EDUCATION be demonstrated without complex adsorptions , which can take several hours or more to perform .” These delays can threaten a safe transfusion . Many transfusion physicians will recommend transfusion of “ antigen-matched ” red cells when compatibility cannot be demonstrated by routine methods , Dr . Westhoff said .
“ This involves testing the patient ’ s blood to determine which common antigens are lacking , which makes the blood more likely to be recognized as foreign if encountered on transfused red cells , and triggers an immune response ,” she said . Donor units lacking antigen ( typed as negative ) are then selected for transfusion .
In Dr . Westhoff ’ s experience , patients with multiple antibodies who require intermittent or chronic transfusion often become well-known to the hospital transfusion and blood center referral laboratory staff . Between transfusion encounters , the staff attempt to identify and sequester potentially compatible units , based on donor units with complete antigen profiles ( i . e ., more than ABO and Rh typing ).
HDFN , which occurs when a pregnant woman ’ s immune system attacks the blood cells of the fetus , is diagnosed in the transfusion service laboratory by testing maternal plasma for the presence of an antibody that will cross the placenta and bind to the red cells of the fetus . After birth , HDFN may be detected by a positive direct antiglobulin test on the baby . In mothers , these antibodies may result from having had a previous blood transfusion or , more commonly , from a previous pregnancy and delivery of a child who inherited a paternal red cell antigen that was lacking in the mother .
HDFN can occur from incompatibility of the Rh antigen system or other blood group antigens , but also from ABO blood group incompatibilities between mother and fetus . Women commonly are found to have antibodies that target Kell antigens , which can cross the placenta and lead to destruction of the fetal red blood cells .
“ When an antibody to a red cell antigen is detected at prenatal screening , the paternal red cells are typed to determine the possibility that the fetus will inherit the corresponding antigen and potentially suffer complications of anemia ,” Dr . Westhoff said . “ DNA testing can now be used to determine paternal zygosity for the antigen in question and the fetal blood type from amniocytes .”
HDFN due to Rh is relatively uncommon in the U . S . because of prevention with injection of Rh immunoglobulin in Rh-negative mothers , but it can still occur . Dr . Cushing recently had a case of HDFN due to an antibody formed by the mother to an uncommon antigen expressed by the father . Since the antigen was uncommon , it was not picked up in the antibody screen on the mother ’ s plasma , but the baby ’ s direct antiglobulin test was positive and the baby had evidence of anemia and hemolysis .
“ The American College of Obstetricians and Gynecologists has specific guidelines for when red cell antibody screening should happen ,” Dr . Cushing said . “ Depending on which antibody is found , there are different thresholds of concern for HDFN .”
When incompatibilities are found , the fetus will be monitored for anemia throughout the pregnancy . If serious anemia occurs , an intrauterine transfusion can be performed . If it is not detected early , HDFN can be extremely dangerous , even fatal .
Managing the Blood Supply
Another important area where hematologists and transfusion services collaborate is the management of the blood supply . Dr . Cushing , who has been in practice for about 15 years , said the blood supply issues since the start of the pandemic have been some of the most challenging she has ever seen . This was true even for plasma and cryoprecipitate , products that are typically unaffected by acute blood shortages because of their longer shelf life in the frozen state .
The goal of every transfusion service is to avoid the under- or overuse of blood and blood products , Dr . Cushing said .
“ Competition among nonprofit blood providers for hospital contracts leaves little for investment or exploration of new technologies .”
— Connie M . Westhoff , SBB , PhD
“ Most programs have guidelines for when transfusion is indicated and provide information that all practitioners should follow when deciding to order blood ,” Dr . Cushing said . “ During times of shortage , transfusion services will send messages alerting that the blood supply is low and that guidelines will be strictly enforced with prospective auditing .”
According to David F . Friedman , MD , associate medical director of the Transfusion Service and Apheresis Program at Children ’ s Hospital of Philadelphia , strategies for managing limited blood supply vary by the circumstance .
For example , when platelet needs cannot immediately be filled , the blood product supplier may be able to provide a more exact estimate of when the products will be available – whether in a few hours or a few days . Transfusion services may also call clinicians to discuss the clinical situations of the patients for whom platelets were ordered .
“ Then the whole situation becomes a barrage of brokering and communication that we call ‘ platelet triage .’ In these settings , the dilemma is mostly about determining which patients can wait ,” Dr . Friedman said . “ For example , an outpatient with a platelet count of 18 × 10 9 / L who is not bleeding may be able to wait . On the other hand , a patient bleeding after cardiopulmonary bypass probably cannot wait .”
Dr . Friedman explained that the communications with the blood product suppliers and clinicians are psychologically complicated . They involve a lot of negotiation and should be assigned to more experienced personnel .
Communication is also key for long-term shortages , starting with letting clinical services know that there may be problems with supply . Dr . Friedman noted , though , that there is a delicate balance between alerting clinicians about potential issues : One does not want to be an alarmist and cancel scheduled elective surgeries , but it is also necessary to save units for emergencies .
Dr . Friedman ’ s institution is trying to develop objective criteria for transfusion of red cells in intensive care units ( ICUs ). These efforts include defining trigger hemoglobin levels and developing computerized decision support for patients in all sorts of clinical scenarios . The process is complicated and requires buy-in from ICU specialists .
Ongoing Challenges
Blood shortages are almost always present in one form or another , Dr . Fontaine noted . In many centers , particularly in tertiary centers like hers , they “ live and breathe inventory .”
Dr . Westhoff added that maintaining adequate inventory is likely one of the biggest ongoing challenges in the field . “ The last few years have seen significant reduction in number of red cell transfusions , due to patient blood management programs and the realization that a treatment hemoglobin goal of 7 g / dL rather than 10 g / dL is safe ,” she said . “ But , at the same time , there has been a continued increase in platelet product usage as cancer immunotherapies expand .”
Dr . Westhoff said that investing in research and development around transfusion services is also a major challenge . “ Health-care reimbursement in the United States with its diagnosis-related group system unlinks blood product usage from direct compensation , resulting in pressure on the hospital transfusion service laboratory to manage and reduce costs ,” Dr . Westhoff said . “ Competition among nonprofit blood providers for hospital contracts leaves little for investment or exploration of new technologies without guaranteed return or direct cost savings .”
Together , these hamper innovation in transfusion medicine therapy , she said .
Finally , one of the biggest challenges that remain for blood centers is obtaining and retaining qualified staff .
“ Staffing is a challenge across both collection centers and hospital-based transfusion services ,” Dr . Fontaine said . “ Especially after two years of a pandemic , staff are getting burned out and turnover is high .”
Technologies within these centers are improving and more automation is being incorporated into processes , Dr . Fontaine said , but there will always be a need for technical staff at the bench .
— By Leah Lawrence
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