bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood group genotyping: the power and limitations of the Hemo ID Panel and MassARRAY platform
Authors: McBean R.S. , Hyland C.A. , Flower R.L.
Published: May 2021

Matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS), is a sensitive analytical method capable of resolving DNA fragments varying in mass by a single nucleotide. MALDI-TOF MS is applicable to blood group genotyping, as the majority of blood group antigens are encoded by single nucleotide polymorphisms. Blood group genotyping by MALDI-TOF MS can be performed using a panel (Hemo ID Blood Group Genotyping Panel, Agena Bioscience Inc., San Diego, CA) that is a set of genotyping assays that predict the phenotype for 101 antigens from 16 blood group systems. These assays involve three fundamental stages: multiplex target-specific polymerase chain reaction amplification, allele-specific single base primer extension, and MALDI-TOFMS analysis using the MassARRAY system. MALDI-TOF MS–based genotyping has many advantages over alternative methods including high throughput, high multiplex capability, flexibility and adaptability, and the high level of accuracy based on the direct detection method. Currently available platforms for MALDI-TOF MS–based genotyping are not without limitations, including high upfront instrumentation costs and the number of non-automated steps. The Hemo ID Blood Group Genotyping Panel, developed and optimized in a collaboration between the vendor and the Blood Transfusion Service of the Swiss Red Cross in Zurich, Switzerland, is not yet widely utilized, although several laboratories are currently evaluating the MassARRAY system for blood group genotyping. Based on the accuracy and other advantages offered by MALDI-TOF MS analysis, in the future, this method is likely to become widely adopted for blood group genotyping, in particular, for population screening.
Immunohematology

2015;31:75–80.
Clinical and reference lab characteristics of patients with suspected direct antiglobulin test (DAT)-negative immune hemolytic anemia
Authors: Karafin M.S. , Denomme G.A. , Schanen M. , Gottschall J.L.
Published: May 2021

Clinical evidence of warm autoimmune hemolytic anemia is present in 1 percent to 10 percent of patients whose direct antiglobulin test (DAT) is negative. The clinical underpinnings associated with DAT-negative immune hemolysis are poorly understood, and the current study aimed to further define the clinical characteristics associated with this form of anemia. A 19-question survey, requesting clinical information about each patient, was retrospectively mailed to all referring labs that had sent patient samples for an enhanced DAT evaluation from January 2011 through June 2013. An enhanced DAT evaluation involved a standard DAT and DATs performed using gel, polyethylene glycol, and 4°C low-ionic strength saline wash. We obtained detailed clinical information from 57 patients with an enhanced DAT investigation. Eighteen of these 57 patients (31.6%) were found to have a positive DAT, 11 (19.3%) of which were found to have a positive enhanced DAT (2 were positive by enhanced methods and negative by standard methods). The reported mean nadir hemoglobin for all 57 patients was 7.8 g/dL (range 3.2–12.7), and lactate dehydrogenase was 827.8 U/L (range 136–6917). Thirty-seven (88.1%) presented with a haptoglobin <10 mg/dL, and 21 (48.8%) reported spherocytes on peripheral smear. About half of the respondents reported using steroids as treatment for the anemia, and 4 of the 18 DAT-positive respondents (23.5%) changed their treatment plan because of the reference laboratory results. One patient died as a result of the reported hemolytic anemia (2.0%). We conclude that immune hemolysis detected by enhanced DAT methods is relatively common, and enhanced DAT methods are valuable tools in the diagnosis and management of patients with DAT-negative hemolytic anemia.
Immunohematology

2015;31:108–115.
Severe hemolytic disease of the fetus and newborn due to anti-C+G
Authors: Jernman R. , Korhonen A. , Haimila K. , Sareneva I. , Stefanovic V. , Sulin K. , Kuosmanen M. , Sainio S.
Published: May 2021

Anti-G is commonly present with anti-D and/or anti-C and can confuse serological investigations. In general, anti-G is not considered a likely cause of severe hemolytic disease of the fetus and newborn (HDFN), but it is important to differentiate it from anti-D in women who should be administered anti-D immunoglobulin prophylaxis. We report one woman with three pregnancies severely affected by anti-C+G requiring intrauterine treatment and a review of the literature. In our case, the identification of the correct antibody was delayed because the differentiation of anti-C+G and anti-D+C was not considered important during pregnancy since the father was D–. In addition, anti-C+G and anti-G titer levels were not found to be as reliable as is generally considered in Rh immunization. Severe HDFN occurred at a maternal anti-C+G antibody titer of 8 and anti-G titer of 1 in comparison with the critical titer level of 16 or more in our laboratory. Close collaboration between the immunohematology laboratory and the obstetric unit is essential. In previously affected families, early assessment for fetal anemia is required even when titers are low.
Immunohematology

2015;31:123–127.
Recovery of autologous reticulocytes by microhematocrit cell separation
Authors: Hall C.W.
Published: May 2021

Reticulocytes can be separated from more mature red blood cells based on differences in density. A method for obtaining autologous reticulocytes in ethylenediaminetetraacetic acid (EDTA) whole blood samples containing both autologous and transfused cells uses a microhematocrit centrifuge. The less dense reticulocytes harvested from the top 5 mm of microhematocrit tubes can be used to determine the patient’s phenotype or assess whether a transfusion reaction is taking place. This method can be performed using equipment, reagents, and supplies readily available in most laboratories.
Immunohematology

2015;31:152–154.
Transfusion-related acute lung injury in an era of TRALI risk mitigation
Authors: Lavelle J.C. , Grant M.L. , Karp J.K.
Published: May 2021

Transfusion-related acute lung injury (TRALI) is a rare complication of transfusion, for which the true incidence remains obscure, since there are a number of factors that may lead to misdiagnosis. Despite this, it continues to be the leading cause of transfusion-associated mortality. Here we present a historical case of TRALI in an elderly female who received group AB plasma and discuss how current mitigation strategies would likely have prevented its occurrence. It is important to remember that both immune and non-immune factors play a role in TRALI pathogenesis, and although current preventative strategies may decrease TRALI’s incidence, they likely will not eliminate it.
Immunohematology

2015;31:155–158.
Weak D type 67 in four related Canadian blood donors
Authors: Berardi P. , Bessette E. , Ng M. , Angus N. , Lane D. , Gariepy L. , Pavenski K. , Ochoa-Garay G. , Cote J. , Goldman M.
Published: May 2021

Correct donor D typing is critical to prevent recipient alloimmunization. No method can detect all variants, and the immunogenicity of many variants is unknown. Routine ABO and D serologic typings are performed in our laboratory by automated microplate testing. Until 2011, routine confirmation of D– status of first-time donors was performed by the manual tube indirect antiglobulin test (IAT); this was replaced by automated solid-phase testing including weak D testing by IAT. Selected donors are investigated by other methods. We describe four weak D type 67 (RHD*01W.67) donors whose samples tested as D– by automated microplate and manual methods but were later determined to be D+ by automated solid-phase and RHD gene analysis. Solid-phase serologic and molecular typing results of all four donors were identical. It was identified that the donors are of English-Irish descent; two are brothers and the others are cousins. Transfusion of blood from one of these donors likely resulted in alloimmunization to D in one of three recipients tested since no other documented exposures were identified. Lookback studies determined that two other D– recipients were not alloimmunized.
Immunohematology

2015;31:159–162.
Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors
Authors: Aranda L.I. , Smith L.A. , Jones S. , Beddard R.
Published: May 2021

Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group O or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or R0r were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black –R0r (44.4%), Hispanic –R1R1 (59.0%), and Caucasian –R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b–) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b–) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a–b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M–N+S–s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of each. Molecular red blood cell genotyping allows transfusion services to increase their availability of rare phenotypes for chronically transfused patients.
Immunohematology

2015;31:166–173.
How we investigate drug-induced immune hemolytic anemia
Authors: Leger R.M. , Arndt P.A. , Garratty G.
Published: May 2021

Drugs are a rare cause of immune hemolytic anemia, but an investigation for a drug antibody may be warranted if a patient has definitive evidence of immune hemolysis, other more common causes of hemolysis have been excluded, and there is a good temporal relationship between the administration of a drug and the hemolytic event. Drug antibodies are either drug-dependent (require drug to be in the test system) or drug-independent (reactive without drug present in the test). Drug-dependent antibodies are investigated by testing drug-treated red blood cells (RBCs) or by testing RBCs in the presence of a solution of drug. Drug-independent antibodies are serologically indistinct from idiopathic warm autoantibodies and cannot be defined or excluded by serologic testing. Nonimmunologic protein adsorption, caused by some drugs, is independent of antibody production but may also cause immune hemolytic anemia. Serologic methods for testing for drug antibodies are presented, and observations from more than 30 years of this laboratory’s experience are discussed.
Immunohematology

2014;30:85–94.
Cold acid elution (ELU Kit II)
Authors: Hinrichs M. , Keith M.A.
Published: May 2021

Elution is a procedure for recovery of antibody attached to intact, immunoglobulin-coated red blood cells (RBCs) by disrupting the antigen–antibody bonds. The recovered antibody is collected in an inert diluent and is referred to as an eluate. Testing of an eluate may be desired to identify antibody(ies) coating the RBCs of patients with a positive direct antiglobulin test. Many types of elution procedures have been developed and described; however, an acid elution is suitable for antibody recovery in most cases, such as recovery of alloantibodies and warm-reactive autoantibodies. Studies have compared methods such as xylene, chloroform, digitonin acid, dichloromethane, citric acid, and Immucor Elu-Kit II (cold acid elution). The ELU-Kit II has been shown to be quick and effective at eluting a wide range of alloantibodies as well as autoantibodies without the use of hazardous chemicals or costly reagent preparation time that some methods use. It is for these reasons that the ELU-Kit II is a very popular method for the elution of immunoglobulin G (IgG) antibodies.
Immunohematology

2014;30:113–116.
RHCE variant allele: RHCE*ce254G,733G
Authors: Keller J.A. , Horn T. , Chiappa C. , Melland C. , Vietz C. , Castilho L. , Keller M.A.
Published: May 2021

A novel RHCE allele was identified in a 53-year-old African-American female blood donor with an Rh phenotype of D+ C– E– c+ e+ and a negative antibody screen. The donor’s cells typed e+ with all antisera tested. By gel-based genotyping and cDNA analysis, the two RHCE alleles in this donor were characterized. One allele was found to be the known allele RHCE*01.20.01 (RHCE*ce733G) and the second was novel: RHCE*01.06.02 (RHCE*ce254G,733G).

Immunohematology

2014;30:121– 122.
Detection and identification of platelet-associated alloantibodies by a solid-phase modified antigen capture enzyme-linked immunosorbent assay method and its correlation to platelet refractoriness in multiplatelet concentrate–transfused patients
Authors: Jain N. , Sarkar R.S. , Philip J.
Published: May 2021

Platelets express a variety of polymorphic glycoproteins (GPs), such as GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and class I human leukocyte antigen. In the platelet transfusion setting, alloimmunization involves the production of antibodies against these glycoproteins. Patients transfused with multiple units of platelet concentrates for longer periods are the main individuals with platelet alloimmunization. This study was performed to detect the development of platelet antibodies in patients who are transfused with multiple units of leukodepleted platelet concentrates, such as those with hemato-oncologic diseases and bone marrow failure syndromes. The method used was solid-phase modified antigen capture enzyme-linked immunosorbent assay. Platelet refractoriness was assessed by measuring the corrected count increment at 1 and 24 hours after transfusion.
Immunohematology

2014;30:123–125.
Effects of pH changes of stock normal saline solution on 5 percent red cell suspension
Authors: Martin G.L. , Caraan P.J.M. , Chua J.J.S. , Crescini J.A.L. , Diokno J.M.C. , Javier C.B.Dlr. , Reyes M.K.B.O. , Soliven R.Y.
Published: May 2021

The red cell suspension (RCS) is a universally used indicator system to demonstrate antigen and antibody reactions in vitro. Saline solutions that are used in its preparation are preferred to be fresh to avoid changes in pH that may affect the results. Thus, buffered saline such as phosphate-buffered saline (PBS) is the ideal diluent because its pH is maintained for a certain period. However, normal saline solution (NSS) is more commonly used because it is inexpensive and easy to make. pH changes in the saline solutions and the RCSs were monitored for 1 week. Macroscopic examination of changes in degree of redness of RCS was also observed. Red blood cell (RBC) indices of the ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood used in the preparation of the RCS were measured in the performance of an automated complete blood count. Qualitative examination of the crenation of RBCs was done on the prepared blood smears and graded by three registered medical technologists. Percentage crenation was then determined using an improved Neubauer counting chamber. Three trials were performed, and results were averaged. Statistical analysis showed that there were significant differences in the average pH of PBS and NSS and the average pH of RCS-PBS and RCS-NSS over 1 week. RBC indices measured in EDTA-anticoagulated donor blood showed no significant difference. Macroscopic examination of changes in degree of redness of the RCS showed that color darkened over 1 week but only by a small degree. Qualitative and quantitative examination of crenation of RBCs in RCS-PBS and RCS-NSS both showed no significant differences over 1 week. The experimental group (RCS-NSS) continuously showed a higher grade of crenation than the control group (RCS-PBS). Crenation of RBCs still manifests microscopically despite the lack of a significant relationship between the pH of the saline solutions and the degree and percentage of crenation. Crenation, therefore, cannot be attributed to pH alone but occurs as a result of other factors.
Immunohematology

2014;30:126–134.
Allogeneic red blood cell adsorption for removal of warm autoantibody
Authors: Barron C.
Published: May 2021

Adsorption studies are usually required to confirm or rule out the presence of underlying alloantibodies in samples containing warm autoantibody. Allogeneic adsorptions are necessary if the patient has been recently transfused. Most commonly, allogeneic adsorptions are performed using a trio of phenotyped reagent red blood cells to rule out clinically significant alloantibodies to common antigens. The adsorbing cells may be used untreated or treated with enzymes or with ZZAP before adsorption. Adsorption may also be performed using enhancement such as low-ionic strength saline or polyethylene glycol added to the mixture. Multiple adsorptions may be necessary to remove strongly reactive autoantibodies. Allogeneic adsorptions will not detect alloantibodies to high-prevalence antigens.
Immunohematology

2014;30:153–155.
Anti-Ge2: further evidence for lack of clinical significance
Authors: Karunasiri D. , Lowder F. , Ostrzega N. , Goldfinger D.
Published: May 2021

Anti-Ge2 may be immune or naturally occurring, and it reacts with an antigen on glycophorin D. Ge2 is encoded by a gene, GYPC, which is located on the long arm of chromosome 2. Anti-Ge2 is usually an immunoglobulin G (IgG) antibody. In the available literature, we have not been able to find any reported cases of proven acute hemolytic transfusion reactions caused by anti-Ge2. We present the case of a 67-year-old man with metastatic pancreatic carcinoma who had symptomatic anemia and a hemoglobin concentration of 6.3 g/dL. During pretransfusion testing, anti-Ge2 was identified in his serum. Only a single unit of compatible, Ge:–2 frozen red blood cells (RBCs) could be provided by the blood supplier. A second unit of crossmatched, least-incompatible, leukocyte-reduced RBCs, presumably Ge:2, was also transfused. The transfusion was completed without incident, and the patient’s hemoglobin concentration rose appropriately. Posttransfusion values for haptoglobin, lactate dehydrogenase, and urine hemoglobin were within normal limits. A monocyte monolayer assay performed on this anti-Ge2 supports the data that antibodies of this specificity do not cause hemolysis. The clinical and laboratory data obtained in our patient clearly indicated that no hemolysis of transfused RBCs occurred during and for 24 hours after transfusion. We believe that this report adds to a limited experience with anti-Ge2 and provides further evidence for concluding that, in all likelihood, this is not a clinically important RBC antibody. The risk of transfusing apparently “incompatible” (Ge:2) RBCs seems remote and should allow for timely administration of RBCs when treating patients with serious anemia.
Immunohematology

2014;30:156–157.
Polyethylene glycol antiglobulin test (PEG-AGT)
Authors: Weldy L.
Published: May 2021

Polyethylene glycol (PEG) was described in 1987 as a new technique for immunohematology testing. The original paper described its use in detection and identification of weakly reactive antibodies. PEG is used as an additive to enhance reactivity and to reduce incubation time when testing for unexpected antibodies. PEG can be used as an alternative to low-ionic-strength saline and whenever weak reactions are encountered.
Immunohematology

2014;30:158–160.
An AQP1 allele associated with Co(a–b–) phenotype
Authors: Vege S. , Nance S. , Kavitsky D. , Li X. , Horn T. , Meny G. , Westhoff C.M.
Published: May 2021

The Colton (CO) blood group system consists of four antigens, Coa, Cob, Co3, and Co4, located on aquaporin-1 (AQP1),with Coahighly prevalent in all populations (99.8%). The Colton null phenotype, Co(a–b–), is very rare, and individuals with this phenotype lack the high-prevalence antigen Co3. To date, only six Co(a–b–) probands have been reported and four silencing alleles characterized. We identified an AQP1-null allele in a white woman with anti-Co3 caused by deletion of a G at nucleotide 601 (nt601delG) that results in a frameshift and premature termination (Val201Stop). Available family members were tested for the allele. Although anti-Co3 has been associated with mild to severe hemolytic disease of the fetus and newborn, the antibody was not clinically significant as evidenced by a low titer and delivery of asymptomatic newborns with moderate to weakly positive direct antiglobulin tests for all four pregnancies.
Immunohematology

2013;29:1–4.
Warm autoantibodies: time for a change
Authors: Nobles J.R. , Wong C.
Published: May 2021

Routine adsorption procedures to remove autoantibodies from patients’ serum often require many hours to perform. This time-consuming process can create significant delays that affect patient care. This study modified the current adsorption method to reduce total adsorption time to 1 hour. A ratio of one part serum to three parts red blood cells (RBCs; 1:3 method) was maintained for all samples. The one part serum was split into three tubes. Each of these three aliquots of serum was mixed with one full part RBCs, creating three adsorbing tubes. All tubes were incubated for 1 hour with periodic mixing. Adsorbed serum from the three tubes was harvested, combined, and tested for reactivity. Fifty-eight samples were evaluated using both the current method and the 1:3 method. Forty-eight (83%) samples successfully adsorbed using both methods. Twenty (34.5%) samples contained underlying alloantibodies. The 1:3 method demonstrated the same antibody specificities and strengths in all 20 samples. Eight samples failed to adsorb by either method. The 1:3 method found previously undetected alloantibodies in three samples. Two samples successfully autoadsorbed but failed to alloadsorb by either method. The 1:3 method proved to be efficient and effective for quick removal of autoantibodies while allowing for the detection of underlying alloantibodies.
Immunohematology

2013;29:5–10.
An update on the GLOB blood group system and collection
Authors: Hellberg Å. , Westman J.S. , Olsson M.L.
Published: May 2021

The P blood group antigen of the GLOB system is a glycolipid structure, also known as globoside, on the red blood cells (RBCs) of almost all individuals worldwide. The P antigen is intimately related to the Pkand NOR antigens discussed in the review about the P1PK blood group system. Naturally occurring anti-P is present in the serum of individuals with the rare globoside-deficient phenotypes p, P1
k, and P2
kand has been implicated in hemolytic transfusion reactions as well as unfavorable outcomes of pregnancy. The molecular genetic basis of globoside deficiency is absence of functional P synthase as a result of mutations at the B3GALNT1locus. Other related glycolipid structures, the LKE and PX2 antigens, remain in the GLOB blood group collection pending further evidence about the genes and gene products responsible for their synthesis.
Immunohematology

2013;29:19–24.
Hemolytic disease of the fetus and newborn owing to anti-U, successfully treated with repeated intrauterine transfusions
Authors: Strindberg J. , Lundahl J. , Ajne G.
Published: May 2021

Hemolytic disease of the fetus and newborn (HDFN) owing to anti-U has rarely been reported. U is part of the MNS system. M and N glycoproteins are located on glycophorin A (GPA); S and s antigens are on glycophorin B (GPB). Individuals who lack GPB are S– and s– and also lack U. The U– phenotype occurs almost exclusively in the African population and has a very low frequency (0.25%). Anti-U is of immunoglobulin G class and can cause hemolytic transfusion reaction and HDFN. In this report we present the use of a noninvasive method to detect anemia in the fetus and the subsequent use of intrauterine transfusion (IUT) with blood of a very rare phenotype. For the first time, we used deglycerolized and 3-week-old red blood cell units for IUT without signs of adverse reactions and with the expected effect on the hemoglobin value. We conclude that this transfusion strategy could be applied safely.
Immunohematology

2013;29:51– 54.
Molecular analysis of patients with weak D and serologic analysis of those with anti-D (excluding type 1 and type 2)
Authors: Pham B.-N. , Roussel M. , Gien D. , Andre-Botte C. , Ripaux M. , Auxerre C. , Le Pennec P.-Y.
Published: May 2021

Whether or not patients whose red blood cells (RBCs) carry certain weak D types produce anti-D, and if they do whether it is allo- or autoanti-D, remains controversial. The aim of this study was to determine the serologic features of anti-D in individuals expressing a weak D other than type 1 or type 2 and to assess whether the anti-D was an allo- or autoantibody. Serologic D typing and molecular analyses were performed on 748 individuals. Serologic characterization of anti-D included autologous controls, direct antiglobulin test, elution, and titration of anti-D before and after adsorption of serum onto autologous RBCs. From molecular analyses, 459 individuals exhibited a weak D type. We described seven novel RHDvariant alleles. The most frequent types of weak D were type 1 (30.1%), type 2 (23.7%), type 4.0 (10.2%), type 4.2.2 (20.3%), type 11 (3.9%), and type 15 (3.7%). Anti-D was identified in the sera of 9 of 47 individuals with weak D type 4.0, in 14 of 93 with weak D type 4.2.2, in 1 of 18 with weak D type 11, in 1 of 17 with weak D type 15, and in 1 weak D type 33 individual. Anti-D was demonstrated to be an alloantibody in weak D type 4.0, type 4.2.2, and type 15 individuals, but an autoantibody in weak D type 11 and type 33 individuals. In conclusion, only a complete serologic investigation of individuals with a given weak D type identified by molecular analysis allows concluding on the nature of the antibody. Transfusing weak D type 4.2.2 and type 15 patients with D– RBC units and proposing anti-D immunoprophylaxis to women with these weak D types should be considered.
Immunohematology

2013;29:55–62.
A review of the JR blood group system
Authors: Castilho L. , Reid M.E.
Published: May 2021

The JR blood group system (ISBT 032) consists of one antigen, Jra, which is of high prevalence in all populations. The rare Jr(a–) phenotype has been found mostly in Japanese and other Asian populations, but also in people of northern European ancestry, in Bedouin Arabs, and in one Mexican. Anti-Jrahas caused transfusion reactions and is involved in hemolytic disease of the fetus and newborn. The Jraantigen is located on ABCG2 transporter, a multipass membrane glycoprotein (also known as the breast cancer resistance protein, BCRP), which is encoded by the ABCG2gene on chromosome 4q22.1. The Jr(a–) phenotype mostly results from recessive inheritance of ABCG2null alleles caused by frameshift or nonsense changes.
Immunohematology

2013;29:63–68.
The Diego blood group system: a review
Authors: Figueroa D.
Published: May 2021

The Diego blood group system (DI) currently encompasses 22 antigens. Three of the antigens are of high prevalence and the other 19 are of low prevalence. The antigens of the Diego blood group system are carried on the erythroid band 3 protein anion exchanger 1 (AE1), the product of a single gene, SLC4A1(solute carrier family 4, anion exchanger, member 1). AE1 is a member of a family of three anion exchangers or transporters expressed in a variety of tissues. This protein is involved in carbon dioxide transport from tissues to lungs. It is also found in the kidney, where it is involved in acid secretion. Antibodies to Diego system antigens with the exception of anti-Dia, -Dib, -Wra, -ELO and -DISK do not seem to be of clinical significance for transfusion or of importance in hemolytic disease of the fetus and newborn.
Immunohematology

2013;29:73–81.
Red blood cell phenotyping after transfusion: an in vitro model
Authors: Gonsalkorale K. , Vanhecke C. , Badami K.G.
Published: May 2021

Recipient red blood cell (RBC) phenotyping using serologic techniques, within 3 months of a transfusion, is considered unreliable. We conducted in vitro experiments to determine how long recipient RBC phenotyping results would be compromised after an allogeneic transfusion. In vitro models were created to mimic in vivo posttransfusion ratios of “transfused” RBCs with either a single or a double dose of an antigen and “autologous” RBCs negative for the corresponding antigen at 10-day intervals from day 0 to day 90 in hypothetical recipients with varying weights and hematocrits (Hct) receiving varying numbers of RBC units. In general, a reliable recipient RBC phenotype was possible earlier after transfusion in larger recipients, those with higher Hct, and those transfused with fewer RBC units and if the transfused units had the antigen of interest in single, rather than double, dose. We believe that a reliable RBC phenotype, using routine serologic techniques, can often be obtained well before 3 months after transfusion. Similar studies with other donors, antigens, antisera, and methods and in actual patients will be useful.
Immunohematology

2013;29:93–6.
Identifying D-positive donors using a second automated testing platform
Authors: Goldman M. , Resz I. , Cote J. , Ochoa G. , Angus N.
Published: May 2021

Because of the variability of D expression, one method may be inadequate to correctly classify donors with variant RHDalleles. We evaluated the use of a solid-phase automated platform (ImmucorGamma Galileo) to confirm D– test results obtained on first-time donors on the Beckman Coulter PK7300 automated microplate test system. Samples with discordant results were analyzed by serologic tube methods, RHD genotyping using the BLOODchip platform (Progenika), and, if necessary, sequencing. We estimated the number of cases of alloimmunization in women younger than 50 years likely to be prevented by the addition of Galileo testing. From May 2011 to May 2012, 910,220 donor samples were tested; 15,441 were first-time donors with concordant D– results. Five donors tested D– on the PK7300 and weak D+ on the Galileo; one was found to be a false positive on further testing. On manual testing, the other four donors had positive indirect antiglobulin test results with one to three of the antisera used and were C+. On BLOODchip testing, two donors were classified as D+, and two were assigned a “no call.” D variants included weak D type 67, weak D type 9, and two novel variants. Approximately 10 percent of D– units are transfused to women younger than 50 years. Assuming an alloimmunization rate of 30 percent, use of the Galileo would prevent approximately one alloimmunization every 5 to 6 years in this patient group. We conclude that the yield of preventing alloimmunization in this population by adding a second automated serologic testing platform is very low.
Immunohematology

2013; 29:97–100.
Immunosuppressive protocols for transplantation and certain hematologic malignancies can prevent the primary immune response to the D blood group antigen
Authors: Seager A. , Sandler S.G.
Published: May 2021

A review of the published literature on Rh alloimmunization reveals that its incidence varies with the volume of infused D+ red blood cells (RBCs), the probable Rh genotype of the RBCs, and the immune competency of the D– recipient. Among the reports of Rh alloimmunization in different clinical circumstances, we identified five studies in which a combined total of 62 D– recipients of hematopoietic stem cell or solid-organ transplants were transfused with D+ RBCs and none (0%) formed anti-D. The observation that immunosuppressive protocols developed to prevent rejection of tissue and organ transplants also prevented alloimmunization to the D blood group antigen raises the possibility of practical applications in blood transfusion practice.
Immunohematology

2013;29:110–14.
Prevalence of clinically significant red blood cell alloantibodies in pregnant women at a large tertiary-care facility
Authors: Smith H.M. , Shirey R.S. , Thoman S.K. , Jackson J.B.
Published: May 2021

More than 50 red blood cell (RBC) alloantibodies are known to cause hemolytic disease of the fetus and newborn (HDFN). Although Rh immune globulin (RhIG) prophylaxis has significantly reduced the incidence of pregnancies complicated by anti-D, the need to detect and monitor maternal alloantibodies capable of causing HDFN is still a concern. The prevalence and specificity of these alloantibodies were determined. In this retrospective study, the prevalence and specificities of unexpected RBC alloantibodies known to cause HDFN in pregnant women at a tertiary-care facility during a 5-year period were compiled and analyzed. Patient selection was carried out by computerized search of patient data based on an obstetric location and the presence or history of RBC antibody between January 1, 2007, and December 31, 2011. The information was organized by ABO and D status of the patient, antibody specificity, and transfusion needs. Of the 8894 obstetric patients identified during the 5-year period, 264 (3.0%) had one or more unexpected RBC antibodies. Of these 264 women, 107 (40.5%), or 1.2 percent overall, had an alloantibody known to cause HDFN, with a total of 15 different alloantibodies identified. The most common alloantibody found was anti-E (n = 33), followed by anti-M (n = 26) and anti-D (n = 20). In pregnancies of D– women, the most common clinically significant antibodies found were anti-D (n = 20), anti-C (n = 11), and anti-E (n = 2). In pregnancies of D+ women, the most common antibodies were anti-E (n = 31), anti-M (n = 25), and anti-K (n = 16). A total of eight pregnancies with alloantibodies required intrauterine transfusions with the specificities of anti-D; anti-D,-C (n = 2); anti-D,-C,-E; anti-D,-C,-K; anti-D,-C,-Jkb; anti-D,-S; and anti-E,-c. At a large academic tertiary-care center, approximately 1 in 83 obstetric patients had one or more RBC alloantibodies capable of causing HDFN. Anti-E, -M, and -D were the most frequent specificities, respectively.
Immunohematology

2013;29:127–130.
GIL: a blood group system review
Authors: Rumsey D.M. , Mallory D.A.
Published: May 2021

The GIL blood group system was added to the list of systems already recognized by the International Society for Blood Transfusion in 2002. It was designated as system 29 after the antigen was located on the aquaglyceroporin 3 (AQP3) protein and the gene encoding the protein was identified in 2002. There is only one antigen in the system, GIL, and the antigen, as well as the system, was named after the antigen-negative proband identified in the United States who had made anti-GIL. It was later shown to be the same as an unidentified high-incidence antigen lacking from the red blood cells of a French woman. Coincidentally all the antibodies found have been produced as a result of pregnancy. While there has not been a direct link to a disease, the absence of the AQP3 protein may result in a worse than expected rate of survival of patients with bladder cancer as compared with patients with the same disease who express the protein. Future work may center on using GIL as a marker for AQP3 and involving it in targeted cancer therapies.
Immunohematology

2013;29:141–144
Differences in the views of obstetricians-gynecologists and intensivists based on the survey “Provision of medical care to patients with stillbirth”. Original article
Authors: Mysovskaya Yulya S. , Marshalov D. V. , Shifman E. M. , Shindyapina N. V. , Ioscovich A.
Published: May 2021

Introduction. The Russian Federation’s stillbirth rate is almost twice that of the United States and Europe, while domestic treatment protocols are still lacking.
Objectives. To analyze the results of a survey of obstetricians-gynecologists and intensivists on the problems of providing medical care to patients with stillbirth.
Materials and methods. We have developed a questionnaire, which consisted of 23 questions in Russian. A total of 369 Russian-speaking doctors, intensivists and obstetricians-gynecologists took part in the survey.
Results. The need to turn off the mother’s consciousness at the time of giving birth to a dead fetus caused great disagreement between the related specialists (p = 0.0001). 56 % of intensivists and 35 % of obstetricians-gynecologists were in favor of turning off the mother’s consciousness. According to 23 % of obstetricians-gynecologists and only 9 % of intensivists, visual and tactile contact of a mother and her dead fetus has a positive impact on the psychoemotional state of the woman (p = 0.002). Respondents from both specialties preferred epidural analgesia in more than half of the cases.
Conclusions. A list of issues for which the greatest differences in ratings were obtained has been identified, which will further help to identify priority issues for discussion and points of application for creating agreed documents on the best management of pregnant women with stillbirth.
Pathogenesis and clinical significance of the hyperdynamic circulatory syndrome in liver cirrhosis. Review
Authors: Katsin M. L. , Hurava M. Y. , Prylutski Pavel S. , Dzyadz’ko A. M. , Rummo O. O.
Published: May 2021

Portal hypertension is the major consequences of liver cirrhosis and is accompanied by pathologic increase in portal blood flow resistance. As portal hypertension develops that results in formation of vessel’s collaterals and arterial vasodilatation. Hyperdynamic alternations become more significant due to hyporesponsiveness to vasoconstrictors and increased shunts formation with autonomic neuropathy. This combination of liver failure and portal hypertension leads to the hyperdynamic circulatory state partly owing to simultaneous vasodilatation of splanchnic and peripheral arterial vessels. So hyperdynamic circulatory syndrome is a late complication of portal hypertension due to liver cirrhosis. The main features of hyperdynamic circulatory syndrome are high cardiac output, increased heart rate and total blood volume coupled with decreased total systemic vascular resistance. Some of these cardiovascular changes are reversible after liver transplantation what show pathophysiological significance of portal hypertension. In this paper, we aimed to review pathophysiology and features of hyperdynamic syndrome that are well-known and directly related to portal hypertension (varices, ascites, hepatic encephalopathy and hepatorenal syndrome), while others are more rare and therefore further investigations are necessary (portopulmonary hypertension, cirrhotic cardiomyopathy).
Predictive signs of fat embolism syndrome. Case-control study
Authors: Pevnev A. A. , Yakovlev Alexey Yu. , Belous M. S. , Ryabikov D. V. , Zagrekov V. I.
Published: May 2021

Objectives. To study the significance of biochemical parameters and fat globulemia in predicting the development of fat embolism in severe combined trauma.
Materials and methods. The study included 637 patients with severe combined trauma (615 patients — without developing fat embolism and 22 patients — with fat embolism). We determined the relationship of increased glucose, lactate, non-esterified fatty acids, and fat globulemia at the time of admission to the hospital with the development of fat embolism.
Results. The presence of hyperglycemia and hyperlactatemia does not affect the prediction of fat embolism. In 20 out of 22 patients with fat embolism, the values of non-esterified fatty acids during hospitalization exceeded 1.3 mmol/l. Trauma with an Injury Severity Score of ≥ 17 points is accompanied by fat globulemia in 100 % of cases. The relationship between the number of globules larger than 50 microns at the time of admission to the hospital and the development of fat embolism was determined.
Conclusion. In patients with trauma at the time of admission to the hospital, an increase in the content of non-esterified fatty acids in venous blood and the presence of fat globules larger than 50 microns in the blood plasma can serve as a prognostic criterion for the development of fat embolism in the early post-traumatic period.
Comparison of REMS, NEWS, qSOFA scales and SIRS criteria in sepsis prediction for patients with confirmed SARS-CoV-2 infection: retrospective observational study
Authors: Zybin Konstantin D. , Noskov А. А. , Musaeva T. S. , Kuznetsova М. P. , Goncharenko S. I. , Vysotsky O. V. , Danilyuk P. I. , Petrushenko E. S. , Veselenko M. I. , Potapova A. A. , Sinkov S. V. , Durleshter V. M.
Published: May 2021

Introduction. Novel coronavirus disease is often accompanied by sepsis. This leads us to search of sepsis prediction tools.
Objectives. Comparison of REMS, NEWS, qSOFA scales and SIRS criteria in sepsis prediction for patients with confirmed SARS-CoV-2 infection.
Materials and methods. 167 medical cards retrospective analysis of patients with confirmed SARS-CoV-2 infection on admission to ICU.
Results. In sepsis prediction only NEWS (0,819 [95% CI 0.738–0,884]) showed resolution high enough to serve as supplemental clinical information. REMS (0.798 [95% CI 0.715–0.866]), qSOFA (0.716 [95% CI 0.626–0.795]) and SIRS criteria (0.710 [95% CI 0.620–0.790]) showed insufficient resolution in sepsis prediction for patients with SARS-CoV-2. NEWS in pairwise comparison showed significantly better resolution than qSOFA (p = 0.002) and SIRS criteria (p = 0.013). All scales showed good calibration.
Conclusions. Only NEWS scale showed good resolution and calibration and can be used as supplemental clinical information in sepsis prediction for patients with SARS-CoV-2 infection.
Critical appraisal of the “cytokine storm” concept in new coronavirus disease COVID-19. Review
Authors: Bobkova S. S. , Zhukov A. A. , Protsenko D. N. , Samoylenko Valery V. , Tyurin I. N.
Published: May 2021

Introduction. Novel coronavirus infection (COVID-19) is characterized by systemic hyper-inflammation with elevated inflammatory cytokines referred to cytokine storm. It has been recognized as a leading cause of severe COVID-19 and its progression to multi-organ failure.
Objectives. To make a synthesis if the literature sources and to critical appraise “cytokine storm” concept in COVID-19.
Results. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory immunomodulation therapy in severe COVID-19. Although a number of studies have been conducted on target immunomodulatory therapy for severe COVID-19, no specific recommendations have been made yet. Moreover, there are some evidence against cytokine storm as pivotal pathogenetic mechanism for clinical deterioration in COVID-19 patients.
Conclusion. There are enough evidence supporting cytokine response impairment as one of leading cause of COVID-19 progression to multiorgan failure. However, cytokine response abnormalities couldn’t explain clinical deterioration in some patients, so further studies are needed to find possible alternative pathogenetic mechanisms.
The role of proinflammatory and anti-inflammatory cytokines in bacterial pneumonia. Review
Authors: Zinina Elizaveta P. , Tsarenko S. V. , Logunov D. Y. , Tukhvatulin A. I. , Babayants A. V. , Avramov А. А.
Published: May 2021

Hospital-acquired pneumonia is a common cause of mortality in intensive care units. Therapy effectiveness depends on the antibiotic regimen chosen. Serum cytokines concentrations could be used as sensitive predictors of hospital-acquired pneumonia outcomes and therapy response. Analysis of literature in the Pubmed database shows, that using the key terms “pneumonia”, “cytokines” and “biomarkers”, 1062 publications can be found. By narrowing the search with key terms “nosocomial pneumonia” and “cytokines” it is possible to discover 212 publications. The search for literature, regarding information on specific cytokines and their role in bacterial pneumonia yields another 258 articles. Both experimental and clinical studies revealed the potential prognostic value of cytokines as diagnostic biomarkers in bacterial pneumonia. In this paper we review the pathogenesis of pneumonia-related inflammation, related cytokines, and their practical value. Information regarding interleukins, interferons, tumor necrosis factor superfamily proteins, matrix metalloproteinases, colony-stimulating factors, chemokines, and anti-inflammatory cytokines was reviewed. Many inflammatory factors have yet to be thoroughly researched. Furthermore, more studies are necessary to determine the prognostic potential of cytokines as markers of the effectiveness of antibacterial therapy in nosocomial pneumonia.
Consensus technologies in the analysis of guidelines: international experience of application of Delphi method in anesthesiology and intensive care. Systematic review
Authors: Zabolotskikh Igor B. , Grigoryev S. V. , Belkin A. A. , Lakhin R. E.
Published: May 2021

Introduction. To perform research aimed at solving problems, checking existing and formulating new hypotheses, making decisions or judging on any problem, the Delphi method and its modifications are often used. In recent years, the use of this method in research in various fields of medicine is gaining popularity; nevertheless, the technique is rarely used in domestic practice.
Objectives. To describe the features of the application of the Delphi method in the expert assessment of recommendations and to evaluate its application in anesthesia and intensive care.
Materials and methods. The publications were searched in the electronic databases PubMed and RSCI. Date of last search query is January 15, 2021. The search was carried out using the keywords “clinical practice”, “anesthesia intensive care guidelines”, “clinical practice guidelines”, “anesthesia intensive care guidelines”, “Delphi method”.
Results. This review describes the principles of the Delphi method, its advantages and limitations, provides examples of its use in clinical trials and in the analysis and development of recommendations in relation to anesthesiology and intensive care. The example of the analysis of recommendations shows the implementation of the quality assessment of the provisions being developed.
Conclusions. The Delphi method can be used to assess the adequacy and effectiveness of the diagnostic and treatment methods proposed in the framework of the recommendations.
Acute Myeloid Leukemia as Second Tumor in a Patient with Burkitt’s Lymphoma: Literature Review and a Case Report
Authors: Valiev Timur Teimurazovich , Pavlova T.Yu. , Kovrigina A.M. , Serebryakova I.N.
Published: May 2021

The application of highly effective tumor treatment protocols in children and increasing number of patients healed resulted in a growing focus on long-term effects of chemotherapy. One of the most dangerous complications of a first malignant neoplasm (MN) is the development of second MNs. Cytostatic drugs of the epipodophyllotoxin group and alkylating agents contribute to secondary acute myeloid leukemias (AML), the rare and prognostically very unfavorable second MNs. The present article provides a review of literature on risks of secondary hematological MNs associated with the therapy of first tumors. It also contains a case report of successful treatment of AML which occurred after Burkitt’s lymphoma therapy.