillance of a drug is the most common method of
establishing the incidence of adverse drug reactions.The MedWatch program supported by the
Food and Drug Administration is one such program.
• Furthermore, pharmacogenetic research to identify patients who may be slow or normal
metabolizers of drugs can increase the clinician’s ability to predict the development of aplastic
anaemia.
• The problem of polypharmacy is of particular concern in an aging society because elderly
patients tends to have many underlying disease as well as conditions that require medications.