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C Kaplan

Publications and source records attributed to C Kaplan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Platelet phenotyping in carriers for Glanzmann's thrombasthenia: a simple screening test for assessment of the molecular defect.

Glanzmann's thrombasthenia (GT) is a recessive autosomal bleeding disorder characterized by the abnormality of aggregation due to a platelet glycoprotein (GP) IIb-IIIa deficiency or a dysfunctional complex. Molecular abnormalities have been localized on the gene coding for GP IIb or IIIa. The aim of our work was an attempt to obtain indirectly information on the putative localization of the molecular defect in patients with GT type I or II by the determination of the HPA-1 (GP IIIa) and HPA-3 (GP IIb) alloantigenic systems' expression in GT carriers. If GT results from a defective GP IIb gene, a GT carrier would appear homozygous for HPA-3 by serology, because the normal gene product will be expressed while the abnormal GP IIb gene product will not be present. Conversely, if the abnormality is in the GP IIIa gene, such an individual would appear homozygous for HPA-1. Therefore, the heterozygous status for HPA would result from the normal expression of the two genes for the considered alloantigenic system. Among the four families studied with informative members, our presumptions were strengthened by the preliminary genetic results in one family showing a mutation in the GP IIb gene. Thus, serology could be a simple screening test for the possible defective gene responsible for GT allowing molecular investigation focusing only on GP IIb or IIIa gene.

Antigens, Human Platelet↗
PubMed1995

A structural/functional domain on human CD36 is involved in the binding of anti-Nak(a) antibodies.

The human CD36 antigen is an integral membrane glycoprotein expressed by platelets, monocytes, endothelial cells and various tumor cell lines. CD36 acts as a receptor for thrombospondin, collagen, Plasmodium falciparum-infected erythrocytes and oxidized low-density lipoprotein. Individuals possessing the Nak(a)-negative phenotype do not express CD36 and risk developing anti-CD36 isoantibodies upon blood transfusion or during pregnancy. In the present study, we have examined the interaction of an anti-Nak(a) serum with recombinantly expressed CD36. Results obtained show that five functional CD36 monoclonal antibodies (OKM5, FA6-152, L103, ESIV-C7 and 10/5) prevent the binding of the anti-Nak(a) serum whereas a single monoclonal antibody (13/10) has no effect. Consistent with this result, an epitope map of CD36 generated using cross-blocking experiments, indicates that the inhibitory monoclonal antibodies recognize closely-related epitopes whereas 13/10 reacts with a distinct CD36 determinant. Furthermore, we have demonstrated, in a recent study, that OKM5, FA6-152, L103 and 10/5 bind to the same CD36 domain defined by amino acids 155 to 183. Taken together, our results indicate that the 155-183 sequence is important for the binding of the anti-Nak(a) serum to CD36 and may represent a surface-exposed, immunogenic and presumably functional region on human CD36.

Animals↗
PubMed1994

Fetal thrombocytopenia: a retrospective survey of 5,194 fetal blood samplings.

Fetal platelet counts were retrospectively studied in a series of 5,194 consecutive fetal blood samplings (FBS). The mean value was 245 +/- 65 x 10(9)/L, without significant variation between 17 and 41 weeks' gestation. After exclusion of false thrombocytopenia due to contamination with amniotic fluid, 247 fetuses had platelet counts less than 150 x 10(9)/L. In 70 cases, thrombocytopenia was due to congenital infectious diseases (toxoplasmosis, rubella, and cytomegalovirus). It was related to immune causes in 45 cases: anti-HPA-1a (n = 23), anti-HPA-5b (n = 2) or possible anti-HLA (n = 2) alloimmunizations, and immune thrombocytopenic purpura (n = 18). Chromosomal abnormality was the etiology in 43 cases (trisomy 13, 18, and 21, Turner's syndrome, triploidy), and other disorders (multiple birth defects, intrauterine growth retardation, rhesus disease, and gestational thrombocytopenia) in 62 cases. No specific cause for the low platelet count could be established in 27 fetuses (range, 115 to 149 x 10(9)/L). Severe thrombocytopenia (< or = 50 x 10(9)/L) occurred mainly in immune cases (16%), congenital infectious diseases (7%), and chromosomal abnormalities (1%). Diagnosis, prognosis, and management of fetal thrombocytopenia are presented in the different clinical situations. In this series, FBS was never associated with serious bleeding, and no fetal exsanguination was observed.

Chromosome Aberrations↗
PubMed1994

Susceptibility to alloimmunization to platelet HPA-1a antigen involves TAP1 polymorphism.

The alloimmunization against platelet HPA-1a antigen in mothers of thrombocytopenic neonates is strongly associated with HLA class II structures (DR3 and DR13) and especially with HLA-DR52a antigen (98% of the cases reported here). Because new genes have recently been mapped within the MHC class II region, we typed TAP1 and TAP2 gene polymorphisms by ARMS-PCR in order to characterize more effectively MHC genes involved in this alloimmunization. Our results showed that TAP1*0102 allele was significantly associated with NAIT only in the population of HLA-DR 13-DR52a-immunized women (50%) versus HLA-DR 13-DR52a controls (20%) (p < 0.05), and not in HLA-DR3-DR52a-immunized women versus HLA-DR3-DR52a controls. There is no linkage disequilibrium between TAP1*0102 and DRB1*13 alleles (delta = -0.0063) that could account for this result. The higher frequency of TAP1*0102 allele among HLA-DR 13-DR52a-immunized women suggests that HPA-1a antigen presentation and recognition may be influenced by nonclassic HLA class II gene polymorphisms, or that other linked but yet unknown genes could interfere.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

An improved DNA-based identification of fetuses at risk for HPA-1a (PlA1) neonatal alloimmune thrombocytopenia.

A simple and reliable procedure, based on DNA amplification and HpaII mapping, is proposed for the identification of fetuses at risk for HPA-1a (PlA1) neonatal alloimmune thrombocytopenia which could cause life-threatening haemorrhage, even in early fetal life. This typing procedure for HPA-1 alleles should help in deciding, very early, the therapeutic management of the fetuses at risk.

Antigens, Human Platelet↗
PubMed1994

Human platelet alloantigen typing: PCR analysis is not a substitute for serological methods.

Currently, five platelet alloantigen (alloAg) systems have been established (HPA-1, -2, -3, -4, -5). Three of these are expressed on the glycoprotein (GP) IIb-IIIa complex, HPA-1, HPA-3 and HPA-4, inherited in an autosomal codominant mode. Recent investigations of the molecular basis of these platelet alloantigen systems have shown that only one nucleic acid base substitution in the genes encoding for GP IIb and GP IIIa is responsible for the polymorphism. This substitution is reflected in a difference in restriction enzyme recognition allowing platelet alloantigen typing by restriction fragment length polymorphism (RFLP) analysis of DNA amplified by the polymerase chain reaction (PCR). To validate the PCR technology for platelet typing, we have compared PCR-RFLP with monoclonal-antibody-specific immobilization of platelet antigens (MAIPA). For this purpose, we have studied different Glanzmann thrombasthenic families and particularly heterozygous individuals, who are not lacking GP IIb-IIIa, as a model to detect the occurrence of discrepancies between these two technologies. In two families, we have found differences between molecular biology and serological methods with the lack of expression of one antigen on the platelet membrane surface. In the first family, the abnormality is related to the HPA-1 alloantigen system with three informative members; in the second, the HPA-3 alloantigen system is concerned with two informative members. Considering these results, there may not always be a perfect correlation between molecular biology and serological methods, as an unknown molecular defect could interfere with the PCR results and lead to false platelet typing.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1994

[Fetal-neonatal thrombocytopenia of immunologic origin: current aspects].

Fetal/neonatal immune thrombocytopenias result from increased platelet destruction by maternal antiplatelet antibodies. There is a risk of intracerebral haemorrhage and therefore of neurological impairment or death during the thrombocytopenic period, especially if a defective platelet function co-exists. As no maternal parameter is predictive of the fetal platelet count, the only reliable assessment of the fetal status depends on the fetal blood sampling. Only in case of materno-fetal alloimmunisation the therapy initiated to reverse fetal thrombocytopenia was shown to be effective, but the optimal mode of antenatal treatment is currently under study. As the neonatal therapy and the management of subsequent pregnancies are somehow different it is mandatory to make the distinction between the auto or allo-origin of the fetal thrombocytopenia. The definition of high risk pregnancies will be of help for the development of a routine screening program.

Antigens, Human Platelet↗
PubMed1993

Infusion of Fc gamma fragments for treatment of children with acute immune thrombocytopenic purpura.

Treatment of acute immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIG) induces partial or complete responses, shown by transient or persistent increases in platelet count. The clinical benefit could be due to blockade of the Fc gamma receptor (Fc gamma R); platelets sensitised by IgG could not be cleared by cells of the reticuloendothelial system if Fc gamma R on these cells was blocked with IVIG. To find out whether this putative mechanism is correct, we treated twelve children who had acute ITP with intravenous infusions of Fc gamma fragments. Eleven children showed rapid increases in platelet counts to above the critical value of 50 x 10(9)/L, thereby avoiding major haemorrhagic risk. The response was stable in six patients and transient in five. No adverse reactions were observed. In responders who had detectable platelet-associated IgG before treatment (> 1500 IgG per platelet), platelet IgG fell substantially with treatment. Serum soluble CD16 (sCD16 or sFc gamma RIII) concentrations, measured in five children, showed transient or stable increases that correlated with the rise in platelet count. No sCD16 was detected in the Fc gamma preparation used. We conclude that the infusion of Fc gamma fragments is an efficient treatment of acute ITP in children. The efficacy of Fc gamma fragments strengthens the hypothesis that Fc gamma R blockade is the main mechanism of action of IVIG in ITP, although other immunoregulatory mechanisms triggered by the presence of increased sCD16 concentrations in serum could be involved in the clinical benefit observed.

Adolescent↗
PubMed1993

Role of platelet membrane glycoproteins Ib/IX and IIb/IIIa, and of platelet alpha-granule proteins in platelet aggregation induced by human osteosarcoma cells.

We have previously shown that the platelet-aggregating activity of human MG-63 and HOS osteosarcoma cells depends at least in part upon tumor cell surface-associated thrombospondin, and suggested that platelet-osteosarcoma cell interactions could occur through interactions with specific platelet membrane receptors. In this study, the platelet-aggregating activity of MG-63 and HOS cells was studied by using a variety of platelet disorders. Both osteosarcoma cell lines induced a biphasic platelet aggregation response when added to normal platelet-rich plasma, while the second phase of aggregation was absent when added to gray platelets (deficiency in alpha-granule proteins) and to aspirin-treated platelets. Platelets from two unrelated patients with type I Glanzmann's thrombasthenia (deficiency in glycoprotein (GP) GPIIb/IIIa) did not aggregate at all with osteosarcoma cells. Using giant platelets from three patients with Bernard-Soulier syndrome (deficiency in GPIb/IX), the aggregation response induced by MG-63 and HOS cells was monophasic and reversible when compared to normal-sized platelets and to giant platelets from a patient with May-Hegglin anomaly (no membrane GP defect). Because GPIb serves as a receptor for von Willebrand factor during hemostasis, aggregation experiments were also conducted with the platelet-rich plasma of two patients with a low plasma von Willebrand factor concentration (type I von Willebrand's disease) before and after the infusion of deamino-D-arginine vasopressin. MG-63 and HOS cells induced biphasic platelet aggregation both before and after deamino-D-arginine vasopressin treatment, while the ristocetin-dependent binding of von Willebrand factor to platelets only occurred after deamino-D-arginine vasopressin treatment. Preincubation of normal platelet-rich plasma with monoclonal antibody SZ-2 directed against the von Willebrand binding domain of GPIb did not inhibit the platelet-aggregation activity of osteosarcoma cells, whereas anti-GPIb antibody SZ-2 did inhibit ristocetin-induced platelet agglutination. In addition, anti-GPIX antibodies did not affect platelet-osteosarcoma cell interactions. In conclusion, our data demonstrate that the first phase of the platelet-aggregating activity of human osteosarcoma cells is initiated by the interaction of these tumor cells with platelet membrane GPIIb/IIIa, whereas the second phase, even if plasma von Willebrand factor is deficient, involves platelet membrane GPIb and the participation of platelet alpha-granule proteins in membrane-mediated events, making aggregation irreversible.

Antibodies, Monoclonal↗
PubMed1993

Neonatal thrombocytopenia and hidden maternal autoimmunity.

Severe transient thrombocytopenia was observed in 17 newborns delivered by 11 mothers who persistently exhibited normal platelet counts and had no previous immunological or platelet disorder. Maternofetal alloimmunization as well as other causes for fetal thrombocytopenia were ruled out. A specific circulating autoantibody directed against the platelet glycoprotein Ib/IX complex was found in 10/11 mothers and in 3/4 offspring. After delivery, maternal compensated thrombocytolysis and/or hypersplenism were demonstrated by 111Indium labelled platelet studies in 10/11 women. The association of a compensated thrombocytolysis and of a specific maternal circulating antiplatelet autoantibody makes likely the diagnosis of mild maternal chronic autoimmune thrombocytopenic purpura (AITP) only expressed by the fetal or neonatal thrombocytopenia. The finding of anti-IbIX autoantibody in control women who gave birth to neonates without thrombocytopenia raises the question of the incidence and clinical significance of such antibodies which could be natural autoantibodies as well as associated with compensated thrombocytolysis or with overt immune thrombocytopenia. The cause of the discrepancy between the fetal and maternal platelet status, which could be explained by a different conformational state of fetal as compared to adult GP Ib/IX, deserves further investigation.

Adolescent↗