Masja de Haas

Red cell alloimmunisation in patients with different types of infections.

Red cell alloantigen exposure can cause alloantibody‐associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case–control study within a source population of patients receiving their first and subsequent red cell transfusions during an 8‐year follow‐up period. Patients developing a first transfusion‐induced red cell alloantibody (N = 505) were each compared with two similarly exposed, but non‐alloimmunised controls (N = 1010) during a 5‐week ‘alloimmunisation risk period’ using multivariate logistic regression analysis. Transfusions during ‘severe’ bacterial (tissue‐invasive) infections were associated with increased risks of alloantibody development [adjusted relative risk (RR) 1·34, 95% confidence interval (95% CI) 0·97–1·85], especially when these infections were accompanied with long‐standing fever (RR 3·06, 95% CI 1·57–5·96). Disseminated viral disorders demonstrated a trend towards increased risks (RR 2·41, 95% CI 0·89–6·53), in apparent contrast to a possible protection associated with Gram‐negative bacteraemia (RR 0·58, 95% CI 0·13–1·14). ‘Simple’ bacterial infections, Gram‐positive bacteraemia, fungal infections, maximum C‐reactive protein values and leucocytosis were not associated with red cell alloimmunisation. These findings are consistent with murine models. Confirmatory research is needed before patients likely to develop alloantibodies may be identified based on their infectious conditions at time of transfusion.

RhIg-prophylaxis is not influenced by FCGR2/3 polymorphisms involved in red blood cell clearance

To the editor:nnRed blood cell (RBC) alloimmunization against the RhD antigen may occur in RhD-negative women during pregnancy or at delivery of a RhD-positive child.[1][1] The administration of Rh-immunoglobulin (Rh-Ig) prevents anti-D alloimmunization and subsequent hemolytic disease of the fetus

Immunoglobulin for alloimmune hemolytic disease in neonates

BACKGROUNDnExchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion.nnnOBJECTIVESnTo assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions.nnnSEARCH METHODSnWe performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies.nnnSELECTION CRITERIAnWe considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included.nnnDATA COLLECTION AND ANALYSISnWe used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence.nnnMAIN RESULTSnNine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy.nnnAUTHORS CONCLUSIONSnAlthough overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

With its unique anatomy and location amidst the circulatory system, the spleen allows an intimate contact between its resident cells and blood passing through the organ. Senescent and damaged red cells are primarily sequestered in the splenic red pulp and consumed by its macrophages.[1][1]

Women's attitude towards routine human platelet antigen-screening in pregnancy

Fetal and neonatal alloimmune thrombocytopenia is a potentially life‐threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population‐based screening program has been suggested repeatedly. Therefore, we aimed to evaluate womens attitude towards possible future human platelet antigen‐screening in pregnancy.

Facilitators and barriers for RhD-immunized women to become and remain anti-D donors

The successful introduction of prophylaxis with anti‐RhD immunoglobulin has resulted in a significant decline of pregnancy‐related RhD immunizations but also has decreased the availability of naturally immunized women as (new) anti‐D donors. An influx of new donors is necessary to maintain a sufficient pool of anti‐D donors. We investigated motivators, barriers, and predictors for anti‐D donorship in RhD‐immunized women.

ABO incompatibility and RhIG immunoprophylaxis protect against non-D alloimmunization by pregnancy: PREVENTION OF NON-D IMMUNIZATION

Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies against fetal red blood cell antigens, most often anti‐D, ‐K, or ‐c. ABO incompatibility between mother and child and anti‐D immunoprophylaxis (RhIG) are known to reduce the risk of D immunization and subsequent HDFN. However, no immunoprophylaxis has been developed to prevent non‐D immunizations.

Acute hemolytic transfusion reaction due to a warm reactive anti-A1 : STRONG ANTI-A1 AGGLUTININS

Anti‐A1 are regularly observed by reverse testing and are generally considered clinically irrelevant. For compatibility testing and the selection of blood, we use the type‐and‐screen (T&S) strategy, in which ABO confirmation of patients with a definitive blood group is performed by forward grouping only. Because anti‐A1 seem clinically irrelevant, it is our policy to provide group A blood in patients with an anti‐A1.

The near disappearance of fetal hydrops in relation to current state‐of‐the‐art management of red cell alloimmunization

In this study, we aim to evaluate trends in the condition of fetuses and neonates with hemolytic disease at the time of first intrauterine transfusion (IUT) and at birth, in relation to routine first‐trimester antibody screening, referral guidelines, and centralization of fetal therapy.

A subset of anti-HLA antibodies induces FcγRIIa-dependent platelet activation

HLA antibodies are associated with refractoriness to platelet transfusion, leading to rapid platelet clearance, sometimes coinciding with clinical side effects such as fever and chills. The presence of HLA antibodies is not always manifested by clinical symptoms. It is currently unclear why refractoriness to platelet transfusion is only observed in a subset of patients. Here, we utilized the availability of a unique panel of human monoclonal antibodies to study whether these were capable of activating platelets. Three out of eight human HLA-specific monoclonal antibodies induced activation of HLA-matched platelets from healthy donors as evidenced by enhanced α-granule release, aggregation, and αIIbb3 activation. The propensity of HLA monoclonal antibodies to activate platelets was independent of the HLA subtype to which they were directed, but was dependent on the recognized epitope. Activation was fully inhibited either by blocking FcγRIIa, or by blocking FcγRIIa-dependent signaling with Syk inhibitor IV. Furthermore, activation required the presence of the IgG-Fc part, as F(ab’)2 fragments of HLA monoclonal antibodies were unable to induce platelet activation. Mixing experiments revealed that activation of platelets occurred in an intra-platelet dependent manner. Accordingly, a proportion of sera from refractory patients with HLA antibodies induced FcγRIIa-dependent platelet activation. Our data show that a subset of HLA antibodies is capable of crosslinking HLA and FcγRIIa thereby promoting platelet activation and enhancing these cells’ phagocytosis by macrophages. Based on these findings we suggest that FcγRIIa-dependent platelet activation may contribute to the decreased platelet survival in platelet-transfusion-dependent patients with HLA antibodies.