ANEAMIA AND SICKLE CELL DISEASE.

Presenters; Sabiiti Alvin & Nyakana Ronald.

Tutor; DR Munube Deo
Date;26/11/2019
ANEAMIA
OUTLINE
• Definition
• Epidemiology
• Classification
• Aetiology
• Pathophysiology
• Diagnosis and Investigation
• Management
• Long term effects of aneamia.
Definition
• Anaemia is defined as a low haemoglobin (Hb) concentration, and
may be due either to a low red cell mass or increased plasma volume
e.g in pregnancy.(Oxford hand book of clinical medicine).

• Anaemia is also defined as a haemoglobin concentration in blood

below the lower limit of the normal range for the age and sex of the
individual.( Harsh Mohan text book of pathology).
(Neonates)
EPIDEMIOLOGY
• Anaemia is a public health problem affecting over 1.62 billion people
globally. It affects all age groups of people and is particularly more
prevalent in pregnant women. Africa carries a high burden of
anaemia.
• Prevalence of anemia among children under 5years in Uganda was
51.1% as of 2016. The highest value over the past 26 years was 78.4%
in 1990, while its lowest value was 51.1% in 2016.
• Source: (World Health Organization, Global Health Observatory Data Repository/World Health Statistics
(http://apps.who.int/gho/data/node.main.1?lang=en ).
Prevalence in different regions of Uganda.
Epidemiology…
In a research conducted by Gerald Obai, Pancras Odongo and Ronald
Waya of Hoima regional referral hospital reported the following findings;
The prevalence of anaemia was significantly higher in Gulu than in
Hoima (P < 0.001).
This was reflected to a twenty-year war that ranged Gulu between the
LRA and the Government of Uganda that left most of the social services in
the district in ruins and a large majority of its population in poverty.
Findings also show that being a housewife is an independent risk factor
for anaemia. Because most housewives depend solely on their
husbands’ earnings for their financial needs, the majority of them tend
to be of low socio-economic status.
Epidemiology….
Anaemia prevalence was highest (24.3 %) during the third trimester
as compared to the first trimester (14.6 %) and second trimester
(20.7 %).
This was refrected to haemodilution in pregnancy which increases to
peak during the second trimester.
However, the increased incidence of anaemia during the third trimester
may also indicate poor antenatal care and nutrition.
 CLASSIFICATION
A. PATHOPHYSIOLOGIC/ AETIOLOGIC CLASSIFICATION
I. Anaemia due to increased blood loss
a) Acute post-haemorrhagic anaemia
b) Chronic blood loss
II. Anaemias due to impaired red cell production
a) Cytoplasmic maturation defects
1. Deficient haem synthesis: -Iron deficiency anaemia
2. Deficient globin synthesis: -Thalassaemic syndromes
b) Nuclear maturation defects
Vitamin B12 and/or folic acid deficiency: -Megaloblastic anaemia
c) Defect in stem cell proliferation and differentiation
1. Aplastic anaemia
2. Pure red cell aplasia
Classification……..
d) Anaemia of chronic disorders. Bone marrow failure due to chronic illnesses eg,
1.Anaemia of inflammation/infections, disseminated malignancy
2. Anaemia in renal disease
3. Anaemia due to endocrine and nutritional deficiencies (hypometabolic
states)
4. Anaemia in liver disease

e) Bone marrow infiltration eg;Leukaemias, Lymphomas,Myelosclerosis,

Multiple myeloma

f) Congenital anaemia eg Sideroblastic anaemia, Congenital

dyserythropoietic anaemia.
Classification…..
III. Anaemias due to increased red cell destruction (Haemolytic
anaemias)
a). Extrinsic (extracorpuscular) red cell abnormalities
b). Intrinsic (intracorpuscular) red cell abnormalities

These are further sub-classified as below;

Classification……
B. MORPHOLOGIC CLASSIFICATION.

1. Microcytic, hypochromic: MCV, MCH, MCHC are all reduced e.g.-

in iron deficiency anaemia and in certain noniron deficient anaemias
(sideroblastic anaemia, thalassaemia,anaemia of chronic disorders).

2. Normocytic, normochromic: MCV, MCH, MCHC are all normal

e.g. after acute blood loss, haemolytic anaemias, bone marrow failure,
anaemia of chronic disorders.

3. Macrocytic: MCV is raised e.g. in megaloblastic anaemia

due to deficiency of vitamin B12 or folic acid.
Etiology
Basically only 3 causes of aneamia exist;
1. Blood loss
2. Increased destruction of RBCs( hemolysis)
3. Decreased production of RBCs
Common cause of anaemia in neonates
 Blood loss:
• antepartum haemorrhage (especially vasa praevia, which although uncommon may be catastrophic)
• feto-maternal haemorrhage (may be acute or chronic)
• feto-fetal haemorrhage (twin-to-twin transfusion.acute or chronic)
• umbilical cord accidents
• intraventricular haemorrhage (iVH)
• pulmonary haemorrhage
 Haemolysis (Haemolytic disease of the newborn)
Iatrogenic (blood sampling): this is the commonest cause of anaemia in the preterm baby
 Anaemia of prematurity: this is a multifactorial condition due to:
• immature erythropoiesis
• reduced erythropoietin production in response to hypoxia
• illness
• recurrent phlebotomy
Bone marrow disorders—uncommon (e.g. Fanconi anaemia, Diamond
Blackfan anaemia)
Pathophysiology of anemia
Erythrocyte life cycle
Erythroid precursors develop in bone marrow at rates usually determined by the requirement for
sufficient circulating Hb to oxygenate tissues adequately. Erythroid precursors differentiate
sequentially from stem cells to progenitor cells to erythroblasts to normoblasts in a process requiring
growth factors and cytokines. This process of differentiation requires several days. Normally, erythroid
precursors are released into circulation as reticulocytes. They remain in the circulation for
approximately 1 day before they mature into erythrocytes, after the digestion of RNA by
reticuloendothelial cells.
Erythrocyte life cycle…..
• The mature erythrocyte remains in circulation for about 120 days
before being engulfed and destroyed by phagocytic cells of the
reticuloendothelial system.
• Many enzymes required by the aerobic and anaerobic glycolytic
pathways decrease within the cell as it ages. In addition, the aging cell
has a decrease in potassium concentration and an increase in sodium
concentration.
• These factors contribute to the demise of the erythrocyte at the end
of its 120-day lifespan
Response to anemia

Subnormal level of haemoglobin causes lowered oxygen carrying capacity of the

blood. This, in turn, initiates compensatory physiologic adaptations such as follows.
• Increased release of oxygen from haemoglobin;
• Increased blood flow to the tissues;
• Maintenance of the blood volume; and
• Redistribution of blood flow to maintain the cerebral blood
supply.

Eventually, however, tissue hypoxia develops causing impaired functions of the

affected tissues. The degree of functional impairment of individual tissues is variable
depending upon their oxygen requirements. Tissues with
high oxygen requirement such as the heart, CNS and the skeletal muscle during
exercise, bear the brunt of clinical effects of anaemia.
Symptoms and signs of aneamia in
children
• Fatigue, lethargy.
• Pallor.
• Poor feeding, anorexia.
• Poor growth.
• Dyspnoea on exertion.
• Rarely stomatitis or koilonychia.
Investigations
Take a full detailed history. Interested in;
• Familial/ethnic causes (sickle cell, thalassaemia).
• Diet (cow’s milk, vegan).
• Overt blood loss.
• Duration of symptoms.
• Drug history, e.g. NSAIDs.

Examine for evidence of anaemia.

• Height and weight (FTT, malabsorption).
• Dysmorphic features, e.g. micrognathia, cleft palate, abnormal/absent thumbs (Fanconi’s anaemia,
Diamond–Blackfan anaemia).
• Jaundice (haemolysis).
• Adenopathy/organomegaly (underlying malignancy)

 In order to confirm or deny the presence of anaemia, its type and its cause, the
following plan of investigations is generally followed,
Investigations……..
• A. COMPLETE BLOOD COUNT(CBC), Intrested majory in;
Hb level, red cell indices, leticulocyte & platelet count , reticulocyte
count,
• B. PERIPHERAL BLOOD FILM EXAMINATION. For morphologic
features after staining it with the Romanowsky dyes. Ie.
-Variation in size (Anisocytosis),
-Variation in shape (Poikilocytosis),
-Inadequate haemoglobin formation (Hypochromasia),
-Compensatory erythropoiesis(i) Polychromasia, ii) Erythroblastaemia
iii) Punctate basophilia or basophilic stippling,iv) Howell-Jolly bodies
Investigations…
-In addition to the morphologic changes of red cells described above,
several other abnormal red cells may be found in different
haematological disorders
Investigations….
F. ERYTHROCYTE SEDIMENTATION RATE. The ESR is a non-specific test
used as a screening test for anaemia. It usually gives a clue to the
underlying organic disease but anaemia itself may also cause rise in the
ESR.
G. BONE MARROW EXAMINATION. Bone marrow aspiration is done in
cases where the cause for anaemia is not obvious.
In addition to these general tests, certain specific tests are done in
different types of anaemias as you will read!!
Management of anaemia
• Non-severe anaemia
Young children (aged < 6 years) are anaemic if their Hb is < 9.3 g/dl (approximately equivalent
to an EVF of < 27%). If anaemia is present, begin treatment, unless the child has severe acute
malnutrition.
Give (home) treatment with iron (daily iron–folate tablet or dose of iron syrup) for 14 days.
• Ask the parent to return with the child in 14 days. Treat for 3 months when possible, as it
takes 2–4 weeks to correct anaemia and 1–3 months to build
up iron stores.

If the child is 1 year and has not received mebendazole in the previous 6
months, give one dose of mebendazole (500 mg) for possible hookworm or whipworm
infestation.
Advise the mother about good feeding practice
Severe anaemia
Give a blood transfusion as soon as possible to:
■ all children with an EVF of 12% or Hb of 4 g/dl
■ less severely anaemic children (EVF, 13–18%; Hb, 4–6 g/dl) with any of the following clinical
features:
– clinically detectable dehydration
– shock
– impaired consciousness
– heart failure
– deep, laboured breathing
– very high malaria parasitaemia (> 10% of red cells with parasites).

• If packed cells are available, give 10 ml/kg over 3–4 h in preference to whole blood. If not
available, give fresh whole blood (20 ml/kg) over 3–4 h.
 severe anemia…..
• Check the respiratory rate and pulse rate every 15 min.
If either rises or there is other evidence of heart failure, such as basal lung
crepitations, enlarged liver or raised jugular venous pressure, transfuse more
slowly. If there is any evidence of fluid overload due to the blood transfusion, give
IV furosemide at 1–2 mg/kg, up to a maximum total of 20 mg.
• After the transfusion, if the Hb remains as low as before, repeat the transfusion.
• In children with severe acute malnutrition, fl uid overload is a common and
serious complication. Give packed cells when available or whole blood at 10 ml/kg
(rather than 20 ml/kg), and do not repeat transfusion based on the Hb level, or
within 4 days of transfusion.
Long term effects of aneamia
The most serious complications of severe anemia arise from tissue
hypoxia.
 Shock
Hypotension
Coronary
pulmonary insufficiency . This is more common in older individuals
with underlying pulmonary and cardiovascular disease