2. WHAT IS APLASTIC ANEMIA?
• A rare condition in which body stops producing enough new
blood cells.
• It develops as a result of Bone Marrow Damage.
• Bone Marrow- Soft fatty tissue in the center of the bones giving
rise to other blood cell types (Red, White & Platelets). Damage
to bone marrow decreases concentration of these blood cells.
by Priyanka Dupatne
3. WHAT CAUSES AA?
• A. Damage may be present at birth [Inherited causes- Fanconi anemia, Diamond
–Blackfan anemia)
• B. Or occur during pregnancy (often goes away after pregnancy) or after exposure
to radiation, chemotherapy (chemicals) , cancer (cancer to other part of the body
may spread to bones & cause AA) toxic chemicals, auto-immune disorders (lupus
& rheumatoid arthritis) some drugs or infection (Hepatitis, Epstein barr virus,
cytomegalovirus, HIV) [Acquired Causes]
by Priyanka Dupatne
4. WHAT PESTICIDES (INSECTICIDES) CAUSE AA
• Chloramphenicol (now banned), major AA inducing pesticide.
• Organochlonrines (Lindane)
• Organophosphate
• Carbamate and
• Paraquat pesticides
by Priyanka Dupatne
5. SYMPTOMS OF AA
• Requires a medical diagnosis
• Symptoms may develop slowly or suddenly.
• Whole body : Dizziness, fatigue or fever
• Skin : Rashes of purplish or red spots
• Low Red cell count (anemia) :
• Fatigue
• Pallor ( Paleness)
• Rapid heart rate
• Shortness of breath with exercise
• Weakness
• Lightheadedness upon standing
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• Low White cell count ( Leukopenia) :
Increased risk of infection
• Low Platelet count (thrombocytopenia) :
Bleeding gums
Easy bruising
Frequent or severe infections
Nose bleeds
Rash- Small pinpoint red marks on the skin
(Petechiae)
7. • Blood test from a physical exam provide
following information:
• Low Red blood cells count (Anemia)
• Low white blood cells count
• Low reticulocyte count (immature blood
cells)
• Low platelet count
• Bone marrow biopsy shows fewer than normal
blood cells and an increased amount of fat.
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Signs
8. BIOCHEMICAL BACKGROUND OF PESTICIDE INDUCED
AA
-EFFECTS DOWNREGULATION OF HEDGEHOG
SIGNALING
• Long term pesticide exposure results in induced bone marrow aplasia or AA - direct
effect on downregulating hedgehog signaling in the bone marrow
microenvironment.
• The Hedgehog signaling pathway is a signaling pathway that transmits
information to embryonic cells required for proper cell differentiation. Different
parts of the embryo have different concentrations of hedgehog signaling proteins.
The pathway also has roles in the adult.
• Name Hedgehog came from Drosophila's segment polarity gene products Hh
(Hedgehog) ,involved in establishing the basis of the fly body plan
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9. • Mammals have three Hedgehog homologues, Desert
(DHH), Indian (IHH), and Sonic (SHH), of which Sonic
is the best studied.
• The pathway is important during vertebrate embryonic
development and is therefore of interest in evolutionary
developmental biology.
• Any damage or downregulation in the pathway affects the
brain, skeleton, musculature, gastrointestinal
tract and lungs which fail to develop correctly.
• Hedgehog signaling plays an important role in
regulating adult stem cells involved in maintenance and
regeneration of adult tissues
by Priyanka Dupatne
10. SPREAD OF AA ON GLOBAL SCALE
A rare disease, first described late in the 19th century, initially benzene, later other chemicals
& drugs.
An annual incidence of 2-5 per million, with higher incidence in Asia than in the west.
More frequently occur to people aged 60 and above.
Chloramphenicol, a then-widely used (banned now) antibiotic drug against various bacterial
diseases of plants, was reported to be a major causative of Pesticide- induced AA.
by Priyanka Dupatne
11. WORKS & CASE STUDIES ON AA
• A. A case-control study was conducted in Bangkok & 2 rural regions of Thialand.
– The effect of household pesticides was evaluated among 253 incident cases of AA & 1174
hospital controls.
– Results – A total of 54% of the cases & 61% of the controls were exposed 1-6 months
previously. For most individuals among the pesticides like OP’s, Pyrethins & Oc’s the
relative risk estimates done, showed a significant association was observed for the
exposure to combination products containing DDVP & Propoxur with a high overall
Relative Risk. Although most Household-pesticides did not report to have an increased
risk of AA
– Epidemics in Thialand.
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12. B. LINDANE (KWELL) -INDUCED APLASTIC ANEMIA
• 13 cases of aplastic anemia and 5 cases of other blood dyscrasias (Increasing or
lowering of blood cells) , eg, red blood cell aplasia and thrombocytopenia, associated
with lindane, have been reported.
• The case of a 21-year-old man with a diagnosis of aplastic anemia, known prolonged
exposure to lindane.
• Documented elevated serum lindane levels. His clinical course is described as well as
various defects are explored for the aplasia.
by Priyanka Dupatne
Alan E. Rauch et.al
1990
13. C. CASE STUDY IN WEST BENGAL
DEPARTMENT OF PATHOLOGY, NORTH BENGAL
MEDICAL COLLEGE, DARJEELING, INDIA
• The annual incidence of aplastic anemia is about 2 cases per million population.
• Aplastic anemia is 2-3 times more common in Asia than in the West.
• Acquired aplastic anemia most commonly presents between the ages of 15 and 25 years,
but there is a second smaller peak in incidence after age 60 years
by Priyanka Dupatne
Haldar Biswajit et.al 2012
14. PREVENTION
Generally there’s no prevention for most cases of aplastic anemia.
Avoiding exposure to insecticides, herbicides, organic solvents, paint
removers & other toxic chemicals may lower the risk of the disease.
by Priyanka Dupatne
15. TREATMENT
• Blood Transfusion
-over time transfusion might stop working; it isn’t a cure but a
treatment to relieve symptoms
-Blood components added to replace deficiencies within the bloodstream
• Bone marrow stimulant
-helps bone marrow produce new blood cells
• Blood marrow transplant or stem cell transplants
-for patients under the age of 40 ; works best when there is a
Matched Sibling Donor
-Immunosuppressive drugs given during transplants
-reduces immune response to allow blood transfusion or transplants
• BM transplant with unrelated donor
- If medicines don’t do well or if there’s relapse of disease
by Priyanka Dupatne
Untreated AA may lead to death. BMT is successful in young people.
16. CASE-CONTROLLED STUDY TO ASSES EFFECT OF
INJECTING CYCLOSPORIN- A MONOTHERAPY
- IN INDIA
• A study on 19 patients of acquired Aplastic Anemia (AA) from the SMS Medical College Hospital, Jaipur,
India.
• A careful evaluation for pesticide exposure, haematological profile, serum organochlorine levels and response
to oral Cyclosporine-A (Cyc-A) were recorded as per a preset Performa.
Observations & Results:
• Of the 19 patients included in the study, 15 (78%) were males & the mean age was 23 years (range 7 to 64
years) in the study.
• 13 of the 19 patients (68.4%) were from rural habitat; 9/19 (47.4%) –showed pesticide exposure - rural
background.
• 6 patients (31.6%) had non-severe AA, 9/19 (47.4%) had severe AA and 4/19 (21%) had very severe AA.
• Overall response to Cyc-A at 3 months was 47.4% [complete response (CR) 10.6%] and at 6 months was
47.4% (CR 21.1%).
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17. • Response rate in Non-severe AA - 83.3% versus 33.3% in the severe AA and 25% in the
very severe AA group.
• Mean serum organoclorine levels appear to correlate with the severity of AA.
• Patients with higher serum organochlorine levels were less likely to respond to Cyc-A
therapy.
• Cyc-A therapy worked best on patients with mild AA.
by Priyanka Dupatne
Hemant Malhotra,
(2008)
18. COMPLICATIONS DURING TREATMENT
Severe infections or bleeding
Complications of BMT
Reactions to medicines
Hemochromatosis
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20. SCOPE OF STUDYING EFFECTS OF PESTICIDES ON
AA?
Study effects of Pesticide induced AA in order to awareness regarding reducing or atleast
precautionary use of inevitable pesticides
To study effects on Hedgehog signaling pathway
To discover most efficient and affordable treatment for AA.
AA is increasing at rapid growth in all the developing countries (especially in Asia) including
countries like India, Bangladesh, Nepal, Thailand etc., that depend mainly on agriculturally
important insecticides to combat crop pest and increase the crop yields. Hence an alternative to
the use of such pesticides has to be developed (IPM)
by Priyanka Dupatne
21. CONCLUSIONS
Pesticide induce AA occurs 2-5 in a million
It is a rare but a fatal syndrome
Could be both inherited or induced
Inherited AA shows up from 15-22 years or age and induced AA shows up in people
more than 60 years of age.
High in males than in females.
Results in downregulation of Hedgehog signaling pathway
Therapies act best only when severity of AA is low/mild.
Judicious use of pesticides is important
Depending wholly on chemical pesticides should be avoided.
Integrate other non-chemical control measures along with chemical methods of
controlling crop pests.
by Priyanka Dupatne
