Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

Abstract

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 x 10 9 /L. ABSTRACT antepartum intracranial hemorrhage. On this basis, it has been concluded that bBSS is associated with a very high risk of serious bleeding in the mother and the neonate. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopeniaSome information on pregnancy outcome is available also for MYH9-related disease (MYH9-RD), one of the most frequent forms of IT. A recent review of the literature examined 25 case reports and one case series describing a total of 75 pregnancies in 40 women.5 Postpartum hemorrhage in the mother occurred in 4 cases, while no obvious bleeding complications were reported among the newborns. Based on these data, MYH9-RD does not seem to increase bleeding risk either in mothers or neonates.Limited data on pregnancy outcomes have been provided for patients with mild to moderate thrombocytopenia due to monoallelic BSS (mBSS), in all cases induced by the p.Ala156Val substitution in GPIb alpha (Bolzano mutation). 6 Overall, 20 women delivered 34 children with no excessive maternal or neonatal bleeding. Although the authors did not provide information on management of pregnancies and childbirths, this study suggests that women with mBSS have gestational outcomes similar to healthy subjects.A moderate risk of bleeding during delivery has been reported in a series of subjects with thrombocytopenia induced by ANKRD26 mutations (ANKRD26-related thrombocytopenia, ANKRD26-RT).7 Thirteen patients gave birth, either vaginally or by caesarean section, with bleeding complications in 3 women. No information was provided o...

Fetal-maternal complications and their association with gestational thrombocytopenia

“…Some studies consider the following as important predictors of an increased risk of neonatal thrombocytopenia: maternal history of splenectomy, maternal platelet count of < 50 × 10 9 /L at some point during the pregnancy, and a previous pregnancy complicated with neonatal thrombocytopenia [23][24][25][26]. Noris et al [27], performed a multicenter, retrospective study evaluating 339 pregnancies in 181 women. In their study, very early preterm deliveries, the lowest birth weight, the lowest Apgar scores, the greatest number with serious post-partum hemorrhage (> 500 mL) were reported only in severely thrombocytopenic women.…”

The European Hematology Association Roadmap for European Hematology Research: a consensus document

“…As a consequence, affected patients often receive misdiagnoses and inappropriate treatments. 208 Moreover, when the right diagnosis is suspected, its confirmation requires tests that are available in only a few specialized laboratories. 209 The resulting diagnostic delay due to logistic difficulties can even put the lives of patients at risk because, as in thrombotic microangiopathies, a very early therapeutic intervention maximizes the chances of survival.…”

Inherited thrombocytopenias in the era of personalized medicine

“…However, preliminary tests are expensive and are only available in a few centers, and, in fact, diagnosis is often missed. 20 Targeted sequencing of all known IT genes as an initial diagnostic approach could be advantageous with respect to the traditional multi-step methodology both in terms of cost and of efficacy. Sequencing technologies are becoming increasingly effective and affordable, and such a test for ITs is expected to cost less than 1000 euros, a sum that compares favorably with that required for the complex and time-consuming methodology currently in use.…”