Perinatal Management of Haemophilia

Abstract

The aim of this review is to provide practical guidance for the treatment of carriers of haemophilia and newborns presenting with haemophilia. Both mother and newborn have an increased risk for clinically relevant bleeding. An experienced team should manage genetic counselling, prenatal diagnosis, pregnancy, delivery and the newborn presenting with haemophilia. Published and regularly updated guidelines must guide this team. Vaginal and caesarean deliveries before labour entail a comparable bleeding risk. Haemophilia carriers should receive factor concentrate (FC) at the time of delivery if their factor level is below normal. Evidence remains insufficient to recommend systemic desmopressin and tranexamic acid for the prevention of peripartum haemorrhage. Primary prophylaxis with FC for all newborns with severe haemophilia is not justified. The pattern of bleeding seen in the affected newborns is essentially different from that seen in older children. Estimated frequency of intracranial haemorrhage (ICH) is 2 to 3%. Cranial ultrasound is a good screening method for ICH in newborns. Many neonatal bleeds are iatrogenic in origin. The most prominent concerns regarding neonatal factor replacement are the risk for inhibitor development, followed by local bleeding and issues related to poor vascular access. The preference for plasma-derived FC and recombinant FC differs widely between centres and countries. Replacement therapy should be monitored since newborns may require higher doses of FC. Emicizumab, licensed for all age groups since 2019, should not be used in newborns with severe haemophilia A and acute bleeding, although “non-factor” agents are expected to revolutionise haemophilia therapy.

Zusammenfassung

Ziel dieser Übersicht ist eine praktische Anleitung zum Umgang mit Überträgerinnen von Hämophilie (Konduktorinnen) und Neugeborenen mit Hämophilie zu geben. Sowohl Konduktorinnen als auch betroffene Nachkommen haben ein relevant erhöhtes Blutungsrisiko. Nur ein erfahrenes Team sollte genetische Beratung, Pränatal diagnostik, Schwangerschaft, Geburt und das betroffene Neugeborene betreuen. Publizierte und regelmäßig aktualisierte Leit- und Richtlinien müssen immer die Grundlage des Handelns sein. Die vaginale Entbindung und der elektive Kaiserschnitt haben ein vergleichbares Blutungsrisiko. Für Konduktorinnen, die bei der Geburt einen Faktorspiegel unter dem Normalwert aufweisen, sind Faktorkonzentrate empfohlen. Die Wirksamkeit von Desmopressin und Tranexamsäure zur Behandlung peri- und postpartaler Blutungen ist nicht gesichert. Eine primäre Prophylaxe mit Faktorkonzentraten aller Neugeborenen mit schwerer Hämophilie ist nicht gerechtfertigt. Blutungen des Neugeborenen unterscheiden sich grundsätzlich von denen des älteren Kindes. In 2 bis 3% treten intrakranielle Blutungen auf. Die Ultraschalluntersuchung ist eine gute Suchmethode zum Ausschluss einer intrakraniellen Blutung beim Neugeborenen. Viele Blutungen werden erst durch medizinische Manipulationen verursacht. Die größten Bedenken gegen eine frühe Behandlung mit Faktorenkonzentraten von hämophilen Neugeborenen sind die Entwicklung eines Hemmkörpers gegen FVIII/ IX, lokale Blutungskomplikationen und der problematische venöse Zugang. Unterschiedlich nach Land und Zentrum werden bevorzugt aus Plasma hergestellte oder rekombinante Faktorkonzentrate verabreicht. Bei jeder Faktorgabe sollte der Faktorspiegel überwacht werden, da Neugeborene mehr Faktor benötigen können als ältere Kinder. Zurzeit wird von der Verwendung von Emicizumab, das seit 2019 für alle Altersgruppen zugelassen ist, für Neugeborene mit schwerer Hämophilie A und akuter Blutung abgeraten, auch wenn zu erwarten ist, dass “non-factor” Medikamente die Behandlung der Hämophilie revolutionieren werden.

Keywords

haemophilia - pregnancy - bleeding disorders

Schlüsselwörter

Hämophilie - Schwangerschaft - Blutungsrisiko

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