Dosering av trombocytt- og erytrocyttkonsentrater- tid for nytenkning ?

1. Dosering av trombocytt- og erytrocyttkonsentrater- tid for nytenkning ? Tor Hervig Avdeling for immunologi og transfusjonsmedisin, Haukeland universitetssykehus

2. Disposisjon • Innledning • Dosering av trombocyttkonsentrater • Dosering av erytrocyttkonsentrater • Oppsummering (Ola var fra Sandefjord: “Det gikk på engelsk og norsk, engelsk og norsk)

3. Vi vil hjelpe pasientene! • Hva er et trombocyttkonsentrat? • Hva er et erytrocyttkonsentrat? • Hva er en pasient? • Til barn: Dosering ml/kg, men en enhet SAG-erytrocyttkonsentrat kan ha 40-70g hemoglobin

4. Hva trenger pasientene ? • Erytrocyttkonsentrat Oksygen til vevene Celler til å presse trombocyttene mot karveggen Hva er ønsket hb etter transfusjon? • Trombocyttkonsentrat Stoppe blødning Forhindre blødning

5. Trombocyttransfusjoner • Profylaktisk transfusjon? • “On demand” transfusjon? To store randomiserte studier pågår Andreas Greinacher, personlig meddelelse

6. A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia Nancy M. Heddle, Richard J. Cook, Alan Tinmouth, C. Tom Kouroukis, Tor Hervig, Ellen Klapper, Joseph M. Brandwein, Zbigniew M. Szczepiorkowski, James P. AuBuchon, Rebecca L. Barty, and Ker-Ai Lee, for the SToP Study investigators of the BEST Collaborative Blood, 2009

7. Platedose • Lav: 2,4 x 1011 • Middels/standard: 4,8 x 1011 • Høy: 7,2 x 1011

8. WHO blødningsskala • Grad 1: Hudblødning, kortvarig neseblødning • Grad 2: Hematom, langvarig neseblødning, melena, hematemese, blødning fra stikksted (trenger ikke transfusjon) • Grad 3: Som grad 2, men trenger transfusjon • Grad 4: Livstruende/dødelig blødning

16. Mye større, amerikansk, trearmet studie • Sherril Sclichter et al: Foreløpige data: Ingen significant forskjell mellom blødningsfrekvens hos pasienter i de tre armene

17. Foreløpig konklusjon • Ikke grunnlag for å endre norsk praksis • Transfusjon ved blødning???

18. OPTIMIZING STANDARDS FOR TRANSFUSION OF RED BLOOD CELL CONCENTRATE Håkon Reikvam and Tor Hervig Haukeland University hospital and University of Bergen, Norway Chris Prowse, Products and Components R&D Group, National Science Laboratory, SNBTS, Edinburgh, UK Nancy M. Heddle, Department of Medicine, McMaster University, Hamilton, ON, Canada

19. OPTIMIZING STANDARDS FOR TRANSFUSION OF RED BLOOD CELL CONCENTRATE An important approach to the goal of reducing number of transfusions, is to give each patient the most exact hemoglobin (Hb) dosage which is needed to achieve the wanted post-transfusion Hb.

20. The rule of thumb used in the clinical practice: • 1 unit of red blood cells transfused to an adult increases hemoglobin concentration with 1 g/dl

21. Unfortunately, the Hb content of the units does not represent a homogeneity. The blood volumes of the patients vary significantly

22. Today situation

23. Ideal situation

24. Methods • Two different concepts are proposed to overcome this challenges: • Standardize the units. • Adjust the Hb dose according to the patient’s blood volume; Hemoglobin dosing.

25. STANDARIZATION OF THE UNITS The term “unit” is derived from the time when “one unit of whole blood” referred to the source, i.e. a whole blood donation

26. Standardization of the red cell product • The advantage of a standardized red cell product lies in the greater degree of predictability of clinical outcome for any predefined recipient. • This could result in an alteration in physician’s prescribing practices, avoiding over-transfusion, especially in low volume recipients. • The current situation where red cell products are prescribed in non-standard 'units' is outdated and unscientific. Sweeney JD: Standardization of the red cell product. Transfus Apher Sci 2006, 34(2):213-218.

27. Hemoglobin dosing As high as a 50-percent difference in Hb content can be encountered between two units (40-60g) Indicating that RBC transfusions should be based on Hb content of the products instead of units. Gorlin J, Cable R: What is a unit?Transfusion 2000, 40:263-265.

28. Matching the Hb dose to the individual needs of the patients reduced the total usage of red cell concentrates by approximately 30 % in a study from Turkey. • Calculating the patients’ total need of Hb to achieve the targeted Hb made this possibly. • The total amount of transfused RBCc was reduced to 72 from the original 104 units required (ca 30%). • The success rate was closely linked to patients’ weight; increased weight correlated with failure to comply with the goal. Arslan O, Toprak S, Arat M, Kayalak Y: Hb content-based transfusion policy successfully reduces the number of RBC units transfused. Transfusion 2004, 44(4):485-488.

29. Pilot study Bergen, Norway Hamilton, Canada Edinburgh, UK

30. Pilot study Hemodynamically stable patients needing “pop-up” transfusions Measure hemoglobin content in red cell concentrates Measure height and weight of patients -> calculate blood volume Record pre- and post transfusion hemoglobin concentration

31. Goals To evaluate feasibility (practicability) of such procedures To evaluate if there is correlation between hemoglobin transfused and hemoglobin increment in patients – per litre of estimated blood volume

32. Body surface (BSA) Body surface was calculated by method described by DuBois BSA (m2) = Weight (kg)0.425 x Height (cm)0.725 x 0.007184

33. Blood volume – alternative (BV) Males BSA x3.29-1.229 Females BSA x3.47-1.954

34. 50 patients were included in the study • Total number of 52 transfusions episodes: -27 for women, 25 for men

36. 114 units

37. Resultater • Videre resultater kan ikke legges ut pga rettigheter til artikkel under vurdering. • Det var signifikant samnmenheng mellom hb dose gitt og hb stigning korrigert for kroppsvolum. Dette gir grunnlag for videre arbeid.

38. Discussion Feasibility Hemoglobin measurements were not causing a lot of extra work In the laboratory: Sterile docking of sample bag; transfer to test tube, hemoglobin measurement

39. Simplification By just measuring the weight of each unit, correlation and calculation of the actually Hb content in each unit can easily be done.

40. Allow the blood banks to use high-Hb-content units rationally by using an in-house blood-banking software. • Adopting a policy of transfusing RBC in single-unit, instead of the standard two units. • Alter the physicians prescribing practice and stimulate to increased cooperation with the blood bank. • Avoiding potential both over-transfusion (in low weight patient) and under-transfusion (in high weight patient). • Potential of reducing iron overload for patients depending on multiple transfusions.

41. By just measuring the weight of each unit, correlation and calculation of the actually Hb content in each unit can easily be done.

42. How to go on? Planning a large randomized study on hemoglobin increment after red cell transfusion in Bergen (NORWAY?) Using the method of : Targeting hemoglobin concentration after transfusion. Measuring the weight of each unit

43. That about qualitative aspects?

44. Koch CG, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229-1239.

45. Take home message • Hemoglobin content in the units show great variability • Blood volume in patients vary as well • A hemoglobin increment lower than expectant does not necessary indicate active loss (bleeding, hemolytic reaction, etc.) • Future aspects of more standardized procedures.

46. Hva skal vi gjøre? • Tenke oss om • Samtale med kliniske leger (og pasienter?) • Gjennomføre en større studie med samme design? • Ny, randomisert studie: Tilfeldige SAG mot utvalgte SAG? • Hvem vil være med?

47. Oppsummering • Platedose har neppe betydning for utfall hos pasienten • Vi venter i spenning på kunnskap om forebyggende versus terapeutiske trombocyttransfusjoner • Erytrocyttransfusjoner basert på “enhetstanken” gir vilkårlige konsekvenser for pasientene, på en eller annen måte må vi forbedre praksis: Til beste for pasient og blodbeholdning