IM9.1-17 | Anaemia — Graded Quiz

Correct. Oral iron absorption is SIGNIFICANTLY reduced when taken with food — studies show a 40-60% reduction in iron absorption when taken with meals compared to taken on an empty stomach. The correct instruction is to take ferrous sulphate 30-60 minutes BEFORE meals, with water or dilute fruit juice (vitamin C enhances absorption). Common reasons for inadequate response: taken with food, tea or antacids (all chelate iron), ongoing blood loss, non-compliance, or concurrent malabsorption.

Iron absorption is maximised when taken on an empty stomach (30-60 min before meals) with water or ascorbic acid. Inhibitors: tea/coffee (tannins), phytates (cereals), calcium (dairy), antacids, proton pump inhibitors. Expected response to oral iron: reticulocyte peak at day 7-10; Hb rise 1-2 g/dL per 3-4 weeks. Continue treatment for 3-6 months after Hb normalises to replenish stores.

Ferrous sulphate 200 mg contains 65 mg elemental iron; three times daily provides 195 mg elemental iron — an adequate dose. The problem is administration with meals: food (particularly tannins in tea, phytates, antacids, dairy) chelates iron and reduces absorption by 40-60%. Iron must be taken 30-60 minutes before meals on an empty stomach. Adequate Hb response is a rise of 1-2 g/dL per 3-4 weeks.

Correct. Beta-thalassaemia major presents in childhood with severe transfusion-dependent anaemia, hepatosplenomegaly from extramedullary haemopoiesis, bone deformities (frontal bossing, maxillary overgrowth — thalassaemic facies), and markedly elevated iron stores (secondary iron overload from repeated transfusions). HPLC showing NO HbA (with predominantly HbF and elevated HbA2) confirms beta-zero thalassaemia — homozygous state where no normal beta-globin chains are produced.

Beta-thalassaemia major (transfusion-dependent): HPLC shows HbF predominantly + elevated HbA2, NO HbA in severe forms. Iron overload from transfusions requires iron chelation (deferasirox or desferrioxamine). Thalassaemia trait (carrier): mild microcytosis, elevated HbA2 >3.5%, normal Hb. Prenatal diagnosis by chorionic villus sampling prevents new cases. India has ~40 million carriers and ~10,000 new major births/year.

Beta-thalassaemia trait is asymptomatic with Hb near normal. Beta-thalassaemia major presents in infancy/childhood with severe anaemia requiring regular transfusions. The HPLC result (no HbA, elevated HbF and HbA2) indicates a homozygous beta-zero mutation. Sickle cell disease would show HbS by HPLC. HbE-thalassaemia is common in Northeast India and shows HbE on HPLC.

Correct. Anti-intrinsic factor antibodies are HIGHLY SPECIFIC (> 95%) for pernicious anaemia — an autoimmune gastritis causing loss of parietal cells (which produce both intrinsic factor and gastric acid). Upper GI endoscopy confirms atrophic gastritis and allows biopsy to exclude gastric carcinoma, which has a significantly higher incidence in pernicious anaemia (2-3x risk). Endoscopy is the investigation that provides both confirmation and cancer surveillance.

Pernicious anaemia (autoimmune gastritis): anti-intrinsic factor antibodies (high specificity, ~50% sensitivity); anti-parietal cell antibodies (high sensitivity, low specificity — present in 10% of normal elderly). Management: IM cyanocobalamin (1000 mcg) daily for 1 week, then weekly for 4 weeks, then monthly for life. Oral B12 (1000-2000 mcg/day) is alternative if no malabsorption. Gastric cancer surveillance by endoscopy.

Anti-intrinsic factor antibodies are essentially diagnostic of pernicious anaemia. Endoscopy confirms atrophic gastritis and provides cancer surveillance — pernicious anaemia carries a 2-3-fold increased risk of gastric carcinoma. Bone marrow aspiration is not needed when B12 deficiency is confirmed serologically. Serum methylmalonic acid confirms functional B12 deficiency but is used for borderline B12 levels, not when B12 is undetectable.

Correct. Parvovirus B19 infects erythroid precursors and causes transient aplastic crisis — the reticulocyte count drops to near zero (0.4%), causing acute severe anaemia in patients with underlying haemolytic anaemias (hereditary spherocytosis, sickle cell, G6PD). This is different from a haemolytic crisis (where reticulocytosis would be high). Treatment is urgent red cell transfusion to correct severe symptomatic anaemia; the aplasia is self-limiting (7-14 days) as the immune system clears parvovirus.

Parvovirus B19 aplastic crisis: occurs in all chronic haemolytic anaemias (HS, SCD, G6PD, thalassaemia). Reticulocytes drop to 0-1% (vs haemolytic crisis: reticulocytes 10-20%). Duration: 7-14 days (self-limited). Treatment: PRBC transfusion for severe anaemia; IVIG for immunocompromised patients who cannot clear the virus. Isolate from pregnant women (parvovirus causes hydrops fetalis).

Aplastic crisis (parvovirus B19): reticulocytes FALL to near zero because parvovirus B19 selectively infects and destroys erythroid precursors in the bone marrow. In haemolytic crisis, reticulocyte count is HIGH (8-20%). The near-zero reticulocyte count with acute Hb drop in the context of positive parvovirus B19 IgM and hereditary spherocytosis = aplastic crisis. Transfusion is life-saving; the aplasia is self-limited.

Correct. When CRP is elevated, ferritin is an acute-phase reactant and may be falsely elevated — even a ferritin of 22-50 mcg/L can represent true iron deficiency in the context of inflammation. The co-existence of IDA and ACD (sometimes called IDA on a background of ACD) is common. When iron studies are ambiguous, bone marrow staining for haemosiderin (Prussian blue) remains the gold standard — absent stainable iron = IDA; present iron = ACD or combined.

The IDA vs ACD diagnostic dilemma: serum ferritin < 12 mcg/L = IDA (definitive); > 100 mcg/L = unlikely IDA; 12-100 mcg/L with elevated CRP = equivocal — bone marrow iron staining is definitive. Soluble transferrin receptor (sTfR) is elevated in IDA but NOT in ACD (unaffected by inflammation); sTfR/log ferritin ratio > 2.0 suggests IDA. This is the most specific non-invasive marker when inflammation is present.

Ferritin is an acute-phase reactant — when CRP is elevated, ferritin may be falsely elevated, masking true iron deficiency. A ferritin of 22 mcg/L with elevated CRP does NOT exclude IDA; up to 50 mcg/L can represent IDA in inflammatory states. Bone marrow iron staining (Prussian blue) is the definitive test to distinguish IDA from ACD when serum markers are equivocal.

Correct. A positive direct Coombs test confirms immunologically-mediated haemolysis — autoimmune haemolytic anaemia (AIHA). Warm AIHA (IgG-mediated, active at 37°C) is the most common type and is a recognised extra-renal manifestation of SLE. The elevated reticulocyte count (8%), raised LDH, and undetectable haptoglobin confirm active haemolysis. Mycophenolate causes myelosuppression (low reticulocytes), not haemolysis.

Direct Coombs test: detects antibody/complement on the RBC surface — POSITIVE = immune haemolysis (AIHA, drug-induced, haemolytic transfusion reaction). Indirect Coombs: detects circulating antibodies in serum. Warm AIHA (IgG): SLE, CLL, drugs; treated with steroids, then rituximab or splenectomy. Cold AIHA (IgM): mycoplasma, EBV, lymphoma; treated with avoiding cold, rituximab.

The positive direct Coombs test is the pathognomonic finding distinguishing immune from non-immune haemolysis. AIHA in SLE is warm-type (IgG), with extravascular haemolysis occurring in the spleen (not intravascular). ACD from SLE would show normocytic anaemia with low reticulocyte count — not reticulocytosis. Microangiopathic haemolytic anaemia (MAHA) shows fragmented cells (schistocytes) on smear, not a positive Coombs.

Correct. Acute chest syndrome (ACS) — new pulmonary infiltrate + respiratory symptoms + fever in SCD — is a haematological emergency with significant mortality. The treatment is exchange transfusion (preferred — reduces HbS percentage without increasing viscosity) plus antibiotics (covering atypical organisms: ceftriaxone + azithromycin), oxygen, incentive spirometry, and analgesia. Simple transfusion is used if exchange is not immediately available, with caution to avoid hyperviscosity.

Acute chest syndrome is the leading cause of death in sickle cell disease. Triggers: fat embolism from infarcted bone marrow, infection, pulmonary vaso-occlusion. Management: oxygen, analgesia, bronchodilators, incentive spirometry, IV antibiotics (ceftriaxone + azithromycin), exchange transfusion. Simple transfusion if exchange unavailable. Target HbS < 30% post-exchange.

Acute chest syndrome is a life-threatening complication of sickle cell disease (new infiltrate + respiratory symptoms). Exchange transfusion is preferred over simple transfusion because it reduces the percentage of HbS (the sickle haemoglobin) while keeping total Hb from rising too high, thereby preventing the hyperviscosity that worsens vaso-occlusion. Antibiotics are added to cover fat embolism-mimicking pneumonia (atypical organisms).

Correct. Ring sideroblasts in a hypercellular bone marrow with dysplastic erythroid precursors (ineffective erythropoiesis) in a middle-aged man without toxic exposure or heavy alcohol use indicates myelodysplastic syndrome with ring sideroblasts (MDS-RS) — formerly RARS (refractory anaemia with ring sideroblasts). Ring sideroblasts (> 15% or >5% with SF3B1 mutation, per WHO 2022) with dysplasia characterise this subtype.

Indications for bone marrow examination in anaemia: unexplained anaemia with abnormal WBC/platelets, suspected marrow infiltration (lymphoma, metastatic carcinoma), haematological malignancy workup, aplastic anaemia diagnosis, MDS diagnosis. Ring sideroblasts on Prussian blue stain: iron-laden mitochondria arranged in a ring around the erythroid nucleus. MDS classification per WHO 2022 requires blast percentage, dysplasia lineage count, and molecular genetics (SF3B1 for MDS-RS).

Aplastic anaemia shows a hypoCELLULAR marrow (fatty replacement, not dysplasia). Lead poisoning and alcohol-related sideroblastic anaemia are reversible causes with acquired ring sideroblasts, but they do not cause multi-lineage dysplasia. Dysplastic marrow morphology with ring sideroblasts in the absence of a reversible cause indicates MDS-RS, a clonal haematopoietic disorder.

Correct. The clinical picture — acute onset rigors, fever, back pain, and haematuria within minutes of starting a transfusion — is ACUTE HAEMOLYTIC TRANSFUSION REACTION (AHTR) due to ABO incompatibility until proven otherwise. The FIRST and most critical action is to STOP the transfusion immediately. Then: maintain IV access (saline), send blood bag + new patient sample to the blood bank, check identity bands (human error is the most common cause), support circulation, monitor urine output, and manage renal complications. Haematuria indicates haemoglobinuria from intravascular haemolysis.

Transfusion reactions: immediate acute haemolytic (ABO incompatibility) — stop immediately, haematuria, back pain, hypotension; febrile non-haemolytic (FNHTR) — fever without haemolysis, due to cytokines in WBC-containing products, managed with paracetamol; allergic/urticarial — antihistamines, slow transfusion; anaphylaxis (IgA deficiency) — adrenaline, stop; TRALI (transfusion-related acute lung injury) — acute hypoxia within 6 hours, stop, supportive. STOP is the first action for ALL serious reactions.

Haematuria + back pain + fever + rigors within minutes of a transfusion = acute haemolytic transfusion reaction (AHTR). The FIRST step is always to STOP the transfusion. AHTR from ABO incompatibility carries up to 10% mortality. Most cases are due to clerical errors (wrong blood given to wrong patient). After stopping: IV saline, send bag + patient sample to blood bank, monitor renal function, treat DIC and renal failure if they develop.

Correct. IV iron sucrose (ferric sucrose) is safe in pregnancy (after the first trimester) and is the preferred parenteral iron preparation when oral iron is not tolerated or is inadequate. It avoids the staining, pain, and inconsistent absorption of IM iron. IV iron should always be given with anaphylaxis preparedness (resuscitation equipment, monitoring for 30 minutes post-infusion). Iron dextran (IM) is associated with more systemic reactions; IM iron sorbitol has GI side-effects. IV iron is the standard in many national programmes for severely anaemic pregnant women in India.

Oral iron failure indications for parenteral therapy: genuine GI intolerance, malabsorption syndrome, IBD (active), or severe anaemia requiring rapid correction (e.g., near-term pregnancy). Preparations: IV iron sucrose (safest; multiple doses, maximum 300 mg/dose), IV ferric carboxymaltose (single large dose, 1000 mg), IV low-molecular-weight iron dextran. All require anaphylaxis precautions (resuscitation equipment, 30-min observation). IM iron is now rarely used due to inconsistent absorption and skin discolouration.

Parenteral iron indications: intolerance of oral iron, malabsorption, inflammatory bowel disease, severe anaemia near term requiring rapid correction. IV iron sucrose is the safest parenteral preparation — well-established safety profile in pregnancy. IM preparations (sorbitol, dextran) are less predictable, more painful, and associated with skin staining. IV iron must be given as a slow infusion with anaphylaxis preparedness.

Correct. Haemoglobin normalises within 4-8 weeks of adequate iron treatment, but iron STORES (ferritin) take an additional 3-6 months to replenish. Stopping when symptoms improve but before stores are replenished inevitably leads to relapse — patients often return 3-6 months later with recurrent IDA. The patient communication message: the blood count improves first, but the body's iron reserves take months longer to refill. Treat for at least 3 months after Hb normalises.

IDA treatment duration: treat until Hb normalises (4-8 weeks), then continue for a minimum of 3 months (ideally until ferritin > 30 mcg/L) to replenish stores. Total treatment: usually 4-6 months. Patient counselling must address: take before meals, avoid tea/coffee, expect black stools (normal), side effects (nausea, constipation) are manageable. Address the underlying cause (GI bleeding, menorrhagia, dietary deficiency) concurrently.

Recovery from IDA has two phases: (1) Hb normalisation (4-8 weeks) — symptoms improve; (2) iron store replenishment (additional 3-6 months) — ferritin reaches normal. Stopping at phase 1 leaves stores depleted; any minor bleeding or dietary shortfall will trigger relapse. Always explain this to patients to improve adherence. The target ferritin at treatment completion should be > 30 mcg/L.