Red blood cell alloimmunisation after platelet transfusion (excluding ABO blood group system).

Red blood cell alloimmunisation after transfusion of red blood cell concentrates carries a risk for every recipient. This risk is particularly high for patients with conditions such as sickle cell disease. However, red blood cell alloimmunisation can also occur after platelet concentrate transfusion. All blood group systems other than ABO are affected, and there are several mechanisms responsible for this alloimmunisation. The practical implications of this are a need to match red blood cell concentrates in all alloimmunised patients and, in pregnant women, recongnition of the risk of developing haemolytic disease of the foetus and newborn. Several measures can be taken to prevent alloimmunisation: in the case of the D antigen, for example, anti-RhD immunoglobulins can be infused before transfusing platelet concentrates from an RhD-positive donor in a RhD-negative recipient.

Adverse transfusion reactions with neurological signs in transfused patients.

OBJECTIVES: Many transfused patients present severe, sometimes critical, clinical conditions. The occurrence of adverse transfusion reactions may cause the clinical condition to deteriorate. A study was conducted aimed at establishing whether the presence of neurological signs during an adverse transfusion reaction increases its severity. METHODS: From 1 January 2010 to 30 June 2019, adverse reactions with neurological signs were extracted from the French haemovigilance database system. Two signs observed at the time of the reaction were analysed: unconsciousness and convulsions. Stroke was excluded. The type of reaction, its severity, the blood product involved and its imputability were all studied. RESULTS: During the study period, 10,670 reactions were reported, including 20 (0.19%) imputed to the transfusion with unconsciousness and/or convulsions. Unconsciousness without convulsions was frequently observed (14 reports, 70.0%). Convulsions were reported in 5 cases (25.0%), with 1 case being associated with unconsciousness. Unconsciousness and/or convulsions were present in 9 allergic reactions (45.0%) and 4 transfusion-associated circulatory overloads (20.0%). Nine reactions were severe (45.0%), 7 were life-threatening (35.0%) and 1 case resulted in the recipient's death (5.0%). A red blood cell and a platelet concentrate transfusion were involved in 8 reactions (40.0%) each, although the imputability of the blood product was certain in only 2 of the reactions. CONCLUSION: Unconsciousness and/or convulsions were rarely observed in adverse reactions reported in transfused patients. Nevertheless, the presence of these signs highlights the severity of the adverse reactions (17 reactions, 85.0%).

Adverse transfusion reactions in transfused children.

Transfusion in paediatrics requires specific guidelines, because child physiology and pathology differ significantly as compared to adults. Adverse transfusion reactions in transfused children also vary in type and frequency, but there is a better understanding of these reactions in adults than in children. However, for the most frequent adverse transfusion reactions, the overall prevalence is higher in children than in adults, with the exception of post-transfusion red blood cell alloimmunisation, which is lower, excluding patients with haemoglobinopathies. In several studies, allergic reactions were the most frequently reported adverse transfusion reaction in paediatrics, and the platelet concentrate the most frequently implicated blood product. Early diagnosis of certain adverse transfusion reactions such as haemosiderosis, is essential in order to initiate the best therapy and obtain a good clinical outcome. The prevention of adverse transfusion reactions in children is required, but needs further clinical studies in paediatrics. Lastly, changes in technology, policy and clinical practices will improve transfusion safety in children.

Adverse transfusion reactions in recipients transfused in out-of-hospital.

OBJECTIVES: Transfusion in environments other than inpatient hospitalisation requires a specific management of the patient, particularly concerning adverse transfusion reactions. A three-year study was carried out in order to appreciate the nature of adverse transfusion reactions and their incidence in these patients. MATERIAL AND METHODS: Adverse transfusion reaction reports of outpatient clinic, ambulatory hospital, health and dialysis centres and home-transfused patients in the Auvergne Rhône Alpes region were obtained. Diagnosis of adverse transfusion reactions, their incidence, their degree of severity, the imputability of the blood component concerned were evaluated. RESULTS: From 1 January 2014 to 31 December 2016, 3,284 reports were notified. Excluding allo-immunisations, 416 reports were obtained, including 376 (90.4%) in outpatient clinic. The febrile non-haemolytic transfusion reaction was the most frequent adverse transfusion reaction (119 cases, 28.6%) followed by allergy (112 cases, 26.9%). A transfusion-associated circulatory overload was notified in 26 cases (6.3%). Among the 416 reports, 363 were non-severe and in 251, a red blood cell concentrate was involved (60.3%). The imputability of the blood product was certain in 50 cases (12.0%) only. CONCLUSION: With the exception of inpatient hospitalisation and allo-immunisation, the majority of adverse transfusion reactions was notified in outpatient clinic. The febrile non-haemolytic transfusion reaction was the most frequent.

Platelet component transfusion and alloimmunization: Where do we stand?

Platelet transfusion in patients, particularly in onco-haematology, is frequent and can become chronic in some cases. Post-transfusion alloimmunization is often seen, in practice. The risk of this is significantly improved in multitransfused patients. Several classes of antigens binding on platelets (HLA and HPA) are involved and also red blood cell antigens (residual red blood cells in platelet concentrates). Platelet alloimmunization causes a poor transfusion response, refractoriness and, more rarely, post-transfusion purpura. In an alloimmunized recipient, the efficiency of platelet transfusion is based on the selection of compatible products. Significant technical progress means that several methods are currently available to ensure a good post-transfusion platelet count and a satisfactory clinical outcome for the patient.

[Adverse transfusion reactions in recipients with anti-vitamin K treatment]. / Effets indésirables transfusionnels chez les receveurs sous médicaments anti-vitamine K.

PURPOSE OF THE STUDY: Vitamin K antagonist treated patients are exposed to a risk of haemorrhage in case of overdose leading to a need for transfusion. In order to determine the incidence of adverse transfusion reactions in these patients, the reports indicating a vitamin K antagonist treatment were analyzed. PATIENTS AND METHODS: In the treated and transfused patient population, the diagnosis following the adverse transfusion reactions, the incidence, the degree of severity, the blood component involved and its imputability were evaluated. RESULTS: From January 1st 2000 to December 31st 2014, 142 reports were notified in 141 patients. Haemorrhage was observed in 102 cases (71.8%). Overdose of anti-vitamin K was reported in 43 cases only (30.3%). The most frequent adverse transfusion reaction was the anti-erythrocyte alloimmunization (66 cases, 46.5%) followed by the febrile non-haemolytic reaction (37 cases, 26.1%). Most adverse reactions were non-severe (131 cases, 92.3%). The most involved blood component was the red blood cells concentrate (139 cases, 97.9%). The imputability of the blood product was certain in 39 cases only (27.5%). CONCLUSION: In patients treated with vitamin K antagonists and transfused, the anti-erythrocyte alloimmunization was the most frequent adverse transfusion reaction. Overdose of the vitamin K antagonists was notified in approximately a third of cases.

[Association of red blood cell and platelet allo-antibodies in platelet alloimmunized patients]. / Association d'allo-anticorps anti-érythrocytaires et anti-plaquettes chez les patients avec allo-immunisation anti-plaquettaire.

PURPOSE OF THE STUDY: Use of matched red blood cell (RBC) concentrates is imperative in patients with RBC allo-antibodies (Abs) and when platelet (PLT) specific allo-Abs are present additional difficulties occur for PLT transfusions. In order to evaluate the prevalence of the PLT and RBC allo-Abs association, a study on patients with PLT specific allo-Acs was performed. This association is not a rare event. PATIENTS AND METHODS: In the database of a PLT immunohaematology laboratory, patients with PLT specific allo-Abs were selected and the presence and specificity of RBC allo-Abs was evaluated. RESULTS: Six hundred and eighty seven patients (673 females, 14 males) with PLT specific allo-Abs were found. Six hundred and seventy-five patients (98.3%) had PLT specific allo-Abs with only one specificity. Anti-HPA-5b was the most frequent (539 cases). Twenty-nine (4.2%) patients had also RBC allo-Abs, including 27 females (93.1%) and two males. Seventy (58.6%) had RBC allo-Abs with only one specificity, 10 several and two unknown. Among the first, RBC allo-Abs directed against Rhesus blood group antigens were predominant (11 cases [64.7%]). Among the 29 patients with associated PLT and RBC allo-Abs, 15 (51.7%) were 50 or more years old and 14 (48.3%) under 50. CONCLUSION: In PLT specific alloimmunized patients, detection of RBC alloimmunization is not a rare event. When RBC and PLT transfusions are required, the supply of matched RBC and PLT concentrates is more difficult.

[Allergic adverse transfusion reactions in paediatrics, a 3-year study]. / Effets indésirables transfusionnels de nature allergique en pédiatrie, étude sur 3ans.

PURPOSE OF THE STUDY: In the transfused patients, in France, in 2011, allergy ranked as the third adverse transfusion reaction. In order to evaluate the incidence and symptomatology of allergic adverse transfusion reactions in the paediatric people, a study was performed. PATIENTS AND METHODS: It was focused on patients under 18years of age cared for in hospitals of the Rhone-Alpes area. The national haemovigilance database (e-FIT) reports of allergic transfusion reactions were reviewed. RESULTS: From January 1st 2009 to December 31st 2011, among 2,165 reports, 141 (6.5%) adverse transfusion reaction reports were collected in paediatric patients. Sixty-eight (48.2%) indicated allergic reactions and corresponded to 64 recipients. As regards clinical manifestations, forty-eight (70.6%) indicated cutaneous signs only, 3 (4.4%) mentioned pulmonary signs only and 9 (13.2%) reported both. Urticaria was observed in 38 cases (55.9%). Bronchospasm was notified in 4 cases but there was no angioedema. As for the severity of reactions, one adverse transfusion reaction was severe (grade 2) and 2 were life-threatening (grade 3). The most involved blood component was the apheresis platelet concentrate (40 cases, 58.8%) followed by the red blood cell concentrate (17 cases, 25.0%) and the methylene blue-treated fresh-frozen plasma (11 cases, 16.2%). CONCLUSION: This study shows that among paediatric recipients, cutaneous signs are predominant in allergic adverse transfusion reactions and that the apheresis platelet concentrate is the most frequently involved blood component.

[Prevalence of platelet-specific antibodies in the recipients of platelet units with transfusion adverse event]. / Prévalence des anticorps antiplaquettes spécifiques chez les receveurs de concentrés plaquettaires avec effet indésirable transfusionnel.

PURPOSE OF THE STUDY: In practice, platelet transfusions are frequently performed in patients with haematologic and/or oncologic diseases. Subsequent to these transfusions, platelet specific antibodies may develop and could induce adverse events, such as platelet transfusion refractoriness or post-transfusion purpura. In order to evaluate the prevalence of platelet specific antibodies in these recipients, adverse events with a request for platelet specific antibodies testing, were studied. PATIENTS AND METHODS: Recipients of platelet units with adverse event, excluding platelet transfusion refractoriness or post-transfusion purpura, were evaluated. RESULTS: From January 1st 2009 to October 31st 2011, 125 adverse events with platelet specific antibodies screening, corresponding to 116 recipients (64 females, 52 males) were included. The main aetiology of the adverse event was a febrile non-haemolytic transfusion reaction in 62 cases (49.6%) and allergy in 40 (32.0%). Most samples tested were post-transfusion solely (101 adverse events, 80.8%). Seven of these samples had free platelet specific antibodies, including four anti-HPA-5b, one anti-HPA-2a and two anti-GPIaIIa. In the cross-match test, platelet specific antibodies were found in two pre-transfusion samples (anti-GP IaIIa) and in five post-transfusion samples (anti-GPIaIIa, three cases; anti-GP IbIX, one case; anti-GP IIbIIIa and -GPIbIX, one case). CONCLUSION: According to this study on platelet transfusion related adverse event, few platelet specific antibodies were detected on pre- and post-transfusion samples. The implementation of platelet specific antibodies testing before transfusion would give more accurate data and help prevent adverse events as typed platelets would be given when platelet specific antibodies were found.

[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.

[Guidelines for blood transfusion teaching to medical laboratory technology students]. / Référentiel d'enseignement de la transfusion sanguine aux étudiants techniciens de laboratoire de biologie médicale.

PURPOSE OF THE STUDY: The new French law about clinical laboratory medicine, the requirements of the ISO/CEI 15189 standard, the numerous abilities expected from the medical laboratory technologists and their involvement in blood bank management has led the working group "Recherche et démarche qualité" of the French Society of Blood Transfusion to initiate an inventory of blood transfusion teaching syllabus for medical laboratory technology students and to propose transfusion medicine teaching guidelines. MATERIAL AND METHODS: Seven worksheets have been established for that purpose including red blood cell antigen typing and antibody screening, blood sampling in immunohaematology, automation, clinical practices, blood products, blood delivery and haemovigilance. RESULTS: These guidelines aim at contributing to the harmonization of transfusion medicine teaching and at providing objective elements to the medical laboratory managers regarding the practical and theoretical skills of theirs collaborators.

[Appearance of anti-red blood cell antibodies in 80 years old and over transfused patients: result of 3 years haemovigilance survey]. / Apparition d'anticorps irréguliers anti-érythrocytaires chez les patients transfusés âgés de 80 ans et plus : résultats du suivi par l'hémovigilance sur trois ans.

PURPOSE: Today most transfusions are given to people over 70. In order to evaluate the production and the circumstances of the appearance of red blood cells (RBC) allo-antibodies (Ab), a three-year study was performed in transfused patients aged 80 and over. MATERIAL AND METHODS: Based on the Adverse Event Reports (AER) on RBC Ab from 2007 to 2009 in the Rhône-Alpes area, the prevalence and specificity of the RBC Ab, the type of blood component involved, the imputability and the previous transfusion and obstetrical history were studied. RESULTS: Of 2,169 AER, 240 (11.1%) related to the appearance of RBC Ab; they included 150 females (F) patients (62.5%) and 90 males (M) (37.5%). The Rhesus (RH) blood group was most involved (75 AER) and anti-E was the most frequent Ab (52 cases; 69.3%). Packed RBC were predominantly involved (233 cases; 97,1%). Absolute imputability could be established in 120 cases only (50.0%). Previous transfusion history was observed in 85 F patients (56.7%) and 52M (57.8%). Pretransfusion Ab was noted in 18 F patients (12.0%) and five M (5.6%). Seventy-three F patients (48.7%) had had a pregnancy but the number of unknown data was high (71 F patients; 47.3%). CONCLUSION: In the transfused patient population aged 80 and over, RBC Ab are common and in most cases are due to RBC transfusions. On the contrary, pretransfusion RBC Ab are not frequent.

Severe HPA-15b related neonatal alloimmune thrombocytopenia.

UNLABELLED: The HPA-15 platelet (PLT) group was recently described. Severe neonatal thrombocytopenia due to alloimmunization by HPA-15b has very rarely been observed. A 22-year-old mother, gravida 1/para 1, gave birth to a male infant who presented with a severe thrombocytopenia, the PLT count recorded to be 3 x10(9)/L. A few hours after birth, he developed purpura with extensive haematomas but without visceral or intracranial haemorrhage (ICH). Two PLT transfusions were given including one using maternal PLTs. The infant's PLT count was 267 x 10(9)/L on day 6. The maternal platelet group was HPA-15a/a and her infant was HPA-15a/b. Anti-HPA-15b antibodies was found in maternal serum. CONCLUSION: HPA-15b maternal alloimmunization may induce severe neonatal thrombocytopenia. In order to establish the frequency of neonatal alloimmune thrombocytopenia (NAIT) due to anti-HPA-15b antibodies, an improved detection method is necessary.

IgA anti-red blood cell auto-antibodies in Evans syndrome.

In Evans syndrome, IgG auto-antibodies (Abs) and/or complement components are frequently detected on red blood cells (RBC) in the direct antiglobulin test (DAT). A 70-year-old man with Evans syndrome diagnosed four years previously presented with a persistent autoimmune haemolytic anaemia, despite immunosuppressive treatment and normalization of platelet count. The RBC allo- and auto-Abs screening and identification were performed by indirect antiglobulin test (IAT) and DAT. In March 2006, no circulating anti-RBC auto-Abs were found in IAT but the DAT was positive with anti-IgG (++), -C3d (weak) and -IgA (++). Follow up for 11 months revealed anti-RBC IgA auto-Abs on five out of six samples. IAT was positive for RBC auto-Abs on three samples. No correlation between the haemoglobin level and the strength of reactivity of IgG and IgA auto-Abs was observed. IgA anti-RBC auto-Abs are present in Evans syndrome. To detect these Abs and characterize their role, DAT procedures should systematically include anti-IgA.

[Intravenous human immunoglobulin treatment for neonatal alloimmune thrombocytopenia due to anti-HPA-5b with severe previous history]. / Traitement par immunoglobulines intraveineuses dans 2 cas d'allo-immunisation foetomaternelle plaquettaire HPA-5b avec antécédents sévères.

Fetal and neonatal alloimmune thrombocytopenia due to mothers' anti-HPA-5b alloimmunization has generally a milder clinical presentation compared to anti-HPA-1a alloimmunization. Nevertheless, a case with infant's death probably due to intracranial haemorrhage has been reported. However, if platelet-specific alloimmunized mothers with prior fetal or neonate injury receive intravenous immunoglobulins during pregnancy, thrombocytopenia in heterozygous fetus and neonate may be prevented. Here are reported 2 cases of anti-HPA-5b fetal-maternal alloimmunization, one with prior fetal death, the other with prior severe fetal intracranial haemorrhage, which were successfully treated with intraveinous immunoglobulins alone during a second pregnancy with HPA-5b incompatibility.

HLA antibodies and neonatal alloimmune thrombocytopenia.

A female baby with a severe thrombocytopenia at 18 x 10(9)/l was born to a 29-year-old (gestation 2/partum 2) mother. Scattered petechiae were present on her legs, arms, chest and face, but there was no bleeding, infection, fever or hepatosplenomegaly. A platelet antibody screening immunocapture test was positive, which was performed on the mother's serum 3, 12 and 38 days after delivery, but no platelet-specific antibodies were found by the monoclonal-antibody-specific immobilization of platelet antigen assay. The baby's platelets and lymphocytes and the father's platelets reacted strongly with the HLA antibodies present in the mother's serum. The neonate was treated with intravenous human immunoglobulin (Tegeline), 1 g/kg per day) 1, 2 and 3 days after delivery. The platelet count rose from 18 x 10(9)/l on day 0 to 37 x 10(9)/l on day 3 and to 227 x 10(9)/l on day 12. No platelet transfusion was needed. Several factors which developed hereafter lead us to think that this neonatal alloimmune thrombocytopenia is due to the transplacental passage of maternal HLA antibodies to the baby.