Transfusion management in a pediatric patient with febrile neutropenia with red blood cell autoantibodies: a case report

Febrile neutropenia is a common complication of chemotherapy especially in hematological malignancies associated with sepsis or severe infection. We report a case where a seven-year-old girl with T – cell acute lymphoblastic leukemia (ALL) developed febrile neutropenia (absolute neutrophil count - ANC <500/µL). Patient developed transient red blood cell (RBC) autoantibodies which interfered with compatibility testing and posed a challenge in donor selection for granulocyte transfusion. Direct antiglobulin test (DAT) and compatibility testing were done by column agglutination technique (CAT) using polyspecific anti-human globulin gel cards. Antibody screen was also done by CAT using 3-cell panel. Granulocyte concentrate was collected from eligible donors after taking an informed consent using a cell separator based on continuous flow principle. The patient’s blood group was AB RhD positive, however, the auto-control was positive (2+), DAT was positive (1+) but the antibody screen was negative. Monospecific DAT revealed the characteristic of antibody to be IgG (2+). The donor for granulocyte harvesting was selected on the basis of adopting a least incompatible donor approach. During her hospital stay she was transfused with four granulocyte concentrates, and other blood components without any adverse events. The patient’s blood culture was sterile on day 33 of hospital stay and subsequently she remained afebrile and finally discharged on day 41 in a hemodynamically stable state. The hemogram was- Hb:10.7g/dL, Total leucocyte count (TLC): 5610/µL, ANC: 4375/µL, PLT: 22000 /µL. This case draws a special attention to the importance of serological testing in selection of donor for granulocyte transfusion.

Hyperhemolysis Syndrome Following Pre-Operative Red Blood Cell Exchange

Introduction/Objective Pre-operative red blood cell exchange (RBCX) for patients with Sickle Cell Disease (SCD) is a category III indication. In our institution, RBCX is routinely performed pre-operatively when general anesthesia is necessary with the goal of HbS%&lt;30 and reduction in adverse events related to general anesthesia. In the context of elective surgery, the risks and benefits of both the operation and any pre-operative transfusion must be discussed with the patient. Herein, we present an extreme case of Hyperhemolysis Syndrome resulting from a pre-operative RBCX. Methods/Case Report A 23-year-old transgender female with SCD (Hb S Lepore) treated with Hydroxyurea presented for elective breast augmentation for gender-affirmation. Her pre-operative plan included a RBCX. Her pre-exchange hemoglobin (Hb) and hematocrit (Hct) were 10.3 g/dL and 29.3%, respectively. Hb electrophoresis revealed HbS 52%, HbF 41.4%, HbA2 7.4%, and HbA was not detected. Type and Screen (T&S) demonstrated O + blood group, with a negative antibody screen, and with no known historical alloantibodies. RBCX was performed using the Spectra Optia (TerumoBCT, Lakewood, CO, USA) with exchange volume of 1.9 L of group O+ RBCs, phenotypically matched for C, E, and K, an end Hct of 30% and an FCR of 30%. Her post-exchange Hb and Hct were 10.2g/dL and 29.5%, respectively. Hemoglobin fractionation revealed HbS 12% and HbA 73%. She underwent surgery without intraoperative complications. Two weeks post RBCX, her Hb had decreased to 5.3 g/dl, and her LDH and Total Bilirubin had increased to 253 ul and 1.8 mg/dl, respectively. A repeat T&S drawn 8 days after RBCX revealed a positive antibody screen and direct antiglobulin test (DAT). Three new alloantibodies were identified: anti-Fya (present in plasma and eluate); anti-Jkb (present in plasma); anti-S (eluate). She was treated with IVIG, 0.4 g/Kg/day for 5 consecutive days and 2 doses of subcutaneous darbepoetin 100 mcg and subsequently discharged with close outpatient follow up. Her Hb returned to baseline at 11 g/dL, 48 days post RBCX. Results (if a Case Study enter NA) N/A Conclusion Pre-operative RBCX decreases morbidity in sickle cell patients undergoing general anesthesia. In the setting of elective surgery, patients must be counseled on the benefits and risks of surgery as well as the requisite RBCX. In our case, the patient developed multiple alloantibodies, with lifelong implications should she ever need future blood transfusions.

Haemolytic disease of the fetus and newborn: do not miss a positive maternal antierythrocyte antibody screen

Jaundice is one of the most common situations during the neonatal period. Alloimmune haemolytic disease of the fetus and newborn (AHDFN) is a major cause of pathological jaundice during the neonatal period. Since the establishment of anti-D prophylaxis, other antigens have gained greater clinical importance. The maternal antierythrocyte antibody screen is of great importance in monitoring pregnancy and in predicting the risk of AHDFN. A positive result should alert to the possibility of AHDFN and promote close surveillance of fetal anaemia, as well as neonatal anaemia and hyperbilirubinaemia. We describe a case of AHDFN due to incompatibility of the Rhesus c (Rhc) subgroup, diagnosed in pregnancy, but without effective transmission of information in the perinatal period, so a positive maternal antierythrocyte antibody screen was missed. This case highlights the importance of non-RhD antigens in this disease, but also the importance of a successful handoff of information in the delivery room.

Autoimmune haemolytic anaemia: emergency blood transfusion

A 50-year-old woman, with a background of autoimmune haemolytic anaemia, presented to the emergency department with lethargy and shortness of breath. Investigations revealed a haemoglobin level of 50 g/L. High dose steroids were administered and blood transfusion prescribed. However, the blood transfusion was delayed due to a positive antibody screen and concerns regarding administering blood when the patient was pyrexic. The delay resulted in a significant deterioration in the patient’s clinical state with her haemoglobin level falling to 26 g/L 24 hours later. She was urgently transfused with blood and made a full recovery. This report analyses the delays for transfusion and how these could have been minimised. First, guidelines advise that emergency blood should be considered in life-threatening circumstances. Second, fever is not always a contraindication for transfusion, particularly in an emergency setting.

Suitability of Placental Blood Samples of Newborns for Pre-Transfusion Testing

Objective: To show concordance between heel stick and placental blood sample pairs for newborns' pre-transfusion testing and to validate placental blood's tube and gel methodology.Methods: Placental samples were collected for pre-transfusion testing at birth from 78 singleton and twin newborns admitted to our Mother–Baby Unit to compare with the results of heel stick samples taken from same newborns. Gestational age ≥35 weeks, weight ≥2,000 g. The study was approved by the Institutional Review Board (IRB). Informed consent was obtained from newborn parents. ABO blood group, Rhesus factor (Rh), direct antiglobulin test (DAT), and antibody screen were performed. Ortho ProVue Analyzer was used for tube and gel methods. McNemar's test for paired categorical data was performed.Results: One hundred percent concordance in 78 pairs for ABO and Rh. Seventy-four pairs were tested for antibodies, 72 were both negative, 1 was both positive, and 1 gave discordant result. Ninety-nine percent concordance, p = 0.999. Sixty-five pairs were both DAT negative, seven were both DAT positive, and six gave discordant results. Ninety-two percent concordance, p = 0.68. Placental blood gave identical results comparing tube with gel methods.Conclusions: Placental blood is suitable for pre-transfusion testing and can replace heel sticks. Placental blood tube and gel methods are validated.

Acute kidney injury and nephrotic syndrome associated with eltrombopag therapy in chronic idiopathic thrombocytopenic purpura

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

Immune Hemolysis after a Hematopoietic Progenitor Cell Transplantation for Sickle Cell Disease: A Case Report

Background:The incidence of Delayed Hemolytic Transfusion Reaction (DHTR) is 0.04% but is higher in patients with sickle cell disease (SCD). Although it has been reported in hematopoietic progenitor cell (HPC) transplantation, its incidence in SCD following nonmyeloablative HPC transplantation remains unknown. We report a recipient with blood group O who received a nonmyeloablative HPC transplantation with blood group A three years ago. She is now typing as blood group A and developed a DHTR after receiving group A red blood cells (RBC). Case Report:A 42-year-old female was transferred from an outside hospital (OSH) for management of Acute T-Cell Lymphoblastic Leukemia. Three years prior, she received a group A+ matched sibling nonmyeloablative HPC transplantation for SCD. Her original blood group was O+, and she had a history of clinically significant RBC alloantibodies (anti-E, anti-C, anti-Goa, anti-Kell, and anti-Jkb). On admission to OSH (Day 1), the type and screen showed group A+ without ABO discrepancy. The antibody screen was negative. The OSH blood bank was unaware of her immunohematologic history, because it was not communicated to them by the OSH hematologists, and the only documented diagnosis was that of acute leukemia. Per SOP, OSH performed only immediate spin crossmatch. She was transfused three units of A+ RBC at OSH in preparation for her transfer to us on Day 3 (Fig. 1). At admission to our hospital, her laboratory parameters were suggestive of both tumor lysis syndrome and hemolysis. Her type and screen specimen was grossly hemolyzed. She typed as Group A+. The Direct Antiglobulin Test (DAT) was positive with polyspecific antisera, positive for IgG and negative for bound complement factors. Antibody screen was negative except for the anti-Goa. In the eluate, we identified anti-A or anti-A,B, which were not differentiated for lack of clinical implications. Per our request, OSH retrospectively performed a pre-transfusion DAT, which was negative, and an AHG crossmatch of the pre-transfusion sample. The results showed that the RBC transfused at OSH on Day 1 were incompatible (1+) and those transfused on Day 2 after O+ platelet transfusion were compatible (Fig. 1). This confirmed that the eluted antibodies were not passively transferred from the platelet transfusion but were rather isoagglutinins from the patient's own plasma of her original blood type O. Chimerism studies indicted the presence of only 25% donor CD3 and 30% donor myeloid cells. Further studies at our institution confirmed the hemolysis to be due to anti-A/A,B and not anti-Goa. Antibody titers of the patient's plasma with A1 and A2 cells were low (1) and negative, respectively. The titer of the eluate with A1 cells and B cells was 4 and 2, respectively. The crossmatch of the patient's plasma with A1 cells was negative at immediate spin and 37oC but positive at the IgG phase, which explains the negative crossmatch at immediate spin at OSH. We believe that the exposure of the 2 incompatible A+ RBC at OSH prompted an anamnestic response, causing the hemolysis of the transfused RBC. Subsequently, the patient required the transfusion of 3 additional RBC. Due to the presence of positive DAT developed after 24 hours of transfusion (on Day 3), the positive elution test, inadequate rise of post-transfusion Hb level and rapid fall in Hb back to the concentration pre-transfusion (Fig. 1), this reaction is best classified as a definitive DHTR in accordance with the CDC hemovigilance guidelines. Conclusion:This case is a warning for the perfect storm from the combination of HPC transplantation and SCD. Our patient had a history of transplantation for SCD and clinically significant alloantibodies. OSH blood bank was not aware of her immunohematologic history, and she received incompatible RBC units that were crossmatched at immediate spin only. She subsequently developed a DHTR which was clinically significant, requiring blood transfusion. This is a good reminder of the importance of good communication between clinicians and the transfusion services. The need for caution when using electronic crossmatch or immediate spin is also important, especially in this era of transplantation for SCD. The absence of RBC antibodies cannot be assumed when a transfusion history is lacking. Increasing awareness, prevention and early recognition and treatment are essential to avoid the potential fatal complication of hemolytic transfusion reactions. Disclosures No relevant conflicts of interest to declare.

Passive Transfer Of Allo-Antibodies Following Rhig Administration Given For Rh-Mismatched Platelets Prophylaxis

Introduction/Objective Human platelets (PLTs) do not express any Rh system antigens; however, PLT concentrates can be contaminated with small amounts of red blood cells (RBCs), which may induce alloimmunization when transfused to Rh(D)-negative individuals. RhIG has been utilized to prevent Rh(D) alloantibody development following transfusion of Rh mismatched PLTs. RhIG is manufactured using pooled plasma of healthy Rh(D)-negative donors, with the most common Rh haplotype being ce; treated subjects are exposed to Rh (D)-positive RBCs, with the most common Rh haplotype of donors being DCe. In this report, we detail our experiences with recipients of Rh mismatched apheresis PLTs who were noted to develop anti-D + anti-C post-RhIG administration. Methods Retrospective review was conducted of all Rh mismatched PLTs between December, 2018 and May, 2019 at our facility (Yale-New Haven Hospital, New Haven, CT). Inclusion in the study required: Rh(D)-negative donor receiving one or more Rh(D)-positive apheresis PLTs, Receiving RhIG, &gt;1 antibody screen following RhIG administration demonstrating antibodies other than anti-D Results Our retrospective review identified 8 unique recipients of Rh mismatched apheresis PLTs who acquired anti- C, in addition to the expected anti-D, following administration of RhIG. The product (Rhophylac) was administered in all cases intravenously at a dose of 1500 IU (300 mcg) within 72 hours following Rh mismatched PLTs. In all patients, routine screening following RhIG simultaneously detected anti-D and anti-C 1-3 days after administration of Rh mismatched PLTs/RhIG, the antibody screen remained positive for a range of 27-167 days for both antibodies. Conclusion Based on this case series, which represented entirely men and older women, and coupled with emerging evidence about the extremely low likelihood of D-alloimmunization following Rh mismatched apheresis PLTs,2,3,6 we have changed our practice, limiting immunoprophylaxis for Rh mismatched platelets exclusively to women of reproductive age. The blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible when RhIG is dosed and could account for newly-detected non-D alloimmunization events. This phenomenon is another compelling reason to limit RhIG exposure to cases where it is only absolutely clinically necessary.7

Anti-M–Induced Delayed Hemolytic Transfusion Reaction

Background Anti-M is most often assumed to be naturally occurring and can be comprised of a mixture of predominantly immunoglobulin(Ig)M with a lesser IgG component. Anti-M-antibodies usually do not react at 37°C and therefore are considered to be of little clinical significance. Methods A 28-year-old man presented with hemorrhagic shock from numerous injuries sustained in a motor vehicle collision. The patient received several units of red blood cells (RBCs). The antibody screen, the direct antiglobulin test (DAT), and the RBC genotype were sent for laboratory evaluation. Results A total of 12 days after the first antibody screening result was negative (7 days after transfusion), the lowest hemoglobin value was 5.5 g per dL, and we observed a positive antibody screening result and DAT with immunoglobulin (Ig)G anti-M identified. After transfusion of 4 units of M antigen–negative RBC, the post-transfusion hemoglobin level increased to 8.9 g per dL. Conclusion Obtaining M antigen–negative compatible RBCs is necessary in patients demonstrating IgG anti-M in plasma.