Search

Dear Editor, In transfusion medicine, it can be a challenge to obtain compatible blood for patients who have clinically important alloantibodies to high-prevalence antigens. We describe a case which examples the decision process for autologous blood deposition in the Dutch health care system. In September 2006, a 56-year-old man was admitted to the emergency room after a serious accident. Coagulation and hematology parameters were in normal range except for a low hemoglobin of 7.9 g/dL. His blood group was determined as O, Rhesus D-positive and antibody screening (DiaMed) was negative. Transfusion anamnesis was also negative. Two units of packed erythrocytes were administrated. Eight days later hemoglobin had dropped to 7.1 g/dL. Upon a negative antibody screening, 2 units of erythrocytes were transfused. After 20 days, the patient had to undergo surgery. Now, antibody screening and identification, using standard and papain enzyme-treated panels (DiaMed), demonstrated strong positive reactions with all cells. These results were suggestive for the presence of an alloantibody against a high-prevalence antigen. Further serologic and genetic analysis revealed that C/c and E/e antigens were completely absent on the surface of the patient's erythrocytes, indicating the presence of the rare -D-/-D- phenotype [1]. Adsorption and elution studies revealed the presence of anti-C, -E, -e, -Ce, and -cE alloantibodies and antibodies against the high-prevalence antigens of the RhCcEe polypeptide (anti-Rh17 antibodies) [2]. Furthermore, we identified alloantibodies against Jka and Lea. Hemolytic transfusion reactions due to anti-Lea are rare [3]. Anti-Rh17 [4] and anti-Jka antibodies, however, can lead to massive hemolysis. Therefore, only erythrocytes of donors with the -D- phenotype, negative for Jka, could be selected for transfusion. The -D- haplotype is rare, ranging in frequency from 0.0005 in Sweden [5] to 0.0032 in Japan [6], and homozygosity for RHCE-D-CE hybrid genes appears to account for several examples of -D- [1]. Worldwide, only two suitable donors were registered. Since the risk of substantial blood loss was low, the patient underwent surgery in the absence of compatible donor erythrocytes. The patient was encouraged to donate autologous blood to be stored at the Sanquin Bank of Frozen Blood (SBFB). In November 2009, the patient was scheduled for coronary artery bypass graft surgery. It was estimated that, by optimal use of intraoperative cell salvage, the patient would maximally need 1 unit of blood. Five weeks before surgery, the patient's hemoglobin was 15.1 g/dL, allowing preoperative donation of 2 units of fresh blood. In case of need, frozen units of the SBFB could also be thawed. During surgery in December 2009, 1 unit of fresh autologous blood and 400 mL of cell salvage blood was transfused to the patient. Postoperatively the patient's hemoglobin level was 11.1 g/dL. He was discharged from the hospital 9 days later. To date the clinical relevance of the -D- phenotype has been predominantly described in pregnant women, causing mild to fatal hemolytic disease of the newborn [4, 7–10]. We describe the successful treatment of a patient with recurrent need of transfusions despite the presence of antibodies against the high-prevalence antigens of the RhCcEe polypeptide combined with anti-Jka.

The discovery of the Rh blood group factor in humans was made using the red blood cells of rhesus monkeys. Because of its importance to human medicine and immunogenetics, this finding contributed greatly to the appreciation of the importance of nonhuman primates in research. It is now widely recognized that blood group incompatibility between mother and fetus can lead to differential fertility, fetal death, and hemolytic disease of the newborn (HDN). The blood group systems of several nonhuman primate species have been studied in detail and found to be analogous, although not identical, to those of humans. It is therefore surprising that HDN has been reported in only four nonhuman primate species--marmosets, sacred baboons, chimpanzees, and orangutans. Maternal-fetal blood group incompatibility and its consequences have been extensively studied in rhesus monkeys, and these macaques may well be representative of many nonhuman primates. Rhesus monkeys exhibit all five of the conditions that lead to HDN in humans: (1) blood group incompatible matings; (2) transplacental hemorrhage; (3) maternal immunization to blood group alloantigens on fetal erythrocytes; (4) transplacental transfer of maternal antibodies; and (5) coating of the newborn's erythrocytes. Yet, newborns show no clinical or hematological evidence of HDN. We have shown that the rhesus alloantibodies engendered by transplacental immunization do not mediate immune elimination of the newborn's erythrocytes. Evaluation of the maternal antibodies demonstrated that they have low titers and low avidities and perhaps belong to IgG subclasses that do not bind effectively to receptors on phagocytic cells of the rhesus reticuloendothelial system. The newborn's genotype may also affect the expression of allogeneic blood group antigens and thereby help protect the newborn's cells from destruction. These factors together undoubtedly play a major role in the survival of the antibody-coated newborn's RBC and are thus able to account for the absence of HDN in this species.

The investigation of the free anti-D antibodies in serum was perfotmed in 65 mature Commbs-positive newborn. We found that the gravity of the disease depended in the first line on the presence of absence of free anti-D antibodies in the serum of the infants. No free anti-D antibodies were found in the serum of 27 Coombs-positive infants. In these cases the course of the disease was milder. In 14 infants the serum bilirubin did not rise to 20 mg/100 ml, so the exchange transfusion was not indicated. In 13 cases. a more marked rise of the bilirubin level called for exchange transfusion. Under such conditions if there are no circulating free anti-D antibidies, Rh-positive blood can also be used for the exchange transfusion. After the exchange transfuaion mild bilirubin rebound occurred, no more blood exchange was necessary. Free anti-G antibody was found in the serum of 38 infants. The course of the disease was serious, exchange transfusion was indicated in every case. Nineteen infants were treated, in the usual way, Rh-negative blood. In 9 cases the exchange transfusion had to be repeated; 19 babies were treated with “combined exchange transfusion”, a method first appplied by us. (The transfusion was begun with Rh-positive blood and completed by Rh-negative blood.) In this way free anti-D antibody could be removed efficiently, the exchange had to be repeated only in 4 case.