A tool for improving blood transfusion safety? Lessons from 15 years of hemovigilance in France

Transcription

1 A tool for improving blood transfusion safety? Lessons from 15 years of hemovigilance in France Georges Andreu Institut National de la Transfusion Sanguine G. Andreu, INTS TRIP Bussum

2 Hemovigilance in France History and organization Scope of vigilances : a world in continuous expansion Donor hemovigilance Epidemiology of viral markers Donor hemovigilance Some contributions of «recipient» Hemovigilance : Bacteria contamination Does leucoreduction impact immediate adverse reactions? The case of TRALI in France Is it worth to be transfused by apheresis or whole blood derived platele concentrate? Under transfusion : myth or reality? G. Andreu, INTS TRIP Bussum

3 Hemovigilance in France : milestones 1991 Creation of the word / concept 1992 First mention of the word «hemovigilance» in a regulatory text : Circular DGS/DH N january 1993 legal definition : law of january Hemovigilance decree of january Practical building of the French Hemovigilance Network : Technical Directive N 1 of june First version of an electronic notification system (GIFIT) in March 1999 Hemovigilance responsability entrusted to AFSSAPS G. Andreu, INTS TRIP Bussum

4 vigilance: a world in continuous expansion 1973 : Pharmacovigilance 1992 : Hemovigilance 1992 Donors epidemiology 1994 Traceability of blood components 1994 Adverse reactions in recipients (all severities) 2005 Adverse reactions in donors (severe) 2006 Adverse events (severe) 1996 : Materiovigilance 1996 : Reactovigilance 1998 : Cosmetovigilance 2003 : Biovigilance 2004 : Actovigilance G. Andreu, INTS TRIP Bussum

5 Hæmovigilance Network in France Local level Hospitals correspondents (> 1 800) Blood establishments correspondents (> 150) EFS (civilian) and CTSA (military) Regional level Hemovigilance regional coordinators (28) National level EFS cellule Hemovigilance Commission Nationale d Hémovigilance Responsible bodies AFSSAPS Agence Française de Sécurité Sanitaire des Produits de Santé (French control authority on health products) InVS Institut de veille sanitaire (donors epidemiology) G. Andreu, INTS TRIP Bussum

6 Evolution of Transfusion associated viral risk in France : 1992 to 2007 from 1992 to 2005, dramatic reduction of transfusionassociated transmission risk of tested viruses : 4.5 for HIV, 15 for HBV 30 for HCV This improvement is the result of donor selection policy Residual risk of transmission by transfusion of HIV, HBV and HCV in France : 1992 to ,0 8,0 7,0 6,0 5,0 4,0 3,0 2,0 1,0 0,0 NAT (HIV1 and HCV)) HBV : 1/ HIV : 1/ HCV: 1/ HBV ( 15) HIV ( 4,5) HCV ( 30) Source : InVS, INTS, EFS, CTSA G. Andreu, INTS TRIP Bussum

7 Evolution of recipients adverse reactions * blood commponents transfused ( millions ) 3,30 3,20 3,10 3,00 2,90 2,80 2,70 2,60 2,50 2,40 2,30 3,15 3,17 3,16 3,283,11 2,98 3,00 2,93 2,85 2,95 2,20 2,76 2,69 2,63 2,62 1,01 2,56 2,56 2,52 2,52 2,47 2,47 2,48 0, ,50 3,00 2,50 2,00 1,50 1,00 0,50 0,00 ** Declarations / BC * Blood components **HV notifications G. Andreu, INTS TRIP Bussum

8 Hæmovigilance Network In France 2 grading of transfusion incidents : severity : 0 = no symptom 1 = minor symptoms 2 = long term consequences 3 = life threatening incident 4 =death of the recipient imputability : 0 = excluded (EU 0) 1 = dubious (EU 0) 2 = possible (EU 1) 3 = probable (EU 2) 4 = sure (EU 3) G. Andreu, INTS TRIP Bussum

9 The case of transfusiontransmitted bacteria infection G. Andreu, INTS TRIP Bussum

10 As soon as hemovigilance was implemented in France in 1994, TTBI appeared as a major morbidity and mortality cause among the immediate adverse reactions. An important mobilization began, with the implementation of a great amount of measures until However, when bacteria detection techniques became available, France did not decide to introduce them G. Andreu, INTS TRIP Bussum

11 Measures to prevent TTBI 1 transfusion chain step target actions predonation interview blood collection prevention of bacteria inoculation temporary exclusion for : any identified infection antibiotic treatment any suspected infection dental care cutaneous lesion at venepuncture site skin wounds hygiene of : premises (including bacterial controls) personal material (including donation armchair) skin preparation diversion of the first 35 ml post donation information G. Andreu, INTS TRIP Bussum

12 Diversion of the first 35 ml Nationwide decision : Target for implementation : September 2000 In practice Goal reached without delay for whole blood collection : Red cell concentrates Whole blood derived Platelet concentrates Goal reached with delay for apheresis platelet concentrates (modification of apheresis disposables) 2001 (Haemonetics) 2002 (Baxter) 2004 (Gambro) G. Andreu, INTS TRIP Bussum

13 Post donation information Donors are requested to inform the blood transfusion centre in case : they think they did not answer adequately to one of the questions during the medical interview, or if any health problem occurred within 2 weeks after donation. In case of suspicion of an infectious risk, the blood components already prepared are discarded First proposed in 1993 (but not widely applied) Gathered,analyzed at a national level, and benchmarked among the 17 regional blood centres since 2002 In 2005, 7361 post donation information have been notified in France, and infectious risk account for 5155 (70%), among which 92% have been discarded. G. Andreu, INTS TRIP Bussum

14 Measures to prevent TTBI 2 transfusion chain step target actions transport to processing lab Monitoring transport conditions rigorous temperature control (no cool) processing delivery prevention of bacteria proliferation Controlled waiting time before processing Buffy coat vs PRP PC Leucoreduction Physical examination of blood component platelet swirling Monitoring PC inventory management basic = never more than 5 days advanced = reducing mean storage time G. Andreu, INTS TRIP Bussum

15 Buffy coat technique for whole blood PC and the incidence of TTBI Apheresis PC Whole Blood PC TTBI per million PC % buffy coat technique G. Andreu, INTS TRIP Bussum

16 Measures to prevent TTBI 3 transfusion chain step target actions transport to hospital transfusion prevention of bacteria proliferation Monitoring transport conditions rigorous temperature control no returned blood component accepted except if proven temperature control Monitoring time elapsed between delivery and actual transfusion less than 6 hours in case more time unavoidable organize controlled storage conditiions G. Andreu, INTS TRIP Bussum

17 Incidence of TTBI in France: 1994 to 2007 platelet concentrates G. Andreu, INTS TRIP Bussum

18 incidence of TTBI in the context of bacteria detection or not institution / country bacteria detection policy DRK / Rotterdam / CBS & HQ / added up results Germany Nether land Canada of institutions yes yes yes yes with a detection policy no ARC / USA France time of study total PC transfused total TTBI fatalities TTBI incidence per million PC fatality incidence per million PC , , G. Andreu, INTS TRIP Bussum

19 Incidence of TTBI in France: 1994 to 2007 Red cells concentrates Universal Leuco reduction G. Andreu, INTS TRIP Bussum

20 Number of TTBI cases before and after 3 major measures : leucoreduction, derivation, and BC PC notified TTBI (number of cases) total TTBI total grade G. Andreu, INTS TRIP Bussum

21 Conclusion Overall, TTBI incidence decreased regularly in the period. Measures had an identified effect not only on PC related, but also on RCC related TTBI Some events coincide well with improvements Leucoreduction and the decrease of mortality in RCCs TTBI Generalization of the Buffy Coat technology for platelet processing and the reduction of whole blood derived PCs TTBI TTBI are not eradicated by such a policy. However, the observed residual incidence is comparable to the one observed in institutions / countries that implemented bacteria detection in PC G. Andreu, INTS TRIP Bussum

22 Leucoreduction and adverse reactions Methods (Hemovigilance data from 1996 to 1999) Analysis of adverse reactions notified 18 mths before implementaiton of Universal leucoreduction 18 months after implementation of Universal leucoreduction Results (expressed as reduction of adverse reaction incidence) : Analysis of adverse reactions notified : Adverse reactions incidence variation p HLA antibodies and NHFTR 70% <. 001 bacteria contaminations 65% <. 001 anti HLA antibodies 49% <. 001 Isolated NHFTR 40% <. 001 anaphylactoid reactions 14% 0.10 hemolytic reactions (excluding ABO and Rh) 9% 0.73 Rh incompatibilities 6% 0.88 ABO incompatibilities 13% 0.64 G. Andreu, INTS TRIP Bussum

23 ABO incompatibilities n = Nombre d'eir 25 n = 23 1 n = n = n = n = 13 1 n = Grades 1 3 Grade 4 Année G. Andreu, INTS TRIP Bussum

24 TRALI : not recognized in France until 2002 blood components TRALI cases imputabilities 2 to TOTAL TOTAL RCC Random PC APC Plasma SD plasma 0 autologous RCC 0 TRALI r elated deaths TOTAL TOTAL RCC Random PC 0 APC FFP 0 SD plasma 0 autologous RCC 0 G. Andreu, INTS TRIP Bussum

25 TRALI incidence and plasma volume from individual donors p = (Fisher exact test) Blood component TRALI incidence per million BC volume of plasma from individual donors SD plasma 0 2 RCC random PC (PAS) quarantine FFP APC (no PAS) G. Andreu, INTS TRIP Bussum

26 Apheresis vs whole blood derived PC Since 1985, active policy in France favoring Apheresis PCs, based on : reduction (by a factor 6 to 10) of the number of donors for the same patient s care reduction of the risk of blood transfusion transmissible diseases. In vitro platelet functions more preserved in APC as compared with whole blood derived (PRP) PC What is the validity of this policy in 2008? G. Andreu, INTS TRIP Bussum

27 APC are associated with more «allergic» or «anaphylactoid» reactions than RPC Andreu G, Vasse J et al. TCB 2007, 14 : allergy FNHR 8 7 p = 6,7 x 10 7 incidence / 1000 PC ,95 p = 0,047 3, ,56 1,46 1,56 1,42 0,78 0,24 RPC PAS RPC PAS+ APC PAS APC PAS+ G. Andreu, INTS TRIP Bussum

28 2008 Willaert Transfus Med Hemother 35: G. Andreu, INTS TRIP Bussum

29 Donor Hemovigilance : apheresis vs whole blood donation (2006) Rebibo D, SFH meeting, Lille, december 2006 number of donations Adverse Reaction Incidence / 1000 donations whole blood Apheresis Total Chi2 = 5.7 p = Does apheresis donation lead to more adverse reactions in donors than whole blood donation? G. Andreu, INTS TRIP Bussum

30 Risk of non transfusion Identified «At risk» situations During and immediatly after anesthesia Maternal haemorrhage in obstetric Multiple trauma patients Various causes Fear of transfusion Absence of emergency transfusion protocols Lack of communication between BTC and hospital G. Andreu, INTS TRIP Bussum

31 Mechanisms leading to death during anesthesia Survey of anesthesia related mortality in France Anesthesiology ;105(6): Death totally or partially linked with anesthesia n= 419 respiratoire neurologique cardiaque Cardiac vasculaire vascular médicament. centrale obstructif voies aériennes accès impossible poumons ciment obstructif rythme métabolique Cardiogenic choc cardiogénique shock infarctus hypovolémie True hypovolemia vraie hypovolémie relative sepsis allergie sympath. VAS bronche trachée infection inhalation embolie pulmonaire rythme hypoxie anémie anemia hemorrhage hémorragie AG ALR Lienhart et al 2006 n= 39 n= 49 G. Andreu, INTS TRIP Bussum

32 Case report of under / no transfusion (from the actual series published in 2006) Hip replacement in a 75 years old patient with a history of acute stenotic coronary heart disease Hb = 9.8 g.dl 1 at the end of surgery Blood count prescribed for the next day Blood sample collected next morning Blood count result available by noon (not seen) Patient seen by end of afternoon, for severe cardiogenic shock leading to death (Result of morning Hb = 6.2 g.dl 1 ) G. Andreu, INTS TRIP Bussum

33 Means to detect under transfusion 1. Standard notification through hemovigilance : Data from the French Hemovigilance network since 1994 : 7 deaths related to no or delayed blood transfusion! 2. Analysis of time from blood count prescription to blood transfusion : In a context of low Hb level In a context of emergency 3. Selection of patients files according to criteria : Hb laboratory results And known risk of blood loss G. Andreu, INTS TRIP Bussum

34 2008 Ausset et al. Transf Clin Biol orthopaedic surgery patients analyzed retrospectively 41 (5.9%) with Hb < 8 g/dl at least once. 35 (5%) transfused 18 (2.6%) with two consecutive Hb<8 g/dl and not transfused 8 (1.2%) age >70 considered at higher risk 6 (0.9%) with clinical intolerance to anemia : 2 patients not transfused, age 73 & 94 : the latter died 4 patients transfused lately : 2 post op cognitive dysfunction Undertransfusion may be evaluated : 6 / (35+6) = 14.6% of anemic patients [0.9% of patients] 4 could have been detected by chart review of transfusions 2 (including one death after hip replacement who had clear hypotension + tachycardia + Hb<8g/dL) could not have been detected by any conventional hemovigilance tool G. Andreu, INTS TRIP Bussum

35 «Norm» expanding the scope of hemovigilance deviance Deviance G. Andreu, INTS TRIP Bussum Lienhart 2005

36 The impact of Coffea arabica on hemovigilance correspondents G. Andreu, INTS TRIP Bussum