M de Haas

University Medical Center Utrecht, Utrecht, Provincie Utrecht, Netherlands

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Publications (129)570.56 Total impact

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    ABSTRACT: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver. Abcc6(-/-) mice have been instrumental in demonstrating that PXE is a metabolic disease caused by the absence of an unknown factor in the circulation, the presence of which depends on ABCC6 in the liver. Why absence of this factor results in PXE has remained a mystery. Here we report that medium from HEK293 cells overexpressing either human or rat ABCC6 potently inhibits mineralization in vitro, whereas medium from HEK293 control cells does not. Untargeted metabolomics revealed that cells expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though ABCC6 itself does not transport nucleoside triphosphates. Extracellularly, ectonucleotidases hydrolyze the excreted nucleoside triphosphates to nucleoside monophosphates and inorganic pyrophosphate (PPi), a strong inhibitor of mineralization that plays a pivotal role in several mineralization disorders similar to PXE. The in vivo relevance of our data are demonstrated in Abcc6(-/-) mice, which had plasma PPi levels <40% of those found in WT mice. This study provides insight into how ABCC6 affects PXE. Our data indicate that the factor that normally prevents PXE is PPi, which is provided to the circulation in the form of nucleoside triphosphates via an as-yet unidentified but ABCC6-dependent mechanism.
    Proceedings of the National Academy of Sciences 11/2013; · 9.74 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: HPA-1a antibodies account for 70-80% of cases of fetal-neonatal alloimmune thrombocytopenia (FNAIT) in Caucasians. However, numerous workshops have demonstrated variability in their detection. We recently showed that exposure of αIIbβ3 to ethylene diamine tetraacetic acid (EDTA) affected binding of many anti-αIIbβ3 monoclonal, and HPA-1a allo-, antibodies; this adversely affected sensitivity of the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and indirect platelet immunofluorescence test (PIFT). This study presents results from an international workshop studying the impact of cation chelation on HPA-1a antibody detection in routine diagnostic laboratories. MATERIALS AND METHODS: Serum and EDTA-anticoagulated plasma samples containing anti-HPA-1a were distributed to 39 laboratories. Participants were asked to detect and identify any HPA antibodies present. RESULTS: 2/39 (5·1%) participants were able to detect and identify anti-HPA-1a in the serum, but not in the plasma sample. EDTA plasma reduced MAIPA assay sensitivity by ≥20% in 17/24 (70·8%) laboratories and by ≥50% in 9/24 (37·5%) when using HPA-1a1a platelets (mean: 27·7%, range 0-85·1%); when using HPA-1a1b platelets 3/4 (75%), participants reported ≥50% loss of sensitivity (mean 65·6%, range 0-96·6%). A small but significant increase in optical densities was observed in antigen capture ELISA assays when using plasma (mean difference: 0·081, P < 0·01). Insufficient PIFT data were returned to draw firm conclusions. CONCLUSION: Use of EDTA plasma significantly affects the sensitivity of the MAIPA assay and can affect detection of even potent, FNAIT-causing examples of anti-HPA-1a. These data highlight the importance of use of αIIbβ3 in an appropriate conformation for the sensitive detection of anti-HPA-1a.
    Vox Sanguinis 05/2013; · 2.85 Impact Factor
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    ABSTRACT: Since 2000, Quality Assurance (QA) exercises for the detection and identification of granulocyte antibodies and DNA typing for human neutrophil antigens (HNA) have been distributed within the International Granulocyte Immunobiology Workshops, which are linked to International Society of Blood Transfusion. The exercises were standardised at the outset to enable laboratory performance to be monitored. Between 2000 and 2012, nine exercises were distributed to 20 laboratories. Overall, 45 examples of 42 unique samples containing defined granulocyte reactive antibodies were distributed for serological analysis together with 20 samples for HNA genotyping. The level of satisfactory serological performance was initially set at 50% and later increased to 70%, while the 'cut-off' for HNA genotyping was set at 100% after 2008. Failure to achieve the minimum score in the QA exercises in consecutive years resulted in temporary exclusion. In 2000, the 15 participating laboratories had a mean score of 56.1% for serological analysis and 13 laboratories attempted HNA-1a and -1b genotyping, while 11 attempted HNA-1c typing. Steady improvements in proficiency for serological testing and HNA typing occurred in subsequent exercises. In 2012, the mean score for serology was 88.5% and 12/13 laboratories scored 100% for HNA-1a, -1b, -1c, -3a, -3b, -4a, -4bw, -5a and -5bw genotyping. These QA exercises have provided an invaluable tool to monitor and improve the standard of granulocyte immunology investigations for participating laboratories, thereby enhancing performance for both clinical investigations and donor screening programmes to reduce the incidence of TRALI.
    Vox Sanguinis 05/2013; · 2.85 Impact Factor
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    ABSTRACT: Chromatin governs gene regulation and genome maintenance, yet a substantial fraction of the chromatin proteome is still unexplored. Moreover, a global model of the chromatin protein network is lacking. By screening >100 candidates we identify 42 Drosophila proteins that were not previously associated with chromatin, which all display specific genomic binding patterns. Bayesian network modeling of the binding profiles of these and 70 known chromatin components yields a detailed blueprint of the in vivo chromatin protein network. We demonstrate functional compartmentalization of this network, and predict functions for most of the previously unknown chromatin proteins, including roles in DNA replication and repair, and gene activation and repression.
    Molecular cell 02/2013; 49(4):759-71. · 14.61 Impact Factor
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    ABSTRACT: The ATP-binding cassette (ABC) genes encode the largest family of transmembrane proteins. ABC transporters translocate a wide variety of substrates across membranes, but their physiological function is often incompletely understood. We describe a new method to study the substrate spectrum of ABC transporters: We incubate extracts of mouse urine with membrane vesicles prepared from Spodoptera frugiperda Sf9 insect cells overproducing an ABC transporter and determine the compounds transported into the vesicles by LC/MS-based metabolomics. We illustrate the power of this simple "transportomics" approach using ABCC2, a protein present at sites of uptake and elimination. We identified many new substrates of ABCC2 in urine. These included glucuronides of plant-derived xenobiotics, a class of compounds to which humans are exposed on a daily basis. Moreover, we show that the excretion of these compounds in vivo depends on ABCC2: compared to wild-type mice, the urinary excretion of several glucuronides was increased up to 20-fold in Abcc2(-/-) mice. Transportomics has broad applicability, as it is not restricted to urine and can be applied to other ATP-dependent transport proteins as well.
    The FASEB Journal 02/2012; 26(2):738-47. · 5.70 Impact Factor
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    ABSTRACT: We describe a reliable noninvasive fetal human platelet antigen (HPA)-1a genotyping assay on a real-time polymerase chain reaction (PCR) platform using cell-free fetal DNA isolated from maternal blood. Nonspecific amplification of maternal cell-free DNA is overcome by pre-PCR digestion of the cell-free DNA with the Msp1 restriction enzyme. Noninvasive fetal HPA-1a genotyping offers a safe method for alloimmunised pregnant women to determine whether their fetus is at risk of fetal or neonatal alloimmune thrombocytopenia (FNAIT) and whether interventions to prevent intracranial haemorrhage are required. The availability of this test is relevant to the ongoing debate on screening pregnancies for HPA-1a-mediated FNAIT.
    BJOG An International Journal of Obstetrics & Gynaecology 07/2011; 118(11):1392-5. · 3.76 Impact Factor
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    ABSTRACT: To evaluate the diagnostic performance of noninvasive fetal blood group genotyping. Descriptive analysis. Dutch national reference laboratory for pregnancies complicated by alloimmunisation. All consecutive alloimmunised pregnant women for whom fetal blood group genotyping of rhesus D, c, E or of K in maternal plasma was performed from 2003 up to 2010. The test results of each individual assay were collected. Real-time polymerase chain reaction was performed for RHD exon 5 and RHD exon 7, or the specific allele of the RHCE or KEL gene. A stringent diagnostic algorithm was applied. In the case of a negative result, the presence of fetal DNA was ascertained by the analysis of the Y chromosome-specific SRY gene or other paternal genetic markers. Results were compared with available serology after birth or genotyping results of amniotic fluid cells. Percentage of conclusive test results and diagnostic accuracy. A total of 362 tests was performed (D: n = 168; c: n = 49; E: n = 85; K: n = 60). The median gestational age was 17 weeks (range 7-38 weeks). In 351 women (97%), a test result was issued: in seven samples, the presence of fetal DNA could not be confirmed; in two samples, non-specific amplification in the K assay led to an inconclusive result; in two samples, a maternal silent RHD gene prevented fetal RHD genotyping. No false-positive or false-negative results were found among those women for whom cord blood serology or genotyping results of amniotic fluid cells were available (n = 212). Noninvasive fetal blood group genotyping is accurate and applicable in a clinical diagnostic setting.
    BJOG An International Journal of Obstetrics & Gynaecology 06/2011; 118(11):1340-8. · 3.76 Impact Factor
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    ABSTRACT:   Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological damage as a consequence. In the absence of screening, FNAIT is only diagnosed after bleeding symptoms, with preventive options limited to a next pregnancy.   To estimate the population incidence of FNAIT and its consequences to prepare for study design of a screening programme.   An electronic literature search using MEDLINE, EMBASE and Cochrane database, and references of retrieved articles. No language restrictions were applied.   Prospective studies on screening for human platelet antigen 1a (HPA-1a) alloimmunisation in low-risk pregnant women.   Two reviewers independently assessed studies for inclusion and extracted data. Main outcome data were prevalence of HPA-1a negativity, HPA-1a immunisation, platelet count at birth and perinatal ICH. We aimed to compare outcome with and without intervention.   HPA-1a alloimmunisation occurred in 294/3028 (9.7%) pregnancies at risk. Severe FNAIT occurred in 71/227 (31%) immunised pregnancies, with perinatal ICH in 7/71 (10%). True natural history data were not found because interventions were performed in most screen-positive women.   Screening for HPA-1a alloimmunisation detects about two cases in 1000 pregnancies. The calculated risk for perinatal ICH of 10% in pregnancies with severe FNAIT is an underestimation because studies without interventions were lacking. Screening of all pregnancies together with effective antenatal treatment such as intravenous immunoglobulin may reduce the mortality and morbidity associated with FNAIT.
    BJOG An International Journal of Obstetrics & Gynaecology 10/2010; 117(11):1335-43. · 3.76 Impact Factor
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    ABSTRACT: Antibodies to antigens in the Kell blood group system, especially anti-KEL1, are involved in both haemolytic disease of the newborn and foetus and haemolytic transfusion reactions. Correct typing results are important and discrepancies between serologic and genetic typing must be resolved. Here, we describe the investigation of three healthy individuals who were initially phenotyped as KEL:1,-2. Antigen typing was performed by standard serological techniques and by flow cytometric analysis. The KEL*01/02 polymorphism was tested by an allele-discrimination TaqMan assay as well as by PCR with allele-specific primers and PCR-RFLP. DNA sequencing of the KEL coding region was also performed. RESUlts: Two KEL*02N alleles with mutated splice sites around exon 8 were identified: intron 7 -1g>c (novel) and intron 8 +1g>t (previously reported in one case of K(0)). In the third sample, a missense mutation in exon 8, 787G>A (novel) predicting Gly263Arg, was detected on a KEL*02 allele and associated with dramatically weakened KEL2 antigen expression. Resolution of discrepant phenotype/genotype results identified silencing mutations in or around exon 8. A combination of molecular and serologic methods has the potential to improve the quality of test results and was required to ensure both the accurate KEL2 antigen status and KEL*01 zygosity of these individuals.
    Vox Sanguinis 04/2010; 99(2):150-7. · 2.85 Impact Factor
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    ABSTRACT: Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.
    Vox Sanguinis 03/2010; 99(2):177-92. · 2.85 Impact Factor
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    ABSTRACT: Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.
    Vox Sanguinis 07/2009; 97(3):198-206. · 2.85 Impact Factor
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    ABSTRACT: To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor. Case-control study. Nation-wide evaluation of the Dutch antenatal anti-D-prophylaxis programme. Cases: 42 RhD-immunised parae-1, recognised by first-trimester routine red cell antibody screening in their current pregnancy, who received antenatal and postnatal anti-D Ig prophylaxis (gifts of 1000 iu) in their first pregnancy. Controls: 339 parae-1 without red cell antibodies. Data were collected via obstetric care workers and/or personal interviews with women. Significant risk factors for RhD immunisation in multivariate analysis. Independent risk factors were non-spontaneous delivery (assisted vaginal delivery or caesarean section) (OR 2.23; 95% CI:1.04-4.74), postmaturity (>or=42 weeks of completed gestation: OR 3.07; 95% CI:1.02-9.02), pregnancy-related red blood cell transfusion (OR 3.51; 95% CI:0.97-12.7 and age (OR 0.89/year; 95% CI:0.80-0.98). In 43% of cases, none of the categorical risk factors was present. In at least half of the failures of anti-D Ig prophylaxis, a condition related to increased fetomaternal haemorrhage (FMH) and/or insufficient anti-D Ig levels was observed. Hence, RhD immunisation may be further reduced by strict compliance to guidelines concerning determination of FMH and accordingly adjusted anti-D Ig prophylaxis, or by routine administration of extra anti-D Ig after a non-spontaneous delivery and/or a complicated or prolonged third stage of labour.
    BJOG An International Journal of Obstetrics & Gynaecology 06/2009; 116(10):1307-14. · 3.76 Impact Factor
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    ABSTRACT: To identify risk factors for the presence of non-rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years. Case-control study. Nationwide evaluation of screening programme for non-RhD RBC antibodies. Cases: consecutive pregnancies (n=900) with non-RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n=968): matched for obstetric caregiver and gestational age. Data collection from the medical records and/or from the respondents by a structured phone interview. Significant risk factors for non-RhD immunisation in multivariate analysis. Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4-24.6), parity (para-1 versus para-0: OR 1.3; 95% CI: 1.0-1.7; para-2 versus para-0: OR 1.4; 95% CI: 1.0-2.0; para >2 versus para-0: OR 3.2; 95% CI: 1.8-5.8), haematological disease (OR 2.1; 95% CI: 1.0-4.2), history of major surgery (OR 1.4; 95% CI: 1.1-1.8). For the clinically most important antibodies, anti-K, anti-c and other Rh-nonD-antibodies RBC transfusion was the most important risk factor, especially for anti-K (OR 96.4; 95%-CI: 56.6-164.1); 83% of the K-sensitised women had a history of RBC transfusion. Pregnancy-related risk factors were a prior male child (OR 1.7; 95% CI: 1.2-2.3) and caesarean section (OR 1.7; 95% CI: 1.1-2.7). RBC transfusion is by far the most important independent risk factor for non-RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy-related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD-positive para-0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.
    BJOG An International Journal of Obstetrics & Gynaecology 02/2009; 116(5):655-64. · 3.76 Impact Factor
  • Vox Sanguinis 01/2009; 96(2):167-79. · 2.85 Impact Factor
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    ABSTRACT: The platelet-specific alloantibody anti-human platelet antigen (HPA) 1a is involved in feto-maternal alloimmune thrombocytopenia, post-transfusion purpura and platelet refractoriness. The existing minimum potency preparation for the detection of anti-HPA-1a (NIBSC code 93/710) was established by World Health Organization in 1997 and is used by laboratories to validate new assays or to calibrate 'in-house' controls. However, it has been well-used and a replacement is required. This report describes the production and comparative evaluation of a freeze-dried preparation of pooled human plasma, coded 05/106, containing anti-HPA-1a. Plasma containing anti-HPA-1a was obtained and 2974 1-ml aliquots were prepared and freeze-dried in glass ampoules. In order to characterize the material and compare it to the existing reference material, three collaborative studies were organized, involving a total of 50 different laboratories in 23 countries. As expected only anti-HPA-1a could be detected in the plasma and no additional HPA or human leucocyte antigen antibodies were detected. When tested in titration, there was a wide variation in the sensitivity of antibody detection by different laboratories, irrespective of the technique used. However, there was no significant difference between the two materials when compared using a t-test. When diluted 1 in 2, most laboratories were able to detect the presence of anti-HPA-1a in both materials and the participants agreed that this was an appropriate level to set as the minimum sensitivity required. In October 2007, the World Health Organization Expert Committee on Biological Standardization approved the material 05/106 as an International Reference Reagent.
    Vox Sanguinis 01/2009; 96(2):146-52. · 2.85 Impact Factor
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    ABSTRACT: Acquired Glanzmann's thrombasthenia (GT) is an uncommon bleeding disorder caused by glycoprotein (GP) IIb/IIIa-specific autoantibodies. Covering of the fibrinogen binding site of GPIIb/IIIa results in a moderate-to-severe bleeding tendency. We performed a diagnostic evaluation and evaluated the underlying risk factors in six patients with a bleeding tendency caused by acquired GT. One patient, with GPIIb/IIIa autoantibodies of the immunoglobulin G2 (IgG2) subclass, used diclophenac and recovered after discontinuation of this drug. A second patient was primarily diagnosed with multiple angiodysplastic lesions. In this patient, the acquired GT was caused by GPIIb/IIIa autoantibodies of the IgG4 subclass that was treated with DDAVP and platelet transfusions. A third patient with Hodgkin's lymphoma and anti-GPIIb/IIIa of the IgG2 subclass was treated for haemorrhagic diathesis with corticosteroids and azathioprin. A fourth patient, with IgG2 anti-GPIIb/IIIa autoantibodies, diagnosed with mantle cell lymphoma, responded well to treatment of an axillary mass with local radiotherapy. The fifth and sixth patients, with IgG1 anti-GPIIb/IIIa autoantibodies, appeared to have GT after splenectomy because of autoimmune thrombocytopenia. They were treated with corticosteroids, intravenous immunoglobulin and Rituximab. Although it might be a rare event, one should be aware of acquired GT as a cause of an unexpected primary disorder of haemostasis in patients with lymphoma or autoimmune disease. The lack of platelet destruction in these cases of acquired GT can be explained, either by the subclass of the autoantibodies (i.e. IgG2 or IgG4) or by the arrested platelet destruction by IgG1 (or IgG3) autoantibodies after splenectomy.
    Vox Sanguinis 12/2008; 95(4):324-30. · 2.85 Impact Factor
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    ABSTRACT: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies. Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires. Main outcome measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures. Participants: 233 pregnant women, distributed over five groups, according to the screening result. Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics. Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.
    BMC Pregnancy and Childbirth 12/2008; 8:49. · 2.52 Impact Factor
  • Vox Sanguinis 11/2008; 95(3):236-53. · 2.85 Impact Factor
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    ABSTRACT: We have studied the potential contribution of ABCG2 (breast cancer resistance protein) to resistance to nucleoside analogues. In cells transfected with DNA constructs resulting in overexpression of human or mouse ABCG2, we found resistance against cladribine, clofarabine, fludarabine, 6-mercaptopurine, and 6-mercaptopurine riboside in both MDCKII and HEK293 cells and against gemcitabine only in HEK293 cells. With Transwell studies in MDCK cells and transport experiments with vesicles from Sf9 and HEK293 cells, we show that ABCG2 is able to transport not only the nucleotide CdAMP, like several other ATP-binding cassette transporters of the ABCC (multidrug resistance protein) family, but also the nucleoside cladribine itself. Expression of ABCG2 in cells results in a substantial decrease of intracellular CdATP, explaining the resistance against cladribine. The high transport rate of cladribine and clofarabine by ABCG2 deduced from Transwell experiments raises the possibility that this transporter could affect the disposition of nucleoside analogues in patients or cause resistance in tumors.
    Molecular Cancer Therapeutics 10/2008; 7(9):3092-102. · 5.60 Impact Factor
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    ABSTRACT: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.
    Transfusion 06/2008; 48(5):941-52. · 3.53 Impact Factor

Publication Stats

5k Citations
570.56 Total Impact Points

Institutions

  • 1995–2011
    • University Medical Center Utrecht
      • • Division of Perinatology and Gynaecology
      • • Division of Pediatrics
      Utrecht, Provincie Utrecht, Netherlands
    • Hong Kong Red Cross Blood Transfusion Service
      Hong Kong, Hong Kong
  • 1994–2011
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Medicine
      • • Laboratory for Experimental and Clinical Immunology
      • • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service
      Amsterdam, North Holland, Netherlands
  • 2006–2008
    • Sanquin Blood Supply Foundation
      • Department of Experimental Immunohematology
      Amsterdamo, North Holland, Netherlands
  • 1993–2008
    • Netherlands Cancer Institute
      • Division of Molecular Biology
      Amsterdam, North Holland, Netherlands
  • 1999–2002
    • University of Groningen
      • Department of Internal Medicine
      Groningen, Province of Groningen, Netherlands
  • 1995–2001
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Hematology
      Amsterdamo, North Holland, Netherlands
  • 1998
    • Spaarne Ziekenhuis
      Haarlemmermeer, North Holland, Netherlands