PubMed Health⌕ Search

Biomedical subjects

L Porcelijn

Publications and source records attributed to L Porcelijn.

17 recordsLinked to original sources
PubMed2002

Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia.

Thrombopoietin (Tpo) is the main hematopoietic growth factor for platelet production. Plasma Tpo levels in autoimmune thrombocytopenic patients are normal or slightly elevated. Although thrombocytopenia exists, Tpo levels are not increased because the produced megakaryocytes and platelets can bind circulating Tpo, thereby normalizing Tpo levels. In this study, plasma samples from fetuses and neonates with neonatal alloimmune thrombocytopenia (NAIT), a different form of immune thrombocytopenia, were measured. Umbilical cord samples from 50 fetuses before treatment because of severe thrombocytopenia and 51 fetuses after treatment, and peripheral blood samples of 21 untreated newborns with NAIT were analyzed. As controls, plasma Tpo levels were determined in 21 umbilical cord samples of 14 nonthrombocytopenic fetuses with hemolytic disease resulting from red blood cell alloimmunization and in umbilical cord samples of 51 healthy newborns. The values were also compared with the plasma Tpo levels in 193 healthy adults. Mean Tpo levels from the groups of fetuses and neonates, including both NAIT and control plasma, were slightly but significantly elevated compared with levels in healthy adults. Tpo levels in NAIT samples were not significantly different from the levels in hemolytic disease samples or in samples from healthy newborns. Thus, as in autoimmune thrombocytopenic patients, normal Tpo levels are present in NAIT patients.

Fetus↗
PubMed2001

Anti-HPA-3A induces severe neonatal alloimmune thrombocytopenia.

OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (AIT) caused by feto-maternal incompatibility at the HPA-1a (PLA-1) locus is well characterized. Alloimmunization and disease caused by HPA-3a is rare. STUDY DESIGN: We conducted a retrospective analysis of all known cases of AIT caused by HPA-3a incompatibility identified at 3 major reference laboratories from 1986 to 1996. Platelet antigen typing and antibody specificity were determined by serologic evaluation. In some cases confirmatory genotyping was performed. RESULTS: Fourteen cases of anti-HPA-3a-induced AIT in 11 families were identified. Five patients had a previous affected sibling, and 2 cases were firstborn children. All patients had severe thrombocytopenia at birth (platelet count <20 x 10(9)/L). Regardless of therapy, the median time to platelet recovery was 6 days (range, 3 to 23 days). Two (15%) patients had documented intracranial hemorrhage, 1 with severe sequelae including apnea and convulsions. A literature review describing 16 additional patients corroborates the finding of severe thrombocytopenia and a significant incidence of intracranial hemorrhage caused by HPA-3a incompatibility. CONCLUSION: AIT caused by incompatibility of HPA-3a is similar in severity to disease caused by incompatibility of HPA-1a. Affected families should be appropriately counseled and considered for antenatal therapy.

Antigens, Human Platelet↗
PubMed2000

Neutrophil antigen 5b is carried by a protein, migrating from 70 to 95 kDa, and may be involved in neonatal alloimmune neutropenia.

BACKGROUND: Neutrophil antigen 5b has been described as involved in transfusion reactions and not in neonatal alloimmune neutropenia. CASE REPORT: Anti-5b was found in the serum of a mother of a persistently neutropenic newborn, who had several bacterial infections. The neutropenia responded to treatment with recombinant human granulocyte-colony-stimulating factor. Immunoprecipitation experiments performed with this and three other 5b antisera identified a protein, migrating from 70 to 95 kDa, as carrier of 5b. The observed pattern of migration may point to heavy glycosylation of this protein. RESULTS: Six 5b-negative donors were identified among 54 screened white donors, for a 5b gene frequency of 0.66. CONCLUSION: Alloimmunization to 5b in pregnancy is rare. In the patients with neonatal neutropenia analyzed in the last decade, this was the first case discovered.

Antigens↗
PubMed1998

Immune-mediated thrombocytopenias: basic and immunological aspects.

Acute idiopathic or autoimmune thrombocytopenic purpura (AITP) is a disorder found mainly in children, usually preceded by a viral infection, with a higher incidence in the autumn and winter. The platelet-specific autoantibodies in acute childhood AITP are more often of the IgM class. Chronic AITP occurs mostly in adults. The platelet immunofluorescence test (PIFT) detects platelet-specific autoantibodies with a sensitivity of 65-75%. The autoantibodies in chronic AITP are classified as IgG in 95%, IgM in 26% and IgA in 4% of cases. The antibodies are usually bound to platelets and are detectable as free circulating antibodies in about 40%. AITP in pregnancy may cause neonatal AITP by autoantibodies of the IgG class which pass the placenta barrier. The rare neonatal alloimmune thrombocytopenic purpura (NAITP) are caused by IgG alloantibodies against HPA-1a in 75-90%, HPA1b in 3-5%, HPA 3a in 4-5%, HPA5b in 6-19% and against private platelet antigens in 3%. To confirm the diagnosis of NAITP requires extensive serological testing of the child, and the parents have to be typed for the important platelet-specific antigens by PIFT, monoclonal antibody immobilisation of platelet antigens (MAIPA) and/or enzyme-linked immunosorbent assay (ELISA) techniques. Three mechanisms of drug-induced thrombocytopenias are described. Platelets of both the donor and the patient are destroyed in post-transfusion thrombocytopenic purpura (PTP) but PTP does not occur again if incompatible platelets are re-administered.

Adult↗
PubMed1998

Fetal thrombocytopenia.

In idiopathic thrombocytopenic purpura, the low risk of fetal bleeding in the perinatal period does not justify routine cordocentesis. Platelet counts of second newborns correlates well with that of their siblings. In neonatal alloimmune thrombocytopenia, the initial platelet count at cordocentesis in the second trimester is low in the next pregnancy. Weekly high doses of intravenous gammaglobulin to the mother results in a rise of fetal platelet count in approximately 70% of cases and may protect the fetus against intracranial haemorrhage in cases without significant platelet rise. With the exception of cases with a prior infant with spontaneous fetal intracranial haemorrhage, the use of diagnostic fetal blood sampling to confirm neonatal alloimmune thrombocytopenia is controversial.

Female↗
PubMed1998

The diagnostic value of thrombopoietin level measurements in thrombocytopenia.

It has been reported that blood trombopoietin (TPO) levels can discriminate between thrombocytopenia due to increased platelet destruction and decreased platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a large group of patients in detail and could confirm and amplify the above notion in detail. TPO levels were determined in plasma from 178 clinically and serologically well-defined thrombocytopenic patients: 72 patients with idiopathic autoimmune thrombocytopenia (AITP), 29 patients with secondary AITP, 5 patients with amegakaryocytic thrombocytopenia and 72 patients who suffered from various diseases (46 in whom megakaryocyte deficiency was not and 26 in whom it was expected). In addition, we measured the level of glycocalicin as a marker of total body mass of platelets. In all patients with primary AITP and secondary AITP, TPO levels were within the normal range or in some (n = 7) cases only slightly increased. The level of glycocalicin was not significantly different from that of the controls (n = 95). The patients with amegakaryocytic thrombocytopenia had strongly elevated TPO levels and significantly decreased glycocalicin levels. Similarly, among the 72 thrombocytopenic patients with various disorders, elevated TPO levels were only found in patients in whom platelet production was depressed. The mean level of glycocalicin in these patients was decreased compared to that in controls and patients with AITP, but was not as low as in patients with amegakaryocytic thrombocytopenia. In conclusion, all patients with depressed platelet production had elevated levels of circulating TPO, whereas the TPO levels in patients with an immune-mediated thrombocytopenia were mostly within the normal range. Therefore, measurement of plasma TPO levels provides valuable diagnostic information for the analysis of thrombocytopenia in general. Moreover, treatment with TPO may be an option in AITP.

Adolescent↗
PubMed1997

Maternal DRB1*1501, DQA1*0102, DQB1*0602 haplotype in fetomaternal alloimmunization against human platelet alloantigen HPA-6b (GPIIIa-Gln489).

Fetomaternal incompatibility of platelet alloantigens may lead to alloimmunization and neonatal alloimmune thrombocytopenia (NAIT). Human platelet alloantigen (HPA) 6b, which associates with residue Gln 489 of platelet membrane glycoprotein IIIa, has been described as a cause of NAIT. We have studied the MHC genes of all available family members in the six thus far reported families with a thrombocytopenic newborn and fetomaternal HPA-6b incompatibility. Maternal HPA-6b antibodies could be detected in five mothers to the altogether seven thrombocytopenic male infants. The MHC genes HLA-DRB, -DQA1, -DQB1, -DPB1, TAP1,2 and HSP70-Hom were studied by using polymerase chain reaction (PCR)-based DNA analysis methods. All five mothers with detectable circulating HPA-6b antibodies at the time of delivery shared an identical DRB1*1501, DQA1*0102, DQB1*0602 haplotype. The sixth, HPA antibody negative mother and a HPA-6b-negative mother to a healthy HPA-6b+ child were negative for this haplotype. The frequency of DRB1*15-positive haplotype was increased in immunized mothers (100%) as compared with the general Finnish population (27%), but the association was not statistically significant after correction. We conclude that there is a potential association between the MHC haplotype DRB1*1501, DQA1*0102, DQB1*0602 and alloimmunization to the HPA-6b antigen and that this alloimmunization probably involves different HLA class II molecules from immunization to HPA-1a.

Antigens, Human Platelet↗
PubMed1996

Antenatal care in pregnancies at risk of alloimmune thrombocytopenia: report of 19 cases in 16 families.

OBJECTIVE: To assess accuracy of a management program in patients at risk for alloimmune thrombocytopenia (NAITP) and to describe perinatal outcomes. STUDY DESIGN: Nineteen fetuses at risk of thrombocytopenia were identified using obstetric history, HLA type of the mother and fetal phenotyping in cases where paternal heterozygozity for the offending antigen was present. Cordocentesis was timed according to obstetric history and performed with safety precautions to prevent haemorrhage. High dose intravenous gamma globulin (IVIG) was administered to the mother in cases with a fetal platelet count < 100 x 10(9)/l. RESULTS: The platelet antagonisms were distributed as follows: HPA-1a in 15 patients, HPA-5a in two, HPA-3a in one, with one further woman who had antibodies against a private antigen. All multigravidas (N = 18) had previously given birth to an infant with NAITP and two of those infants had experienced severe bleeding. Two fetuses were negative for the offending antigen. The median and mean platelet count at first cordocentesis was 26 and 75 x 10(9)/l respectively (range 3-276). A total of 46 cordocentesis were carried out, of which 37 were followed by platelet transfusions. Bleeding complications were not observed. IVIG was administered to eight mothers and two fetuses responded. Nine infants were delivered by caesarean section (CS) and 10 vaginally at a mean gestational age of 37 weeks (range 34-41). The median and mean platelet count at birth was 141.5 and 140 x 10(9)/l, respectively (range 36-314). Ultrasound examination, both ante- and postnatally, revealed no intracranial haemorrhages. There was one procedure related neonatal death and one infant suffered from convulsions in the neonatal period due to a sinus thrombosis, possibly related to the platelet transfusions. CONCLUSIONS: When obstetric history is taken into account cordocentesis in NAITP can be postponed. Safety recommendations described in this study allow cordocentesis without bleeding complications. However, our study does not support routine cordocentesis in patients with a history of NAITP. Both the risks of cordocentesis, and the lack of prospective data on the magnitude of the risk of intrauterine or peripartal bleeding, should be considered.

Blood Transfusion, Intrauterine↗
PubMed1996

The RoHar antigenic complex is associated with a limited number of D epitopes and alloanti-D production: a study of three unrelated persons and their families.

BACKGROUND: the RoHar antigenic complex has been characterized serologically by difficulties in D typing, weak e expression, lack of G antigen, presence of Rh33, a low-frequency Rh antigen, and, more recently, a second low-frequency antigen, FPTT. Allocation to one of the partial D catagories was not considered because of the unuaual reactions of RoHar cells and because anti-D production was not observed in RoHar persons. STUDY DESIGN AND METHODS: Three unrelated RoHar donors and their families were studied in detail with special emphasis on D epitope mapping, e and G typing, and screening for antibodies. RESULTS: Only D epitopes 5 and 6/7 were demonstrable, and D epitopes 1, 2, 3, 4, 8, and 9 seem to be absent in the RoHar complex. In one individual, the presence of alloanti-D with limited specificity, not reacting with RoHar red cells of other individuals, was found 6 months after a second D+ pregnancy. CONCLUSION: The finding of alloanti-D in an RoHar r person supports the concept that the D characteristic of this phenotype is a partial D antigen, which is consistent with the presence of the limited number of D epitopes found in epitope mapping. As has been suggested for other partial D antigens, RoHar individuals should be regarded as D- for the receipt of blood, and pregnant RoHar women who have had D+ pregnancies should receive anti-D prophylaxis.

Epitopes↗
PubMed1995

Max(a), a new low-frequency platelet-specific antigen localized on glycoprotein IIb, is associated with neonatal alloimmune thrombocytopenia.

We have identified a new platelet-specific alloantigen, Max(a), responsible for a typical case of neonatal alloimmune thrombocytopenic purpura. The maternal serum reacted strongly with paternal platelets in the platelet immunofluorescence test, whereas platelet alloantigen typing showed that no known human platelet antigen (HPA)-system was involved. In the monoclonal antibody (MoAb)-specific immobilization of platelet antigens (MAIPA) assay, the new antigen was located on the platelet membrane glycoprotein (GP) IIb-IIIa complex, but immunoprecipitation and immunoblot experiments to further localize the antigen failed. However, in the MAIPA assay, the binding of the anti-Max(a) antibodies from the maternal serum was blocked by two anti-GPIIb MoAbs. Thus, the antigen appeared to be located on GPIIb. Analysis of the family lead to the identification of six additional Max(a+) individuals. Three of these six individuals and the father were tested in the platelet aggregation test and were found to be normal. In the analysis of normal donors, three of 500 were typed positive for the new platelet-specific antigen, indicating a phenotype frequency of 0.6% in the normal population. Platelet RNA was isolated from the newborn's Max(a)+ father and from a healthy donor phenotyped as Max(a-), reverse-transcribed, and the entire GPIIb coding region was amplified by polymerase chain reaction. Subsequent nucleotide sequence analysis showed a single G-->A substitution at position 2,603, predicting a valine-->methionine amino acid substitution at position 837 of the mature glycoprotein. This mutation abolished a BsiYI restriction site at the cDNA level and a BstNI restriction site at genomic DNA level, respectively. The genetic association between the new antigen and this point mutation was confirmed by allele-specific restriction analysis on cDNA and on genomic DNA, as well as by allele-specific primer amplification on genomic DNA. The new mutation is 19 bp upstream of the mutation underlying the HPA-3 system. Therefore, we also evaluated the association between Mas and the HPA-3 polymorphism. So far, all Max(a+) individuals were also found to be HPA-3b, whereas 50 HPA-3a individuals were all Max(a-). This may indicate that Max(a) is a variant of the HPA-3 allele.

Alleles↗
PubMedDate not supplied

G-CSF-induced decrease of the anti-granulocyte autoantibody levels in a patient with autoimmune granulocytopenia.

We present a case of an 81-year-old man with secondary autoimmune granulocytopenia in association with autoimmune thrombocytopenia. Treatment with granulocyte colony-stimulating factor (G-CSF) (5 micrograms/ kg/day s.c.) resulted in a rapid increase in the number of circulating granulocytes with a pronounced left shift. These changes were accompanied by up-regulation of the surface expression of Fc gamma RI (CD64) and Fc gamma RII (CD32) on the granulocytes. In addition, we noted a strong up-regulation of the Fc gamma RIII (CD16) and the activation markers CD11b and CD66b on the granulocytes. The increase in the number of circulating granulocytes was followed by a dramatic decrease in the level of cell-bound as well as circulating anti-granulocyte antibodies. It is hypothezised that the decrease in the level of cell-bound as well as circulating anti-granulocyte antibodies may be the result of an increased adsorption of the antibodies by the granulocytes.

Aged↗