In the name of God, Most Gracious, Most Merciful
EVALUATION OF A CASE OF ANAEMIA - Dr. Mohammed Sadiq Azam PG M:1 (Dr. Siraj’s 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:• 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 evaluationTHE APPROACH …
Is anemia associated with other haematological abnormalities? Yes No BM Examination Is there an appropriate reticulocyte response to anaemia? Leukemias Aplastic anaemias Yes No MDS / MF Myelophthisis RBC Indices Megaloblastic anaemia Evidence of haemolysis? MCV >100 MCV 80-100 MCV <80 Yes No Evaluate: Normocytic anemiaEvaluate cause Evaluate: Evaluate: Evaluate:of haemolysis haemorrhagic causes Macrocytic anemia Microcytic anemia (Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s 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 No Nonmegaloblastic anaemia Megaloblastic anaemia – BM to confirm Test for B12/Folate levels ↑ Reticulocytosis B12 def No def Folate def Haemolytic N/↓Schilling’s test: Inherited disorders of DNA syn Poor diet Consider:Corrects with IF Drugs tht interfere with DNA syn Drug induced malabs - Alcohol Jejuneal resection - Hypothyroidism Tropical sprue - Liver diseaseYes No Ileal disease Previous ileal Sx Gluten sensitivity Small bowel bac overgrowth ↑ Needs If NO: BM examPernicious anaemia: Fish tapeworm - PregnancyGastric resection Drug induced malabsorption - Chronic hemolysis - MDS - Red cell aplasia - Acq siderobl anaemia - Herid dyserythropoietic anaemia (I& III) (Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)
Microcytic anaemia Appropriate age: Rule out malignancy Reticulocytes Low / N Increased Iron Profile P/S: Abnorm morphology Labs for ↑ RBC destruc↓ Fe ↓ Fe N. Fe ↑ Fe Hb studies↑ TIBC N/↓ TIBC N. TIBC N. TIBC↓ Ferritin N/↑ Ferritin N. Ferritin ↑ Ferritin - Homozygous β thal - Haemolytic elliptocyt - Herid pyropoikilocytosisIron deficiency ↑ ESR, CRP+ Hb electrophoresis or other studies BM examination with Fe stains s/o underlying Inflammatory disorder - α Thal trait - β Thal trait - Hb E syn AOCD - Hb C disorder Sideroblastic anaemia (Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s Clinical Haematology 11/e, 2004: 951-978)
Normocytic anaemia Reticulocytes ↑ RBC prod N./↓ RBC prodH/o jaundice, splenomegaly - S. Chemistries to screen S.FePresence of P/S abnormalities for renal, hepatic, endocrine↑ Bilirubin / LDH disease - Consider EPO levels, thyroid studies Yes Haemolysis Low Positive Negative N. / High No Haemolytic anaemia AOCD BM aspirate & Bx Early IDA - Anaemia of renal disease - Anaemia of liver disease - Infiltrative disorder - Anaemia due to endocrine failure (Leuk, myeloma, MF, Mets) - Red cell aplasia - MDS - Dyserythropoietic anaemia (Type II) (Ref: Bertil Glader: Anaemia: General Considerations, Wintrobe’s 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 Missed Subacute ChronicNo reticulocytosis Presents ///ar to IDA Observe for 2-3 weeks Signs of recovery Modest reticulocytosis - Hb ↑ - Retic count ↓
HAEMORRHAGIC ANAEMIA:Volume of Blood Symptomsblood loss (ml) volume (%)500-1000 10-20 Few if any symptoms1000-1500 20-30 Asymptomatic while at rest in a recumbent position; light headedness and hypotension when upright; tachycardia1500-2000 30-40 Symptoms present when recumbent; thirst, SOB, clouding or LOC; BP, CO, venous pressure decrease, pulse usually rapid; extremities become cold, clammy & pale2000-2500 40-50 Lactic acidosis, shock; irreversible shock, death
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 (Coomb’s 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 patient’s life. Investigate what’s mandatory.• Delayed diagnosis is better than a wrong diagnosis – DO NOT hurry to treat.