Worldwide policies on epilepsy and blood donation: a survey among blood services.

BACKGROUND AND OBJECTIVES: Epilepsy is a common neurological disorder characterized by the appearance of seizures. Often, epilepsy patients are temporarily or permanently excluded from blood donation. To gain a better understanding of the policies that are currently applied, we performed a survey among blood services. METHODS: A cross-sectional, Web-based questionnaire using the online Questback tool was developed and distributed to 46 representatives of blood services worldwide. The questionnaire was composed of nine questions. RESULTS: A total of 27 respondents, representing blood services in 26 countries on five continents, participated in the survey. Current policies range from permanent acceptance over temporary exclusion to permanent exclusion. Rationales for these different policies are diverse. The majority of blood services (59·3%) apply temporary exclusion as their policy, though no consensus exists on the length of time that epilepsy patients have to be medication-free or seizure-free. None of the respondents could provide data about adverse events in epilepsy patients during the blood donation process. CONCLUSIONS: The results of this survey indicate a large discrepancy in policies applied worldwide. A lack of scientific evidence could be one of the underlying reasons. Therefore, it is of paramount importance to further research the potential risks for donors and recipients regarding blood donation by people with epilepsy. This can then serve as a base for evidence-based policymaking and lead to safer and more effective blood transfusion programmes.

The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation.

Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA- Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Eight new alleles found in Flanders (Belgium), including the HLA-DRB1*12:24N allele.

Human leukocyte antigen (HLA) high-resolution matching is routinely performed in the case of hematopoietic stem cell transplantation. Misdiagnosis of rare or new variants will result in additional unknown mismatches that can trigger graft versus host disease and/or graft failure. Using a mono allelic sequencing strategy, we obtained >90% first-step sequence-based high-resolution typing results, conforming to the standards set down by the European Federation for Immunogenetics. During this routine analysis, eight new HLA alleles were identified, including one DRB1*12 null variant, DRB1*12:24N and three other coding mutants, resulting in a change of properties of the corresponding antigens.

Immediate posttransplantation cotrimoxazole-induced immune thrombocytopenia.

Drug-induced immune thrombocytopenia (DITP) can be caused by numerous drugs. When this condition develops, platelet destruction results from binding of antibodies to normal platelets only in the presence of a sensitizing drug. A recently proposed model suggests that these drug-dependent antibodies are derived from a pool of naturally occurring antibodies with weak affinity for specific epitopes on certain platelet membrane glycoproteins. We describe here a case of DITP secondary to cotrimoxazole exposure in the immediate posttransplantation phase in a renal transplant recipient. Apart from heparin-induced thrombocytopenia, DITP posttransplantation has to the best of our knowledge never been described, perhaps because of its immune-mediated origin. Our case demonstrates that DITP can occur posttransplantation, that cotrimoxazole due to its intensive use in the transplanted population is one of the most likely causative agents and that a timely recognition and treatment might have important consequences for both graft and patient.

A single course of remission reinduction chemotherapy for acute myelogenous leukemia relapsing after allogeneic bone marrow transplantation is complicated by graft-versus-host disease and followed by sustained complete remission.

Graft-versus-host disease (GVHD) remains a major immunological complication after allogeneic bone marrow transplantation (allo-BMT), but also favors development of the beneficial graft-versus-leukemia (GVL) effect. A patient with AML-M4 (inv (16)) is described, who was given non-myeloablative remission reinduction therapy for leukemic relapse (inv (16), trisomy 8) diagnosed on day 184 after HLA-compatible sibling BMT. On day 236, ie about 6 weeks after completion of this course, a clinical syndrome suggestive of acute GVHD grade 3 had developed. Skin biopsy confirmed the clinical diagnosis of GVHD, with a compatible liver biopsy. Transfusion-associated GVHD was ruled out by analysis of short tandem repeat (STR) alleles in the skin biopsy, revealing alleles from donor and recipient but not from third party origin. Cyclosporin A (CsA) therapy, which had been tapered between days 150 and 175, was resumed, resulting in a favorable response and gradual transition to limited chronic GVHD. The patient has since remained in complete remission with an excellent performance status for more than 40 months, without further chemotherapy. Thus this biopsy proven case of GVHD was induced by marrow donor lymphocytes more than 200 days after transplantation and apparently triggered by remission reinduction chemotherapy. The case indicates that intensive non-myeloablative chemotherapy can cure AML relapsing after allo-BMT. The therapeutic effect in this case probably involved a direct pharmacological suppression of the leukemic clone followed by a GVL effect initiated by donor-derived alloreactive T lymphocytes.

Anti-hepatitis G E2 antibody detection and its relation to serum HGV-RNA in patients with clotting disorders: high prevalence of HGV infection and spontaneous remission.

In a previous study, we have determined the prevalence of serum HGV-RNA in patients with congenital clotting disorders. Twenty-six (15%) of 175 patients investigated were serum HGV-RNA positive. In addition, HGV-RNA was detectable in peripheral blood mononuclear cells (PBMC) in ten percent of the cases, three of these patients were serum HGV-RNA negative. In the present study, we have determined the prevalence of anti-HGV-E2 antibodies in the same patient population. Anti-HGV-E2 as determined by ELISA was detected in 45 patients (25.7%). Forty of these patients were serum HGV-RNA negative. Ninety-two percent of the 26 HGV viremic patients and all but one patient (44 patients) with detectable anti-HGV-E2 had coinfection with the hepatitis C virus (HCV). Of these coinfected patients, 62.5% of HGV viremic patients and 53% of anti-HGV-E2 positive patients showed elevated serum ALT levels. Anti-HGV-E2 seroconversion is thus not associated with HCV infection. Two patients who were solely infected with HGV had normal serum ALT levels. In a retrospective longitudinal study, we have observed in 15 patients that serum HGV-RNA persisted during one to 19 years of follow-up, while anti-HGV-E2 was repeatedly negative. Five additional patients who were anti-HGV-E2 positive with concomitant detectable HGV-RNA (4 patients in serum and 1 patient in PBMC) became HGV-RNA negative during follow-up, ranging from 1 to 8 years after the first detection of anti-HGV-E2 antibodies. Two patients had lost anti-HGV-E2 antibodies 3 to 6 years after the seroconversion without the re-appearance of serum HGV-RNA. From these findings, it is clear that the prevalence rate of HGV infection in patients with clotting disorders as determined by PCR assay for HGV-RNA and anti-HGV-E2 by ELISA is actually higher than the prevalence of HGV viremia. Although HGV viremia may persist for longer than 19 years, most of the patients infected with HGV may clear the viremia spontaneously. The clearance of viremia is usually associated with seroconversion to anti-HGV-E2. In addition, anti-HGV-E2 may be lost during years of follow-up without the reappearance of the HGV-RNA. Although HGV infection does not seem to influence the fate of HCV infection and does not induce increased levels of serum ALT, the clinical significance of long-term infection remains to be established.

Successful patching of iatrogenic rupture of the fetal membranes.

Rupture of the fetal membranes is a common, but potentially serious complication of invasive fetal procedures. Quintero described a technique to seal the fetal membrane defect by means of a bloodpatch, usually called 'amniopatch' in this application. The successful use in two consecutive patients with ruptured membranes after a fetoscopic intervention at respectively 17 and 22 weeks' gestational age is described, together with a literature review of published experience.

Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors.

Between December 1981 and March 1994, 24 patients with a myelodysplastic syndrome (MDS) underwent allogeneic bone marrow transplantation (BMT) for RA with trilineage dysplasia (n = 4), CMML (n = 1), RAEB (n = 4), RAEBt (n = 9) and AML following MDS (n = 6). Fifteen patients (two RAEB, seven RAEBt and six sAML) received chemotherapy before BMT resulting in complete remission in 10 patients (six RAEBt and four sAML) at the time of BMT. Sixteen marrow donors were genotypically HLA-identical siblings. Remaining donors were other family members (five) or unrelated donors (three). The status of the underlying disease at the time of conditioning was the major factor determining long-term survival. The disease-freed survival of RA patients and patients presenting with RAEB, RAEBt and AML but transplanted in complete remission, was respectively 50 and 60%. On the contrary, none of the nine high-risk MDS patients transplanted with persistent disease, survived. Outcome after transplantation with alternative donors was inferior with one long-term survivor, mainly related to the high incidence of severe acute GVHD and its accompanying infectious complications. Six patients relapsed resulting in an actuarial probability of relapse of 28%. Twelve patients died of transplant-related complications leading to a non-relapse mortality at 5 years of 50%. At present eight patients are alive and disease-free 20 to 132 months post-transplantation resulting in an actuarial 5-year disease-free survival of 40.7%. Our results suggest that allogeneic bone marrow transplantation is a feasible treatment option for patients with MDS. However, improvement in GVHD prophylaxis and supportive care to reduce transplant-treated mortality and improved relapse prevention are imperative.

Prospective HLA-DR matching in penetrating keratoplasty.

This prospective study examines whether HLA-DR matching has a beneficial effect on corneal graft survival of high risk patients. Until now, 196 donors have been typed in order to provide 20 patients with a matching graft. The results, though preliminary, are very encouraging.

The phenotype and genotype of rheumatoid arthritis in the Democratic Republic of Congo.

INTRODUCTION: Little is known about rheumatoid arthritis in the black, particularly in Congolese, populations. Our objective was to describe the phenotype and genotype of rheumatoid arthritis (RA) in Congolese. METHODS: All consecutive rheumatoid arthritis (RA) patients attending Kinshasa University Hospital in a three-year time period were included. Demographics, clinical features and tobacco consumption were noted. Disease Activity Score (DAS)-28 based on the erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), anti-citrullinated peptide antibodies (CCP) antibodies and rheumatoid factor (RF) were determined. Radiographs were scored according to Sharp-van der Heijde. On a subset of patients and controls HLA-DRB1 typing was performed. RESULTS: A total of 114 females and 14 males aged 51.2 ± 14.9 were included. Mean duration of symptoms was four years. Moderate tobacco consumption was reported in a minority of patients. DAS-28 at first visit was >5.1 and HAQ ≥0.5 in all patients. X-rays showed joint erosions and/or joint space narrowing, mostly of a moderate grade in 55.8% of patients. Anti-CCP and/or RF were present in 48.6% of patients with available data (n = 72) and in 3.0% of controls (n = 67). Radiographic changes and nodules were more frequent in RF or anti-CCP positive patients. One copy of the shared epitope was found in 13 patients (35.1%) and 3 controls (12.5%). Two copies were found in one patient (2.7%) and in one control (4.2%). CONCLUSION: Congolese patients with RA consult long after disease onset. Despite this delay, the majority presents without major damage and is RF, anti-CCP and SE negative. We put forward the hypothesis that besides different environmental factors there is probably also a particular genetic risk profile in Congolese patients, different from the HLA-DRB1 shared epitope.

[Amniopatch to treat iatrogenic rupture of the fetal membranes]. / Traitement de la rupture iatrogène des membranes fœtales par "patch" amniotique.

OBJECTIVE: With the increased use of invasive fetal procedures, the number of patients facing postprocedure membrane rupture is increasing. We aimed to describe the use of platelets and fresh frozen plasma for sealing iatrogenic fetal membrane defects. PATIENTS AND METHODS: We describe the mechanisms of action of the amniopatch procedure as well as published experience. RESULTS: Amniopatch effectively sealed the fetal membranes in over two thirds of published cases (n=44). There is a risk of 17% of in utero fetal death, which may occur remotely from the procedure and is often unexplained. DISCUSSION AND CONCLUSION: In case of early onset but persistent amniotic fluid leakage following an invasive fetal procedure, amniopatch may be offered.

The role of intensive remission induction and consolidation therapy in patients with acute myeloid leukaemia.

Sixty-one patients with AML, 59 adults and two children, were treated with intensive remission induction and consolidation therapy. The median age was 36 years. Forty-four (72%) patients entered complete remission (CR); 11 patients received a bone marrow transplantation. The median survival of complete remitters was 26.5 months; the probability of remaining in CR at respectively 1 and 2 years was 75% and 62%. The only factor significantly correlated with the outcome of remission induction, survival and duration of CR was age. Patients less than 30 years fared significantly better than those 30 years or older; no difference in outcome was observed between patients aged 30-50 and those over 50 years. In patients less than 30 years the CR rate was 95%; 75% of them were still alive at 2 years and only one (5%) has relapsed. In contrast, in patients 30 years or older the CR rate was 60% and the median survival only 11.5 months, 50% of the complete remitters in this age group have relapsed. Morbidity from intensive consolidation therapy was considerable; more than 50% of consolidation courses were complicated by high fever, needing urgent admission; only four (3%) courses had a fatal event. It is concluded that intensive consolidation therapy may be considered as a major advance in the treatment of younger patients with AML, while its role in older individuals remains questionable. A possible explanation for the completely different outcome in younger and older patients with AML is discussed.

An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies.

An enzyme immunoassay (EIA) method based on solubilized human leucocyte antigens (HLA) derived from single donor platelets is described. The EIA results on these solubilized single donor HLA antigens (SDszHLA) correlated well with the complement dependent cytotoxicity (CDC) results on the lymphocytes of the same donors and also with the panel reactivity (PRA) in CDC. A concordancy rate of 78% was found for individual HLA specificities. The EIA+/CDC- ('false positive') discrepancies were more pronounced than EIA-/CDC+ ('false negative') discrepancies and varied for the different donors. To confirm discrepancies, our method was compared with a commercial PRA-STAT EIA method (based on secreted soluble HLA antigens). The same discrepancies between CDC and PRA-STAT EIA were found and are probably due to the higher and different sensitivity (e.g. non complement fixing antibodies) of EIA methods. A SDszHLA EIA method allows the identification of HLA specificities of HLA-antisera. The possibility of using individual and selected donors for the production of SDszHLA allows the directed search for well defined HLA specificities in order to confirm anti-HLA specificities found in other anti-HLA screening methods. An individualized HLA panel can be established with the support of blood banks that have HLA typed blood and platelet donors.

Evaluation of anti-human leukocyte antigen allo-immunization in pediatric cadaveric kidney transplantation.

Forty-eight pediatric cadaveric renal transplantations, performed between May 1986 and February 1997, were retrospectively screened, pre- and post-transplant, for antibodies to human leukocyte antigen (anti-HLA) using complement-dependent cytotoxicity (CDC) assay and enzyme immunoassay (EIA). The correlation between anti-HLA immunization and graft outcome was investigated. The combined analysis of CDC and EIA enabled the differentiation between complement-fixing and non-complement-fixing, anti-HLA class I and anti-HLA class II antibodies. The median post-transplant follow-up for all patients with a functioning graft was 86 months (range 10-138 months). In the whole population, 16 grafts were lost: six following a non-immunologic complication; and 10 as a result of rejection. Of these 10 grafts lost, eight were in patients with pre- and/or post-transplant donor antigen specific (DAS) anti-HLA class I or class I + II antibodies; and two were in patients with DAS anti-HLA class II antibodies only. Three of these grafts were lost in patients with weak pre-existing DAS anti-HLA class I antibodies. Immunological graft loss appeared at a median post-transplant time of 38 months (range 2-68 months). All patients without DAS anti-HLA antibodies had a good graft outcome. The presence of pre- and post-transplant DAS anti-HLA antibodies, especially if directed against HLA class I, were associated with a poor graft outcome. A systematic search for, and identification of, anti-HLA antibodies should therefore be part of a pretransplant evaluation to allow the identification of 'unacceptable' donor HLA antigens, following which the impact of the HLA-cross-match on graft outcome will improve. Screening for DAS anti-HLA antibodies post-transplant could be helpful for detecting patients with an increased risk for graft loss following rejection episodes.

HLA typing in a large family with multiple cases of different autoimmune diseases.

OBJECTIVE: Because of the concurrence, in members of one family, of different autoimmune disorders [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PS), and inflammatory bowel disease (IBD)], we investigated the genotypes of each member and compared the results with current knowledge of genetic inheritance of rheumatic and other autoimmune diseases. METHODS: Sera and peripheral blood lymphocytes of 16 family members were collected for HLA typing and investigation. RESULTS: All patients with RA were DR4 positive ad 4 of 5 showed the maternal A2B51DR4 haplotype. Two of 3 siblings with the genotype HLA-A2/3, B8/35, DR2/3 had SLE. Patients with IBD and psoriasis shared the haplotype HLA-A3, B35 CW4 DR2. CONCLUSION: The results show that the important role of patients, sex and confirm the association between HLA haplotype and RA or SLE. They support the hypothesis that autoimmunity is a mendelian dominant trait, and that secondary genes, including these of the major histocompatibility complex, confer phenotypic specificity.

Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization.

A nonisotopic oligotyping method using reverse dot blot hybridization was developed for HLA class II DQA1, DQB1, DPB1, DRB1, DRB3, DRB4, DRB5 alleles. The polymorphic second exon of the different genes was amplified by the polymerase chain reaction (PCR). For each gene the amplified DNA was hybridized at stringent conditions to membrane-bound sequence-specific oligonucleotides (SSOs) and visualization of positive signals was done by chemiluminescence. A combination of 11, 18, 23 and 31 SSOs was designed to identify 9/13 DQA1, 16/17 DQB1, 23/24 DPB1 and 50/55 DRB1, 4 DRB3, 1 DRB4, 3/4 DRB5 alleles respectively. For the DRB1 locus, an additional DRB1*04 group-specific PCR was developed to make discrimination between the DR4 alleles possible in different heterozygous combinations. The procedure described here provides rapid and nonisotopic genotyping of heterozygous samples from a variety of sources and can be applied for tissue typing, disease susceptibility studies and forensic medicine.

Persistent polyclonal B-cell lymphocytosis.

We present a case of persistent polyclonal B-cell lymphocytosis (PPBL). This syndrome is characterized by a persistent lymphocytosis with circulating atypical binucleated lymphocytes. The patient had serological evidence of a previous EBV infection, had raised polyclonal serum IgM levels and was a heavy smoker. No malignancy was detected.