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Approach to anaemia copy.pptx
- 2. Definitions Anaemia is a condition in which the number of red blood cells, and consequently their oxygen-carrying capacity, is insufficient to meet the body’s physiologic needs – WHO, 2011 Definitions Hb < 13 g/dL in adult males Hb < 12 g/dL in non-pregnant females
- 3. Erythropoiesis Process by which hematopoietic stem cells divide and differentiate into erythrocytes. Occurs in the bone marrow https://www.learnhaem.com/courses/anaemia/lessons/normal-haematopoiesis/topic/normal-
- 4. RBC life cycle 2 x 1011 reticulocytes enter the circulation daily ~1% RBC RBC life span ~120 days. Aged RBCs are removed by macrophage phagocytosis in the liver and spleen https://www.blendspace.com/lessons/hhHtKIAbybVHow/the-life-cycle-of-erythrocyte
- 5. Steady state RBC production RBC removal
- 6. Anaemia RBC production RBC loss - Bleeding - Haemolysis
- 7. Anaemia RBC production RBC loss - Iron/B12/Folate deficiencies - Bone marrow pathologies - MDS / leukaemia - Infiltration – metastasis, TB
- 8. Common causes of anaemia Blood loss Decreased red cell lifespan (haemolytic anaemia) Congenital defect – thalassemia, sickle cell disease, hereditary spherocytosis Acquired defect – autoimmune, malaria, drugs Impairment of red cell formation Pooling and destruction of red cells in an enlarged spleen Increased plasma volume (splenomegaly, pregnancy)
- 10. Red cell indices Index Normal range Mean cell volume (MCV) 82 – 99 fL Mean cell Hb (MCH) 27 – 33 pg Mean cell Hb concentration (MCHC) 32 – 36 g/dL MCV - average size of RBC MCH - average weight of Hb per RBC = Hb/RBC count MCHC - concentration of Hb per unit volume of RBCs = Hb/Hct
- 11. Reticulocyte count Measured as Absolute count / Percentage In steady state Absolute reticulocyte count 0.025 to 0.1 x 106 /µL Retic 1-2% Increased reticulocyte count means normal bone marrow response to anemia.
- 12. Clinical symptoms Bleeding – melena, heavy menses Past medical history Kidney disease Liver disease Hypersplenism Dietary – vegan (B12 deficiency) Travelling history – parasitic infections
- 13. Clinical symptoms Symptoms of anemia reflect the rate of RBC loss. More rapid drop less compensation more symptomatic Hb and Hct may be normal just after acute blood lose. Volume will take time to be replaced by fluid movements. Gradual / chronic anaemia – less symptomatic
- 15. Evaluation based on MCV https://www.uptodate.com/contents/diagnostic-approach-to-anemia-in-adults
- 16. #1 Look at other cell lines
- 17. Look at other cell lines – WBC and Platelet Low WBC / Platelet Increased WBC Increased platelets Hypersplenism Liver disease Lymphoma Autoimmune SLE Myelodysplasia Multiple myeloma Aplastic anaemia Inflammation Leukaemia Myelofibrosis Iron deficiency Myelofibrosis
- 18. #2 Is there haemolysis?
- 19. Is there haemolysis? Hemolysis Jaundice Dark urine History of gallstones Certain food or drug exposures (fava beans, moth ball, oxidant drugs) Haemolytic markers Indirect bilirubin – increased LDH - increased Haptoglobin - reduced Reticulocyte count – increased
- 21. Haemolysis - investigations Coombs test Autoimmune hemolytic anaemia Peripheral blood film Spherocytes – AIHA, hereditary spherocytosis Bite or blister cells – oxidative hemolysis Microcytosis, target cells, teardrop cells – thalassemia Schistocytes - MAHA G6PD – can be falsely normal in acute hemolysis.
- 22. #3 Retic count
- 23. Reticulocyte count Useful marker to differentiate anaemia due to Production failure (retic count not increased) Accelerated red cell destruction (raised retic count) Where there is sufficient bone marrow reserve to mount a good response to anaemia, the reticulocyte count will be high. Increase in hemolysis and blood loss.
- 24. #4 Previous Hb trend?
- 25. Any previous normal Hb? If no previous normal Hb, consider congenital causes Thalassemias Congenital marrow failures – Fanconi anaemia, Diamond–Blackfan anemia Features of thalassemia Microcytic anaemia Hepatosplenomegaly Jaundice Thalassemic facies Growth failure Family history
- 26. Thalassemias Most common cause of congenital anemia is thalassemia Decreased or absent of either α / β globin chain production. If suspected of thalassemia, please send the following prior to transfusion. PBF Hb Analysis Ferritin RBC Phenotyping
- 27. #5 MCV and other blood tests.
- 29. Tests Useful initial tests Peripheral blood film Reticulocyte count Renal function Liver function Ferritin, Iron, TIBC Further Ix Folate / B12 ANA C3/C4 HIV, Hep B, Hep C screen OGDS, colonoscopy
- 32. Ferritin Main storage protein for iron. Serum level correlates with the amount of tissue-storage iron Serum ferritin levels are low in iron deficiency. Acute phase reactant Not sensitive Raised in infection, inflammation and malignancy. Cannot exclude iron deficiency in these settings. Levels <15 µg/l predict a high likelihood of iron deficiency. Up to 30 µg/l can still be consistent with deficiency, although is less specific.
- 33. Serum iron and Transferrin Serum iron Only measures the oxidised ferric iron bound to transferrin and not the functional iron component of Hb. Serum iron alone should not be used in assessment of iron deficiency. It is used in combination with TIBC to calculate the Transferrin Saturation (TSAT) Transferrin / TIBC (total iron binding capacity) TIBC and transferrin rise in iron deficiency. Negative acute phase protein – reduced in inflammation.
- 34. TSAT (total iron binding capacity) Ratio of serum iron to transferrin (or TIBC) expressed as a percentage. Serum iron / TIBC x 100% TSAT <16% support iron deficiency.
- 35. Guideline for the laboratory diagnosis of iron deficiency in adults (excluding pregnancy) and children (BJH, 2021)
- 36. Anaemia of Chronic disease
- 37. Anaemia of Chronic Disease / Inflammation Anaemia of chronic disease a.k.a. anaemia of inflammation Mechanisms Hepcidin – block iron absorption in gut and release of iron from macrophages Inflammation suppresses of erythropoietic activity Decreased RBC survival in inflammation
- 38. Anaemia of Chronic Disease / Inflammation Commonly associated disorders Malignancy Chronic kidney disease Rheumatologic conditions Hypothyroidism Infections
- 39. Anaemia of chronic disease Normochromic, normocytic anemia Low or inappropriately low reticulocyte count Iron studies Low serum iron Normal to low transferrin Low TSAT Normal or high ferritin Raised inflammatory markers – CRP, ESR
- 40. ACD vs IDA Iron Deficiency Anaemia Anaemia of Chronic Disease FBC Hb Decreased Decreased MCV Decreased Normal / Decreased Iron studies Serum iron Decreased Decreased TIBC Increased Decreased TSAT Decreased Normal / Decreased Serum Ferritin Decreased Increased
- 41. ACD vs IDA Iron Deficiency Anaemia Anaemia of Chronic Disease FBC Hb Decreased Decreased MCV Decreased Normal / Decreased Iron studies Serum iron Decreased Decreased TIBC Increased Decreased TSAT Decreased Normal / Decreased Serum Ferritin Decreased Increased
- 42. Ferritin thresholds for concomitant IDA In patients with anaemia of chronic disease Ferritin < 15 mcg/L – suggestive of IDA Ferritin 15 – 150 mcg/L – can be concomitant IDA Ferritin > 150mcg/L – unlikely concomitant IDA (BSH, 2021)
- 43. Iron deficiency in Chronic kidney disease Classical iron deficiency in CKD <100 μg/l in non- haemodialysis <200 μg/l in chronic haemodialysis Functional iron deficiency CKD may have excess iron in liver and spleen, but inadequate within the bone marrow available for erythropoiesis. Ferritin can be up to 800 μg/l BSH Guideline for the laboratory diagnosis of functional iron deficiency (BJH, 2013)
- 44. Take home messages Look at other cell lines – bicytopenia, pancytopenia. Rule out active hemolysis. Reticulocyte count is useful to assess marrow response. If suspect thalassemia, please send the diagnostic workup prior to transfusion. Iron studies – Ferritin and TSAT. Without inflammation, Ferritin <15 µg/l suggest iron deficiency. With inflammation, Ferritin < 150 µg/l can be iron deficient. In CKD, Ferritin up to 800 µg/l can still be iron deficient. TSAT <16% support iron deficiency.
- 45. Thank you