Whole Blood Project ( different clinical needs – different strategies )

Whole Blood Project

( different clinical needs – different strategies )

Dr Soraya AMAR EL DUSOUQUI Dr Emmanuel RIGAL

Regional blood transfusion centre Geneva – Haematology departement HUG 1

Agenda

① Brief description of the project and WB indications

② Definition „s“ of whole blood

③ Distribution of WB and components in 10 BTS in SSA and 10 European countries

④ Plasma production in countries with limited resources

⑤ 2 major aspects of transfusion in Sub Saharan Africa

⑥ Epidemiological facts concerning HIV in Sub Saharan Africa

⑦ Different situation - different needs - different strategies

⑧ Is there an interest in FWB transfusion?

⑨ Conclusions


Regional blood transfusion centre Geneva – Haematology departement HUG

Brief description

collection pathogen inactivation transfusion

research on PI in whole blood bags using Intercept RBC PI technology S-303 combined with glutathione on whole blood

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WB transfusion indications

Indications for whole blood transfusions:

• Where WB cannot be separated into components (75 % of transfusions in low resource countries )

• In the military battlefield where WB can be an alternative to treat acute massive trauma. The US Military has transfused >8000 units of FWB over the last 8 years

• As an alternative in case of acute massive need ? Terrorist attack / epidemic outbreak ?


Description of project phases


•Project plan •resources•Secure budget

•Establish treatment process•product requirements

Phase 1

• Obtain ethic review• in vitro studies to

support clinical trials • Identify potential

sites in Africa• Training of

collaborators in conduction of clinical trials

Phase 2

• ethics and regulatory review approval for the conduct of clinical trials

• Obtain Swiss and African country health authority and haemovigilance board acceptance

• Conducting clinical trials in Africa

• Plan implementation of product

• Creation of a bi-national data and safety management board

Phase 3

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USA WB Definition for military service :

warm Fresh WB used before 8 hours

Fresh WB stored at 1-6 °C cooled within 8 hours for max. 24h

USA WB Definition in civilian context :

fresh WB that is stored at 2°C to 6°C for max. 48 hours

Definition in African transfusion manuals :

warm Fresh WB used before 8 hours or

WB stored at 4°C for 28-35 days

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Definition „s“ of whole blood


Austria Belgium Denmark France Hungary Ireland Holand Slovenia Switzerland Sweden0

10

20

30

40

50

60

70

80

90

100

Whole blood RCCFFPPC

10 European countries

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Distribution of blood products in 10 European countries

The Collection, Testing and Use of Blood and Blood Components in Europe EDQM 2008


Distribution of WB and components in 10 BTS in SSA

Tayou-Tangy et al Trans Clininque et Biologique 2009


Plasma production in countries with limited resources

WHO suggests to low countries to assess the clinical demand and feasibility of component processing

Low income countries are hardly capable of investing their resources in

- Processing whole blood into components - Buying and maintaining material to process plasma in 8-24h and keep at < - 25°C- Monitoring and managing quarantine and stock

- Use surplus for producing medicinal products send to fractionation- Perform up to 5 – NAT testing- Abide to GMP standards

- Buy from pharmaceutical firms drugs derived from plasma


Plasma production in countries with limited resources


2 major aspects of transfusion in Sub Saharan Africa


42%

20%

26%

12%

Transfusion indications in Uganda

PediatricObstetrical and gynecolog-icalMedical surgical

2%2%

55%

41%

Transfusion RBC indications in USA

PediatricObstetrical and gynecolog-icalMedical surgical

The 2011 National Blood

Collection and Utilization Survey

Report

Natukunda et al, Transf Med 2010;20:134

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39%

27%

16%

7%

5%6%

Clinical transfusion indications in Uganda

Malaria

bleeding

Infection

cancer

Trauma/ surg

other

5.70%

1.60%

1.80%

2.10%

15.10%

0.80%

Bleeding causesGI

Epistaxis

Soft tissue

Perinatal

Obstetric

Other

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Natukunda et al, Transf Med 2010;20:134


HIV epidemiological facts on HIV in Sub Saharan Africa


Different situation - different needs - different strategies

WHO Guidelines for the treatment of Malaria 2010

Assessing clinical demand in SSA countries :

BB have to respond very frequently to bleeding indications ( ex. U 27%) Adapt transfusion in hemorrhagic shock and coagulopathy situations :

- Use warm whole blood or components 1:1:1 RBC: FFP: PC or RBC: liquid plasma: PC ( no RCT to compare )

- need for fresh products (PLT functions and CF decrease with storage and cooling at 4°C° and they keep them stored up to 35d)

- Recent studies suggest that storage lesions affects outcome especially in critically ill patients


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BB have to respond even more frequently to paediatric needs - children under 5 y (ex.U 42 %)

Adapt transfusion : - division into smaller bags - Fresh products ( K+) - Malaria : Indicated when Hb < 4 g/dl or <5g/dl if hyperventilation and anaemia- irradiation if family donor or HIV (argument for PI)- CMV neg for HIV patients ( argument for PI)

Adapt treatment strategies - Avoid malnutrition anaemia – food fortification- avoid iatrogenic anaemia- Malaria and parasite prevention- Iron / folate medication - rEPO ( optimal dose and timing ? Retinopathy age < 4 m )


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Vox sanguinis 2010Uganda

biological rational for FWB with life threatening haemorrhagic shock and coagulopathy

Pros

increased concentration of cellular components

less volume transfused

fresh RBC cells - less storage lesions

fresh PLT

Temperature of wFWBhypothermia related dysfunction of coagulopathy

enzymes, platelets, Endothelial cells

lesser donor number exposure

contras

less time for viral screening tests ( need for PI)

transfusion of higher number of leucocytes risk T-GVH

lack of clear clinical evidence

- Irradiation - pre-storage leucoreduction

- PI


Is there an interest in FWB transfusion?

Service - Secteur - Département… Regional blood transfusion centre Geneva – Haematology departement HUG

Clinical data on use of whole blood

Setting References Study Method Patients product primary outcome/study results

combat J trauma 2009 -

Spinella et al.

retrospective US casualties

Iraq /Afghanistan

FWB+CT vs. CT

*24h survival *30d survival

WB vs. CT 96/100(96%)vs. 223/254(88%) - p value 0.01895/100 (95%) vs. 209/254(82%)-p value 0.002

inability to adjust for all confounders-survivorship bias

combat Transfusion

2011 Perkins JG

retrospective US and non US FWB+CT vs. CT

*24h survival *30d survival

WB vs. CT 69/85 [81%] vs. 239/284 [84%] p = 0.52)39/68 [57%] vs. 106/177 [60%] p = 0.72).

significant loss of follow up in CT at

30d (33%)

civilian Transfusion

2011 Ho and

Leonard retrospective

cardiac surgery, trauma,bleeding

FWB+CT vs. CT

coagulation profile30d and 8 year

survival

WB vs. CT fibrinogen 1.7 g/L vs.1.4 g/L, p = 0.006;

worst INR, 2.4 vs. 2.8, p = 0.05no significant increase in BP consumptionno significant long term survival p = 0.93

all used both WB and CT


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Service - Secteur - Département… Regional blood transfusion centre Geneva – Haematology departement HUG

Clinical data on use of whole blood

Setting References Study Method Patients product primary outcome/study results

civilian Blood 1991manno et al

randomized controlled trial

(RCT)

children cardiac surgery n=161 n= 93 < 2y

3 groups

vfWB/48hWB/reconstituted WB

mean 24 h blood loss <2y

mean 24h blood loss > 2y

30 min /3h in vitro PLT aggregation

vfWB vs. two others in < 2y p:0.001

vfWB vs. two others in > 2y p:0.041

PLT aggregation lower in bothWB arms p:0.03

civilian NEMJ 2004MOU SS et al

single centre RCT

children cardiac surgery Reconstituted vs. FWB

composite score survival and length of

stay in ICU

no difference in outcome or survival

FWB longer length of stay RB

70.5 hours vs. 97.0 hours, P=0.04

length of stay was an

unadjusted outcome and FWB was only given intra-

operatively and not post

operatively

civilian paediatric

anaesthesia Friessen et al.

RCT n=32 Children non complex open heart

surgery autologus FWB vs. control

primary outcome was coagulation status

Secondary outcomes post op 24 h blood loss

increased platelet count, PT, and fibrinogen (P <

0.05)PO blood loss less (P = 0.036) in the treatment

group when measured as ml per 24 h, but not

significantly less (P = 0.16) when measured as

ml·kg per 24 h


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Potential mechanisms of potential storage lesions of RBC

Service - Secteur - Département…

Vaso-regulatory systemCoagulations system

Immune system

(Spinella PC, Sparrow RL, Hess JR, Norris PJ. Transfusion 2011;51:894 –900)

Critically ill patients are most vulnerable



Conclusions:

• Most of the transfusions in SSA concern children and young females .

• Main medical indications in SSA are massive haemolysis due to malaria and obstetrical bleedings.

• The point of view of a large number of transfusion specialists in sub-Saharan Africa is that FWB is the product of choice for bleeding.

• Exploring whether FWB is an appropriate option in certain circumstances is warranted ( shock and coagulopathy , combat trauma when components unavailable, extreme disaster situations) .

• Blood banks will probably need to move toward more tailor made answers for patients and for clinical needs

• Warm FWB trials may be possible in the developing world and could help answer our questions.


Acknowledgements :

• Dr Schwabe • Dr Mansouri• Prof. Cazenave, Etablissement Français du Sang (EFS), Alsace, France• CERUS COOPERATION society• The directors of the Suisse Regional Transfusion Centres • Yvonne Fischer• Verena Flück• Daniella Lev


Whole Blood Project ( different clinical needs – different strategies )

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