2010Rh阴性输血策略(尼日利亚Du)

A Strategic Approach to the Problems of Providing Rhesus D–Negative Blood Transfusion in Geographic Areas With Low RhD Negativity:A Nigerian PerspectiveSagir G.AhmedIn contrast to the white prevalence,the frequency of rhesus D(RhD)negativity in the Nigerian population ranges from less than1%to about6%in the different ethnic population groups across the country.Conse-quently,there is often a severe scarcity of RhD-negative blood in Nigeria,leading to undue delay in transfusing RhD-negative patients.This situation has led to the prolongation of hospital stays as well as increased morbidity and mortality in affected patients.The problem is compounded by the general unavailability of donor RhD-negative blood,which is partially related to a suboptimal national blood transfusion service.This situation has thus relegated the responsibilities of donor recruitment and blood collection to individual hospital blood banks.This has led to the necessity of finding a variety of ways to mitigate the daunting problem of the provision of RhD-negative donor blood in Nigeria.In this article,we review the roles,advantages,and disadvan-tages of various methods including the use of auto-logous donations,D u testing,inter–blood bank transfers,voluntary RhD-negative donor recall,family donations,and cryopreservation to ameliorate the problem.The real need is nonetheless to optimize the functional capacity of the Nigerian National Blood Transfusion Service.©2010Elsevier Inc.All rights reserved.T HE RHESUS(Rh)system consists of5major antigens:D,E,e,C,and c,of which D is the most antigenic.1Unlike the ABO system,naturally occurring antibodies are not usually found in individuals who lack the various Rh antigens.1 Antibodies of the Rh system are all alloimmune in nature with the exception of some naturally occurring anti-E antibodies.1The Rh system was the fourth system to be discovered,yet in terms of clinical importance,it is only second to that of the ABO system because most RhD-negative indivi-duals become alloimmunized after exposure to RhD-positive red blood cells(RBCs),and such antibodies can cause severe hemolytic transfusion reactions and hemolytic disease of the newborn.1In the white populations of Europe and North America,the major clinical problem associated with rhesus system is that of hemolytic disease of the newborn(HDN).2The incidence of HDN is significant in white populations because of the relatively high frequency of RhD-negative indivi-duals that constitute approximately15%of the populace.1In contrast to white figures,the frequency of RhD negativity in the Nigerian population ranges from less than1%to about6% in different ethnic population groups across the country.The highest frequency of RhD negativity is found in the southern part of the country where frequencies of 6.01%and 5.46%have been reported in the south central and southwestern regions,respectively.3,4The frequency of RhD negativity is even lower in the northern regions where frequencies of1.44%and0.6%have been reported in the northeastern and northwestern regions,respectively.5,6One advantage of the low frequency of RhD negativity among Nigerians is the low incidence of HDN in the country.7On the other hand,the low frequency of RhD negativity has resulted in the severe scarcity of RhD-negative RBCs in Nigerian blood banks,a situation that has practically made any request for RhD-negative blood a nightmare for both clinicians and blood bank staff.The problem is compounded by the overall inadequacy of allogeneic donor blood provision in Nigeria,coupled with a suboptimal national blood transfusion service.8This situation has virtually relegated the responsibilities of donor recruitment and blood collections to individual hospital blood banks with the predominance of often unsafe commercial donors.8Clinical experience in Nigeria had shown that RhD-negative blood is not readily available in the blood bank at the time of request in the over-whelming majority of cases.The scarcity of RhD-negative blood in Nigerian blood banks had often resulted in undue delay in transfusing RhD-negative patients,a situation that had led toFrom the Aminu Kano Teaching Hospital,Kano State,Nigeria.Address reprint requests to Sagir G.Ahmed,MBBS,FWACP,Department of Haematology,Aminu Kano Teaching Hospital,PMB3452,Kano,Kano State,Nigeria.E-mail:drsagirahmed@0887-7963/09/$-see front matter©2010Elsevier Inc.All rights reserved.doi:10.1016/j.tmrv.2009.11.005Transfusion Medicine Reviews,Vol24,No2(April),2010:pp140-146 140prolongation of hospital stay as well as increased morbidity and mortality in affected patients.It has therefore become necessary to find ways of mitigating the daunting problem of RhD-negative donor blood scarcity in Nigeria.In this article,a multifaceted strategic approach is reviewed as outlined in Table 1.SCALING DOWN THE SIZE OF THE PROBLEMAutologous Blood DonationsAutologous blood donation and transfusion have not yet been given the level of attention it deserves in Nigerian hospital blood banks,and the autolo-gous blood procedure is largely restricted to the elites in whom the main motivation is the avoidance of transfusion transmissible infections.8A rational approach toward solving the problem of RhD-negative blood scarcity in the hospital setting would be to scale down the number of requests for RhD-negative allogeneic blood through a process of mandatory preoperative blood group testing of all elective surgical patients.All those found to be RhD-negative thus would become eligible for the autologous donation program and would be en-couraged to participate in such an autologous program.For each eligible patient with normal bone marrow function and with the use of iron supplementation,it should be possible to collect 1U of blood at weekly intervals leading to up to 5U collected over a 5-week period.9Autologous transfusions could also be expanded to include pregnant women that are clinically stable andwithout anemia.Previous reports on autologous donations from pregnant women,for reasons including the avoidance of transfusion transmissi-ble infections or anticipated obstetric hemorrhage,have proven to be safe even in the third trimes-ter.10,11Thus,eligible pregnant women who are RhD-negative could be scheduled for autologous donation at a gestational period that is close to term to secure autologous blood that can be used for unexpected bleeding.All RhD-eligible patients could thus be encouraged to participate in an autologous transfusion program by explaining to them the potential difficulties associated with the rarity of their blood group and reassuring them on the safety of the program as well as highlighting the added advantage of total reduced risk of disease transmission or alloimmunization that may be associated with allogeneic transfusions.8,12Furthermore,autologous donation programs would have the additional advantage of boosting the blood bank reserve of RhD-negative blood because unused units that had satisfied standard safety criteria could be used to transfuse other RhD-negative patients,particularly those in life-threat-ening emergency situations.13It must however be emphasized that the role of autologous transfusion in alleviating the problem of RhD-negative trans-fusion is to a large extent dependent on the effective collaboration between the blood bank and the attending surgeons.There is therefore the need for individual hospital transfusion committees to promulgate standard guidelines for the use of autologous transfusion that would synchronize theTable 1.Strategic Approaches to the Problem of the Provision of RhD-Negative Blood in NigeriaApproachObjectives and benefitsAutologous donations Scale down demand for allogeneic RhD-negative blood.Freedom fromimmunological and infectious complications of transfusion.D u testingScale down demand for RhD-negative blood by transfusing D u -positive patients with RhD-positive blood.Conserves RhD blood for genuineRhD-negative patients.Inter –blood bank transfer of Rhd-negative blood Effective utilization of ⁎redundant RhD-negative blood units transferred from neighboring blood banks.Recall of accredited voluntary RhD-negative donorsEmergency blood donations from registered voluntary donors (unrelated to patients)to provide RhD-negative blood whenever such blood is notavailable in the blood bank.Donations from RhD-negative family members Emergency blood donations from RhD-negative family members as asupplement to inadequate unrelated donor blood or as the sole source of blood.Cryopreservation of redundant RhD-negative bloodSalvage and freeze ⁎redundant RhD-negative blood units to createRhD-negative RBC reserves for future use.⁎Redundant:RhD-negative units that were randomly donated by voluntary donors in the absence of need by RhD-negative patients.141RHD NEGATIVE BLOOD IN NIGERIAelective preoperative assessments of patients be-tween the surgical departments and the blood banks with the aim of facilitating a program of autologous transfusions.13However,if an RhD-negative pa-tient is not eligible for autologous transfusion and it becomes clear that RBC transfusion is inevitable, the RBCs of such a patient should be subjected to D u testing.D u Testing of RhD-Negative PatientsThe RhD antigen is carried on nonglycosylated proteins of the RBC membrane.1The normal RhD-positive individual has RBCs that express the D antigen within the range of9900to33000 antigenic sites per cell.1Individuals may have RBCs that express fewer D sites per RBC than normal,and such subjects are referred to as having the D u-positive phenotype.1The D u phenotype is subclassified into high grade,low grade,and very low grade,the latter of which has the lowest expression of the D antigen.1RBCs with the D u phenotype have weak expression of the D antigen and thus may be misclassified as D-negative cells in routine rhesus grouping procedures.1However,the direct antiglobin test is potentially capable of detecting all grades of D u with the exception of the very low-grade types.1In clinical practice,it is usually not necessary to determine whether an RhD-negative patient is of the D u phenotype because no harm results from transfusing Rh-negative blood into such patients even if they are D u-positive.1This approach is particularly suitable for white populations in which the frequency of RhD negativity is up to15%.1,2In contradistinction to the situation in whites,the RhD frequency in Nigerians could be less than1%,resulting in severe scarcity of RhD-negative donor blood.6It is therefore rational to attempt to scale down the number of requests for RhD-negative blood by subjecting RBCs of all RhD-negative patients who might require an RBC transfusion to an indirect antiglobin test to detect those that are D u-positive so that they can be transfused with RhD-positive blood,ultimately reducing the burden of RhD-negative RBC transfusions with its attendant problems of blood procurement.Previous studies in Nigeria had shown that the prevalence of D u phenotype among individuals that were grouped as RhD-negative ranged from only 0.95%in the south central to3.4%in the northwest and up to8%in the southwest.4,14,15It is therefore possible to reduce the burden of RhD-negative blood transfusion in Nigeria by the application of the D u test to a variable extent depending on the prevalence of D u phenotype among regional populations.The identification of D u-positive patients thus has a3-fold clinical advantage in the Nigerian environment where RhD-negative blood is scarce.Firstly,the major advantage is that such patients can be transfused with RhD-positive donor blood without the risk of alloimmunization.1 Secondly,valuable and scarce RhD-negative blood would be conserved for use in patients that are genuinely RhD-negative.This is particularly important because donor blood is always in short supply and inadequate with respect to the clinical requirement of patients in Nigeria.8,16Thirdly, female patients that are identified as D u-positive will not be subjected to unnecessary and costly anti-D immunoglobulin(RhIG)injections if they deliver RhD-positive babies.15This is important in Nigeria where RhIG is imported and thus expensive.The identification of the D u phenotype is particularly useful in patients having high RBC transfusion requirements,such as patients with HIV/AIDS,hemophilia,renal failure,malignancies, aplastic anemia,and other types of bone marrow failure,sickle cell anemia(SCA),and other types of chronic anemia.17,18With a population of more than140million,Nigeria is the most populous black nation that carries a heavy disease burden due to SCA,which affects about2%of the general population.17Therefore,from global perspective, Nigeria has more patients with SCA than any other country in the world.17It is therefore imperative that patients with SCA and other transfusion-dependent patients that are RhD-negative be tested for the D u phenotype so that their high transfusion requirements may be easily met with the use of RhD-positive blood if they are D u-positive.Occa-sionally,multiple anemia-causing diseases may coexist in a particular RhD-negative patient,thus amplifying transfusion requirements.For example, the author had the rare opportunity of participating in the management of1RhD-negative patient with both SCA and hemophilia and another RhD-negative patient with both SCA and chronic renal failure.It is in these types of patients that a positive D u test would be particularly helpful.It must however be appreciated that although the D u test has the potential of easing the RBC transfusion requirements if an RhD-negative patient is found to142SAGIR G.AHMEDbe D u-positive,the test must be carried out with caution under rigorously controlled laboratory and reagent conditions so as to avoid the possibility of false-positive results that may lead to wrongful administration of RhD-positive blood to RhD-negative patients.1,19RhD-negative patients who require transfusion and are neither eligible for autologous transfusion nor D u-positive must eventually be given alloge-neic RhD-negative blood,the sourcing of which may be associated with considerable difficulty.SOURCING ALLOGENEICRhD-NEGATIVE BLOODInter–Blood Bank Transfer of RhD-Negative Blood Most RhD-negative patients that require RBC transfusions would not qualify for autologous transfusion.Moreover,clinical experience had shown that most requests for RhD-negative blood are for emergency cases that need blood urgently, and only a few,0.95%to8%,of such patients would be D u-positive.4,14,15We must therefore find ways of dealing with requests for RhD-negative patients that are neither eligible for autologous transfusions nor D u-positive.However,the hard reality in Nigeria is that RhD-negative blood is usually not available in the blood bank at the time of request.It is only on rare occasions that a unit or two may be found,a quantity that is often grossly inadequate.In such circumstances,it is reasonable to solicit RhD-negative blood from neighboring hospital blood banks.It is therefore important for individual blood bank consultants to create a reliable communication network for emergency situations.Personal experience has shown that units of RhD-negative blood might occasionally and unexpectedly be found in a neighboring blood bank in the absence of any needy RhD-negative patient in that institution.Such units could thus be quickly transferred to be transfused to acutely needy RhD-negative patients.Failure to locate RhD-negative blood within the network of neighboring blood banks should immediately prompt the call of registered RhD-negative donors.Recall of Accredited VoluntaryRhD-Negative DonorsVoluntary blood donors are generally scarce in Nigeria.8Moreover,the voluntary donor base appears to be shrinking as a result of rising donor default generally attributable to the worsening economic hardships and fear of predonation HIV testing within the general population.20Nonethe-less,it is important that every hospital blood bank keep a comprehensive register of its available voluntary donors,particularly those with a clearly identifiable RhD-negative donor type that can be contacted in cases of urgent need.Such donors should be appropriately counseled regarding the significance of their blood type and should be made to understand the need for them to respond positively to urgent calls for blood donation. Voluntary donors in Nigeria usually donate no more than once every6months in accordance with standard recommendation.2Therefore,1foresee-able impediment is that RhD-negative blood donors may decline to respond if called upon to redonate any time less than the traditional interval of6 months after the last blood donation.However,it is safe to donate blood any time after8weeks from the date of last donation without the risk of significant iron depletion,and donors should be counseled accordingly.21Nonetheless,persons who donate more frequently than usual should probably be given iron supplementation to prevent the depletion of their iron stores.2Consistent with its level of underdevelopment, Nigeria is bedeviled by inadequate street and house numbering,erratic communication services,and a poor public transportation network,all of which mitigate easy tracing of registered donors.If the search for registered donors is not fruitful,blood bank officials must be prepared to solicit blood donations from a patient's relatives.Family Members as the Source ofRhD-Negative BloodFamily ties are particularly strong in Nigerians as it is in the rest of Africa.Patients in Nigeria are usually looked after by many family members who keep close contact with the patient during hospital admissions.Thus,family blood donations are commonly requested to supplement the scarce voluntary donor blood base.8Therefore,family members of RhD-negative patients should be contacted with regards the possibility of finding persons who are of the correct blood group that could donate for a particular patient.The blood bank may apply a method of mass blood group testing of a patient's relatives in general,but it should be noted that the chances of getting an RhD-143RHD NEGATIVE BLOOD IN NIGERIAnegative individual is higher in first degree than in distant relatives of the patient who requires the transfusion.The genetics of RhD antigen inheri-tance would suggest that the biological parents of an RhD-negative patient must be genotypically D/d or d/d with several possible combinations of D/d vs d/D,D/d vs d/d or d/d vs d/d.22However,in view of the rarity of the RhD-negative phenotype in Nigerians,the parental genotypic combination for couples is more likely to be D/d vs d/D than D/d vs d/d,whereas the combination d/d vs d/d would be quite unusual.23Thus,in the family of any given RhD-negative patient,the probability of a first-degree sibling being RhD-negative(genotype d/d) would be25%if the parents are both D/d or50%if 1parent is D/d and the other parent is d/d.22Hence, it is always worthwhile to search for donors within family members of any RhD-negative patient.Such a search may even be extended to distant relatives because personal experience had shown that RhD-negative individuals were sometimes found in cousins of RhD-negative patients.It must be appreciated that family donor blood transfusions have certain problems that must be addressed in the interest of the patient.For example, in patients with diseases such as SCA,leukemia, and aplastic anemia for whom bone marrow transplantation is being contemplated,multiple transfusions with the blood from a first-degree relative could lead to alloimmunization against a number of HLA antigens,a situation that would disqualify such a relative as a prospective bone marrow donor for the patient.24Hence,family donor blood should only be used as a last resort in patients scheduled for bone marrow transplant. Conversely,multiple transfusions with family donor blood would be beneficial if the patient has end-stage renal disease and the blood donor is the prospective kidney donor because pretransplant donor-specific transfusions maybe associated with enhanced allograft survival.25Nigeria,like many other sub-Saharan African nations,carries a heavy disease burden due to HIV/AIDS,which is also strongly associated with high transfusion require-ments for affected patients.18Caution must be exercised while transfusing such immunocompro-mised patients because of the risk of donor lymphocyte engraftment and graft-vs-host disease, the risk of which is higher with the use of blood from first-degree relatives.26,27Although the risk can be abolished by pretransfusionγ-irradiation of the donor blood unit,such facilities are not readily available in Nigeria.28One important consideration for patients with SCA is that many of their apparently healthy siblings would also be carriers of the sickle cell gene and their RBCs would contain both hemoglobins A and S.Because the parents of patients with SCA are obligate sickle cell carriers,the probability of a first-degree sibling being a sickle cell carrier(HbAS)is50%,with only a25%probability of having a normal genotype (HbAA).29Hemoglobin S constitutes20%to40% of the total hemoglobin in the RBCs of sickle cell carriers.30Therefore,blood from sickle cell carriers is not recommended for transfusion to patients with SCA.31,32This situation makes family donor selection for patients with SCA particularly restric-tive and difficult.Therefore,care must be taken to ensure that all prospective family donors of patients with SCA are screened by hemoglobin electropho-resis so as to select only those individuals that are free from the sickle cell trait.31,32One major disadvantage of family donation that potentially impacts on safety is the fact such donors may be under covert family pressures and as such may go ahead to donate even if they know they belong to high-risk groups for HIV infection.8This could potentially jeopardize blood safety in a country where blood testing in hospital blood banks is usually done using rapid test kits,which vary in quality.33The virtual absence of viral nucleic acid tests for window period detection in Nigerian blood banks makes any donations from high-risk donors particularly dangerous.33It is obvious that RhD-negative blood transfusion in Nigeria is a major challenge for the blood bank staff,registered donors,and patients and their relatives.Nonetheless,there is the need to consider RhD-negative as a rare blood group in Nigeria and to strategically aim at raising RBC stock levels through the process of cryopreservation.CRYOPRESERVATION OFRhD-NEGATIVE BLOODThe frequency of RhD negativity among Niger-ian blood donors ranges from less than1%to about 6%.3-6Therefore,a similar proportion of voluntary donor blood that is donated in Nigeria would be RhD-negative.However,it must be appreciated that such RhD-negative blood donations come random-ly,sporadically,and in single units that are usually interspersed by several weeks.Blood banking144SAGIR G.AHMEDexperience in Nigeria had shown that on several occasions over the period of a year,such randomly donated RhD-negative units could be found unused in some blood banks in the absence of any needy RhD-negative patient.Such units are eventually used,in a rather less effective way,to transfuse RhD-positive patients in order prevent wastage due to expiry.The best way of handling such redundant units of RhD-negative blood is to store them in the frozen state(cryopreservation),which would allow donor RBCs to be stored for a period of up to10 years,rather than for5weeks in liquid state.21This is an established procedure in countries with developed blood transfusion services.The main indications for RBC cryopreservation includes storage of rare blood groups,extended storage for autologous units,prevention of alloimmunization to HLA antigens in potential bone marrow transplant patients,and prevention of nonhemolytic febrile transfusion reactions.21,34It is therefore possible to continually salvage any redundant RhD-negative RBC units in Nigerian blood banks and cryopre-serve them to create a sustainable reserve that can be thawed for use whenever the need arises. Cryopreservation techniques are being developed in many developing Asian countries such as India, with the long-term objective of offsetting the problems of RhD-negative RBCs and that of other rare blood groups.35,36There is therefore an urgent need for the introduction of RBC cryopreservation techniques in the Nigerian national blood transfu-sion service.THE NIGERIAN NATIONAL BLOODTRANSFUSION SERVICEThe decision to establish a sustainable National Blood Transfusion Service in Nigeria was con-ceived in1975at the World Health Assembly.37 However,since the signing and adoption of the World Health Assembly resolution in1975,very little has been done by successive Nigerian governments to achieve the objectives of establish-ing a National Blood Transfusion Service that could be comparable to what is available in the developed countries of the world.Consequently,the Nigerian Blood Transfusion Service has virtually remained as a hospital-based transfusion service provided by individual hospital blood banks and is characterized by voluntary donor scarcity with predominance of commercial and family donors.8,16,20Nonetheless, the federal government had recently rekindled its commitment by setting up the first blood transfu-sion center in the federal capital,Abuja,in2004.38 This was followed by the establishment of several zonal and state blood transfusion centers across the country.38The Nigerian National Blood Transfu-sion Service,which is administratively under the federal ministry of health,is currently facing many challenges including voluntary donor inertia due to ignorance,economic hardships,and fear of HIV screening in the general population.8,16,20In similarity to many other blood transfusion services in developing countries,inadequate funding is a major problem that militates against optimal performance of the Nigerian National Blood Transfusion Service.33Meanwhile,the Nigerian National Blood transfusion service has gone into partnership with nongovernmental organizations including Safe Blood for Africa Foundation,Center for Disease Control,President's Emergency Plan for AIDS Relief,and the World Health Organiza-tion with the aim of optimizing its services.38CONCLUSIONSThe solution to the problems of RhD-negative donor blood scarcity in Nigeria should be through a multifaceted approach that includes autologous donations,D u testing,inter–blood bank transfers, voluntary RhD-negative donor recall,family dona-tions,and cryopreservation.In addition,there is an urgent need for upgrading and optimizing the capabilities of the Nigerian National Blood Trans-fusion Service.REFERENCES1.Contreras M,Lubenko A:Antigens in human blood.In: Hoffbrand AV,Lewis SM,Tuddenham EGD,editors:Post-graduate haematology.Ed 4.London:Heinemann,2001, pp182-2142.Contreras M,Hewitt PE:Clinical blood transfusion.In: Hoffbrand AV,Lewis SM,Tuddenham EGD,editors:Post-graduate haematology.Ed 4.London:Heinemann,2001, pp215-2343.Enosolease ME,Bazuaye GN:Distribution of ABO and RhD blood groups in the Benin area of Niger-Delta:Implication for regional blood n J Transf Sci2:3-5,20084.Worlledge S,Ogiemudia SE,Thomas CO,et al:Blood group antigens and antibodies in Nigeria.Ann Trop Med Parasitol68:249-264,19745.Ahmed SG,Obi SO:The incidence of ABO and rhesus-D blood groups in northeast Nigeria.Nig J Med7:68-70,1998145RHD NEGATIVE BLOOD IN NIGERIA6.Ahmed SG,Umar BA,Saidu AT,et al:Pattern and clinical significance of ABO and rhesus-D red cell phenotypes among blood donors in Birnin Kudu,Nigeria.Borno Med J 1:1-6,20047.Onwukeme KE:Blood group distribution in blood donors in a Nigerian population.Nig J Physiol Sci6:67-70,19908.Ahmed SG,Ibrahim UA,Hassan AW:Adequacy and pattern of blood donations in northeast Nigeria:The implications for blood safety.Ann Trop Med Parasitol101:725-731,20079.Brozovic B,Brozovic M:Special problems in blood transfusion.In:Brozovic B,Brozovic M,editors:Manual of clinical blood transfusion.Ed1.London:Churchill Livingstone, 1986,pp31-4410.Kruskall MS,Leonard S,Klapholz H:Autologous blood donation during pregnancy:Analysis of safety and blood use. 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