Downloaded 28 times
![RBC Indices
• MCV – Average volume (size)
• MCH – Average hemoglobin content
• MCHC – Average hemoglobin per RBC
• RDW: Variation in RBC size (Anisocytosis)
• Low MCH : Hypochromia
• Low MCHC : Iron deficiency anemia
• High MCHC : Spherocytosis
• High RDW : Iron deficiency, Vitamin B12 or
folate deficiency, MDS, hemoglobinopathies,
received transfusions
Ref : Harrison’s Principles of Internal Medicine 2022
RBC
Index
Normal
Value
Mean cell volume (MCV) =
(hematocrit × 10)/(red cell count × 106)
90 ± 8 fL
Mean cell hemoglobin (MCH) =
(hemoglobin × 10)/(red cell count × 106)
30 ± 3 pg
Mean cell hemoglobin concentration =
(hemoglobin × 10)/hematocrit
Or MCH/MCV
33 ± 2%
Red cell Distribution Width =
[standard deviation of MCV/MCV] x 100
11.5-14.5](https://image.slidesharecdn.com/approachtoanemiafinal-221025005911-b1399dd3/75/Approach-to-Anemia-pptx-12-2048.jpg)
![2 Corrections of Reticulocyte count
• Absolute reticulocyte count (millions of cells/microL)
= Reticulocytes (%) × RBC count (millions of cells/microL)
• Corrected reticulocyte count (%)
= Reticulocytes (%) × (observed patient HCT [percent] ÷ 45 [percent]) or
= Reticulocytes (%) × (observed patient hemoglobin [g/dL] ÷ 15 [g/dL])
• Reticulocyte production index (no units)
= Corrected reticulocyte count (%) ÷ maturation correction factor (days)
Maturation correction (in days): HCT >35%: 1; HCT 26 to 35%: 1.5; HCT 16 to 25%: 2; HCT <15%: 2.5
Hillman RS. Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia. J Clin Invest 1969; 48:443.](https://image.slidesharecdn.com/approachtoanemiafinal-221025005911-b1399dd3/75/Approach-to-Anemia-pptx-26-2048.jpg)
![1. Hereditary, non-immune causes of Hemolysis
• Hemoglobinopathies
• Sickle cell disease
• Thalassemias
• Unstable hemoglobins
• Enzyme deficiencies
• Glucose-6-phosphate dehydrogenase
[G6PD]
• Pyruvate kinase [PK]
• Glucose phosphate isomerase
• 5’ nucleotidase
• Membrane defects
• Hereditary spherocytosis
• Hereditary elliptocytosis [HE]
• Hereditary stomatocytosis [HSt]](https://image.slidesharecdn.com/approachtoanemiafinal-221025005911-b1399dd3/75/Approach-to-Anemia-pptx-34-2048.jpg)
![3. Acquired, immune-mediated causes of Hemolysis
• Autoimmune
• Warm autoimmune hemolytic anemia [AIHA]
• Cold agglutinin disease
• Paroxysmal cold hemoglobinuria
• Hemolytic transfusion reactions
• Drug-induced](https://image.slidesharecdn.com/approachtoanemiafinal-221025005911-b1399dd3/75/Approach-to-Anemia-pptx-36-2048.jpg)
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Approach to Anemia.pptx
- 1. Approach to Anemia Dr.Prabin Bhattarai MD Internal Medicine Resident 2079/04/02
- 2. Contents • Definition • Erythropoiesis •History and Examination • Lab investigations • Classification • Treatment
- 3. Definition of Anemia “Statein which the level of hemoglobin in the blood is below the reference range appropriate for age and sex.” • Normal Hemoglobin in Adult males is 13.5–17.5 g/dL • Normal Hemoglobin in Adult females is 12–15 g/dL • WHO: <13 g/dL in men and post menopausal females and <12 g/dL in women • Hematocrit levels less useful and Previous values are helpful • Varies with ethnicity and physiological status Ref : World Health Organization. Nutritional anaemias: Report of a WHO scientific group. Geneva, Switzerland: World Health Organization; 1968
- 4. Haemoglobin levels todiagnose anaemia at sea level World Health Organization. Vol. 405. Geneva: World Health Organization; 1968. Nutritional anaemias. Report of a WHO group of experts. World Health Organization - Technical report series.
- 5.
- 6. EPO and Erythron •Normal : 10–25 U/L • Hgb < 10–12 g/dL, levels increase in proportion to the severity of anemia • Half life : 6–9 h • Binding to specific receptors on the surface of marrow erythroid precursors • RBC production can increase 4x-5x within a 1- 2-week period in the presence of adequate nutrients, especially iron
- 7. Criteria for normalerythropoiesis • Normal renal production of EPO • Functioning erythroid marrow • Adequate supply of substrates for hemoglobin synthesis • Iron • Vitamin B12 • Folate • Effective maturation of red cell precursors
- 8. Symptoms : Nonspecific • Tiredness • Lightheadedness • Breathlessness • Development/worsening of ischemic symptoms, e.g. angina or claudication • Bleeding • Fever • Weight loss • Night sweats • Other symptoms of systemic diseases
- 9. History : Causeand Complications • Age (premenopausal : IDA) • Sex and ethnicity (hemoglobinopathy and G6PD deficiency) • Acute vs Chronic • Underlying medical conditions; liver or kidney disease; Connective tissue diseases; Chronic inflammatory state • History of GI surgery and GI symptoms (bleeding, bowel habits) • Menstrual history (Menorrhagia) • Medications (NSAIDs, Sulfonamides, Chloramphenicol) • Family history or Congenital; Most are hemolytic • Dietary practices (fava bean, veg), Travel, Infections • Hemolysis : Dark urine, Jaundice, gallstones • Malabsorption : Greasy Stools, Nutrient deficiency symptoms
- 10. Examination • Pallor • Tachycardiaand tachypnea • Flow murmur • Signs of cardiac failure • Lymphadenopathy • Petechiae • Postural hypotension • Abdominal Mass : Carcinoma • B12 deficiency : Neurological symptoms • Sickle cell : Leg ulcers, Stroke, Pulmonary Hypertension • Hemolysis : Icterus, splenomegaly, dark urine
- 11. Laboratory tests :Old reports help ! • Complete Blood Count (TLC, Hemoglobin, PCV, RBC) • Differential Blood Count • Peripheral blood smear : Other cytopenias, RBC shapes • RBC Indices : Micro vs Macro • Reticulocyte count : Bone marrow functional? • Folic Acid and Vitamin B12 level • Urea, Creatinine • Hemolysis : LDH, Bilirubin, and Haptoglobin • Coagulation profile • Iron profile • Serum Proteins, poly/monoclonal light chains
- 12. RBC Indices • MCV– Average volume (size) • MCH – Average hemoglobin content • MCHC – Average hemoglobin per RBC • RDW: Variation in RBC size (Anisocytosis) • Low MCH : Hypochromia • Low MCHC : Iron deficiency anemia • High MCHC : Spherocytosis • High RDW : Iron deficiency, Vitamin B12 or folate deficiency, MDS, hemoglobinopathies, received transfusions Ref : Harrison’s Principles of Internal Medicine 2022 RBC Index Normal Value Mean cell volume (MCV) = (hematocrit × 10)/(red cell count × 106) 90 ± 8 fL Mean cell hemoglobin (MCH) = (hemoglobin × 10)/(red cell count × 106) 30 ± 3 pg Mean cell hemoglobin concentration = (hemoglobin × 10)/hematocrit Or MCH/MCV 33 ± 2% Red cell Distribution Width = [standard deviation of MCV/MCV] x 100 11.5-14.5
- 13. Ref : Uptodate2022 Algorithm
- 14. Microcytosis (MCV <80fL) : Hgb synthesis defect • Absolute Iron deficiency • Some cases of ACD/AI due to functional iron deficiency • Globin defects • Thalassemia • Hemoglobin (Hb) C • Hemoglobin E • Heme defects • Congenital sideroblastic anemia • Lead poisoning ACD/AI : Anemia of Chronic Disease / Inflammtion
- 15. Approach to Microcytosis: Iron profile for all • Low Ferritin and TSAT : IDA • Hemoglobin electrophoresis if Iron Profile Normal • Basophilic stippling • Beta thalassemia (Abnormal Hgb) • Lead poisoning (Normal Hgb) • Sideroblastic anemia (Bone marrow examination) Iron deficiency Thalassemia ACD/AI Serum Iron ↓ Normal or Increased Decreased TIBC Increased Normal or decreased Normal or Decreased % Iron Saturation Decreased <10% Normal or Increased Decreased Ferritin Decreased Increased High Normal to Increased
- 16. Peripheral Blood Smearin Microcytic anemia Basophilic stippling Microcytic hypochromic anemia
- 17. Macrocytosis (>100 fL) Asynchronousmaturation of nuclear chromatin Megaloblastic Anemia Membrane changes Reticulocytosis (↑RDW) Spurious (Lab artifact) Vitamin B12 deficiency Excess alcohol Hemolytic anemias ↑Immunoglobulin ↑Acute phase proteins Small rouleaux that are counted by electronic counters as single large cells. Folate deficiency Liver disease Recovery from bleeding Copper deficiency Hypothyroidism Repletion of iron or other deficient nutrient Myelodysplastic syndrome (MDS) Stomatocytosis Recovery from bone marrow suppression such as binge drinking alcohol Aplastic anemia Diamond Blackfan anemia Drugs that interfere with DNA synthesis
- 18. Approach to macrocyticanemia : B12 for all • Folate for Malnourished and Gastric Surgery • MMA level if Vitamin B12 normal Individuals with normal vitamin B12 and folate • TSH • Alcohol use • Copper level if neutropenia and/or neuropathy, zinc ingestion • Target cells : Do LFT • Stomatocytosis • Dysplasia (Bilobed or immature neutrophils or binucleate RBCs, or other cytopenias) : Do Bone marrow examination for MDS
- 19. Normocytic (80-100 MCV) Multifactorialand Challenging • Nutrient deficiency – Early stages of deficiency of iron, vitamin B12, folate, or copper • Combined microcytic plus macrocytic anemia : Simultaneous deficiency of vitamin B12 and iron (celiac disease or autoimmune gastritis). • Hemolysis without reticulocytosis (due to concomitant bone marrow suppression ) • Chronic kidney disease (CKD) and ACD/AI • Anemia of heart failure and cardio-renal syndrome • Endocrine deficiency : Hypothyroidism, Androgen deficiency, or adrenal insufficiency • Cancer – Cancer-associated anemia, including monoclonal gammopathies • Clonal hematopoietic stem cell disorders : myelodysplastic syndrome, aplastic anemia • Early Blood loss that has not yet caused iron deficiency • Pure red cell aplasia • Partially treated anemia – Iron deficiency or megaloblastic anemia in process of correction or following transfusion
- 20. Approach to NormocyticAnemia : Retics for all Normocytosis Reticulocyte count Iron Profile Hemolysis Cancer Endocrine disorders Blood loss Nutrient deficiencies N N N
- 21. Peripheral Blood Smearin Anemia • Variations in cell size (anisocytosis = ↑RDW ) and shape (poikilocytosis) • Hemoglobin content • Polychromatophilia : Reticulocytosis • Inclusions : Howell Jolly Bodies, Basophilic stippling, Malaria • Rouleaux • Poikilocytosis : Maturation defect or fragmentation • Nucleated red cells • Target cells • Sickle cells
- 22. Bite Cells inG6PD Deficiency Target Cells in Thalassemia Teardrop Cells in Thalassemia Spherocytes Elliptocytes Stomatocytes
- 23. Anemia as apart of Pancytopenia • Drug-induced pancytopenia (cytotoxic drugs, anti-infective drugs, anticonvulsants) • Viral infections : Hepatitis, cytomegalovirus, Epstein Barr virus • Severe non-viral infection : Clostridial sepsis, malaria, leishmaniasis, leptospirosis, babesiosis • Bone marrow failure (aplastic anemia), myelodysplasia, myelofibrosis, clonal disorders such as paroxysmal nocturnal hemoglobinuria (PNH), and hematologic malignancies • Hypersplenism – Cirrhosis (Macrocytosis and target cells) • Deficiency of vitamin B12, copper, folate • Autoimmune – SLE, CLL • Hemophagocytic Lymphohistiocytosis • Thrombotic microangiopathies (TMAs) : TTP, DIC
- 24. Reticulocyte • Irregular borderand lack of central pallor • Reflects the rate of RBC production in bone marrow • Lifespan : 4 days ( 3 in marrow + 1 in blood) • Normal count is 1% to 2% • Reflects daily replacement of 0.8–1.0% of the circulating RBC • Manual count (supravital dye) : Percentage • Automated (fluorescent dye) : Absolute count (million cells/uL) • Compared with expected reticulocyte response • Hemoglobin <10 g/dL : RBC production rate increases to 2-3x normal within 10 days
- 25. Reticulocyte count =1-2% =25,000 - 100,000/uL Normally functioning marrow replete with iron, folate, cobalamin, and copper Normally functioning kidney with erythropoietin Decreased • Deficiency of iron, vitamin B12, folate, or copper • Medications that suppress the bone marrow • Primary bone marrow disorders : MDS, myelofibrosis, or leukemia • Very recent bleeding (within five to seven days, before bone marrow compensation) Increased • Hemolysis • Repletion of deficient iron, vitamin B12, folate, or copper (within 1-2 weeks) • Recovery from bleeding
- 26. 2 Corrections ofReticulocyte count • Absolute reticulocyte count (millions of cells/microL) = Reticulocytes (%) × RBC count (millions of cells/microL) • Corrected reticulocyte count (%) = Reticulocytes (%) × (observed patient HCT [percent] ÷ 45 [percent]) or = Reticulocytes (%) × (observed patient hemoglobin [g/dL] ÷ 15 [g/dL]) • Reticulocyte production index (no units) = Corrected reticulocyte count (%) ÷ maturation correction factor (days) Maturation correction (in days): HCT >35%: 1; HCT 26 to 35%: 1.5; HCT 16 to 25%: 2; HCT <15%: 2.5 Hillman RS. Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia. J Clin Invest 1969; 48:443.
- 27. Functional Classification • Marrowproduction defect (hypoproliferation) • Red cell maturation defects (ineffective erythropoiesis) • Decreased red cell survival (blood loss/hemolysis)
- 28. Hypoproliferative Anemias • LowRPI • Little or no change in red cell morphology • Normocytic, normochromic anemia • Absolute or relative marrow failure (drugs, infiltrative diseases) • Mild to moderate iron deficiency • Inadequate EPO stimulation • Inflammatory cytokines such as interleukin 1 • Reduced tissue needs for O2 ; hypothyroidism
- 29. Maturation Disorders • Ineffectiveerythropoiesis due to destruction of developing erythroblasts in marrow • Bone marrow examination shows erythroid hyperplasia (M/E ratio <1:1) • Low reticulocyte production index and Abnormal red cell indices Nuclear maturation defects (macrocytosis) Cytoplasmic maturation defects (microcytosis and hypochromia due to hemoglobin synthesis defects) Vitamin B12 deficiency Severe iron deficiency Folic acid deficiency Myelodysplasia can cause both micro and macrocytic anemia with ring sideroblasts Drugs that interfere with cellular DNA synthesis (methotrexate or alkylating agents) Alcohol
- 30. Normal bone marrow M:E= 1:1 Erythroid hyperplasia M:E > 1:1 (Acute blood loss/hemolysis RPI >3) Myeloid hyperplasia M:E >3:1 (Usually after infections)
- 31. Blood Loss Anemia •Acute not associated with an increased reticulocyte production index because of the time required to increase EPO production and, subsequently, marrow proliferation • Subacute blood loss : Modest reticulocytosis • Chronic blood loss presents : Iron deficiency picture • Recovering state (2–3 weeks) : Hemoglobin concentration rise and the RPI fall
- 32. Hemolytic Anemia :Active marrow • Alloimmune / Autoimmune / Nonimmune based on mechanism • Intravascular / Extravascular based on site • RPI ≥2.5 times normal (provided that iron is sufficient) and marrow examination rarely needed • Stimulated erythropoiesis : Increased numbers of polychromatophilic macrocytes • Normocytic or slightly macrocytic
- 33. Presentation of HemolyticAnemia • Acute, self-limited episode of intravascular or extravascular hemolysis: • Autoimmune hemolysis • Inherited defects of the Embden-Meyerhof pathway or the glutathione reductase pathway. • Chronic hemolytic disease : lifelong clinical history typical • Hereditary spherocytosis : complications like gallstones and splenomegaly • Aplastic crises if infectious process interrupts red cell production. • Jaundice, Pigmented gallstones, Splenomegaly • Leg ulcers : Sickle cell, Hereditary Spherocytosis
- 34. 1. Hereditary, non-immunecauses of Hemolysis • Hemoglobinopathies • Sickle cell disease • Thalassemias • Unstable hemoglobins • Enzyme deficiencies • Glucose-6-phosphate dehydrogenase [G6PD] • Pyruvate kinase [PK] • Glucose phosphate isomerase • 5’ nucleotidase • Membrane defects • Hereditary spherocytosis • Hereditary elliptocytosis [HE] • Hereditary stomatocytosis [HSt]
- 35. 2. Acquired, non-immunecauses of hemolysis • Membrane defects (liver disease, acquired acanthocytosis) • Infections (malaria, babesiosis, clostridial sepsis, trypanosomiasis, leishmaniasis) • Drug-induced (oxidant stress) • Severe burns • Thrombotic microangiopathies (TTP, HUS) • Hypersplenism • Vasculitis • Severe hypertension • Heavy metals (Wilson disease, copper toxicity, arsenic toxicity) • Envenomation (snake, brown recluse spider, hobo spider) • Mechanical (intravascular devices, artificial heart valve, giant hemangioma) TTP : Thrombotic Thrombocytopenic Purpura , HUS : Hemolytic Uremic Syndrome
- 36. 3. Acquired, immune-mediatedcauses of Hemolysis • Autoimmune • Warm autoimmune hemolytic anemia [AIHA] • Cold agglutinin disease • Paroxysmal cold hemoglobinuria • Hemolytic transfusion reactions • Drug-induced
- 37. Labs in hemolyticanemia • Bilirubin is usually not > 4mg per dL • Acute hemolysis : ↑ LDH +↓ Haptoglobin • Chronic hemolysis : Stable hemoglobin + ↑Retics + Normal LDH and Bilirubin • Rule out hemolysis : Normal LDH and haptoglobin (> 25 mg/dL) • Intramedullary hemolysis (ineffective erythropoiesis) Thalassemia or B12 deficiency : ↑ Bilirubin + LDH without reticulocytosis • Thrombotic Microangiopathy : Schistocytes + Thrombocytopenia • Intravascular hemolysis : Urine hemosiderin (1-3 weeks after)
- 38. Blood picture ofhemolytic anemia • Different Cells • Elliptocyte • Acanthocyte / Spur cell : CLD • Sickle Cell • Burr Cell / Echinocyte : Uremia • Target Cell (Thalassemia) • Spherocyte Do Coomb Test • Positive : Immune hemolysis • Negative : Hereditary Spherocytosis Schistocytes • Big vessel disease or trauma • Prosthetic valves and Valve disease • Atrial Myxoma • Bongo drumming • Small Vessel Disease • TTP and DIC • Malignant Hypertension • Adenocarcinoma • Eclampsia
- 39. Acanthocyte (Spur cell) Schistocyte ElliptocyteSpherocyte Sickle Cell Echinocyte (Burr cell)
- 40. Algorithm based onRPI Ref : Harrison’s principles of Internal Medicine 21st Edition
- 41. Treatment : Findtype and treat cause • Acute severe anemia : Stabilization and Red cell transfusions before diagnosis • Mild to moderate anemia : Treat after diagnosis • Iron status before and during the treatment of any anemia • Oral and IV Iron therapy • Disorders of globin gene, such as sickle cell disease : Targeted genetic therapy • The route chosen for iron repletion (oral vs IV) depends upon • Degree of iron insufficiency • Likelihood of oral absorption • Gastrointestinal comorbidities • Drug-drug interactions • Erythropoiesis Stimulating Agents : Erythropoietin, Epoietin, Darbepoietin • HIF-PHI : Daprodustat, roxadustat and vadadustat
- 42. Treatment : Modalities Ref: Blood (2020) 136 (7): 801–813
- 43. Treatment : Findtype and treat cause Ref : Blood (2020) 136 (7): 801–813
- 44. Indications of BloodTransfusion • Short-term treatment with a mixed risk-benefit profile • Consider many factors, rather than basing the decision solely on the presence or absence of symptoms or on a specified hemoglobin level. • Restrictive transfusion strategy for most stable patients (giving less blood; transfusing at a lower hemoglobin level (typically 7 to 8 g/dL); and aiming for a lower target) • Transfusion at a higher hemoglobin level for symptomatic patients • Transfusing one unit of RBCs at a time Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021;12(12):CD002042. Published 2021 Dec 21. doi:10.1002/14651858.CD002042.pub5
- 45. Thresholds for RBCtransfusion in adults “Clinical Judgement advised” Group Threshold in g/dL Symptomatic patient (eg, myocardial ischemia, hemodynamic instability) 10 Preexisting coronary artery disease ; stable 8 Acute coronary syndromes, including acute MI 8 to 10 (Target ≥10) ICU (hemodynamically stable) and Septic Shock 7 Gastrointestinal bleeding (hemodynamically stable) 7 Orthopedic surgery 8 Cardiac surgery 7.5 Oncology patient in treatment 7 to 8 Heart Failure 7 to 8 Palliative care setting As needed for symptoms Ref : Various RCT and Metaanalyses published in JAMA and NEJM, cited by Uptodate 2022
- 46. Restrictive transfusion Strategy Ref :Uptodate 2022
- 47. Anemia in CKD •Target : 10-11.5 g/dL • Non dialysing : Oral or IV Iron • TSAT ≤20% and or Ferritin ≤100 ng/mL : Iron to most • TSAT = 20-30 % and Ferritin = 100-500 ng/mL : Iron to some • TSAT >30% and Ferritin >500 ng/mL : No Iron • Dialysing : IV Iron and ESA • Hgb <10 g/dL and TSAT ≤30% : IV iron till TSAT >30%, Still if Hgb <10 g/dL : ESA • Hgb <10 g/dL and TSAT >30% and Ferritin >500 ng/mL : ESA • Hgb ≥10 g/dL and TSAT ≤20% and Ferritin ≤ 200 ng/mL : Loading dose of IV Iron • Hgb ≥10 g/dL and TSAT >20% and Ferritin > 200 ng/mL : Maintenance IV Iron KDIGO guidelines 2012 , NICE guidelines
- 48. Take Home Message •Always think of multifactorial causes of anemia • Is anemia isolated or other cell lines affected? • RBC indices esp. MCV, Peripheral Blood Smear for all • Iron Profile must for Microcytic anemia • Vitamin B12 and Folate must for Macrocytic anemia • RPI must for Normocytic anemia • Always try to identify the cause and treat • Individualization based on risk benefit analysis may be necessary
- 49.
- 50. References • Harrison's Principlesof Internal Medicine; 21st edition; 2022 • Davidson's Principles and Practice of Medicine; 23rd edition; 2018 • Current Medical Diagnosis & Treatment 2022 • Cappellini MD, Motta I. Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?. Semin Hematol. 2015;52(4):261-269. doi:10.1053/j.seminhematol.2015.07.006 • Diagnostic approach to anemia in adults; Uptodate 2022 • KDIGO Guidelines 2012
Editor's Notes
- #4 Gaussian distribution, The aging of population, especially in Western countries, causes an increase of anemia in elderly people. In this population, anemia, recently defined by levels of Hb <12 g/dL in both sexes, is mostly of mild degree (10-12 g/dL).
- #6 Some EPO by liver, EPO for maintenance of committed erythroid progenitor cells that, in the absence apoptosis, Following lineage commitment, hematopoietic progenitor and precursor cells come increasingly under the regulatory influence of growth factors and hormones. In the bone marrow, the first morphologically recognizable erythroid precursor is the pronormoblast. This cell can undergo four to five cell divisions, which result in the production of 16–32 mature red cells. Role of typical shape of RBC, membrane integrity by ATP, 1% of all rbc replaced daily,
- #7 The organ responsible for red cell production is called the erythron. The erythron is a dynamic organ made up of a rapidly proliferating pool of marrow erythroid precursor cells and a large mass of mature circulating red blood cells. In the presence of O2, HIF-1α is hydroxylated at a key proline, allowing HIF-1α to be ubiquitinated and degraded via the proteasome pathway. If O2 becomes limiting, this critical hydroxylation step does not occur, allowing HIF-1α to partner with other proteins, translocate to the nucleus, and upregulate the expression of the EPO gene, among others.
- #10 Glucose-6-phosphate dehydrogenase (G6PD) deficiency and certain hemoglobinopathies are seen more commonly in those of Middle Eastern or African origin, including blacks who have a high frequency of G6PD deficiency
- #11 pale if the hemoglobin is <8–10 g/dL, vessels are close to the surface such as the mucous membranes, nail beds, and palmar creases. <8 g/dL in palmar crease
- #12 tests more needed in critically ill, tests can be decreased in typical cases. Obtaining the studies after an overnight fast may be useful as it avoids interference by dietary iron or iron-containing vitamins, which can increase the serum iron and calculated TSAT
- #13 MCH : Not Useful, tends to track with MCV, Central pallor > one-third of the RBC diameter, RDW : Iron deficiency vs Thalassemia, A finding of high RBC count in an individual with anemia suggests thalassemia
- #14 Always think the anemia is multifactorial
- #15 but not Hb S Mentzer index : MCV/RBC count <13, Thalassemia > IDA While in the marrow compartment, red cell precursors undergo cell division, driven by erythropoietin. If red cells cannot acquire haemoglobin at a normal rate, they will undergo more divisions than normal and will have a low MCV when finally released into the blood. The MCV is low because component parts of the haemoglobin molecule are not fully available.
- #16 Serum iron concentration is not a reliable indicator of iron stores because it can be increased acutely by recent transfusion (due to iron release from damaged RBCs in the transfused product) . Ferritin: 10-15 ug/L : depletion of iron store, >200 ug/L means iron is in strore Iron has diurnal variation TSAT : Iron/TIBC x 100 : 25-50% TIBC : 54–64 μmol/L ferritin 100 μg/L = Iron stores of 1 g
- #18 Megaloblastic anemia – Asynchronous nuclear maturation (megaloblastosis) In megaloblastic anaemia, the biochemical consequence of vitamin B12 or folate deficiency is an inability to synthesise new bases to make DNA. A similar defect of cell division is seen in the presence of cytotoxic drugs or haematological disease in the marrow, such as myelodysplasia. In these states, cells haemoglobinise normally but undergo fewer cell divisions, resulting in circulating red cells with a raised MCV. Conditions such as liver disease, hypothyroidism, hyperlipidaemia and pregnancy are associated with raised lipids and may also cause a raised MCV.
- #19 MCV typically is not >105 fL in alcohol-induced macrocytosis Conditions such as liver disease, hypothyroidism, hyperlipidaemia and pregnancy are associated with raised lipids and may also cause a raised MCV.
- #20 NN Aemia has slightly increased RDW and retix is not substantially increased or even decreased. Normocytic is common in hypothyroidism than microcytic. In adrenal insufficiency, anemia may be masked by volume contraction. Dimorphic RBC in Partially treated anemia and sideroblastic anemia
- #21 eGFR <45 mL/min/1.73 sq m without any cause : Anemia of CKD Older adults : Rule out Monoclonal gammopathies, clonal cytopenias, androgen deficiency, and bone marrow evaluation for myelodysplasia and pure red cell aplasia
- #22 Polychromasia : Slightly larger than normal and grayish blue in color on the Wright-Giemsa stain. These cells are reticulocytes that have been released prematurely from the bone marrow and their color represents residual amounts of ribosomal RNA. These cells appear in circulation in response to EPO stimulation or to architectural damage of the bone marrow (fibrosis, infiltration of the marrow by malignant cells, etc.) that results in their disordered release from the marrow.
- #24 Hemophagocytic lymphohistiocytosis (HLH) may be primary (typically in children) or secondary to an infection, malignancy, or rheumatologic condition; TTP : MAHA+TCP+Schistocytes
- #25 Staining with a supravital dye that precipitates the ribosomal RNA. Why RPI?
- #26 If both bone marrow suppression and hemolysis or blood loss are present, the reticulocyte count will be inappropriately low. If the reticulocyte count does not increase with correction of a deficiency, this suggests an additional cause of anemia is interfering with bone marrow function.
- #27 WHY RPI? First correction adjusts the reticulocyte count based on the reduced number of circulating red cells. With anemia, the percentage of reticulocytes may be increased while the absolute number is unchanged. To convert the corrected reticulocyte count to an index of marrow production, a further correction is required, depending on whether some of the reticulocytes in circulation have been released from the marrow prematurely. For this second correction, the peripheral blood smear is examined to see if there are polychromatophilic macrocytes present and not done if polychromatophils not present. RPI provides an estimate of marrow production relative to normal
- #29 75% are hypoproliferative
- #30 Iron deficiency occupies an unusual position in the classification of anemia. If the anemia is severe and prolonged, the erythroid marrow will become hyperplastic despite the inadequate iron supply, and the anemia will be classified as ineffective erythropoiesis with a cytoplasmic maturation defect.
- #31 A patient with a hypoproliferative anemia and a reticulocyte production index <2 will demonstrate an M/E ratio of 2 or 3:1 Maturation disorders are identified from the discrepancy between the M/E ratio and the reticulocyte production index
- #33 Among the least common forms of anemia. Alloimmune : Blood group mismatch Extravascular hemolysis : Recycling of iron from the destroyed red cells support red cell production. Intravascular hemolysis, such as paroxysmal nocturnal hemoglobinuria, the loss of iron may limit the marrow response.
- #39 Schistocyte due to Mechanical destruction of RBC
- #41 Hemorrhagic anemia does not typically result in production indices of more than 2.0–2.5 times normal because of the limitations placed on expansion of the erythroid marrow by iron availability
- #42 Retix peak occurs 1 week after treatment when treated with Fe, B12, Folate Hb and Hct increases to normal in 6-8 weeks 1% reticulocytosis increases MCV by 1fl seen in chronic reticulocytosis Recombinant EPO : CKD on dialysis, chemotherapy ESA therapy should not precede treatment of iron deficiency because ESAs will be less effective and may exacerbate thrombocytosis.
- #43 Hypoxia-inducible factor prolyl hydroxylase inhibitors
- #44 Green boxes indicate benefits of IV iron therapy. Yellow boxes indicate that an iron trial may be beneficial. Red boxes indicate that iron should not be given. Patients with TSAT <20% and inflammation elevating the serum ferritin (up to 100 ng/mL) will likely respond in a manner similar to that of classic AIDA; patients with ferritin >100 ng/mL may exhibit slightly lower Hb responses. A CHr and reticulocyte count may help to determine whether to give iron in this instance.
- #46 200 mg of iron are delivered per unit of RBC Restrictive strategy except : Symptomatic, ACS, MI, Massive transfusion, chronic transfusion dependent
- #48 Severe iron deficiency (ie, transferrin saturation [TSAT] <12 percent) ●Severe anemia (hemoglobin [Hb] <7 g/dL) in asymptomatic patients ●Risk of ongoing blood loss (such as a patient with chronic gastrointestinal blood loss) ●History of side effects to oral iron ●History of not responding adequately to oral iron