[Management of high-risk pregnancies in a context of maternal antiplatelet alloimmunization: Expert opinion of the French-speaking working group]. / Prise en charge des grossesses à risque dans un contexte d'incompatibilité fœto-maternelle plaquettaire et/ou d'allo-immunisation : avis du groupe d'experts du GFHT (Groupe français d'études sur l'hémostase et la thrombose).

INTRODUCTION: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800-1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT). OBJECTIVES: The objective was to survey clinical practices for management of high-risk pregnancies in a context of suspected or confirmed FNAIT. METHODS: Recommendations published by the ICTMG were translated in French, and discussed (Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. British J of Haematology, 2019, 185, 549-562). RESULTS: The study involved centers from France, Switzerland and Belgium: Angers, Besançon, Bordeaux, Brest, Créteil/Clamart, Genève, Grenoble, Liège, Lille, Lyon, Marseille, Nantes, Nîmes, Paris (hôpitaux Necker, Robert Debré et Trousseau), Poitiers, Rennes, Saint-Etienne, Strasbourg, Toulouse, Tours. CONCLUSIONS: Expert opinion was validated on September 23, 2020 (consensus≥90%).

Bidirectional graft-host hematological traffic in liver transplantation.

The highly complex immuno-hematological system of the recipient has to rebalance itself when the liver is replaced with a graft that has its own system. This gives us an opportunity for observation. Here we consider the graft-to-recipient direction with passenger lymphocyte syndrome (PLS) as well as the recipient-to-graft direction with Factor VIII (FVIII) inhibitors, paroxysmal nocturnal hemoglobinuria (PNH) and graft endothelial replacement with liver transplantation. PLS extends beyond the ABO blood groups to any situation where the donor has been sensitized to a recipient antigen. PLS directed against ABO or minor blood group antigens is usually self limiting whereas Rhesus (Rh) PLS persists with life threatening immune hemolysis. Human platelet antigen (HPA) 1A PLS results in life threatening immune thrombocytopenia. Treatments of severe PLS may include reduction in immunosuppression, anti-B-cell therapy, plasmapheresis and splenectomy. Liver transplantation into recipients with FVIII inhibitors has been difficult. Donors with acquired hemophilia may transmit the capacity to make FVIII inhibitors by PLS and should be avoided. Patients with PNH have been transplanted successfully but a considerable cost in the continued use of high dose eculizumab. We speculate that combined bone marrow and liver transplantation would be a better option for recipients with FVIII inhibitors or PNH. Replacement of liver graft endothelium with recipient cells is common and may explain relative transplant tolerance that is believed to occur with liver transplantation.

Management of neonatal thrombocytopenia in a context of maternal antiplatelet alloimmunization: Expert opinion of the French-speaking working group.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800-1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. The most feared complication of this disorder is intracranial hemorrhage, leading to death or neurological sequelae. There is no systematic screening of at-risk pregnancies and FNAIT is often discovered when fetal or neonatal bleeding is observed. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT). The first objective of this group was to survey clinical practices for treatment of thrombocytopenic neonates in a context of suspected or confirmed FNAIT.

Human platelet antigens in disease.

Platelets have various functions and participate in primary hemostasis, inflammation, and immune responses. Human platelet antigens (HPAs) are alloantigens expressed on the platelet membrane. Each HPA represent one of six platelet glycoproteins GPIIb, GPIIIa, GPIa, GPIbα, GPIbß, and CD109, and six biallelic systems are grouped. A single nucleotide polymorphism (SNP) in the gene sequence causes a single amino acid substitution of relevant platelet glycoprotein with the exception of HPA-14bw. High-throughput next-generation sequencing-based method has been developed, which enable accurately identification of HPA polymorphisms. The roles of HPA in disease were reviewed. HPAs mediate platelet-microorganism and platelet-malignant cell interactions, and they also participate in pathogenesis of hemorrhagic fever with renal syndrome and infective endocarditis. The exploration of HPA polymorphisms in association with disease susceptibility of individuals will benefit prevention or management of disease.

Human platelet antigens are associated with febrile non-hemolytic transfusion reactions.

BACKGROUND: Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reactions, and it could be reduced by transfusing patients with leukocyte-poor blood products. However, FNHTR still occur in certain patients transfused with leukocyte-poor red blood cell (LPR) products. It is examined whether human platelet antigen (HPA) could be a potential membrane antigen that plays a role in FNHTR. METHODS: A total of 120 inpatient subjects who transfused with LPR (60 in FNHTR group, 60 in control group) were typed for HPA-2, HPA-3, and HPA-15 using sequence specific primer-polymerase chain reaction (SSP-PCR) and electrophoresis. RESULTS: HPA-2 unmatched rate between donors and patients in FNHTR group was 18%, and only 3% unmatched rate was observed in control group (p=0.0082). FNHTR group was further classified according to the imputability. There was a significant difference (p=0.0041) between FNHTR (probable imputability, infection) group and control group, and more significant difference (p=0.0008) was seen between FNHTR (probable imputability, febrile neutropenia) group and control group. CONCLUSIONS: Those results indicated that HPA-2 might play roles on inducing FNHTR in patients suffering from infectious diseases and febrile neutropenia. HPA-2 genotyping between donors and recipients might be worth integrating in pre-transfusion testing to increase transfusion safety.