1. Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness Robert O. Opoka 1, Sarah Kiguli 1, Peter Olupot- Olupot 2, Charles Engoru 3, Kathryn Maitland 4 (On behalf of the FEAST trial team). UMA conference 29 th Aug 2015, Mbale 1

2. Severe anemia Severe anemia significantly low Hb < 5 g/dL (WHO) Requires hospitalization and urgent correction of anemia (transfusion) It is a common clinical presentation Accounts for 9.7-29% of pediatric admissions (Muoneke, Okechukwu) Yet there are limited published data on blood transfusion in this vulnerable group. 2

3. Management of severe anemia 3 Blood transfusion is the mainstay of managements and can be lifesaving Challenges are equitable access to adequate supplies of safe WHO guidelines encourages the rational use of blood Transfusion. However, adherence to the guidelines vary between countries.

4. Objectives We analyze the FEAST data and describe The prevalence, clinical features, and transfusion management of anaemia In children presenting to hospitals in three East African countries with serious febrile illness 4

5. FEAST TRIAL FLUID EXPANSION AS SUPPORTIVE THERAPY IN CRITICALLY ILL AFRICAN CHILDREN

6. Study design Children with impaired consciousness and/or respiratory distress and impaired perfusion Bolus 5% albumin 20 ml/Kg (40 ml/Kg after Aug 2010) over 1 hour Bolus 0.9% saline 20 ml/Kg (40 ml/Kg after Aug 2010) over 1 hour Control (No bolus) Maintenance fluids only Children with respiratory distress and clinical evidence of impaired perfusion Follow-up to 4 weeks (24 weeks if developed neurological sequelae by 4 weeks) Clinical assessments at 1, 4, 8, 24, 48 hours and at 4 weeks Impaired perfusion Any one of: Cap refill > 2 secs, Severe tachycardia, temperature gradient weak pulse Excluded: Gastroenteritis Severe malnutrition Non-medical admission (burns,trauma)

7. FEAST: Sites

8. Methodology Venous blood was taken on admission for immediate measurement of Hb. We used HaemoCue Hb 301 (HaemoCue AB, Angelholm, Sweden) Also measured blood glucose, lactate, malaria parasitaemia, and HIV status. Children were managed on general paediatric wards according to hospital guidelines 8

9. Blood transfusion Clinicians followed national and WHO blood transfusion guidelines. Hb ≤ 4 g/dL, transfused regardless of clinical symptoms Hb 4-6 g/dL, transfused if has signs of severity 20 mL/kg whole blood or 10 mL/kg packed cells, given over 4 hours, Hb levels were checked at 8, 24, and 48 hours post- transfusion Repeat blood transfusion was permitted when Hb levels fell below transfusion thresholds. 9

10. Results Of 3170 children in the FEAST trial, 3082 (97%) had a baseline haemoglobin (Hb) measurement 2346/3082 (76%) were anaemic (Hb <10g/dL) and the anaemia was severe (Hb< 5g/dl) in 33%. Children with moderate or severe anaemia had worse nutritional status than those with mild anaemia or no anaemia 10

11. Table 1 11

12. Anemia and transfusions Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda Overall, 1,387/3,082 (45%) children were transfused, of whom 23% (317/1,387) required re-transfusion; 81% (1,118/1,387) were transfused within 8 hours of admission. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6-13% at the 4 Ugandan centres 12

13. Per site 13

14. Outcome of transfusion In total, 94% (933/1,002) of severely anaemic children were transfused, 275/933 (29%) received more than two transfusions, This proportion varying from ≤ 5% in Kenya and Tanzania to between 23% and 38% in the four Ugandan centres Whole blood was used for 1,459/1,767 (83%) and Packed cells for 308/1,767 (17%) transfusions. 14

15. Outcomes 15

16. Outcomes of treatment Overall, 67% (93/139) of deaths among severely anaemic children occurred within 8 hours of admission and 92% (128/139) by 24 hours. At 8 hrs 39 (4%) of transfused while 54 (52%) of non transfused children had died; 90% of these deaths occurred within 2.5 hours of transfusion and 100% within 5 hours At 8 hours 10 (5%) transfused while 12 (4%) of children with mod anemai not transfused had died. 16

17. Transfusion reaction 6 of the 1,387 children in receipt of one or more transfusions (0.4%) were considered to have had a “ probable” blood transfusion reaction. These children all developed fever and an urticarial rash 1 to 3 hours after the start of blood transfusion. In all cases, the transfusion was discontinued and the child treated with intravenous hydrocortisone, and recovered fully. 17

18. Conclusions Adherence to WHO transfusion guidelines was poor. There was no evidence of an association Transfusion with 10 mL/kg of packed red cells provided inadequate treatment for children with severe anaemia. The high proportion of repeat transfusions also suggests that 20 mL/kg whole blood may be insufficient for children with severe anaemia and ongoing haemolysis. 18

19. Recommendations Our data confirm the importance of rapidly identifying sick, severely anaemic children and ensuring that they are promptly transfused. Training needed for health workers to adhere to transfusion guidelines. Need to review transfusion guidelines, the products and doses of blood given 19

20. Thank you for listening 20