Clinical medicine for the hematology course In this sheet we will discus 3 medical cases together, but before that I would like to revise some basic concepts which hopefully will help you ….. Clinical points in diagnosing anemia : - Serum ferritin is largely derived from the storage pool of iron; its concentration is a good indicator of the adequacy of body iron stores - Red cell kinetic is determined by reticulocyte count (which indicates BM activity) -Red cell size: determined by MCV - Hb ( roughly) =HcT/3 *Anemia could be due to: 1) decrease in the production of RBCs 2) Increase in their destruction 3) Extensive bleeding The key test through which we can identify the cause of the anemia is the reticulocyte count. If we have an increase in the reticulocyte count: the anemia here is properly due to increase in destruction or bleeding. But if the lab test shows low reticulocyte count that reflects a low level of BM production * Note: Increased reticulocytes (greater than 2-3% or 100,000/mm3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemia's will present with a normal reticulocyte count due to immune destruction of red cell precursors. Retic counts are most helpful if extremely low (<0.1%) or greater than 3% (100,000/mm3 total). The causes behind erythrocytes low level production : 1) Decreased erythropoietin production (like in anemia of chronic disease as in chronic renal failure) 2) Inadequate marrow response to erythropoietin Another classification of anemia according to MCV: Macrocytic (MCV>115) B12, Folate, MDS(myelo dysplastic syndrome) Normocytic - Anemia of chronic disease - Mixed deficiencies - Renal failure - Acute bleeding (for 48hrs) -Sickle cell anemia - Hereditary spherocytosis Microcytic - Iron deficiency -Thalassemia - Anemia of chronic disease (30-40%) -sideroblastic anemias -Chronic bleeding Acute bleeding for 48 hrs produce normocytic anemia after that it will change to be microcytic (usually due to its association with iron deficiency) ********************************************************************* Clinical cases Normal findings: ferritin =150 / Fe = 150 / retic = 1000 / TIBC= 290-400 # The First case: A 29 yr female artist is referred to you because of anemia which has not responded to oral iron therapy. PMH (premedical history): She had gastric resection 3 yrs ago and has lost a lot of weight. PE (physical examination) shows a pale woman, liver and spleen are not enlarged, stool guaiac is negative. Labs Hgb 8.8 g/dl, MCV 75 fl WBC 5500/ul Plts 490,000/ul, Retic ct 20,000/ul Fe 25 ug/dl, TIBC 460 ug/dl, ferritin 11 ug/l The Interpretation is: - When we say Paleness first thing that comes in mind is anemia in addition the Hb is low) - By the absences of hepatosplenomegaly we can exclude extavascular hemolysis - Stool guaiac –ve : which means no GI bleeding - WBC within the normal limits - Here the MCV is lower than the normal range …….microcytic anemia -mainly in the cases of the microcytic anemia's (where we don’t have a previous history of a chronic disease) we would think of either IDA or thalassemia. - We have low ferritin (which is very clear in IDA) - in IDA the TIBC will increase just like what we have here while in thalassemia the TIBC is low or normal) - Platelet count is slightly elevated (& that is what usually is seen with IDA) $$$$ So it's atypical case of IDA § The PLTs increase in number: 1) Due to hidden bleeding (here for example if we have one, it's not from the GIT) 2) Increase BM production and release It's good to know: -if ferritin level is <15g/dl …its an iron deficiency anemia, But if its 150 g/dl ….its not IDA If it's between 15-150 g/dl =we can't tell *Inadequate iron supply could be from: - Poor nutritional intake in children (not a common independent mechanism in adults but often a contributing factor) - Gastric bypass surgery for ulcers or obesity - Achlorhydria from gastritis or drug therapy - Severe malabsorption (for example, celiac disease [nontropical sprue]) ♣ the treatment is by giving oral iron supplements then if this doesn’t work we give it intraperentrally ₪ Oral iron failure? -Incorrect diagnosis (eg, thalassemia) -Anemia of chronic disease? -Patient is not taking the medication -Not absorbed (enteric coated?) -Rapid iron loss? 2nd case: 55 yr F with moderately severe Rheumatoid Arthritis taking Prednisone (immune suppressant) =10 mg/day, Celecoxib, is referred to you for an anemia workup *CBC: Hct = 30%, MCV = 82, WBC = 5.4 thou/l, plt = 345 thou/ l Smear - Normal -Retic count = 2 % -Fe = 20 g/dL (55-155), TIBC = 200 g/dL (270-400), Transferrin saturation = 20/200 = 10% (15-50) -Ferritin = 330 g/dL (20-160) The interpretation is - Hb=HcT/3 = 10 (low Hb indicating anemic case) - MCV=82…… normocytic - Normocytic anemias include many cases but because the patient is 55yrs old if she has sickle cell anemia or spherocytosis for sure you will notice that in her medical history!!!!! , & there is no information of recent acute bleeding, so we are going to stuck with what we have ((chronic disease))…..trying to see if her lab results support our theory-that she has anemia of chronic diseaseor not !!! - Iron & TIBC & trasferrin saturation are low - Ferritin level is high - All these results confirm our previous diagnose ,because what we have in this kind of anemia is elevated serum ferritin & elevated iron stores & the TIBC will decrease ,so where is the problem !!!! *the problem will appear with the inflammatory cytokines which will: 1) Enhance hepcidin synthesis in the liver 2) Inhibit the compensatory increase in erythropoietin ♫ Its cute simple to differentiate between IDA & anemia of chronic disease: - First of all anemia's of chronic disease is not always hypochromic microcyctic, it could be normochromic normocytic(as in the previous example) - iron stores increase -increase in serum ferritin - Decrease in TIBC # Here we treat the patient by giving her erythropoietin & iron * High ferritin could be found in: 1) Infections 2) Thalassemia 3rd case: A 69 yrs woman is referred to you for progressive anemia. The most recent blood counts reveal leukopenia and thrombocytopenia. Examination of the peripheral blood shows hypersegmented granulocytes. The neurologic examination is normal, and her serum folate is normal. CBC: Hb 9, MCV 105, RDW 15, Retics (corrected <0.1%), WBC 3500 (n diff), Plt 103. DCT is –ve. The interpretation is - Hb is low….unexpectedly anemia again!!! - MCV is high …macrocytic (so we could think of in B12 vit or folate) - Leucopenia &thrombocytopenia (in both) - hypersegmented granulocvtes (in both) - The neurologic examination is normal (this doesn’t exclude B12 deficiency because it only occurs in very sever cases of B12deficiency - Now…serum folate is normal So its B12 deficiency - DCT is –ve just to tell you its not autoimmune disease Seema maraqa