IVH in VLBW Preterm Babies – Therapy with Recombinant Activated F VII?

Abstract

Backround Intraventricular hemorrhage (IVH) remains a dangerous and frequent complication in very low birth weight (VLBW) infants. Activated factor VII (aFVII) activates the coagulation cascade and is a potential tool for stopping active bleeding, including limiting the extent of an IVH. This retrospective treatment observation compared data for infants with IVH progression treated with fresh frozen plasma (FFP) alone or with a combination of FFP and aFVII.

Methods/Intervention All infants were subject to cranial ultrasonography at least twice daily. When an IVH was detected, treatment with FFP (5–20 ml/kg every 4–6 h) was commenced and the parents were informed. If the parents endorsed aFVII treatment and the IVH showed progress, aFVII (30–50 µg/kg body weight 4–6 times within 16–24 h) was given. Otherwise, infants were treated with FFP only. We compared the course of IVH between the aFVII+FFP treated infants and a control group (FFP only).

Results 35 patients throughout were included in the analysis (17 control and 18 aFVII group). Demographic data was not different between groups. The progress of IVH was significantly less in the aFVII group (p<0.01). During the hospital stay, 2 of the infants in the aFVII group died compared to 4 in the control group. A posthemorrhagic hydrocephalus developed in 3 aFVII and 6 control infants. All other outcome parameters and follow-up-results 2 years after treatment did not differ significantly.

Conclusion These data show that in the case of a progressing IVH, aFVII may be a candidate for limiting its extent. A prospective randomized trial is warranted.

Zusammenfassung

Hintergrund Trotz großer Erfolge der Neonatologie gehört das Management der intraventrikulären Hirnblutung (IVH) weiterhin zu den schwierigen Problemen bei der Behandlung von Frühgeborenen. Rekombinanter aktivierter Faktor VII (aFVII) aktiviert die Gerinnungskaskade und ist damit eine potentielle Option, das Wachstum eine früh entdeckten IVH zu stoppen. Die retrospektive Analyse vergleicht Daten von Patienten die, im Falle einer früh entdeckten IVH 1–2°, entweder nur mit gerinnungsaktivem Plasma (FFP) oder mit einer Kombination von FFP und aFVII behandelt wurden.

Methoden/Intervention Zwischen 2008 und 2013 wurde bei alle in unsere NICU aufgenommenen VLBW-Frühgeborenen in den ersten fünf Lebenstagen 2-mal täglich eine zerebraler Ultraschall durchgeführt. Im Falle einer nachgewiesenen IVH wurde eine Behandlung mit FFP initiert (5–20 ml/kg 4–6x tgl.) und die Entwicklung der Blutung wurde alle 3–6 h beobachtet. Gleichzeitig wurden die Eltern über die Möglichkeit einer off-Label-Therapie mit aFVII aufgeklärt, die gestartet werden sollte, wenn es zu einem signifikanten Wachstum der Blutung kommt. Bei Nachweis einer IVH-Progredienz und positivem Einverständnis der Eltern therapierten wir mit aFVII (30–50 (100) µg/kg KG 4–6x innerhalb von 16–24 h). Ohne Zustimmung der Eltern erfolgte nur die Therapie mit FFP.

Ergebnisse 35 Patienten wurden eingeschlossen (17 FFP und 18 FFP/aFVII). Demografische Daten waren nicht different. Im Vergleich zu FFP-Behandlung zeigten FFP/aFVII behandelte Kinder weniger Progredienz der IVH (p<0,01), weniger Mortalität (2 vs. 4, ns.) und entwickelten weniger oft einen ableitungsbedürftigen Hydrocephalus (3 vs. 6, ns.).

Schlussfolgerung Diese retrospektiven Daten erlauben die Hypothese, dass aFVII in der Behandlung der IVH eine Rolle spielen kann.

Key words

preterm - IVH - activated factor VII - bleeding

Schlüsselwörter

Frühgeburt - Intraventrikuläre Hirnblutung - aktivierter Faktor VII - VLBW

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