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APPROACH TO ANAEMIA IN GENERAL PRACTICE
DR.S.ABBAS ALI
MD DNB MNAMS
Fellowship in cardiology
PGDCC (ultrasonography)
PGDCC(Echocardiogram)
FCGP,MCCP (Cardiology)
Lecturer, department of medicine
KD MEDICAL COLLEGE, MATHURA

Anaemia is usually defined clinically as a reduction of the haemoglobin concentration to less than 13g/dl (males) or less than 12g/dl (females). Haemoglobin constitutes about 1% of total body weight. It is a common problem in general practice.
Degree of Anaemia: Anaemia is often classified as mild degree (9-11 gm %), moderate
(7-9 gms %), severe (4-7 gm %) and very severe (<4gm %). It is also classified according to Haematocrit (PCV) %.
While evaluating of the patient with anemia and making of specific diagnosis requires a clinical assessment and laboratory investigations. The two must be put together for a comprehensive diagnosis.
Clinical assessment requires careful history and physical examination.
A careful evaluation of medical history often gives vital clues to the cause of anemia. The acuity of anemia, association with other symptoms & history of any chronic illness are important. Some important points
History Comments
Age Iron def. rare before 6 months
Neonatal anemia with reticulocytosis suggests blood loss or Hemolysis.
B-thal. sickle cell anemia appear by 4-8 mths. of age

Genetic & family history X-linked: G-6-PD def
Autosomal dominant: Spherocytosis
Autosomal recessive: Sickle cell anemia, Fanconi
Family member with h/o early cholecystectomy/ biliary calculus
Race & Ethnicity

Nutrition Cows milk & iron deficiency
Strict vegetarian: B12 deficiency
Goat’s milk: Folate def.
Pica, Plumbism & iron def.

Drugs G-6-PD def
Immune mediated hemolysis (Penicillin)
Bone marrow suppression
Phenytoin & folate def.

Diarrhea Malabsorption of iron, B12 &E
Inflammatory bowel disease
Milk protein allergy- chronic blood loss
Intestinal resection & B12 def

Infection Giardia- iron def
Intestinal bacterialovergrowth- blind loop & B12
Epstein barr, CMV & Parvo virus- Bone marrow suppression
Malaria, Kalazar, Chronic infection


Nutritional history related to drugs or alcohol intake and family history of anemia should always be assessed. Certain geographic backgrounds and ethnic origins are associated with an increased likelihood of an inherited disorder of the hemoglobin molecule or intermediary metabolism. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and certain hemoglobinopathies are seen more commonly in those of Middle Eastern or African origin, including African Americans who have a high frequency of G6PD deficiency. Other information that may be useful includes exposure to certain toxic agents or drugs and symptoms related to other disorders commonly associated with anemia.
Physical Examination
 General appearance of child & assessment of growth parameters helps decide the acuity or chronicity of anemia & other associated illnesses.
 Look for signs of trauma
 Presence of petecie, bruising & ecchymosis
 Lymphadenopathy, Hepato-spleenomegaly & abdominal mass. Splenomegaly and lymphadenopathy suggest an underlying lymphoproliferative disease,
 Prominent cheek bones, frontal bossing indicates hemolytic anemia
 Associated congenital malformations- Fanconi anemia.
 Tell tale signs of any chronic illness e.g. hypertension, short stature, arthritis, cluubing, cyanosis etc.
 petechiae suggest platelet dysfunction
 blood in the stool
 In the anemic patient, physical examination may demonstrate a forceful heartbeat, strong peripheral pulses, and a systolic "flow" murmur. The skin and mucous membranes may be pale if the hemoglobin is <80–100 g/L (8–10 g/dL). This part of the physical examination should focus on areas where vessels are close to the surface such as the mucous membranes, nail beds, and palmar creases. If the palmar creases are lighter in color than the surrounding skin when the hand is hyperextended, the hemoglobin level is usually <80 g/L
Laboratory Evaluation: Initial Laboratoryy workup of anemia requires

1. Complete blood count (CBC) and it is the single most important investigation in anaemia. It
should include Hb, Hct, WBC, platelet count and RBC indices viz. RBC count, MCV, MCH, and RDW. The components of the CBC also help in the classification of anemia. Microcytosis is reflected by a lower than normal MCV (<80), whereas high values (>100) reflect macrocytosis. The MCH and MCHC reflect defects in hemoglobin synthesis (hypochromia). Automated cell counters describe the red cell volume distribution width (RDW).
2. Peripheral blood smear examination: A careful evaluation of the peripheral blood smear is important, and clinical laboratories often provide a description of both the red and white cells, a white cell differential count, and the platelet count. In patients with severe anemia and abnormalities in red blood cell morphology and/or low reticulocyte counts, a bone marrow aspirate or biopsy can assist in the diagnosis. The peripheral blood smear also provides important information about defects in red cell production. As a complement to the red cell indices, the blood smear also reveals variations in cell size (anisocytosis) and shape (poikilocytosis).
3. Reticulocyte count: An accurate reticulocyte count is key to the initial classification of anemia. Normally, reticulocytes are red cells that have been recently released from the bone marrow. Normally, the reticulocyte count ranges from 1 to 2% and reflects the daily replacement of 0.8–1.0% of the circulating red cell population.

The above triad comprises the primary investigations in anaemia and can be performed
on a single EDTA blood sample.
Secondary investigations are guided by the results of the above tests in a given clinical context, and may include
1. Tests of Iron Supply and Storage: they include serum ferritin, total iron binding capacity, serum iron, serum transferring percentage. This tests reflect the availability of iron for hemoglobin synthesis. The percent transferrin saturation is derived by dividing the serum iron level (x 100) by the TIBC. The normal serum iron ranges from 9 to 27 mol/L (50–150 g/dL), while the normal TIBC is 54–64 mol/L (300–360 g/dL); the normal transferrin saturation ranges from 25 to 50%. A diurnal variation in the serum iron leads to a variation in the percent transferrin saturation. The serum ferritin is used to evaluate total body iron stores. Adult males have serum ferritin levels that average ~100 g/L, corresponding to iron stores of ~1 g. Adult females have lower serum ferritin levels averaging 30 g/L, reflecting lower iron stores (~300 mg). A serum ferritin level of 10–15 g/L represents depletion of body iron stores. However, ferritin is also an acute-phase reactant and, in the presence of acute or chronic inflammation, may rise several-fold above baseline levels. As a rule, a serum ferritin more than 200 g/L means there is at least some iron in tissue stores.
2. vitamin B12, and RBC folate levels
3. Hb electrophoresis and quantitation (Hb A2, Hb F etc)
4. Blood biochemistry for hepatic and renal functions
5. Bone-marrow aspiration
6. Trephine biopsy from bone marrow
7. Imaging studies may include X-ray chest/ skull/ other bones as warranted, ultrasound abdomen, radio-isotope studies
8. Other specialized tests include Coombs test, osmotic fragility, Ham s test, erythropoietin level, immunocytochemistry, cytogenetics etc
CLINICAL APPROACH TO A PATIENT WITH ANAEMIA
Anaemia is not a disease by itself but only a manifestation of disease. Hence, it is imperative to look for the underlying disease responsible for anaemia.
KEY ISSUES to decide in a patient with anaemia are:
1. Is it a TRUE anaemia?
2. Is the anaemia HEREDIATARY or ACQUIRED?
3. Is there any ABNORMAL BLEEDING?
4. Is there exposure to DRUGS, CHEMICALS, or TOXINS?
5. Is there a co-existing SYSTEMIC DISEASE
6. What is the nature of DIET and ETHNICITY.
CLASSIFICATION OF ANAEMIA broadly anaemia is classified in to
Hereditary : the defect often lies within the RBC. It means its Hb or- its enzyme or- its membrane. Reticulocyte count is high in hereditary anemias.
Acquired: here The defect is often extra-corpuscular
Classification Based on RETICULOCYTE INDEX Normal 0.2 – 2.0%
Reticulocyte count Very Low indicates a decreased RBC production in bone-marrow.
RETICULOCYTE COUNT Very High indicates an excessiveproduction of RBCs in bone-marrow anaemia results from either excessive destruction or excessiveloss of RBCs
RETICULOCYTE Normal (0.2- 2.0%) indicates no positive diagnostic
Classification of anaemia based on MCV (RBC Size) : MCV or mean corpuscular volume is an important parameter to classify anemia.
Microcytic (MCV <80 fl or femtolitres): it is due to inadequate Hb synthesis
Causes
1. Iron deficiency anaemia – commonest
2. Thalasmia
3. Lead toxicity
4. Anaemia of chronic disease
5. Sideroblastic anaemia
Macrocytic (MCV >100 fl)
Causes
MEGALOBLASTIC: Altered DNA synthesisleading to large & fluffy nucleus in the early RBCs
1. Usually from vitamin B12, folate deficiency, or some enzymatic involvement. Segmented nutrophils commonly associated with B12 or folate deficiency anaemia
2. Diet and drugs are the commonest culprit.
3. Increased demand may occur in haemolysis and during pregnancy & lactation
NON-MEGALOBLASTIC: DNA in red cells is normal or OK.
Causes:
1. Liver diseases
2. Alcoholism
3. Aplastic anemia
4. Hypothyroidism
Normocytic (MCV 80-100 fl) Most anaemias start as normocytic. In most diseases, it remains normocytic only
Causes
1. Anaemia of blood loss
2. Anaemia of chronic disease ( sometimes low MCV)
3. Bone marrow failure
4. Renal failure
Differential diagnosis of microcytic anaemia
IRON DIFICIENCY ANAEMIA – DIAGN0SIS THROUGH LAB INVESTIGATIONS
Hb% -- ---low
Serum ferritin ------ low
Total iron binding capacity -----very high
Serum iron ------low
MCV -----low
THALASMIA: It is due to defect in globin chain.
Hb%------normal
Serum ferritin ------normal
Total iron binding capacity------- normal
Serum iron --------normal
MCV ------low
Sideroblastic anaemia
Serum iron : increased
Serum ferritin: increased
Total iron binding capacity: normal
MCV----low
Anaemia of chronic disease:
Serum iron : low
Serum ferritin : increased
Total iron binding capacity : decreased
MCV-----low

Management
The treatment of anemia depends on the cause. Deficiency anemia can be effectively treated by therapeutic doses of the deficient mineral or vitamins. In anaemias, a right treatment may bring patient back to life whereas an inappropriate or delayed treatment may take life away

Cavity: a cavity is gas containing space with in the lung surrounded by a wall greater than 1mm thick (a gas containing space possessing wall 1mm or thinner is a bulla). The wall thickness up to 5mm is benign and between 5 to 15 mm may be benign or malignant and above 15mm is definitely malignant. see example in photo album nazira x-ray

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