1. Swissmedic Schweizerisches Heilmittelinstitut Hallerstrasse 7 CH-3000 Bern www.swissmedic.ch Prevention of TACO – what Haemovigilance data tell us Swisstransfusion, Genève 6. Septembre 2013 Markus Jutzi, Morven Rüesch Clinical Reviewer Haemovigilance, Swissmedic

2. Current Haemovigilance data 2 Swisstransfusion, 06.09.2013 59 % High imputability TR‘s

3. Imputability and severity High imputability: ~ 60 % of all reported transfusion reactions (TR‘s) ~ 60 % of reported TACO Severity grade 3 or 4 (life threatening or fatal) 2.7 % of all reported TR‘s 25 % of reported TACO 3 Swisstransfusion, 06.09.2013

4. Life threatening and fatal cases 4 Swisstransfusion, 06.09.2013

5. Comparison of cumulative incidence (reported TACO cases per blood components transfused) 5 Swisstransfusion, 06.09.2013 Blood component Québec 2000 - 2008 * Switzerland 2008 - 2013 Ireland 2000 – 2008 ** France 2000 - 2006 ** All components 1: 3‘9321: 9‘6551:10‘0001: 13‘210 Red cell concentrates 1: 2‘9401: 7‘4771:8‘0001: 11‘450 * Robillard, P. et al; Transfusion associated circulatory overload: The new leading cause of transfusion associated fatalities reported to the Québec Haemovigilance system. Presentation IHS 2010 in Dubrovnik ** ANSM; Mise au point sur les oedèmes aigus pulmonaires de sucharge posttransfusionnels. Juillet 2012

6. Definition(s) of TACO ISBT WP on Haemovigilance, July 2011 : Acute respiratory distress Tachycardia Increased blood pressure Acute or worsening pulmonary oedema on frontal chest X-ray Evidence of positive fluid balance within 6 hours of transfusion. An elevated BNP is supportive of TACO 6 Swisstransfusion, 06.09.2013 Transfusion reactions (Popovsky et al, AABB Press, 3rd edition) Dyspnoea Orthopnoea Cyanosis Tachycardia Increased blood pressure Pulmonary / pedal oedema within several hours of transfusion Nonspecific manifestations Headache Tightness in the chest Dry cough Occurrence of any 4 of the following: Occurrence of any or all of the following:

7. Reports of TACO 2008 - 2013 7 Swisstransfusion, 06.09.2013

8. Reports of TACO 2008 - 2013 8 Swisstransfusion, 06.09.2013

9. Reports of TACO 2008 - 2013 9 Swisstransfusion, 06.09.2013 Possible TACO: Only mild cases, except 1 severe in 2012

10. TACO reports 2012 & 2013 10 Swisstransfusion, 06.09.2013 49 TACO, imputability possible, probable or certain 35 high Imputability 14 possible Patient demographics Product type Severity Risk factors Signs and symptoms Preventability (transfusion rate?)

11. TACO reports 2012 & 2013 11 Swisstransfusion, 06.09.2013

12. Severity 2012 & 2013 12 Swisstransfusion, 06.09.2013

13. Severity 2012 & 2013 13 Swisstransfusion, 06.09.2013 Possibles: RBC12 RBC + PC 1 RBC + FFP 1 PC 1

14. Risk factors 14 Swisstransfusion, 06.09.2013

15. Risk factors 15 Swisstransfusion, 06.09.2013 > 60y as only risk: ~ 20 % life threatening events

16. Risk factors 16 Swisstransfusion, 06.09.2013 > 60y as only risk: ~ 20 % life threatening events Additional risk factors: 30 - 50 % life threatening/fatal events

17. Reported TACO symptoms 17 Swisstransfusion, 06.09.2013

18. Reported TACO symptoms 18 Swisstransfusion, 06.09.2013

19. Reported TACO symptoms 19 Swisstransfusion, 06.09.2013

20. Reported TACO symptoms 20 Swisstransfusion, 06.09.2013

21. Grade 3 &4 TACO - Preventability 21 Swisstransfusion, 06.09.2013

22. Grade 3 & 4 TACO - Preventability 22 Swisstransfusion, 06.09.2013 Absence of risk factors transfusion rate: 2-4 ml/minute One known risk factor Several risk factors Recommended precautions: limit transfusion rate: 1 ml/kg bw/h assess fluid balance careful monitoring of patient consider therapeutic options evaluate patient for each transfusion

23. Key findings 23 Swisstransfusion, 06.09.2013  Most reported TACO cases occurred in patients > 60y  TACO is mainly associated with RBC transfusion  25 % were life threatening or fatal  Age > 60 is the most common single risk factor  Several risk factors  increased severity

24. Main clinical aspects 24 Swisstransfusion, 06.09.2013 Presentation  hypertension and dyspnoea are the most common but non-specific symptoms  The combination of dyspnoea and hypoxaemia indicate an increased likelihood for a life-threatening or fatal course of the event ► measure saturation ! Management of TACO  Recognise and act on unspecific symptoms  In case of dyspnoea check O2-saturation  Look out for additional symptoms  Consider diuretics, nitrates and oxygen

25. Prevention 25 Swisstransfusion, 06.09.2013  Assess risk factors  Base decision to transfuse on benefit/risk assessment  Take overall fluid balance into account  In presence of one or more risk factors: Prescribe low transfusion rate of max. 1 ml/kg bw/h Monitor patient carefully (BP, HR, respiration, SaO2)  Assess patient anew for each unit to be transfused

26. Conclusions 26 Swisstransfusion, 06.09.2013  TACO is the major remaining preventable risk of transfusion in Switzerland  It is mainly observed in elderly patients receiving RBC transfusions  Pre-transfusion patient risk assessment is essential  Less restrictive definition than proposed by ISBT allows recognition of beginning TACO and probably prevention of a life threatening or fatal course of reaction

27. Conclusions 27 Swisstransfusion, 06.09.2013  Preventive measures focus on individualised prescription (medical staff) Low transfusion rate in patients at risk for TACO close monitoring of patient during transfusion (nursing staff)  Diuretics as premedication were found to have no effect on the severity of reaction* * Robillard, P. et al; Transfusion associated circulatory overload: The new leading cause of transfusion associated fatalities reported to the Québec Haemovigilance system. Presentation at IHS 2010 in Dubrovnik