Hematology & Laboratory Medicine & Family Medicine
Red blood cells (erythrocytes)
Red blood cells, or erythrocytes, are the most numerous blood cells in the body - there are around 25,000 billion of them in an adult, or 70 % of all cells in the human body. Devoid of nuclei and mitochondria at maturity, these biconcave discs measuring around 6-8 µm in diameter are specialized for a single function: transporting oxygen from the lungs to the tissues, and carbon dioxide in the opposite direction, thanks to hemoglobin, which occupies 33 % of their volume and accounts for 97 % of their proteins. Produced in the red bone marrow by erythropoiesis (the process by which hematopoietic stem cells differentiate into mature erythrocytes in 7 days), they circulate for a lifespan of 100-120 days before being phagocytosed by splenic and hepatic macrophages (reticuloendothelial system). Their production is finely regulated by erythropoietin (EPO), a glycoprotein synthesized at 90 % by kidney peritubular cells in response to tissue hypoxia. The red cell count is an integral part of the complete blood count (CBC), which also includes the calculated erythrocyte indices: mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin content (MCHC) and red cell distribution index (RCI). The combined interpretation of these parameters and the blood smear enables the etiological diagnosis of anemia, polycythemia and erythrocyte morphological abnormalities to be directed towards deficiency, hemolytic, bone marrow or constitutional causes.
Physiology, Normal Values, and Erythrocyte Indices
- Erythropoiesis and regulation of erythrocyte production: medullary erythropoiesis: differentiation of pluripotent stem cells (HSC) → erythroid progenitors (BFU-E → CFU-E) → proerythroblast → basophilic erythroblast → polychromatophilic erythroblast → orthochromatic erythroblast → reticulocyte (extruded nucleus) → mature erythrocyte (loss of organelles) → total duration: 7 days in marrow → reticulocytes complete maturation in 1-2 days in peripheral blood (loss of residual ribosomes); EPO regulation: tissue hypoxia (altitude + anemia + hypoxemia) → renal peritubular cells → EPO secretion → binding to EPOR receptor on erythroid precursors → proliferation + differentiation + survival (inhibition of apoptosis) → increased erythrocyte production - human recombinant EPO (epoetin alfa - Eprex + darbepoetin alfa - Aranesp): used in anemia of chronic renal failure + chemotherapy + surgery + myelodysplastic syndromes; iron regulation: hemoglobin synthesis requires iron - its intestinal absorption is regulated by hepcidin (hepatic protein): elevated hepcidin (inflammation + martial overload) → degradation of ferroportin → blockage of iron absorption and release → inflammatory anemia; regulation by vitamins: vitamin B12 (cobalamin) and folate (vitamin B9): cofactors of DNA synthesis → essential for cell division of erythroid precursors → deficiency → inefficient erythropoiesis → megaloblastosis → macrocytosis + anemia; erythrocyte lifespan and destruction: 100-120 days → aging → reduced membrane deformability → splenic sequestration → phagocytosis by macrophages → hemoglobin degradation → globin → recycled amino acids + heme → biliverdin → unconjugated bilirubin → conjugated by liver → stercobilin (stool) + urobilinogen (urine) + iron → transferrin → marrow → recycling
- Normal ranges for red blood cell count in adults: red blood cells (RBCs - erythrocytes): adult male: 4.5–5.9 × 10¹²/L + adult female: 4.0–5.2 × 10¹²/L + pregnant female: physiologically lowered values (hemodilution - normal or slightly increased MCV); hemoglobin (Hb): male: 130–175 g/L (13.0–17.5 g/dL) + female: 120–155 g/L (12.0–15.5 g/dL) + pregnant female: >110 g/L (WHO - T1 and T3) + >105 g/L (WHO - T2) + newborn: 140–220 g/L (fetal Hb - dominant HbF) → physiological decline in the first weeks of life; hematocrit (Hct): male: 40–52 % + female: 36–48 %; calculated erythrocyte indices - MCV (mean corpuscular volume): normal adult value: 80–100 fL - microcytosis: <80 fl (carence martiale + thalassémie anémie inflammatoire) — macrocytose :>100 fL (B12 or folate deficiency + alcohol + hypothyroidism + medications) — normocytosis: 80–100 fL (hemolytic anemia + kidney failure + aplasia); MCHC (mean corpuscular hemoglobin concentration): normal: 320–360 g/L — hypochromia: <320 gl (carence martiale + thalassémie) — hyperchromie :>360 g/L (hereditary spherocytosis — MCHC sometimes >360 + severe dehydration); MCH (mean corpuscular hemoglobin): normal: 27–33 pg; RDW (red blood cell distribution width — anisocytosis): normal: 11.5–14.5 %— elevated RDW (>14.5 %): anisocytosis (size heterogeneity) → iron deficiency + B12 deficiency + folate deficiency + hemolytic anemia + recent transfusion; reticulocytes: immature red blood cells — normal values: 20–100 x 10⁹/L (0.5–2.0 % of RBCs) — reticulocytosis (>100–120 x 10⁹/L): regenerative anemia (hemolysis + hemorrhage) → functional bone marrow that compensates — areticulocytosis (<20 × 10⁹/L): aregenerative anemia (aplastic + erythroblastopenia + deficiency) → insufficient or substrate-deficient bone marrow
- Erythrocyte morphology on blood smear — main abnormalities: The stained blood smear (May-Grünwald-Giemsa - MGG) is irreplaceable for the morphological analysis of red blood cells – in addition to automated indices; size anomalies: microcytes (diameter <6 µm — vgm bas) : carence martiale + thalassémie anémie sidéroblastique des maladies chroniques (rare) macrocytes (diamètre>9 µm - high GMV): B12 deficiency + folate deficiency + alcohol + hypothyroidism + drugs (hydroxyurea + methotrexate + azathioprine + antiretrovirals) + round macrocytes (non-ovalocytic): alcohol + hypothyroidism + liver disease + megaloblasts (ovalocytic macrocytes): B12 + folate deficiency; shape anomalies (poikilocytosis): sickle cells (sickle-shaped): sickle cell disease (HbS) - pathognomonic + spherocytes (small round RBCs without central pallor): hereditary spherocytosis + autoimmune hemolytic anemia (AHAI) + schizocytes (erythrocyte fragments): thrombotic microangiopathy (TAM - PTT + HUS + DIC + malignant AH) + acanthocytes (irregular spicules): abetalipoproteinemia + severe hepatopathies + target cells: thalassemia + hemoglobinopathies + hepatopathy + martial deficiency + stomatocytes (central cleft): hereditary stomatocytosis + alcohol + elliptocytes: hereditary elliptocytosis + martial deficiency (mild) + dacryocytes (tears): myelofibrosis + extramedullary hematopoiesis + echinocytes (regularly crenulated): uremia + artifact + ATP depletion; intraerythrocyte inclusions: Heinz bodies (denatured hemoglobin - G6PD deficiency + unstable hemoglobinopathies - visible with cresyl blue only) + Howell-Jolly bodies (nucleus fragments - functional or surgical asplenia + megaloblastosis) + Cabot rings (mitotic spindle remnants - severe megaloblastosis + lead poisoning) + basophilic punctations (ribosome granules - lead poisoning + thalassemia + dyserythropoiesis) + intracellular parasites (Plasmodium - malaria + Babesia)
Clinical Interpretation and Management of Red Blood Cell Abnormalities
| Erythrocyte anomaly | Etiologies and diagnostic approach | Care and referral |
|---|---|---|
| Hypochromic microcytic anemia VGM <80 fL — CCMH <320 g/L |
Microcytic hypochromic anemia is the most frequent form of anemia worldwide - martial deficiency is the cause in the vast majority of cases; martial deficiency (iron deficiency anemia): most frequent cause of anemia worldwide - mechanism: depletion of iron stores → insufficient hemoglobin synthesis → microcytosis + progressive hypochromia - martial workup: serum ferritin (best reflection of reserves - low if <15-20 µg/L) + low serum iron + high transferrin (TIBC) + low transferrin saturation coefficient (TSC) (<16 %) - caution: ferritin is an acute-phase protein - may be falsely normal or elevated in inflammatory context despite true deficiency - in this case : CRP + soluble transferrin receptor (sTfR) + sTfR/log ferritin index (Thomas index) - look for causes of martial deficiency: occult digestive bleeding (colorectal cancer + ulcer + inflammatory bowel disease) in any adult → FOGD + colonoscopy + gynecological bleeding (menorrhagia - main cause in women of childbearing age) + malabsorption (celiac disease + gastrectomy + gastric bypass) + inadequate intakes (strict veganism + infants) + intrapulmonary hemorrhage (hemosiderosis - rare); thalassemias (alpha and beta): genetic abnormality of globin chain synthesis → microcytosis disproportionate to degree of anemia (VGM often 3.5 % in beta-thalassemia minor + normal HbA2 in alpha-thalassemia - molecular diagnosis PCR) + normal or elevated ferritin (no deficiency) - target population: natives of the Mediterranean basin + Africa + Middle East + Southeast Asia; anemia of chronic diseases (ACD): moderate microcytosis (often normocytic - GMV 75-85 fL) + hypochromia + normal or high ferritin + low TIBC + normal or low CST - mechanism: hepcidin elevated by inflammation → blockade of ferroportin → sequestration of iron in macrophages → reduced availability for erythropoiesis - context: chronic inflammatory diseases (RA + Crohn's + lupus) + cancers + chronic infections (HIV + tuberculosis + hepatitis) + chronic renal failure; sideroblastic anemia: crown sideroblasts (mitochondrial sideroblasts in perinuclear ring - visible with Perls stain on myelogram) + microcytosis + hypochromia + elevated ferritin (martial overload) → causes: acquired (alcohol ++ + lead + isoniazid + chloramphenicol + pyridoxine deficiency) + congenital (XLSA - X-linked sideroblastic anemia - ALAS2 mutation) | Treatment of martial deficiency: oral iron: ferrous sulfate (Fer-In-Sol + Palafer + generics): 150-200 mg/d of elemental iron in 2-3 doses - optimal absorption on an empty stomach or with vitamin C - frequent digestive side effects (nausea + constipation + black stools) → if intolerant: reduce dose + take with meals (absorption reduced by 40 % but better tolerated) + ferrous gluconate + ferrous fumarate - duration: minimum 3-6 months after Hb normalization (to replenish reserves - target ferritin ≥50 µg/L) - CBC check + ferritin at 1-2 months (expected Hb increase +1 g/dL/week from D10-14 if effective treatment and cause treated); IV iron: ferric carboxymaltose (Ferinject): IV administration as a single infusion (up to 1,000 mg in 15 min) or iron sucrose (Venofer): 200 mg in 3 spaced infusions - indications: intolerance to oral iron + malabsorption (celiac disease + active Crohn's + bariatric) + severe deficiency requiring rapid correction (preoperative + advanced pregnancy) + chronic renal failure on erythropoietin; treatment of cause: indispensable - treatment of menorrhagia (hormonal contraception + Mirena hormonal IUD) + treatment of celiac disease (gluten-free diet) + resection of a bleeding digestive cancer + anti-ulcer treatment (PPI + H. pylori eradication); thalassemias - treatment: thalassemia minor (thalassemic trait): no martial therapy (risk of overload) + genetic counseling if pregnancy planned + prenatal diagnosis if both parents are carriers - thalassemia major (homozygous beta-thalassemia): iterative transfusions + iron chelation (deferasirox - Exjade PO) + hematopoietic stem cell allograft (HSCT) + gene therapy (Zynteglo - available in Europe + under evaluation in Canada) |
| Macrocytic anemia VGM >100 fL — megaloblastosis — alcohol |
Macrocytosis (VGM >100 fL) is a frequent call sign discovered on routine CBC - its causes are varied and require a systematic diagnostic approach; vitamin B12 (cobalamin) deficiency: prevalence: 5-15 % of elderly + vegans + strict vegetarians - mechanism: B12 required for thymidine synthase + methionine synthase → deficiency → blockage of DNA synthesis → megaloblastosis + neurological disorders (subacute combined degeneration - involvement of the posterior and lateral cords of the medulla: paresthesias + ataxia + Lhermitte's sign) - causes: autoimmune atrophic gastritis (Biermer's anemia - antiintrinsic factor + anti-parietal cell antibodies - 60-70 % of B12 deficiencies in developed countries) + gastrectomy + ileal resection + celiac disease + Crohn's + bacterial overgrowth + strict veganism + drugs (metformin - blocks ileal B12 absorption - after ≥5 years of treatment + long-term PPIs + colchicine); folate (vitamin B9) deficiency: mechanism similar to B12 (cofactor in DNA synthesis) - no neurological impairment - causes : inadequate intake (alcoholism + anorexia + malnutrition) + malabsorption (celiac disease) + increased requirements (pregnancy + chronic hemolytic anemia + hemodialysis) + antifolate drugs (methotrexate + trimethoprim + phenytoin); macrocytosis without megaloblastic anemia: alcoholism (VGM often 100-110 fL without frank megaloblastosis - mechanism: direct toxicity of alcohol on erythropoiesis + associated folate deficiency) + hypothyroidism (slightly increased GMV + elevated TSH) + hepatopathies (membrane lipid loading → round - not ovalocytic - macrocytes) + drugs (hydroxyurea + methotrexate + azathioprine + zidovudine + d4T - antiretrovirals) + myelodysplastic syndromes (MDS): macrocytosis + cytopenias ± blastosis → smear + myelogram + osteo-medullary biopsy; diagnostic workup for macrocytosis: serum B12 + erythrocyte folates (more reliable than serum folates) + TSH + liver workup + protein electrophoresis + blood smear (ovalocytic megalocytes + hypersegmented polynuclei = megaloblastosis → B12 or folate) + LDH + bilirubin (ineffective erythropoiesis → intramedullary cytolysis) + antiintrinsic factor + anti-parietal cell antibodies (if Biermer suspected) | Treatment of vitamin B12 deficiency: mild forms without neurological impairment (Biermer + partial gastrectomy + veganism without documented malabsorption): cyanocobalamin or hydroxocobalamin IM: standard protocol: 1,000 µg IM/d × 7 days → then 1,000 µg IM/week × 4 weeks → then 1,000 µg IM/month for life (if uncorrectable cause - Biermer + total gastrectomy); forms with severe neurological impairment: 1,000 µg IM/d × 2-3 weeks → monthly maintenance for life + physiotherapy if ataxia + neurological follow-up; oral B12 (cyanocobalamin PO 1,000-2,000 µg/d): as effective as IM in most situations (passive absorption not dependent on intrinsic factor at high doses) - convenient alternative for patients without severe neurological impairment or complete intestinal malabsorption - increasing Quebec preference for oral route (avoids injections) + less effective in cases of severe Biermer or total ileal resection; sublingual or nasal B12 (Nascobal): possible alternatives; follow-up: reticulocytosis as early as D5-7 (peak at D7-10) + normalization of Hb in 6-8 weeks + normalization of VGM in 2-3 months + monitoring of kalemia (hypokalemia possible in correction phase - rapid erythroid regeneration) + neurological follow-up (improvement possible but incomplete if old damage - spinal cord lesions established >6 months partially recover); treatment of folate deficiency: folic acid 1-5 mg/d PO × 4 months (or for life if uncorrectable cause) + NEVER correct folates without having excluded or treated B12 deficiency: risk of worsening neurological disorders by correcting anemia without correcting B12 deficiency → always treat B12 first or simultaneously if both deficiencies coexist; preventive folate supplementation: 0.4 mg/d periconceptionally (prevention of neural tube closure defects - spina bifida) + 5 mg/d if pregnancy with chronic hemolytic anemia or antifolate treatment |
| Hemolytic anemia Hemolysis - reticulocytosis - Coombs |
Hemolytic anemia results from premature destruction of erythrocytes (lifespan 120 × 10⁹/L or >2 % of RBCs) + elevated LDH (released by erythrocyte lysis) + elevated unconjugated (indirect) bilirubin + collapsed haptoglobin (captures free → saturated and degraded Hb during intravascular hemolysis) + in intravascular hemolysis: hemoglobinemia + hemoglobinuria + methemalbumin; direct Coombs test (DCT): detects antibodies or complement attached to RBCs - positive DCT → immune hemolysis: AHAI (autoimmune hemolytic anemia) + transfusional hemolysis + drugs + hemolytic disease of the newborn (fetal-maternal incompatibility) - TCD negative → non-immune hemolysis: intrinsic RBC abnormalities (hemoglobinopathies + membranopathies + enzymopathies) + thrombotic microangiopathy (TMA - schizocytes +++) + malaria + physical agents (burns); etiological classification of hemolytic anemias: corpuscular causes (intrinsic - most often constitutional): hereditary membranopathies (hereditary spherocytosis + elliptocytosis - mutation of erythrocyte membrane proteins: spectrin + ankyrin + protein 4.2 + band 3) + enzymopathies (G6PD deficiency + pyruvate kinase deficiency) + hemoglobinopathies (sickle cell disease + thalassemias + HbC + HbE) + HPN (paroxysmal nocturnal hemoglobinuria - acquired clonal abnormality of GPI-anchor → complement sensitivity); extra-corpuscular causes: AHAI (autoimmune - TCD+) + allo-immune hemolysis (transfusion + fetal-maternal alloimmunization) + MAT (PTT + SHU - schizocytes + ADAMTS13 low in PTT) + infection (malaria + Clostridium + Bartonella) + drugs (methyldopa + penicillin + ceftriaxone + NSAIDs - variable immunological mechanisms) | Management of autoimmune hemolytic anemias (AHAI): AHAI with warm antibodies (IgG - TCD IgG positive - most frequent - 80 % of AHAI): 1st-line corticosteroid therapy: prednisone 1 mg/kg/d PO → response expected in 1-3 weeks (Hb rises + reticulocytes increase then decrease) → gradual decrease over 3-6 months → 60-80 % initial response - but frequent relapse on decrease (50 % of patients) → 2nd-line treatment: rituximab (anti-CD20 - Rituxan + biosimilar generics): 375 mg/m² IV × 4 weekly infusions → durable remission in 60-80 % - splenectomy: curative option in corticoresistant or corticodependent AHAI (response in 50-70 %) + immunosuppressants (azathioprine + mycophenolate mofetil) + fostamatinib (Syk kinase inhibitor - FDA 2023 approved for refractory AHAI) → awaiting Health Canada approval; Cold antibody AHAI (IgM - cold agglutinins - TCD positive C3 complement): cold avoidance (warm clothing + temperate environment) + rituximab ± bendamustine + no splenectomy (mainly hepatic hemolysis); HPN (paroxysmal nocturnal hemoglobinuria): eculizumab (Soliris - anti-C5 - terminal complement inhibitor): first treatment approved - 900 mg IV/2 weeks then 1,200 mg/4 weeks - normalizes hemolysis + prevents thrombosis (main cause of death in HPN) + meningococcal vaccination mandatory before initiation + ravulizumab (Ultomiris - long-acting anti-C5 - 4 infusions/year) : Health Canada approved + iptacopan (alternate pathway factor B inhibitor - PO - APPLY + APPOINT 2023 trials - response under evaluation Health Canada); transfusion in hemolytic anemias: packed red blood cells compatibilized + phenotyped (prevention of alloimmunization) + washed if severe AHAI or HPN |
| Polycythemia and erythrocytosis Elevated GR - JAK2 mutation - Vaquez |
Polycythemia (erythrocytosis) is defined by an increase in erythrocyte mass - diagnosed in practice by an Hb >185 g/L in men + >165 g/L in women (WHO 2016) or a hematocrit >52 % (men) + >48 % (women); erythrocytosis classification: true absolute erythrocytosis (actual increase in erythrocyte mass): primary - Vaquez disease (polycythemia vera - PV): clonal myeloproliferative neoplasm - JAK2 V617F mutation (exon 14) in >95 % of cases + JAK2 exon 12 mutation in <5 % - workup: CBC (polycythemia + often associated thrombocytosis + leukocytosis) + low EPO (autonomous GR production - physiological EPO braking) + JAK2 V617F mutation (key diagnostic test) + bone-medullary biopsy (tri-lineage hypercellularity with panmyelosis) - WHO 2016 diagnostic criteria (3 major criteria or 2 major + 1 minor required); secondary erythrocytosis (high EPO): hypoxic causes: severe COPD + obstructive sleep apnea syndrome (OSAS) + cyanogenic congenital heart disease + high altitude + smoking (CO → HbCO → functional tissue hypoxia → smoker's polyglobulia) + high-affinity hemoglobin for O2 (high-affinity hemoglobins: left-shifted dissociation curve → tissue hypoxia → high EPO → polyglobulia); non-hypoxic causes (non-physiological high EPO): clear cell renal cell carcinoma (ectopic EPO secretion - paraneoplastic polycythemia) + hepatocarcinoma + cerebellar hemangioblastoma (Von Hippel-Lindau) + renal cyst + renal artery stenosis (focal renal ischemia → elevated local EPO); relative erythrocytosis (Gaisbock pseudopolycythemia): normal erythrocyte mass - hemoconcentration by reduction of plasma volume (dehydration + diuretics + visceral obesity + hypertension + smoking + stress) → hematocrit and Hb elevated but RBCs normal on isotopic measurement of erythrocyte mass | Treatment of Vaquez disease (polycythemia vera): main therapeutic objective: reduce the risk of thrombosis (main cause of mortality in PV) by maintaining hematocrit <45 % (male) + 60 + history of thrombosis + platelets >1,500 G/L + polycythemia difficult to control with bloodletting alone): hydroxyurea (Hydrea): 1st line of cytoreduction - 500-1,500 mg/d PO + theoretical leukemogenic risk (low but real in the long term) + pegylated interferon alfa (Besremi - ropeginterferon alfa-2b): approved by Health Canada 2022 for PV - SC every 2 weeks → reduction of JAK2 allelic load (possible molecular remission) → preferred alternative in young patients + pregnancy considered (with precautions) + intolerance or resistance to hydroxyurea + ruxolitinib (Jakafi - JAK1/JAK2 inhibitor): 2nd line if resistant or intolerant to hydroxyurea - approved by Health Canada for refractory PV; secondary erythrocytosis : treatment of cause (smoking cessation + CPAP if OSAS + COPD treatment + renal cell carcinoma resection) + bloodletting if polycythaemia-related symptoms (hyperviscosity - headache + facial erythrosis + tinnitus + aquagenic pruritus) + target hematocrit <50 % in hypoxic secondary polycythaemias |
| Normocytic aregenerative anemia Aplasia - kidney failure - MDS |
Aregenerative normocytic anemia (low reticulocytes + normal GMV) points to insufficient bone marrow production (aplasia) or inefficient erythropoiesis (MDS + incipient deficiencies); chronic renal failure (CKD): anemia in CKD is the most frequent of the aregenerative anemias - mechanism: insufficient EPO production by fibrosed renal peritubular cells + reduced erythrocyte lifespan + frequent relative martial deficiency + uremic toxicity on erythropoiesis + chronic inflammation (hepcidin) - prevalence: 40-50 % of stage 3b-5 CKD patients (GFR <45 mL/min/1.73 m²) - workup: serum EPO (inadequately low for degree of anemia) + ferritin + CST + inflammatory workup; bone marrow aplasia (pure aplasia or aplastic pancytopenia): disappearance of hematopoietic cells from marrow → anemia + thrombocytopenia + neutropenia - acquired aplasia (idiopathic - autoimmune mechanism T → 70 % of acquired aplasias + drugs: chloramphenicol + carbamazepine + ticlopidine + sulfonamides + gold) + constitutional aplasias (Fanconi anemia - chromosomal breaks + congenital anomalies + dyskeratosis congenita - TERC + TERT mutation); pure red cell aplasia (PRCA) : selective aplasia of the erythroid lineage → severe aregenerative anemia without thrombocytopenia or neutropenia - causes: parvovirus B19 (in immunocompromised or chronic hemolytics) + thymoma + autoimmune + drugs (epoetin - anti-EPO antibodies); myelodysplastic syndromes (MDS): dysplastic bone marrow clones → ineffective erythropoiesis → anemia + sometimes macrocytosis + smear: dysgranulopoiesis + abnormal megakaryocytes + myelogram + BOM + karyotype + NGS → WHO 2022 classification → IPSS-R score → therapeutic decision (monitoring + azacitidine + allograft); acquired aplastic anemia - severity criteria: severe aplasia (SAA): neutrophils <0.5 G/L + platelets <20 G/L + reticulocytes <20 G/L + marrow <25 % cellularity + very severe aplasia (VSAA): neutrophils <0.2 G/L | Treatment of anemia in CKD: erythropoiesis-stimulating agents (ESAs): epoetin alfa (Eprex) + epoetin beta (NeoRecormon) + darbepoetin alfa (Aranesp): EPO → receptor agonists stimulate erythropoiesis → indications: Hb <100 g/L + GFR 130 g/L - increased cardiovascular and thromboembolic risk) - administration: SC (better than IV for efficacy) or IV if hemodialysis + concomitant martial supplementation mandatory (IV iron preferably in hemodialysis) → target ferritin >200 µg/L + CST >20 %; HIF-PH (hypoxia-inducible factor prolyl hydroxylase) inhibitors: new oral therapeutic class: roxadustat (Evrenzo - AstraZeneca): approved by Health Canada 2021 for CKD anemia in dialysis and pre-dialysis - mechanism: inhibition of HIF prolyl hydroxylases → stabilization of HIF-1α and HIF-2α factors → endogenous increase in EPO secretion + increase in intestinal iron absorption → dual effect - advantages vs ESA: oral route + effective in inflammatory setting (reduced hepcidin) + lower risk of hypertension - monitoring: HbA1c + lipids (decreased under roxadustat) + thromboses; treatment of acquired bone marrow aplasia: hematopoietic stem cell allograft transplantation (HSCT): reference curative treatment for patients 40 years old): anti-thymocyte serum (SAT - horse or rabbit) + cyclosporine + eltrombopag (Revolade - thrombopoietin receptor agonist - TPO-RA): data RACE + STRONG-SAA → improved response rate + complete remission rate 40-50 % under triple therapy SAT + cyclosporine + eltrombopag |
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Interpretation of Erythrocyte NFS — A Systematic 4-Step Approach: (1) The presence or absence of anemia (low Hb) or polycythemia (high Hb) — (2) MCV: microcytosis (<80 fl) → carence martiale ou thalassémie ; normocytose (80–100 hémolyse aplasie macrocytose (>100 fL) → B12/folate deficiency or medications — (3) Regenerative nature (reticulocytes >120 × 10⁹/L → hemolysis or hemorrhage) or aregenerative (low reticulocytes → insufficient production) — (4) Blood smear for morphology (schistocytes → MA T; sickle cells → sickle cell disease; hypersegmented neutrophils → megaloblastosis). This cascade approach guides towards a precise etiological diagnosis before prescribing targeted additional tests.
Situations requiring urgent medical assessment
Severe anemia (Hb <70 g/L) + signs of poor tolerance (dyspnea at rest + tachycardia + hypotension + chest pain + confusion) → urgent erythrocyte transfusion + etiological workup + hospitalization.
Schistocytes on smear + anemia + severe thrombocytopenia ± fever + neurological or renal involvement → thrombotic microangiopathy (PTT or SHU) → ADAMTS13 urgently + plasma exchanges if PTT → urgent hematology opinion.
Polycythemia (Hb >185 g/L male + >165 g/L female) + thrombosis (stroke + MI + Budd-Chiari) or signs of hyperviscosity → Probable Vaquez's disease → JAK2 V617F mutation + urgent phlebotomy if hematocrit >55% % + aspirin + hematology.
Pancytopenia (anemia + neutropenia + thrombocytopenia) + fever in a patient taking a potentially myelotoxic medication → drug-induced bone marrow aplasia → immediate discontinuation of incriminating drug + urgent CBC + hematology opinion + hospitalization if severe neutropenia.
Consult at Clinique Omicron
The doctors at Clinique Omicron prescribe and interpret red blood cell counts as part of the workup for unexplained fatigue, incidentally discovered anemia, pregnancy monitoring, chronic illness, or a pre-operative assessment. Referral to specialized hematology (hemolytic anemias, polycythemia, aplasia), prescription of appropriate iron or vitamin supplementation, and screening for underlying causes (digestive bleeding, celiac disease, nutritional deficiencies) are part of the clinical approach available at several service points in Quebec and via telemedicine. To make an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute for advice from a physician or hematologist. The interpretation of a CBC should always be done within the patient's clinical context.
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