Adverse reactions following transfusion of blood components, with a focus on some rare reactions: Reports to the International Haemovigilance Network Database (ISTARE) in 2012-2016.

OBJECTIVES: The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. MATERIALS AND METHODS: National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. RESULTS: Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. CONCLUSIONS: ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.

Delayed hemolytic transfusion reaction in the French hemovigilance system.

In France, reporting of adverse events related, or likely to be related, to transfusion is mandatory. Since its creation in 1993, the French hemovigilance system has contributed to a better recognition of unappreciated risks like delayed hemolytic transfusion reactions (DHTR) in sickle-cell disease (SCD) patients. Long under-reported or misclassified, reports of this serious complication of transfusion have improved, particularly through the dissemination of information within the hemovigilance network. To our knowledge, the French hemovigilance system has one of the largest series of DHTR in SCD patients. Guidelines for diagnosis and reporting to hemovigilance system as well as a specific reporting form are being developed, which should contribute to the quality of data essential for epidemiological studies.

[Delayed hemolytic transfusion reaction in sicle cell disease patients: a new challenge for the Hemovigilance network]. / Les hémolyses retardées post-transfusionnelles chez les patients drépanocytaires : un nouveau défi pour le réseau d'hémovigilance.

Delayed hemolytic reaction transfusion in patients with sickle cell disease (SCD) is a serious and still under diagnosed event. Clinical and biological presentation mimics an acute SCD complication. It is a life-threatening event, especially in hyperhemolysis syndrome (HS) characterized by a massive destruction of both the donor's and patient's red blood cells. The main cause is related to the presence of alloantibodies directed against red blood cell antigens, more rarely autoantibodies. In approximately a third of the cases, no new antibody is highlighted. Pathophysiological hypotheses are still under debate but most of the authors agree on the role played by the SCD inflammatory state. Several therapeutic approaches are used but the data are still insufficient to estimate their efficiency. It is admitted that a new transfusion may exacerbate the phenomenon and the benefit-risk of any transfusion must be carefully evaluated. Measures limiting alloimmunization and rigorous follow-up of SCD patients and their immunohematologic status can prevent some of these accidents. The Hemovigilance network has a role to play in the recognition and the description of this risk. A first analysis realized on the French national Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM) over the period 2000-2013, shows us interesting information but some inadequacies, described here, must be taken into account to strengthen these data and insure in the future a better reporting quality.

Impact of HLA mismatch direction on outcomes after umbilical cord blood transplantation for hematological malignant disorders: a retrospective Eurocord-EBMT analysis.

HLA matching is a critical determinant of outcomes for patients who have undergone umbilical cord blood transplantation (UCBT). Data have been published on the importance of donor/recipient HLA mismatch direction on UCBT outcomes. HLA mismatch in the graft-versus-host (GVH) direction is defined as a donor homozygous at an HLA locus, while the recipient shares one HLA Ag with the donor. HLA mismatch in the host-versus-graft (HVG) direction is defined as a recipient homozygous with the donor sharing one HLA Ag. In our study we focused on confirming, using an independent population, whether transplantation outcomes would be different when HLA mismatch direction was considered. We analyzed 1565 patients who received a single-unit UCBT for malignant disease. Median age was 15 years and 72% of patients were transplanted for leukemia. In multivariate analysis, using the 5/6 HLA-matched population as reference, one or two HLA mismatches in the GVH or HVG direction were not associated with non-relapse related mortality and survival. On the basis of our results, there is no evidence to support a change in the current practice for cord blood unit selection.

[Transfusion and allergy]. / Allergie et transfusion.

Hypersensitivity or allergic reactions can occur after transfusion of any kind of blood products. They represent the second or third causes adverse events related to labile blood product administration. This review summarizes their physiopathology, and the current guidelines regarding their diagnosis and treatment.

[Transfusion-associated circulatory overload]. / Œdèmes aigus pulmonaires de surcharge post-transfusionnels.

A working group of the French National Hemovigilance Committee has been in charge of heightening awareness of Transfusion-Associated Circulatory Overload (TACO) among physicians and nurses. This multidisciplinary group has produced the present document that focuses on epidemiological data provided by the French haemovigilance network, physiopathology, diagnosis, treatment and specific actions that could prevent or minimize the risk of TACO.

[Factsheets: support in the analysis of recipients' adverse reactions]. / Fiches techniques: aide à l'analyse des effets indésirables receveurs.

In order to help the analysis of adverse effects of transfusion, factsheets have been written by working groups of the French agency for the safety of health products ANSM. Each factsheet deals with a blood transfusion side effect and is composed of five parts, including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules for filing the notification form to ANSM. Since 2006, 11 factsheets have been published on the French haemovigilance network website. The major characteristics of the two last sheets published "post-transfusion purpura" and "non erythrocyte incompatibility reaction" are presented, followed by the updated card for "allergy". These factsheets give relevant guidelines allowing better evaluation of recipients' adverse reactions, particularly their diagnosis, severity and accountability. They also could initiate studies among European and international haemovigilance networks.

KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia.

Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS.