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Biomedical subjects

F Daffos

Publications and source records attributed to F Daffos.

At least 91 records · Page 5Linked to original sources
PubMed1988

Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets.

Neonatal alloimmune thrombocytopenia (NAIT) can cause severe bleeding in the central nervous system (CNS) and death or severe neurologic sequelae. The expression of the PLA1 antigen is detectable as early as 19 weeks of gestation. Alloimmunization can therefore lead to fetal thrombocytopenia very early in pregnancy. Until recently, we have had no means of detecting and assessing the severity of fetal thrombocytopenia during pregnancy. The level of the maternal antibody is not of a predictable value since 20% of the mothers had no circulating antibodies in our series. An alternative approach is to carry out investigations on fetal blood samplings. This management leads to an exact knowledge of the fetal status and antenatal diagnosis is feasible as early as the 21st week of gestation. Early diagnosis facilitates appropriate management and makes possible such therapeutic options as in utero maternal platelet transfusions. We report our experience in the antenatal diagnosis and management of nine cases with in utero transfusion in the six cases with severe thrombocytopenia. All neonates did well, with no signs of bleeding at birth. No side effects of therapy were noted after a period ranging from 6 months to 3 years.

Antigens, Human Platelet↗
PubMed1987

Prenatal diagnosis of hereditary elliptocytosis with molecular defect of spectrin.

Hereditary elliptocytosis (HE) is, in the heterozygous state, a common mild congenital hemolytic disease. In contrast, homozygous elliptocytosis is a severe transfusion-dependent hemolytic anemia. The major determinant of red cell membrane shape and stability is a two-dimensional proteinaceous meshwork named membrane skeleton. Spectrin, the most important protein of the membrane skeleton, is basically a heterodimer composed of alpha and beta chains. Within the membrane, spectrin dimers self-associate to form tetramers. In type I HE spectrin dimer self-association is defective and an excess of spectrin dimer is present in the patient's red cell membranes. The defective self-association is often correlated with an abnormality of the spectrin alpha chain which is depicted by limited tryptic digest of spectrin. In a family previously studied by us (Dhermy et al., 1984), the search for a spectrin defect in the red cells of the fetus of the pregnant mother was indicated for the following reasons: the diagnosis of heterozygous type I HE with the same spectrin variant had been made in the mother as well as in the father. Moreover, homozygous HE had been recognized in one of the children born two years previously with a persistent and severe transfusion dependent hemolytic anemia. Preliminary studies of normal fetal erythrocytes at twenty weeks gestation have shown that fetal and adult spectrin molecules are identical. The results obtained in the fetus at risk allowed us to diagnose type I HE (though elliptocytes were not present in the blood) for the following reasons: (i) erythrocyte deformability was decreased (ii) spectrin self-association was defective with an excess of dimer species in the membrane (iii) limited tryptic digest of spectrin showed the same abnormal pattern as seen in the heterozygous mother, with a decrease in the 80,000-dalton peptide and a concomitant increase in the 74,000-dalton peptide. The heterozygous state, strongly suspected on the tryptic digest pattern of fetal spectrin, was confirmed when the mother gave birth to a baby who did not have hemolytic anemia during the first 18 months of life.

Elliptocytosis, Hereditary↗
PubMed1987

Characterization of mononuclear cell subpopulations in normal fetal peripheral blood.

It is now possible to characterize fetal peripheral blood mononuclear cells (FPBMC) from normal fetuses sampled in utero under ultrasound guidance. The surface phenotype of FPBMC from 25 fetuses, between the 20th and the 26th week of gestation, was studied using standard reagents that are known to delineate mononuclear cell subsets in adult peripheral blood. Results were compared with those obtained in neonates (cord blood) and adults. The major subsets of adult PBMC are represented in fetal blood with few qualitative differences: 20% of FPBMC are not recognized, the percentage of T cells is lower with a higher ratio T4/T8, the fraction of cells that express DR molecule is very high, and the distribution of NK antigens is different in fetuses. B cells and monocytes are in equal proportion. This work represents a prerequisite for future functional studies, and provides normal fetal values that will be useful for prenatal diagnosis of congenital immunodeficiency.

Adult↗
PubMed1987

Blood chemistry of normal human fetuses at midtrimester of pregnancy.

Thirteen biochemical parameters and five enzymatic activities were determined on sera of 63 normal human fetuses sampled by direct puncture under ultrasound guidance, between the 20th and the 26th wk of gestation, and on their mothers. They were referred to us for various prenatal diagnoses but were well and confirmed healthy at birth. Some parameters were found to be very similar in both groups, mainly creatinine, calcium, creatine kinase, aspartate aminotransferase, and gamma-glutamyl transferase. Some values were significantly higher in the fetuses, such as total bilirubin, direct bilirubin, phosphorus, lactic dehydrogenase and alkaline phosphatase activities, and alpha-fetoprotein. Urea, uric acid, glucose, triglycerides, cholesterol, total protein, and albumin levels were found to be lower in fetuses. These data indicate a slower metabolism in fetuses compared to their mothers, a lower level of energy requirement, and a relative liver immaturity. These normal values of fetal biochemistry will improve our knowledge of physiology and help to determine the specific values of a test in fetal pathology.

Blood Chemical Analysis↗
PubMed1987

Serum growth-promoting activity in normal and hypotrophic fetuses at midpregnancy.

Blood from 24 human fetuses aged 19-24 wk was collected by ultrasound-guided puncture of the umbilical cord in utero, performed for prenatal diagnosis of mother to fetus transmissible infections. Fetal serum growth-promoting activity (thymidine activity) was measured by its effect on 3H-thymidine incorporation into human lectin-activated lymphocytes. Ten blood samples were obtained at 19-22 wk of pregnancy and 14 at 23-24 wk. The pregnancies were maintained and the fetuses delivered, free of infection, at 38-40 wk, nine of them being small for date and 15 having a normal weight for gestation age. The bioassayable thymidine activity was significantly lower in the hypotrophic (0.84 +/- 0.04 U/ml) than in the normal fetuses (1.28 +/- 0.09 U/ml) whatever the time of sampling. Thymidine activity was significantly negatively correlated with gestational age in the normal for date fetuses, not in the small for date. It is suggested that early measurement of thymidine activity in fetal blood might be of value in the assessment of fetal growth despite the fact that the tissue growth factors may be more important in fetus than are the serum factors.

Adult↗
PubMed1987

[Prenatal pharmacology of low molecular weight heparin and pentosan polysulfate].

The aim of prenatal pharmacology is to evaluate the biologic effects to the fetus of a drug taken during pregnancy. Development of a new technic for collection of fetal blood samples in utero under ultrasound guidance allowed, by evaluation of maternal and fetal hemostasis, study of two low molecular weight heparins, PK 10169 (Lovenox) (table I) and CY 216 (Fraxiparine) (tableau II) and of pentosan polysulfate (Hemoclar) (table III). Under the operating conditions applied, the three molecules failed to diffuse across placenta during 2nd and 3rd pregnancy trimesters. This permitted treatment of eleven women at risk for eclampsia or thromboembolism with good clinical results, white confirming absence of circulating heparinemia at birth (umbilical cord blood).

Anticoagulants↗
PubMed1987

[Absence of transplacental passage of Fraxiparin (low molecular weight heparin) during the 3d trimester of pregnancy].

Using low molecular weight fractions of heparin (HBPM) can be at least potentially useful in pregnant women for certain indications. After animal studies had been carried out for toxic effects, one HBPM, CY216, which has been put on the market under the name of Fraxiparin, was studied to see whether it crosses the placenta in pregnant women by analysing fetal blood directly. Seven women who had fetal indications for terminating their pregnancies in the third trimester received a subcutaneous injection of 17,500 Choay units of Fraxiparin (0.7 ml). The haemostatic state was assessed in the mothers before the injection and three hours after it, and in the fetus approximately three hours after the injection into the mother. The fetal blood was taken in the uterus by direct aspiration using ultrasound guidance techniques. Anti Xa, anti IIa, and cephalin-kaolin time (TCK) were estimated. The anti Xa, anti IIa and the TCK were not changed in the 7 fetuses that were studied, 3 hours after the subcutaneous injection of a large dose of CY 216 although marked changes were noted in the mothers.

Blood Coagulation↗
PubMed1987

Fetal blood sampling in twin pregnancies. Prenatal diagnosis and management of 19 cases.

Twin pregnancies pose particular problems in both prenatal diagnosis and obstetric management. We present 19 twin pregnancies that underwent fetal blood sampling (FBS). The indications were mostly similar to those for singleton pregnancies, with both fetuses being sampled. There was one indication specific to twin pregnancies; disseminated intravascular coagulation in the retained twin after the death-in-utero (DIU) of the other. In 5 cases, only 1 twin was sampled; in 2 because the second twin was female in the diagnosis of an X-linked disorder; in 1 because of technical failure, and in 2 the other twin had predeceased. Eight pregnancies continued after the FBS delivering 2 live, healthy infants, though 5 were delivered before 37 weeks of gestation. In 7 cases there was a discordance in the diagnosis between the twins. In 3 of these cases the affected fetus underwent selective termination by air embolism; in 2 cases the pregnancies were continued and the affected twin not resuscitated; 1 pregnancy is still in progress, and 1 patient had a non-medically supervised termination of both twins in another country. Two patients miscarried within a week of the FBS. Two patients had only 1 living twin at the time of FBS; 1 had a second DIU a month after the FBS and the other a neonatal death at 11 days of age in an infant with severe porencephaly. FBS is technically feasible for similar indications as for singleton pregnancies though discordance in diagnosis raises specific management problems.

Blood Specimen Collection↗
PubMed1986

Absence of transplacental passage of pentosan polysulfate during mid trimester of pregnancy.

Eight women who were going to have an abortion between the 18th and 23 week of gestation for chromosomal abnormalities or haemoglobinopathies received intravenously 50 mg of pentosan polysulfate (PSP). Maternal results of haemostasis prior and after the injection of the drug were compared. Fetal coagulation parameters were tested on samples obtained by direct puncture of the umbilical cord under ultrasound guidance, 30 min after injection. Results were compared to those of normal fetuses at the same stage of gestation, obtained in the same conditions. In mothers' plasma, 30 min after injection, APTT was prolonged, factor Xa generation was markedly impaired, and factor V level was deeply decreased. By contrast, no modifications of these parameters were observed in fetal plasma, 30 min after the injection of PSP to their related mothers when compared to control fetuses. Thus the absence of biological modifications induced by PSP injection could demonstrate that this drug does not cross through the placenta.

Blood Coagulation↗
PubMed1986

Allogeneic responses of human fetal (22- to 25-week) peripheral blood lymphocytes: preferential recruitment of cytotoxic effector cells with both CTL activity and NK-like function.

In the present study, we have characterized human cytotoxic effector lymphocytes generated following in vitro immunization of normal fetal (22- to 25-week) peripheral blood mononuclear cells (FPBMC) by an allogeneic Epstein-Barr virus-transformed B-cell line termed LAZ388. Primary stimulations led to strong FPBMC proliferation. However, subsequent addition of LAZ388 cells to the cultures on Day 8 did not trigger conventional secondary responses. In fact, further proliferation of activated FPBMC required the addition of exogeneous interleukin 2. Cytotoxic activity generated in the mixed-lymphocyte reactions was assayed against LAZ388 immunizing cells as well as against the highly susceptible natural killer (NK) target cell line K562. Eight days after stimulation by LAZ388, there was no specific lysis and a moderate NK-like activity. However, following second and subsequent stimulations a strong killing was measured against both LAZ388 and K562 cells. Blocking experiments performed with relevant monoclonal antibodies suggested that cytotoxicity against immunizing cells was conventionally directed at MHC gene products. Effector cells were further studied using cloning procedures; it was found that all cloned cell lines able to kill LAZ388 cells were also strongly active against K562. Both types of cytotoxic function appeared to be mediated via surface receptors physically or at least functionally associated with T3 proteins.

B-Lymphocytes↗