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G6PD DEFICIENCY IN G6PD DEFICIENCY IN DONOR’S BLOODDONOR’S BLOOD

Is it an issue in Blood Is it an issue in Blood Transfusion?Transfusion?Akram Al-HilaliAkram Al-Hilali

20092009

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Articles of the ArgumentArticles of the Argument• If we know the donor is G6PD-deficient, by

questionnaire answer or by predonation testing, should we bleed the patient?

• Should we screen for G6PD, within the test battery we do after donation?

• If we do it and discover that donor is deficient should we use the blood?

• If we decide to use the blood shall we give it the same shelf life as normal blood?

• If we transfuse such blood shall we give to any patient or to a restricted category list of patients?

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BASIC PRINCIPLESBASIC PRINCIPLES• By transfusing blood we are not supposed to

knowingly cause any harm to the recipient.• Red cell storage period is currently taken

mostly as universal and does not give G6PD deficiency in donor special consideration.

• Some recipients are themselves deficient in G6PD.

• If we prove harmful effect to certain recipients from certain blood category we should not give that blood at least to that recipient group.

• The issue has been under continuous argument for decades. There is no consensus on a policy.

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Existing Policies and opinions on Existing Policies and opinions on subjectsubject

• AABB standards and code of Federal Regulations in the USA: No specific guidelines.

• Mollison (Blood Transfusion in Clinical Medicine-11th Edition): Some enzyme variants render the cells unsuitable for transfusion. “In African variant GdA- (10% of African Americans) relatively small number of red cells are severely affected. However, GdMed and others render red cells particularly sensitive to oxidative stress”.

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Existing Policies and opinions on subjectExisting Policies and opinions on subject

• Singapore Blood Transfusion Services answers to FAQ in educational publications:I have G6PD Deficiency, can I still donate blood? People with G6PD deficiency can make blood donations. However, we usually advise these donors to donate plasma and platelets instead of whole blood. This is because G6PD affects the body’s red cells, making them more vulnerable to biochemical stress… As such, the red cells of people with G6PD deficiency are not suitable for transfusion.

• Riyadh & Jeddah Armed Forces Hospitals: All donors are checked for G6PD. Deficient blood is labeled and is not used for certain patient categories.

• A study from Taiwan showed no significant difference in Hb, bilirubin and haptoglobin in normal adult patients receiving 1 unit G6PD-deficient blood, compared to those receiving non-deficient units. Authors concluded that it is not necessary to screen donors for G6PD. Study did not include patients with G6PD deficiency nor neonates.

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Blood Unit from Riyadh Armed Forces

Hospital, 1984

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Existing policies and opinions on the Existing policies and opinions on the subjectsubject

• A study from Shiraz, Iran: Patients studied are G6PD-deficient with hemolysis. Rise in patients’ Hb levels after transfusing normal and G6PD-deficient blood was compared. Hb rose more in first group, but difference was not statistically significant. Only 14 bags of deficient blood were used and sample number was considered small. However, authors recommend checking G6PD on all bags destined for transfusion to G6PD-deficient patients, premature neonates, exchange transfusion and patients who need repeated transfusion.

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Metabolic Role of G6PD Metabolic Role of G6PD in red cellsin red cells

2H2O

G-6-P 6-P-GG6PD

NADP NADP-HH

GSSG

GSH

Meth-Hb (Fe+++)

Red. Hb (Fe++)

H2O2

Meth-Hbreductase

Glutathioneperoxidase

Glutathionereductase

2H

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G6PD DEFICIENCYG6PD DEFICIENCYVariation in SeverityVariation in Severity

• Mild cases with just a little reduced activity

• Severe cases with low activity and /or quantity that will not support normal metabolism and cause chronic hemolysis [Class I] (e.g. G6PDBarcelona)

• Cases with moderate deficiency that will not be able to withstand oxidative or other stress [Class II and Class III](G6PD B- and G6PD A-).

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What happens to stored blood?What happens to stored blood?NORMAL BLOOD• Normal blood stored will have lower metabolic activity as

time passes.• This is due to drop in enzymes, NADPH availability and

anti-oxidant activity.• These phenomena will be exaggerated with lower enzyme

at the outset.G6PD DEFICIENT BLOOD• In G6PD deficient blood reduced Glutathione is lower, at

each storage age interval, than normal blood (Huang CS, Yung-Chan H, May-Jen H et al 1998)

• Membrane lipid peroxidation is also higher than normal blood (Ondei LS, Silveira, LM, Leite AA, et al, 2009).

• Less viability of G6PD deficient red cells on storage, even if not subjected to oxidative stress. Orlina AR, Josephson AM, AcDonald BJ. The post-storage viability of G6PD deficient erythrocytes.1970. J Lab Med; 75: 930.

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WHAT DOES EXPIRATION OF WHAT DOES EXPIRATION OF RED CELL UNIT MEAN?RED CELL UNIT MEAN?

• A red cell unit (whatever is the additive) is to be considered expired if 20-30% or more of red cells will be non-viable in vivo after transfusion.

• The red cells which become non-viable first are the oldest at donation.

• Lipid peroxidation is high on storage and anti-oxidant activity is lower. Iron turns into ferric and membrane reduced glutathione is diminished.

• This is because the older the red cell the lower are the metabolic enzymes and NADPH in it.

• If an enzyme is low in a young red cell then it will become non-viable earlier than normal young red cells. In other words, it will behave like an old red cell.

• Scientifically, blood with G6PD deficiency should not be stored for the same period as normal, as the non-viable cells will be higher at any given time under the same conditions of storage. It will expire, by definition, earlier than a normal unit.

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Effect of stored normal blood Effect of stored normal blood (>14 days)(>14 days)

* There is an increasing talk in the medical literature about the possibility of harm posed by transfusing > 14 days old blood. In March 2008 there was a paper (Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery.N Engl J Med 2008;358:1229-39) and an editorial in The NEJM

(John Adamson. New Blood, Old Blood, or No Blood? N Engl J Med 2008. 358;12: 1295-1296). In that study patients were of cardiac surgery. Earlier studies on cancer surgery, sepsis and later trauma patients have hinted to the same conclusion. These studies were retrospective and blood used was not G6PD deficient.

* If we accept the findings what will be our appraisal of the G6PD deficient stored blood?

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Confirmed inferior quality of G6PD-Confirmed inferior quality of G6PD-deficient blood on Transfusiondeficient blood on Transfusion* Probably no harmful effect if one deficient unit is given to a

normal adult. Zekavat OR, Karimi M and Rahmanian F.(Indian J Hematol Blood Transfus; 25(1):23-26.

• In neonatal exchange transfusion– Samanta S, Kumar P, Kishore SS, et al. Donor Blood G6PD

deficiency reduces the efficacy of exchange transfusion in neonatal hyperbilirubinemia. Pediatrics. Jan 2009;123(1): e96-100.

– Mimouni F, Shohat S, Reisner SH. G6PD-deficient blood donor as a cause of hemolysis in 2 preterm Infants. Isr J Med Sci, 1986; 22(2): 120-122.

– Lower quality, with possible problems if given to a patient with hemolytic attack due to stress drug or illness and for neonatal exchange transfusion (E. Beutler, Reviw article on G6PD (Blood 1994;84:3613-3636)

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Confirmed Inferior Quality of G6PD-Confirmed Inferior Quality of G6PD-deficient blood on Transfusiondeficient blood on Transfusion

• In patients with hemolysis due to G6PD deficiency

– Zekavat OR,Karimi M, and Rehmanian F. Is red cell of otherwise healthy G6PD deficient donor efficient for transfusion to favism patient? 2009Ind J Hematol Blood Transfus 25 (1): 23-26. Less Hb rise, not statistically significant

• In cardiac surgery where red cells are exposed to mechanical stress. Surgeons prefer “fresh blood” for such patients for this reason. (Colleen Gorman et al, NEJM, March 2008). Can G6PD-deficient red cell stand the stress?

• Irradiation of the G6PD deficient blood unit.– Proven to cause higher free Hb, LDH and K+ in the G6PD

deficient units on days 7, 14 and 21 after irradiation (statistically not significant because only 10 cases and 10 controls were tested). [Agarwal P, Ray VL, Chodhury N, et al. Hematology 2007;12(3):267-70].

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How common is the deficiency?How common is the deficiency?• Male Saudi Donors

(1984): 4.26%• 11% in one study in

UAE. Majority were of non-UAE origin

• Shiraz study (4%)• Indian study (3%)

NATIONALITY No. of Donors

G6PD deficient

% deficient

Saudis 8956 382 4.26

Non-Saudis

4952 152 3.07

All donors 13,908 534 3.84

Type of G6PD (and hence its stability) is as important as its activity level.G6PD of the Mediterranean type is moderately severe.

Chinese: <1 to 8.6% deficientMalays: 2.6% deficientThailand:11.98% deficientFilipinos: 7.1% WHO: >1% IS COMMON

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Should we check donors for Should we check donors for G6PD?G6PD?

• Policies differ in various countries and blood banks.

• There is cost involvement and it involves additional time.

• Screening test by fluorescence will be able to exclude those with less than 20% activity of the enzyme. This is the category that matters.

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If we check G6PD in donor’s blood what If we check G6PD in donor’s blood what should we do to the deficient units?should we do to the deficient units?

• Many blood banks will not take a donation if donor admits deficiency before donation.

SUGGESTIONS• If tested pre-donation, deficient donor can be

bled.• Label red cell unit to indicate that the it is G6PD-

deficient• It should go in the LIS as well.• Policy needs to be drawn on expiry date limitation

and patients who should not receive the unit. It can be given to all other potential recipients.

• This applies to red cell units only

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If we don’t check G6PD in If we don’t check G6PD in donors’ blooddonors’ blood

• How do we know which unit is deficient? A unit selected randomly from stock can be G6PD deficient. There is no label or information in the system to tell.

• For any of the conditions mentioned a unit or more of G6PD deficient blood may be un-intentionally given to the same patient. Probability rises with higher deficiency in population.

• Can we check G6PD at preparation time? Level is unreliable after storage. There may not even be a policy for this checking, anyway.

• What happens if patient is on a redox drug or is having infection or severe diabetes at the time G6PD deficient blood is transfused, especially in parts of the world with high frequency? (Beutler, 1994).

• Transfusion of such blood is more dangerous if patient is a small child and transfused blood will comprise a high percentage of total blood volume.

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How best to store G6PD-How best to store G6PD-deficient blood?deficient blood?

* G6PD deficient red cell units are to be stored under same conditions like those of normal donors*However, they should not have the same expiry date as normal cells. *They should be labeled as deficient.* It is better to segregate such units from general stock.