Neonatal thrombocytopenia (NNT) which is frequent in distressed newborns was uncommon in a non-selected population of neonates. The aim of this prospective study was to determine the frequency of NNT and, in confirmed NNT, to search for maternal antiplatelet antibodies with a monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. Among the 8388 newborns studied, 40 (0.5%, 95% CI 0.3-0.6) had confirmed NNT, which was severe (platelet count < 50 x 10[9]/l) in 10 cases (0.12%, 95% CI 0.05-0.20). Antiplatelet antibodies were detected in 10/31 studied mothers of thrombocytopenic newborns (32.3%): they were alloantibodies in five cases and autoantibodies in five other cases. Among these 10 newborns, seven had severe thrombocytopenia and four had bleeding complications. As controls, antiplatelet antibodies were also searched for in mothers of non-thrombocytopenic newborns: antiplatelet antibodies were present in 8.5% (95% CI 5.9-11.7) of thrombocytopenic mothers (n = 400) and 3.2% (95% CI 0.7-9.0) of non-thrombocytopenic mothers (n = 95). The difference was significant between the control groups and the group of mothers of thrombocytopenic newborns. In conclusion, our data indicate that an immune origin is frequent in NNT and should be looked for, particularly when the platelet count is < 50 x 10(9)/l.
We report on 11 patients (nine unrelated and a brother pair) with severe haemophilia A and factor VIII (FVIII) inhibitor, in whom immune tolerance (IIT) was induced with recombinant FVIII (r-FVIII). Their age ranged from 11 months to 47 years. The number of exposure days (ED) at inhibitor detection varied from 11 to 130. Nine of the 11 patients were high responders ¿>10 Bethesda units (BU) with peak inhibitor levels ranging from 10 to 566 BU. The other two were low responders with peak levels between 0.7 and 2 BU. Before inhibitor detection, the patients had been receiving products of various purities. The IIT regimens were very heterogeneous, and the treatment schedule varied from a short period with 50 IU kg-1 every 2 days, followed by 100 IU kg-1 every 2 days and then 220 IU kg-1 daily. The outcome was considered successful when the inhibitor level fell to 0.6 BU or lower after IIT treatment. The outcome overall was successful in nine out of 11 patients (81.8%), with the nine successful cases comprising seven of the nine high responders (77.8%) and the two low responders. Definite failure of IIT was observed in one high responder after two different IIT regimens. A second high responder is still on IIT treatment. All patients in whom IIT was successful are currently receiving r-FVIII on demand or prophylactically at various dosages. Despite the variability of the patient characteristics and the IIT schedules, this study demonstrates that r-FVIII represents an effective alternative for the eradication of inhibitors through IIT.
Summary. Levels of activated factor XII (FXIIa) and VII (FVIIa) were determined in 100 women with uneventful pregnancies. Samples were divided into five study intervals: three during pregnancy, one at delivery and one 3 d postpartum.The median (range) for FXIIa levels were 3·4 ng/ml (1·2-9·1) from 11 to 20 weeks, 4·6 ng/ml (1·4-15·2) from 21 to 30 weeks, 5·4 ng/ml (1·9-14·3) from 31st week to delivery, 5·2 (1·3-11·4) at delivery and 4·3 (1·8-8·5) ng/ ml in the postpartum sample. For FVIIa the median and range levels for the five periods were 4·9 (1·7-77·3), 7·2 (2·5-80·4), 11·1 (2·9-90·6), 12·0 (3·1-64·1) and 8·2 (4·0-23·5) ng/ml. Although the increase of FVIIa was higher than that of FXIIa during pregnancy, the overall changes of FXIIa and FVIIa were highly correlated (P < 0·0001). At each time period the changes of FVIIa correlated with FVII:C which was not the case with FVII:Ag. These data indicate that during pregnancy both the contact phase and extrinsic pathway are activated.Keywords: activated factor VII, factor VII antigen, factor VII activity, activated factor XII, pregnancy.Activation of coagulation can be mediated by the extrinsic or intrinsic pathways. The first enzyme of the extrinsic pathway is factor VIIa (FVIIa), which is the enzymatically active form of the zymogen factor VII. Activated factor XII (FXIIa), on the other hand, is the central enzyme of the contact phase. Until recently, levels of FVIIa and FXIIa were estimated by indirect methods, but new assays have recently been developed. For FVIIa a clotting assay using a soluble mutant of tissue factor (Morrisey et al, 1993;Ford et al, 1996) and an ELISA are now available (Philippou et al, 1997). These assays, which enable direct measurement of FVIIa in plasma, are apparently free of interference from the FVII zymogen (Wildgoose et al, 1992; Morrisey et al, 1993; Eichinger et al, 1997;Philippou et al, 1997). For FXIIa an immunoassay is now also available (Boisclair et al, 1993); it measures FXIIa directly in plasma with minimal crossreaction with the zymogen factor XII.Due to the many changes observed in haemostatic parameters, pregnancy is a particular subject of interest in understanding the activation of coagulation in a physiological state. Two preliminary reports have indicated either an increase of FVIIa (Morrissey et al, 1993) or of FXIIa (Coppolla et al, 1996) in normal pregnancies. Since no longitudinal studies on a large group of normal pregnant women have been performed, the aim of our study was to extend these preliminary observations by measuring systematically during pregnancy, at delivery and in the postpartum both FVIIa and FXIIa, and by comparing their levels with those of FVII clotting activity, FVII antigen and fibrinogen levels. PATIENTS AND METHODSThe study protocol was approved by the Ethical Committee of the University of Geneva Hospital. 100 women with uneventful pregnancies were included in the final analysis; 21 women were not included due to gestational hypertension, pre-eclampsia, diabetes mellitus and intrauterine...
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