I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation.

BACKGROUND AND OBJECTIVES: ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. METHODS: The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. RESULTS: Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. CONCLUSION: With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

A prospective observational study to compare transfusion outcomes in ABO identical versus ABO non-identical single donor platelet concentrates: An experience from a tertiary healthcare center in India.

ABO incompatible single donor platelet concentrates (SDPC) have a concern about unsatisfactory increments as well as possibility of hemolytic transfusion reaction. But from Indian population no study has commented on the clinical and laboratory outcome of ABO mismatched platelet transfusion. The aim of study was to compare transfusion outcomes in ABO identical versus ABO non-identical single donor platelet concentrates. In this prospective observational study, 400 SDPC transfusions among different patients were included. In group A (n=200), ABO identical SDPC transfusions and in group B (n=200) ABO non-identical SDPC transfusions were added. Corrective count increment (CCI), absolute count increment (ACI), percent platelet recovery (PPR) were calculated and incidents of hemolytic transfusion reactions were noted. In group A mean±SD of ACI, CCI and PPR were as 30.78±12.51, 15.10±6.677, 39,948.9±20,099.392. In group B, mean±SD of ACI, CCI and PPR were - 25.4±15.65, 12.509±5.906, 33,559.2±22,150.304. And when CCI, ACI, PPR were compared with group A and group B, statistically significant differences were noted (P<0.05). There was statistically significant difference in CCI, ACI and PPR in oncology patients and other prophylactic recipients except patients with dengue and other infectious disease. But there was no hemolytic transfusion reaction noted in any group. Our study clearly establish the potential benefits of ABO-identical PLT transfusion. It also points out that in emergency conditions or when there is a paucity in inventory, ABO non-identical SDPC transfusion may be lifesaving and clinically significant.

Therapeutic apheresis in ABO-incompatible kidney and liver transplantation: A single-center experience of 50 patients.

ABO antigens play an important role in solid organ transplantation. Desensitization for ABO incompatibility offers patients awaiting transplant a larger donor pool. The aim of this study was to assess outcome of desensitization using the institutional preconditioning protocol in ABO-incompatible solid organ transplants. A retrospective analysis of ABO-incompatible solid organ transplants between October 2015 and June 2018, at a tertiary healthcare center was performed. The preconditioning regimen consisted of immunosuppression and therapeutic apheresis (TA). Pre- and post-TA titers were performed, until a target titer of 8 or below was achieved, at which transplant was performed. Follow-up data till 1 year was analyzed. A total of 50 ABO-incompatible solid organ transplantations, including 14 liver transplants and 36 renal transplants were analyzed. The median baseline anti-A and anti-B titers were 192 and 256, respectively. A total of 150 therapeutic plasma exchange (TPE) procedures were performed for renal transplant recipients; 19 TPE and eight immunoadsorption procedures (five preoperative and three intraoperative) were performed for liver transplant recipients. Five (10%) patients experienced minor adverse events. Biopsy revealed antibody-mediated rejection was observed in three cases in the immediate posttransplant phase and in three (6.67%) cases over 1 year. There was one death due to transplant-associated thrombotic microangiopathy. Graft survival for renal transplant was 100% and death-censored graft survival for liver transplant was 100%. Despite difficulties, ABO-incompatible transplants can be performed without antibody-mediated rejection with the use of an appropriate protocol.

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases.

BACKGROUND AND AIMS: Preconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility. MATERIALS AND METHODS: This was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant. RESULTS: Median and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15-42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression. CONCLUSION: Simultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.

Red blood cell exchange in sickle cell disease patient with multiple alloantibodies.

There are several reports in medical literature about Red Cell Exchange (RCE) being routinely performed pre-operatively in sickle cell disease patients to provide immediate decrease in HbS concentration and prevent post-operative complications. We would like to present one such case of SCD who also had multiple allo-antibodies and had to undergo hemi-arthroplasty for avascular necrosis of head femur. Grouping and antibody screening was performed using column agglutination technique. 3-cell and 11- cell panel were used for antibody screening and identification, respectively. Automated RBC exchange was performed on apheresis machine Com. Tec using the standard PL1 kit (Fresenius Kabi, Germany). Multiple (anti-c, E) allo-antibodies were identified and successful pre-operative RCE was done with corresponding antigen-negative AHG compatible RBC units. Single RCE procedure reduced HbS concentration from 65% to 25%. The patient underwent uneventful hemi-arthroplasty and was discharged on post-operative day-7. Patient is on regular follow-up and continues to do well two months after the day of surgery. This is possibly the first case report from India, which illustrates successful automated RCE in a SCD patient with alloimmunization.

Outcome of donor lymphocyte infusion for fall in chimerism after hematopoietic stem cell transplant.

Achievement of complete donor chimerism after an allogeneic hematopoietic stem cell transplant is necessary for elimination of underlying malignant disease. A decline in donor chimerism may herald an impending relapse and therefore, early recognition and intervention plays an important role in such cases. A 32 year old male patient diagnosed as a case of Philadelphia positive mixed phenotypic acute leukaemia underwent peripheral blood hematopoietic stem cell transplant (HSCT) with his sibling as donor. During follow-up, a fall in donor chimerism was observed from 91.86% on day +37 to 88.83% on day +57 and 85.34% on day +77. Donor Lymphocyte Infusion (DLI) was harvested via apheresis. A dose of 1 × 106 per kg was infused and the rest was cryopreserved in aliquots of escalating doses. On day +102, he presented with biopsy proven acute mucocutaneous GVHD grade 2 which was managed conservatively and donor chimerism of 57.99%. On day +126, a repeat donor chimerism was performed which showed 100% chimerism. He continues to do well at day +161. Timely use of DLI can improve donor chimerism in patients with Philadelphia positive acute leukaemia who tend to relapse after HSCT.

Utility of grey zone testing strategy in transfusion transmissible infection testing in blood bank is of limited value!

Several blood banks use grey zone (GZ) phenomenon (defined as samples with optical density within 10% below the cut off in enzyme immuno-assay [EIA]/chemiluminescence immunoassay [CLIA]) to further augment blood safety. There is paucity of data regarding usefulness of GZ sample and its application in Transfusion Transmissible Infection (TTI) screening procedures in blood transfusion services. We looked at our GZ sample results and their confirmatory test results to verify if it adds to blood safety in our set-up? We performed a prospective analytical study on blood donors' samples over two years. All the donors' samples were screened for TTI using CLIA. Samples with signal/cut-off ratio between ≥0.90 and <1.00 were classified under GZ. They were re-tested in duplicate and submitted to confirmatory testing: Neutralization Test for HBsAg, Immunoblot for HCV, and Western blot for HIV. Among the 50,064 blood donors donating the blood during study period, 573 (1.14%) donors were reactive for HBsAg, HCV, and HIV. Forty-seven (0.1%) TTI samples were GZ, but none was "confirmed positive." The utility of GZ testing seems to be limited. However, this may be continued for sake of "erring on the side of caution" and since this only results in negligible wastage (0.1%) of blood units.

A prospective, observational study for optimization of antibody screening in pretransfusion compatibility testing.

CONCLUSIONS: Despite known use of antibody screening (AS), it has not been adopted uniformly across blood centers in India. Many centers in India are currently using a type and hold policy with subsequent antihuman globulin (AHG) crossmatch when blood units are requested. The main aim of this study was to assess the benefits of a type and screen (TS) policy in which blood grouping and AS are performed simultaneously during the first hospital visit. If the AS is negative, subsequent requests for blood units would require an immediate spin test (IST) crossmatch with release of blood units, followed by an AHG crossmatch. This prospective, observational study was conducted at a tertiary health care center between July 2014 and December 2018 and included only Indian patients. Blood grouping and AS were performed during the first hospital visit on a total of 22,888 patients; the majority of patients were from hemato-oncology and blood marrow transplant, hepatology and liver transplant, cardiothoracic vascular surgery, and medical intensive care units. Demographic parameters were evaluated for risk of alloimmunization, and a record of the same was maintained. Depending on the AS results, a further course of action was chosen. Clinically significant alloantibodies were detected in 145 patients, and autoantibodies were detected in 53 patients. Alloantibodies were mainly against Rh and Kell blood group antigens. A significantly higher proportion of patients in the AS+ group required blood transfusion when compared with the AS- group. In cases wherein the IST crossmatch was compatible but AHG crossmatch was not, follow-up did not demonstrate any clinical or laboratory evidence of hemolysis. AS is a safe, efficient, and beneficial tool for pretransfusion compatibility testing in both AS+ and AS- patients. With a TS policy, AHG crossmatch can be omitted in AS- patients without compromising safety.

Blood component administration to multiple myeloma patients treated with daratumumab: suggesting a novel approach with use of 0.1 M dithiothreitol.

CONCLUSIONS: Storage of dithiothreitol (DTT)-treated red blood cells (RBCs) leads to hemolysis. The aim of this study was to compare 0.1 M DTT with 0.2 M DTT treatment of RBCs and to share our experience of providing components to seven patients on daratumumab (DARA). This prospective, observational study included patients who required RBC transfusion within 6 months of DARA administration. All patients underwent a baseline serologic evaluation followed by a repeat evaluation after DARA administration. In addition, use of 0.1 M DTT was compared with 0.2 M DTT in terms of concordance of results, hemolysis with storage of treated RBCs, and ease of use. A total of 22 RBC requisitions were received for seven patients. Antibody screen was positive for one patient (anti-C) at baseline; it was panreactive for all patients after DARA. Concordance of results between the two concentrations was 98.5 percent. Laboratory personnel found results obtained with use of 0.1 M DTT-treated RBCs easy to interpret. Supernatant hemoglobin was found to be significantly greater for 0.2 M DTT-treated RBCs at the sixth day of storage. In conclusion, component administration to patients on DARA can be done without delay if adequate policies and procedures are in place. Use of 0.1 M DTT-pretreated RBCs can be used to avoid delay in transfusion and reduce the burden on the laboratory of weekly preparation of 0.2 M DTT-treated RBCs.