Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

Management and outcome of pregnancies in women with red cell isoimmunization: a 15-year observational study from a tertiary care university hospital.

BACKGROUND: The aims of this study were to determine the prevalence of the different anti-erythrocytic alloantibodies, to describe pregnancy outcomes according to a low-risk and high-risk classification for fetal anemia and to determine the factors that influence adverse perinatal outcomes. METHODS: This retrospective observational study included women referred to our center following the identification of maternal anti-erythrocytic alloantibodies between 2002 and 2017. Pregnancies were classified as high risk for fetal anemia in cases with clinically significant antibodies, no fetal-maternal compatibility and titers ≥1:16 or any titration in cases of Kell system incompatibility. In high-risk pregnancies, maternal antibody titration and the fetal middle cerebral artery peak systolic velocity (MCA-PSV) were monitored. Low-risk pregnancies underwent routine pregnancy follow-up. RESULTS: Maternal antibodies were found in 337 pregnancies, and 259 (76.9%) of these antibodies were clinically significant. The most frequent antibodies were anti-D (53%) and anti-K (19%). One hundred forty-three pregnancies were classified as low risk for fetal anemia, 65 (25%) cases were classified as no fetal-maternal incompatibility, 78 had clinically nonsignificant antibodies, 4 (2.8%) resulted in first-trimester pregnancy loss, and 139 (97.2%) resulted in livebirths. Of the 194 high-risk pregnancies, 38 had titers < 1:16 (resulting in 38 livebirths), and 156 had titers ≥1:16 or anti-K antibodies. In the last group, 6 cases miscarried before 18 weeks, 93 had a MCA-PSV < 1.5 multiples of the median (MoM), resulting in 3 perinatal deaths that were unrelated to fetal anemia, one termination and 89 livebirths; and 57 had a MCA-PSV > 1.5 MoM, resulting in 3 intrauterine deaths, 6 terminations and 48 livebirths. Ninety-two intrauterine transfusions were performed in 45 fetuses (87% anti-D). Adverse outcomes were related to a MCA-PSV > 1.5 MoM (p < 0.001), hydrops (p < 0.001) and early gestational age at first transfusion (p = 0.029) CONCLUSION: Anti-D remains the most common antibody in fetuses requiring intrauterine transfusion. A low or high-risk classification for fetal anemia based on the type of antibody, paternal phenotype and fetal antigen allows follow-up of the pregnancy accordingly, with good perinatal outcomes in the low-risk group. In the high-risk group, adverse perinatal outcomes are related to high MCA-PSV, hydrops and early gestational age at first transfusion.

Caracterización de donantes de sangre con rastreo de anticuerpos irregulares positivo en Montería, Colombia 2012-2015 / Blood donors characterization with positive irregular antibodies in Montería, Colombia 2012- 2015

Introducción: Los anticuerpos irregulares corresponden a aquellos distintos a los anticuerpos naturales anti-A o anti-B, los cuales pueden aparecer en respuesta a la exposición a un antígeno eritrocitario extraño (transfusión o trasplante) o por incompatibilidad materno-fetal. Objetivo: Caracterizar a los donantes con rastreo de anticuerpos irregulares positivo de un banco de sangre de Montería, Colombia, durante el periodo 2012-2015. Métodos: Estudio transversal y retrospectivo, con fuente de información secundaria, basada en los resultados del rastreo de anticuerpos en los donantes de un banco de sangre de Montería, Colombia, entre los años 2012 y 2015. La población estuvo conformada por todos los donantes voluntarios registrados en el tiempo del estudio (35 248 donantes), a quienes se les realizó rastreo de anticuerpos. Como muestra, se seleccionaron todos los casos que tuvieron resultados positivos (71 donantes). Los datos fueron organizados en tablas y analizados en el software SPSS 21.0, Microsoft Excel y en Epidat versión 3.1. Resultados: El 0,2 por ciento de la población presentó un rastreo de anticuerpos positivo con un intervalo de confianza entre 0,15 y 0,25 por ciento. Los anticuerpos irregulares fueron más frecuentes en los hombres y en donantes O Rh positivo. Se encontraron Ac irregulares con 13 especificidades diferentes, con predomino de anti-M, anti-Lea, anti-D y anti-E y porcentajes respectivos de 27,78 por ciento, 20,83 por ciento, 9,72 por ciento y 8,33 por ciento. El 50 por ciento de los donantes tenía 30,5 años o menos, el 49,3 por ciento había donado previamente y el 9,9 por ciento recibió al menos una transfusión en algún momento de su vida. Conclusión: La frecuencia de donantes con rastreo de anticuerpos irregulares positivo fue baja, el sexo masculino presentó mayor porcentaje, se detectó principalmente en el grupo sanguíneo O y dentro de los anticuerpos irregulares, anti-M presentó una mayor frecuencia(AU)

Introduction: Irregular antibodies correspond to those other than natural anti-A or anti-B antibodies, which may appear in response to exposure to a foreign erythrocyte antigen (transfusion or transplantation) or due to maternal-fetal incompatibility. Objective: To characterize the donors with positive irregular antibody screening of a blood bank in Monteria, Colombia during the period 2012-2015. Methods: Cross-sectional and retrospective study, with secondary information source, based on the results of the antibody screening in donors of a blood bank in Monteria, Colombia from 2012 to 2015. The population consisted of all voluntary donors registered in the study time (35 248 donors), who were screened for antibodies. As a sample, all cases that had positive results (71 donors) were selected. The data was organized in tables and analyzed in the software SPSS 21.0, Microsoft Excel and in Epidat version 3.1. Results: 0.2 percent of the population presented a positive antibody screen with a confidence interval between 0.15 and 0.25 percent Irregular antibodies were more frequent in men and in O Rh positive donors. Thirteen types of irregular antibodies were found, with predominance of anti-M, anti-Lea, anti-D and anti-E and respective percentages of 27.78 percent, 20.83 percent, 9.72 percent and 8.33 percent. 50 percent of the donors were 30.5 years old or less, 49.3 percent had previously donated and 9.9 percent received at least one transfusion at some point in their lives. Conclusion: The frequency of donors with irregular positive antibody screening was low, the male sex had a higher percentage, it was detected mainly in blood group O and within the irregular antibodies, anti-M showed a higher frequency(AU)

Polyclonal anti T-lymphocyte antibody therapy monitoring in kidney transplant recipients: comparison of CD3+ T cell and total lymphocyte counts.

OBJECTIVE: To investigate the correlation between total lymphocyte and CD3+ T cell counts in peripheral blood in renal transplant patients treated with anti-thymocyte globulin, and discuss related outcomes. METHODS: A single-center, retrospective study involving 226 patients submitted to kidney transplant between 2008 and 2013, and treated with anti-thymocyte globulin for induction or treatment of cellular rejection. Doses were adjusted according to CD3+ T cell or total lymphocyte counts in peripheral blood. RESULTS: A total of 664 paired samples were analyzed. The Spearman's correlation coefficient was 0.416 (p<0.001) for all samples combined; the overall Kappa coefficient was 0.267 (p<0.001). Diagnostic parameters estimated based on total lymphocyte counts were also calculated using the number of CD3+ T cells (gold standard), with a cut off of >20 cells/mm3. CONCLUSION: Total lymphocyte and CD3+ T cell counts in peripheral blood are not equivalent monitoring strategies in anti-thymocyte globulin therapy.

Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline

BACKGROUND Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and ß­thalassemia. Alloimmunization, a well­documented complication of transfusion, increases the risk of delayed hemolytic transfusion reactions, complicates crossmatching and identifying compatible units, and delays provision of transfusions. Guidance is required to optimize the RBC product administered to these patients. STUDY DESIGN AND METHODS An international, multidisciplinary team conducted a systematic review and developed, following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, recommendations to assist treating physicians and transfusion specialists in their decision to select RBCs for these patients. RESULTS Eighteen studies (17 clinical studies and one cost­effectiveness study) were included in the systematic review. The overall quality of the studies was very low. In total, 3696 patients were included: 1680 with ß­thalassemia and 2016 with SCD. CONCLUSION The panel recommends that ABO D CcEe K­matched RBCs are selected for individuals with SCD and ß­thalassemia, even in the absence of alloantibodies, to reduce the risk of alloimmunization. In patients with SCD and ß­thalassemia who have developed clinically significant alloantibodies, selection of RBCs antigen negative to the alloantibody is recommended, if feasible. In these patients, selection of more extended phenotype­matched RBCs will likely reduce the risk of further alloimmunization. However, given the limited availability of extended phenotype­matched units, attention should be given to ensure that a delay in transfusion does not adversely affect patient care.

Polyclonal anti T-lymphocyte antibody therapy monitoring in kidney transplant recipients: comparison of CD3+ T cell and total lymphocyte counts / Monitoramento da terapia com anticorpo policlonal antilinfócitos T em transplantados renais: comparação da contagem de células T CD3+ e de linfócitos totais

ABSTRACT Objective: To investigate the correlation between total lymphocyte and CD3+ T cell counts in peripheral blood in renal transplant patients treated with anti-thymocyte globulin, and discuss related outcomes. Methods: A single-center, retrospective study involving 226 patients submitted to kidney transplant between 2008 and 2013, and treated with anti-thymocyte globulin for induction or treatment of cellular rejection. Doses were adjusted according to CD3+ T cell or total lymphocyte counts in peripheral blood. Results: A total of 664 paired samples were analyzed. The Spearman's correlation coefficient was 0.416 (p<0.001) for all samples combined; the overall Kappa coefficient was 0.267 (p<0.001). Diagnostic parameters estimated based on total lymphocyte counts were also calculated using the number of CD3+ T cells (gold standard), with a cut off of >20 cells/mm3. Conclusion: Total lymphocyte and CD3+ T cell counts in peripheral blood are not equivalent monitoring strategies in anti-thymocyte globulin therapy.

RESUMO Objetivo: Investigar a correlação entre a contagem de linfócitos totais e células T CD3+ no sangue periférico em receptores de transplante renal submetidos a tratamento com globulina antitimocitária, e discutir resultados relacionados. Métodos: Estudo retrospectivo de centro único envolvendo 226 pacientes submetidos a transplante renal entre 2008 e 2013 e tratados com globulina antitimocitária, para fins de indução ou tratamento de rejeição celular. As doses foram ajustadas de acordo com a contagem de células T CD3+ ou linfócitos totais no sangue periférico. Resultados: No total, 664 amostras pareadas foram analisadas. O coeficiente de correlação de Spearman para as amostras em geral foi de 0,416 (p<0,001) e o coeficiente Kappa, de 0,267 (p<0,001). Os parâmetros diagnósticos estimados com base na contagem de linfócitos totais foram recalculados, empregando-se o número de células T CD3+ (padrão-ouro) e adotando-se o ponto de corte >20 células/mm3. Conclusão: A contagem de linfócitos totais no sangue periférico não substitui a contagem de células T CD3+ enquanto estratégia de monitorização da terapia à base de globulina antitimocitária.

Detection of Retinal Pigment Epithelium-Specific Antibody in iPSC-Derived Retinal Pigment Epithelium Transplantation Models.

Antibody-mediated rejection is characterized by donor-specific antibody produced by B cells. However, to our knowledge, B cell invasion and antibody in the inflamed retina after transplantation of retinal pigment epithelial (RPE) cells has not been reported. To determine if RPE transplantation could be performed using allografts, we established in vivo immune rejection models with induced pluripotent stem cell (iPSC)-RPE allografts and determined whether RPE-specific antibody could be detected in these models. We detected alloantibodies in the serum from recipient monkeys that had immune attacks in the retina in an immunofluorescent assay using the transplanted iPSC-RPE cells as the antigen. In addition to T cell and antigen-presenting cell immunity, peripheral blood cells and lymph nodes in animal models with allogeneic iPSC-RPE cells also had activated B cells, which were probably secreting alloantibodies. Using serum and transplanted cells, alloreactive antibody can be detected for the diagnosis of immune rejection after transplantation.

SIPPET: methodology, analysis and generalizability.

The development of anti-FVIII neutralizing alloantibodies (inhibitors), occurring in about one-third of previously untreated patients (PUPs) with severe haemophilia A, depends on various genetic and environmental risk factors. Several previous studies have reported on the immunogenicity of FVIII concentrates, and due to differences in study design, study period, inhibitor testing frequency and follow-up duration the results were inconclusive. The first randomized trial on this unresolved question (SIPPET) included 251 previously untreated or minimally treated patients with severe haemophilia A treated with either a single plasma-derived FVIII (pdFVIII) containing VWF or a recombinant FVIII (rFVIII). The results showed an 87% higher rate of inhibitor development for rFVIII than pdFVIII during the first 50 exposure days of treatment. These results generated interest by patient organizations, physicians and regulatory agencies. This manuscript summarizes answers to the main questions that arose after the full publication of SIPPET.

Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 Study participants.

BACKGROUND: Rabbit antithymocyte globulin (rATG, Thymoglobulin®) is the most common induction immunosuppression therapy in kidney transplantation. We applied a database integration strategy to capture and compare long-term (10-year) outcome data for US participants in a clinical trial of rATG versus FDA-approved basiliximab. METHODS: Records for US participants in an international, 1-year, randomized clinical trial comparing rATG and basiliximab induction in deceased donor kidney transplantation were integrated with records from the US national Organ Procurement and Transplantation (OPTN) registry using center, transplant dates, recipient sex, and birthdates. The OPTN captures center-reported acute rejection, graft failure, death, and cancer events, and incorporates comprehensive death records from the Social Security Death Master File. Ten-year outcomes according to randomized induction regimen were compared by Kaplan-Meier analysis (two-sided P). Non-inferiority of rATG was assessed using a one-tailed equivalence test (a-priori equivalence margins of 0-10 %). RESULTS: Of 183 US trial participants, 89 % (n = 163) matched OPTN records exactly; the remainder were matched by extending agreement windows for transplant and birthdates. Matches were validated by donor and recipient blood types. By Kaplan-Meier analysis, 10 years post-transplant, freedom from acute rejection, graft failure, or death was 32.6 % and 24.0 % in the rATG and basiliximab arms, respectively (P = 0.09). The incidence of acute rejection with rATG versus basiliximab induction was 21.0 % versus 32.8 % (P = 0.07). Patient survival (52.8 % [Corrected] versus 52.2 %, P = 0.92) and graft survival (34.3 % versus 30.9 %, P = 0.56) rates were numerically and statistically similar for both arms. Comparison of the composite outcome meets non-inferiority criteria even with a 0 % equivalence margin (one-sided P = 0.04). With a 10 % equivalence margin, the odds that rATG is no worse than basiliximab for 10-year risk of the composite endpoint are >99 %. CONCLUSIONS: Ten years post-transplant, rATG induction has comparable efficacy and safety to FDA-approved basiliximab. Integration of clinical trial records with national registry data can enable long-term monitoring of trial participants in transplantation, circumventing logistical and cost barriers of extended follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00235300.

Efficacy of homeopathic intervention in subclinical hypothyroidism with or without autoimmune thyroiditis in children: an exploratory randomized control study.

INTRODUCTION: The decision to treat subclinical hypothyroidism (SCH) with or without autoimmune thyroiditis (AIT) in children, presents a clinical dilemma. This study was undertaken to evaluate the efficacy of individualized homeopathy in these cases. METHODS: The study is an exploratory, randomized, placebo controlled, single blind trial. Out of 5059 school children (06-18 years) screened for thyroid disorders, 537 children had SCH/AIT and 194 consented to participate. Based on primary outcome measures (TSH and/or antiTPOab) three major groups were formed: Group A - SCH + AIT (n = 38; high TSH with antiTPOab+), Group B - AIT (n = 47; normal TSH with antiTPOab+) and Group C - SCH (n = 109; only high TSH) and were further randomized to two subgroups-verum and control. Individualized homeopathy or identical placebo was given to respective subgroup. 162 patients completed 18 months of study. RESULTS: Baseline characteristics were similar in all the subgroups. The post treatment serum TSH (Group A and C) returned to normal limits in 85.94% of verum and 64.29% of controls (p < 0.006), while serum AntiTPOab titers (Group A and B) returned within normal limits in 70.27%of verum and 27.02%controls (p < 0.05). Eight children (10.5%) progressed to overt hypothyroidism (OH) from control group. CONCLUSION: A statistically significant decline in serum TSH values and antiTPOab titers indicates that the homeopathic intervention has not only the potential to treat SCH with or without antiTPOab but may also prevent progression to OH.

Incidence of maternal sensitisation to Rh(D) in Christchurch, New Zealand and reasons for prophylaxis failures.

AIM: To estimate the current incidence of maternal sensitisation to Rh(D) and examine reasons for prophylaxis failures. METHOD: Retrospective chart review of new sensitisations to Rh(D) detected in antenatal records, between 2005 and 2012 in Christchurch, New Zealand and systematic examination of circumstances likely to have caused prophylaxis failures. RESULTS: Fifty-four new sensitisations in an at-risk population of about 4624 in 8 years means an incidence of roughly 1.1%. In 86.6% of 45 sensitisations where information was available, there was a recognised sensitising event including previous deliveries while in 13.3% there were none. Of those with recognised sensitising events, 46.1% had anti-D prophylaxis per local guidelines, in 12.8%, prophylaxis was given though it did not conform, entirely, to guideline. No prophylaxis at all was given to 41% despite a sensitising event being recognised. CONCLUSION: The incidence of maternal sensitisation to Rh(D) in Christchurch, New Zealand, is as expected given our prophylaxis regimen. Half the sensitisations were associated with complete or partial failure to follow local guidelines. Better adherence to this may reduce incidence of sensitisation. It is also thrice as high as might be expected with a routine antenatal anti-D prophylaxis (RAADP) program. An economic analysis of RAADP in New Zealand will be useful.

Clinical practice: immune thrombocytopenia in paediatrics.

Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A "watch and wait" strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents.

Conflicts of interest and clinical recommendations: comparison of two concurrent clinical practice guidelines for primary immune thrombocytopenia developed by different methods.

The growing influence of practice guidelines has increased concern for potential sources of bias. Two recent guidelines for primary immune thrombocytopenia (ITP) provided a unique opportunity for a systematic comparison of different methods of practice guideline development. One guideline (International Consensus Report [ICR]) was supported by pharmaceutical companies that produce products for ITP. The ICR panel members were selected for expertise in ITP; 16 (73%) reported associations with pharmaceutical companies. The other guideline was sponsored by the American Society of Hematology (ASH); panel members were selected for lack of conflicts and for expertise in guideline development as well as for ITP. Discrepancies were conspicuous when the guidelines addressed treatment. In contrast to the ASH guideline, the ICR gave stronger recommendations for agents manufactured by companies from which the ICR or its panel members received support. These data provide direct evidence that differences in financial support and methods of evidence evaluation can influence recommendations.

Quality of life in immune thrombocytopenia following treatment.

OBJECTIVE: To determine the impact of therapy on the reported health-related quality of life (HRQoL) in children with primary immune thrombocytopenia (ITP) using the Kids ITP tool (KIT). DESIGN: Secondary data analysis of the international and North American KIT validation studies. RESULTS: 217 children from 6 countries participated in the two studies. The majority of treatments occurred in children with newly diagnosed ITP. There was no statistical difference in age, platelet count and bleeding severity at presentation in those who physicians chose to treat or observe. Self-reported KIT scores did not differ between the two groups. The KIT parent-proxy scores were significantly worse for newly diagnosed children receiving treatment, especially following prednisone. CONCLUSIONS: Treatment of ITP does not improve, and may worsen, the HRQoL of children with ITP as measured using the KIT.

Monoclonal versus polyclonal anti-D in the treatment of ITP.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by low numbers of platelets generally due to the production of anti-platelet antibodies. One effective treatment for ITP patients who express the RhD antigen on their red blood cells has been the use of blood donor-derived pooled polyclonal anti-D. Although anti-D has served us well, it needs to be replaced with a recombinant product. While the mechanism of action of anti-D in ITP remains highly speculative, this has not thwarted attempts to replace anti-D with a monoclonal product. Although a single attempt at a monoclonal antibody was not successful in the 1990s for the treatment of ITP, more recent efforts in mouse models of ITP and ITP patients now show that monoclonal antibodies can be successful in ITP. These studies also finally help substantiate the concept that it is unlikely that contaminants in the original donor-derived preparations mediate the major ameliorative activity of anti-D in ITP.

An analysis of outcomes and treatment costs for children undergoing splenectomy for chronic immune thrombocytopenia purpura.

PURPOSE: Indications and timing for splenectomy in pediatric chronic immune thrombocytopenic purpura (cITP) are controversial because of high spontaneous remission rates and concern for overwhelming postsplenectomy infection. The objective of this study was to assess the risks, costs, and benefits of medical and surgical intervention for children with cITP. METHODS: After receiving institutional review board approval, medical records for all children with cITP who underwent splenectomy from 2002 through 2009 were retrospectively reviewed (n = 22). Preoperative and postoperative data were collected. Medical and surgical costs were calculated based on pharmacy charges per dose and hospital charges, respectively. RESULTS: The median age at diagnosis was 11 years (range, 3-16 years). Medical management included steroids (n = 21), intravenous gamma globulin (n = 19), anti-D antibody (n = 19), or a combination of these therapies (n = 22). Nineteen patients (86%) reported side effects from medical therapy. Median age at splenectomy was 13 years (range, 6-18 years), and time to surgery was 23 months from diagnosis (range, 6-104 months). Splenectomy increased platelet counts in all children from a median of 25,500 to 380,000 postoperatively (P < .0001). One child experienced overwhelming postsplenectomy infection after a dog bite (n = 1). At the last follow-up (15 months; range, 1-79 months), 19 patients (86%) were asymptomatic with platelet counts greater than 50,000. Of the 3 children with persistent thrombocytopenia, 2 were diagnosed with secondary cITP. Median cost of splenectomy was significantly less than the cost of medical therapy ($20,803 vs $146,284; P < .0002). CONCLUSION: Earlier surgical consultation for children with cITP may be justified given the high success rate and low morbidity, particularly given the significant complication rate and cost of continued medical treatment.

[Irregular antibody testing during pregnancy in Tunisia: clinical study of 5369 women]. / Recherche des agglutinines irrégulières en milieu obstétrical en Tunisie: étude à propos de 5369 femmes.

PURPOSE OF THE STUDY: To evaluate the prevalence of alloimmunization in women followed in an obstetrical environment in Tunisia, to identify the specificities of antibodies found and to determine factors that could influence the appearance of this immunization. METHODS: We proceeded to a retrospective analysis of search for irregular antibodies in women followed up in obstetrical environment over nine consecutive years (2000-2008). The panel was officially defined and produced by the Regional Centre for Blood Transfusion in Sfax (Tunisia). RESULTS: Overall 5369 women benefited from 6575 antibody testing (average: 1.22; extremes: 1-14). The results were positive for 278 women (5.17 %), allowing to identify 216 antibodies or associations of antibodies. Among identified antibodies, those immune were found in 198 women. The rate of alloimmunization was 3.68 % (198/5369). The majority of the antibodies found was anti-Rh1, isolated or associated with another antibody, in 84.3 % of the total immunized women. The immunization of women according to the number of gestations showed a significant increasing rate ranging from 2.34 % for a first gestation to 5.27 % for four gestations or more. In addition, a significant difference was also noted between the rate of immunization in women who had received anti-Rh1 immunoglobulin and those who had not. CONCLUSION: Anti-Rh1 immunization is the most frequent in the population of studied women. This could denote of an insufficiency in pregnancies follow-up and immunoprophylaxis protocols.

[Hemolytic disease of the newborn has not vanished from Finland--routine protection of RhD negative mothers during pregnancy is justifiable]. / Vastasyntyneen hemolyyttinen tauti ei ole hävinnyt Suomesta.

Prophylaxis of RhD negative mothers with anti-D immunoglobulin after childbirth is the most important procedure reducing the immunization of the mother and the risk of severe hemolytic disease of the newborn. In spite of this, anti-D antibodies having relevance to pregnancy are later detected in 1.8% of RhD negative mothers. Half of these cases could be prevented by routine anti-D prophylaxis given to the mothers during weeks 28 to 34 of pregnancy. Convincing evidence of the effectiveness of this measure has accumulated in the last few years, and application of the treatment is justified also in Finland.

Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta-analyses adjusted for differences in study design and quality.

BACKGROUND: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. METHODS: Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis. RESULTS: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I²â€Š =  19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I²  =  0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28-30 weeks is least effective. CONCLUSION: There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.