In the name of God, Most Gracious, Most Merciful

EVALUATION OF A CASE OF ANAEMIA

Dr. Mohammed Sadiq Azam PG M:1 (Dr. Sirajs Unit) DCMS @ PEH

CASE HISTORIES:
22/F presented with complaints of shortness of breath (NYHA GR IV), orthopnoea+, chest discomfort and palpitations on exertion which gradually increased over the last 6 months to attain present severity. H/s/o Pica+, H/o passing worms in stools+. No h/o rash, photosensitivity or seizures. O/E: Pallor+, BPPE+, JVP , s3 gallop+, b/l basal creps (fine)+, no organomegaly, no FF. 45/F presented with c/o shortness of breath (NYHA GR II-III), no orthopnoea, no PND. Past h/o jaundice+. H/o blood transfusion in past +. O/E: Pallor++, Icterus+++, Hepatomegaly~2 cm below C/m, Splenomegaly~15cm, no FF. 75/F presented with c/o fatigability and lethargy over last 8 month, initially mild now increased in intensity. H/o sob on exertion (NYHA GR I-II). No H/o orthopnoea/PND. No H/o chest discomfort. Not a known diabetic. H/s/o malena+. H/o loss of appetitie, loss of weight+ over last 5 months. O/E: Pallor++, anicteric no PE, CVS/RS NAD, P/A- NAD.

EVALUATION HISTORY:
Age/Sex Rate of onset Rapid/Slow Blood loss Haematemesis / malena / bleeding piles / menorrhagia / metorrhagia / epistaxis / hematuria / haemoptysis Abdomen Appetitie / weight loss / dysphagia / regurgitation / dyspepsia / abd

pain / diarrhoea / constipation / jaundice / soreness of tongue / previous abd

surgeries Reproductive Menstrual history in detail / number & interval between pregnancies / miscarriages

Urinary system Nocturnal polyuria

CNS Parasthesiae / difficulty in walking

EVALUATION HISTORY:
Bleeding tendency Easy bruising / prolonged bleeding after trivial injuries / bleeding from more than one site Skeletal system Bone pain / Arthritis / Arthralgia Temperature Fever / Night sweats Drug ingestion Previuos / current

Occupation Metal dusts / solvent fumes / lead

Diet Social history Alcoholism Past H/o Previous anaemia: diag & Rx, response to Rx Family H/o Anaemia / recurrent jaundice / IUD & childhood deaths

EVALUATION EXAMINATION:
Skin Colour, texture, petechiae, ecchymoses, scratch marks. Nails Brittleness, longitudinal ridging, koilonychia Conjunctiva/Sclera Pallor, icterus, haemorrhages Retina Haemorrhages, s/o HTN/renal failure, other changes Mouth Mucous membrane: Pallor, petechiae

Gums: Bleeding, hypertrophy

Tongue: Redness, atrophy of papillae Abdomen HSM, either HM or SM, tenderness, mass, ascites

CVS BP, valvular, vascular prosthesis

CNS Peripheral neuritis, s/s/o SADSC

EVALUATION EXAMINATION:
Supf LN Enlargement of cervical, axillary, inguinal, epitrochlear nodes Bones Tenderness (esp. of sternum), tumour Legs Ulcers / scars of healed ulcers P/R Haemorrhoids / CA Rectum Pelvic Menorrhagia, metorrhagia, uterus, cervix Torniquet test Urine Protein, urobilinogen, BS/BP

Provisional Diagnosis: Anaemia for evaluation

THE APPROACH

Is anemia associated with other haematological abnormalities?

Yes BM Examination Leukemias Aplastic anaemias MDS / MF Myelophthisis Megaloblastic anaemia No Is there an appropriate reticulocyte response to anaemia? Yes No RBC Indices

Evidence of haemolysis? Yes No

MCV >100

MCV 80-100 Evaluate: Normocytic anemia

MCV <80

Evaluate cause of haemolysis

Evaluate: haemorrhagic causes

Evaluate: Macrocytic anemia

Evaluate: Microcytic anemia

(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobes Clinical Haematology 11/e, 2004: 951-978)

RETICULOCYTOSIS: A WORD
Retic count = % reticulocytes in RBC population Retic count corrected for anaemia = % retculocytes x pt Hb/15 or pt Hct/45

BUT, Retics released under intense EPO stimulation remain in circulation for approx 2x the usual 1 day survival of non stress retics, so:
Corrected Retic index = Retic count corrected for anaemia x 0.5 < 2.5 = inadequate response hypoprolifertive / maturation disorder (marrow prod impaired) 2.5 = adequate response haemolytic / haemorrahgic

Absolute retic count = %retics x RBC count/l3 Low retic count + active marrow erythropoiesis = ineffective erythropoiesis IDA Sideroblastic anaemia

Thalassemias
(Also associated with LDH)

Macrocytic anaemia
Does the P/S reveal hypersegmented neutrophils / macroovalocytes? Yes Megaloblastic anaemia BM to confirm Test for B12/Folate levels B12 def Schillings test: Corrects with IF Yes No No def Inherited disorders of DNA syn Drugs tht interfere with DNA syn
Ileal disease Previous ileal Sx Small bowel bac overgrowth Fish tapeworm Drug induced malabsorption

No Nonmegaloblastic anaemia Folate def Haemolytic Reticulocytosis N/ Consider: - Alcohol - Hypothyroidism - Liver disease If NO: BM exam
- MDS - Red cell aplasia - Acq siderobl anaemia - Herid dyserythropoietic anaemia (I& III)

Pernicious anaemia: Gastric resection

Poor diet Drug induced malabs Jejuneal resection Tropical sprue Gluten sensitivity Needs - Pregnancy - Chronic hemolysis

(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobes Clinical Haematology 11/e, 2004: 951-978)

Microcytic anaemia
Reticulocytes Low / N Iron Profile

Appropriate age: Rule out malignancy

Increased P/S: Abnorm morphology Labs for RBC destruc Hb studies Homozygous thal Haemolytic elliptocyt Herid pyropoikilocytosis

Fe TIBC Ferritin
Iron deficiency

Fe N/ TIBC N/ Ferritin

N. Fe N. TIBC N. Ferritin

Fe N. TIBC Ferritin

ESR, CRP+ or other studies s/o underlying Inflammatory disorder AOCD

Hb electrophoresis BM examination with Fe stains Thal trait Thal trait Hb E syn Hb C disorder

Sideroblastic anaemia

(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobes Clinical Haematology 11/e, 2004: 951-978)

Normocytic anaemia
Reticulocytes RBC prod H/o jaundice, splenomegaly Presence of P/S abnormalities Bilirubin / LDH Yes No Haemolysis Positive Haemolytic anaemia BM aspirate & Bx Anaemia of renal disease Anaemia of liver disease Anaemia due to endocrine failure Infiltrative disorder
(Leuk, myeloma, MF, Mets)

N./ RBC prod - S. Chemistries to screen for renal, hepatic, endocrine disease - Consider EPO levels, thyroid studies Negative N. / High

S.Fe

Low AOCD Early IDA

Red cell aplasia MDS Dyserythropoietic anaemia (Type II)

(Ref: Bertil Glader: Anaemia: General Considerations, Wintrobes Clinical Haematology 11/e, 2004: 951-978)

HAEMORRHAGIC ANAEMIA:
Retic index 2.5. Polychromatophilic macrocytes ++ in P/S Marrow examination is rarely required if retic index is increased appropriately. RBC indices are typically normocytic or slightly macrocytic (reflects retics)

Blood loss Acute Subacute Chronic Missed

No reticulocytosis

Presents ///ar to IDA

Modest reticulocytosis

Observe for 2-3 weeks Signs of recovery - Hb - Retic count

HAEMORRHAGIC ANAEMIA:
Volume of blood loss (ml)
500-1000

Blood volume (%)

10-20

Symptoms
Few if any symptoms

1000-1500

20-30

Asymptomatic while at rest in a recumbent position; light headedness and hypotension when upright; tachycardia

1500-2000

30-40

Symptoms present when recumbent; thirst, SOB, clouding or LOC; BP, CO, venous pressure decrease, pulse usually rapid; extremities become cold, clammy & pale Lactic acidosis, shock; irreversible shock, death

2000-2500

40-50

HAEMOLYTIC ANAEMIA:
Least common form of anaemia High retic count: Reflects the ability of the erythroid marrow to compensate for haemolysis, and, in the case of extravascular haemolysis, the efficient recycling of iron from the destroyed RBC to support RBC production. Intravascular haemolysis PNH loss of Fe limits marrow response Hence, the level of marrow response depends on: The severity of anaemia The nature of the underlying disease process Hemoglobinopathies mixed picture. (Retic count is but with respect to degree of marrow erythroid hyperplasia).

HAEMOLYTIC ANAEMIA:
Presentation varies: Acute self limiting illness (autoimmune/EM pathway/GR defects) Chronic process (Hb defects/ RBC defects) with a typical history HS: chronic course present with complications such as bilirubin gallstones or splenomegaly and not anaemia per se. Chronic haemolysis also prone to aplastic anaemia if infections occur.

HAEMOLYTIC ANAEMIA: INTRAVASCULAR LYSIS

PNH Erythrocyte fragmentation disorders Transfusion reactions resulting from ABO incompatability Paroxysmal cold haemoglobinuria AIHA (occasionally) Infections:
Blackwater fever in falciparum malaria Clostridial sps

Chemical mediated:
Arsine poisoning

Snake & Spider venoms

Acute drug reactions with G6PD def I.V. admin of distilled water

Thermal injury

HAEMOLYTIC ANAEMIA: LABS

Morphological abnormalities: Spherocytes, Elliptocytes, Stomatocytes, Acanthocytes, Echinocytes, Sickle cells, Target cells, Schistocytes Direct Antiglobulin test (Coombs test): +ve in IHA (2-5% false neg) Osmotic fragility test : HS (Osmotic gradient ektacytometry is more sensitve & specific, but not widely available) Tests for Heinz bodies (supravital staining): G6PD def, unstable Hb disease, thalassemias, chemicals. (Not seen when spleen is intact)

HAEMOLYTIC ANAEMIA: D/D

Asso with anaemia & retculocytosis:
Hemorrhage Recovery from iron, folate or vitamin B12 deficiency

Recovery from marrow failure

Asso with jaundice & anaemia:

Ineffective erythropoiesis (intramedullary erythropoiesis) Bleeding into a body cavity or tissue

Asso with jaundice without anaemia

Defective bilirubin conjugation Crigler-Najjar syndrome Gilbert syndrome

Marrow invasion Myoglobinuria

CONCLUSION:
Any case of anaemia requires a detailed work up starting with history. Stepwise approach is the golden rule. IDA in elderly avoid being Penny wise, Pound foolish In tropical countries, tropical malabsorption syndromes are more rampant than we realize LOOK OUT, it may be missed unless you look for it.

Better not to start any IFA or B12 supplements until we diagnose the cause of anaemia.
Bone marrow is not the answer to every anaemia AVOID indiscriminate use.

No cost is greater than the patients life. Investigate whats mandatory.

Delayed diagnosis is better than a wrong diagnosis DO NOT hurry to treat.