Ruth Namazzi, Amos Odiit, Heather Hume, Chandy John, Robert Opoka . Post Transfusion Changes in Haemoglobin Concentration of Children with Severe Anaemia at a Tertiary Hospital: A prospective study Ruth Namazzi, Amos Odiit, Heather Hume, Chandy John, Robert Opoka . Makerere University, Kampala Uganda

29/08/2015 UMA Conference,Mbale Introduction Severe anaemia (hemoglobin ≤ 5g/dL) contributes to 8 to 17% of in hospital mortality in African children Severe anaemia is usually managed by blood transfusion and a course of haematinics. As per WHO guidelines, children should receive 10mL/kg of packed red cells or 20mL/kg of whole blood. Whether these children achieve haematological recovery after blood transfusion is not well documented . 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Introduction Studies suggest high blood transfusion failure rates, poor haematological recovery and recurrence of severe anaemia in the post discharge period. Due to the difficulties in getting blood to health units, children do not always get the recommended amounts of blood. In addition, blood preparation techniques (sedimenation) used to prepare “packed red cells” may result in units of lower haematocrits(“ red cell concentrate”) 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Rationale Studies suggest high blood transfusion failure rates, poor haematological recovery and recurrence of severe anaemia in the post discharge period. We carried out this study to assess the haematological recovery of children with severe anaemia transfused at Mulago Hospital. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Objectives To describe the change in Hb concentration of children with severe anaemia within: 24 hours of blood transfusion 6 weeks after blood transfusion To describe the factors associated with adequate haematological recovery 6 weeks after blood transfusion. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Methods Study design: A Prospective, cohort study of 188 children Study site: Paediatric Acute Care unit , Mulago National Referral Hospital, Kampala ,Uganda Inclusion criteria: All children 6 to 60 months with Hb ≤ 5g/dL Exclusion criteria: sickle cell anaemia chronic kidney disease malignancies. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Measurements Lab testing: Haemoglobin: pre & post transfusion, at discharge and 6 weeks after blood transfusion Complete blood count Peripheral film for red cell morphology Blood smear for malaria. HIV serological tests Volume of blood transfused: volume per kilogram body by weighing blood bags. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Procedures Managed according to Mulago National Referral Hospital guidelines. Daily ward follow-up till discharge. All participants discharged home on haematinics. Post discharge follow up Hb and blood smear at all hospital sick visits 6 weeks - Hb, complete blood count, peripheral film comment and blood smear for malaria 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Data Analysis Average overall mean change in hemoglobin computed at 24 hours and 6 weeks after discharge Linear regression used to computed unit increase in Hb per unit volume of packed red blood cells Logistic regression used to computed factors associated with hematological recovery 29/08/2015 UMA Conference,Mbale

Results: Baseline characteristics Percent (%) Age <24 months 89 47.4 Sex (male) 103 54.8 Fever at admission 181 96.3 Passing dark urine 87 46.3 Positive blood smear for malaria at admission 128 68.1 HIV status (positive) 5 2.1 Hook worm in stool 4 2.7 29/08/2015 UMA Conference,Mbale

Results: Mean Change in Haemoglobin Mean pre and post transfusion Hb was 3.7g/dL (SD 0.8)and 6.3 (SD1.5) respectively. Mean volume of “red blood cell concentrate” transfused was 12.1mL/kg (S.D 4.1) 24 hours after blood transfusion Mean change 24 hours and 6 weeks after blood transfusion was 2.6g/dL (SD 1.5) and 7.2 (SD2.4) g/dL Unit increase in haemoglobin per 10ml/kg of blood was 1.5g/dL 47/188(25%) required a second transfusion within 24 hours At 6 Weeks: mean change was 7.3g/dL (SD 1.6) 29/08/2015 UMA Conference,Mbale

Change in Hemoglobin by Type of blood received. Variable RCCs (n=169) Whole Blood (n=19) P-valuea Mean volume/kg of blood (mL) (SD) 12.7 (4.2) 19.9 (5.6) <0.001* Mean (SD) Hb change within 24 hours of blood transfusion 2.5(1.4) 3.6(1.9) 0.001* Mean (SD) post-transfusion Hb (g/dL) 6.2 (1.5) 7.6 (1.9) Mean (SD) Hb 6 weeks after blood transfusion c( (g/dL) 11.0 (2.2) 10.4 (3.2) 0.210 Mean (SD) Hb change 6 weeks after blood transfusion (g/dL) 7.4(2.2) 6.5(3.4) 0.127 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Multivariate Analysis for Factors associated with Haematological Recovery Variable Un adjusted OR,95% CI P value Adjusted OR 95% CI P Value Positive malaria slide in the post discharge period 0.3(0.13,0.58) 0.01* 0.3(0.12,0.87) 0.026* No mosquito net use 0.5(0.23,1.05) 0.068 0.8(0.3,2.3) 0.724 HIV Status Negative 6.9(0.75,63.1) 0.088 7.7(0.42,142.6) 0.169 Age ≤24 months 0.4(0.26,0.77) 0.005* 0.3(0.160.67) 0.002* 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Discussion Mean change in haemoglobin within 24 hours of blood transfusion of 2.6g/dL (SD 1.5) is within estimates of WHO(2-3g/dl) Increase per 10mL/kg of red cell concentrate much lower than WHO estimates. Haemocrit of the ‘red cell concentrate ‘is much lower than for packed cells, hence higher volumes of blood needed to correct anaemia adequately.(0.55 vs 0.75) Blood packs are not of standardised volumes. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Discussion Malaria infection during the post discharge retards recovery Malaria causes varying degrees of bone marrow suppression . Child younger than 24 months is 70% less likely to attain adequate haematological recovery. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Conclusions Current transfusion practices do not correct severe anaemia adequately in the immediate post transfusion period. Post discharge malaria infection hinders recovery of haemoglobin levels in children discharged after an episode of severe anaemia. Children younger than 2 years are less likely to recover fully after an episode of severe anaemia. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Recommendations We recommend a review and/or further study of current transfusion guidelines with respect to transfusion volumes and preparation of blood products. Efforts to prevent malaria in the post discharge period, especially in children younger than 24 months should be strengthened. 29/08/2015 UMA Conference,Mbale

29/08/2015 UMA Conference,Mbale Acknowledgements Funding: D43 NSO78380 training grant Study participants and caretakers Makerere University/University of Minnesota Research Collaboration 29/08/2015 UMA Conference,Mbale