Management of a Premature Infant below 1500 g with Hemophilia A

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Management of a Premature Infant below 1500 g with Hemophilia A

C. Bidlingmaier, A. Garhammer, S. Jenkins, M. Deml and K. Kurnik

Introduction

The incidence of prematurity in Germany is approximately 10%. Obtainable litera- ture regarding the management of hemophilic newborns is nearly exclusively tar- geting at mature babies. The recommendations of the World Federation of Hemo- philia for those children are shown in the table (Table). General factor substitution is not recommended [1]. The risk of intraventricular hemorrhage (IVH) is approxi- mately 10% in mature hemophiliacs [2] but already 30% in non-hemophilic prema- ture infants, weighing below 1500 g. Therefore, the prophylaxis and treatment of IVH in hemophilic premature newborns forms a major goal for the pediatrician in care. Information on half-time and recovery of factor VIII concentrate in hemophi- lic newborns is only rarely available. To our knowledge, the case report of G ALE ET AL . forms the only explicit report on the management of a premature boy with mode- rate hemophilia weighing 1590 g [3]. We report the case of an infant weighing only 1200 g with moderate to mild hemophilia A.

Case Report

A known carrier of hemophilia A (reported factor VIII activity in the family: 0.16 IU ml ^–1 ) was admitted at 26 weeks of gestation after spontaneous rupture of membra- nes. No prenatal diagnostics were performed apart from gender determination by sonography. The male patient was born via sectio in the 28+3 gestational week

I. Scharrer/W. Schramm (Ed.)

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Hemophilia Symposium Hamburg 2003

” Springer Medizin Verlag Heidelberg 2005

Table 1. Recommendations of the World Federation of Hemophilia for birth-management of possible hemophiliacs [see Ref. 1]

쐌 if wished by the parents: prenatal diagnostics 쐌 gender determination by sonography

쐌 if possible vaginal delivery (not if problems are to be expected) 쐌 no vacuum extraction

쐌 no fetal-scalp-pH-measurements

쐌 early postpartum determination of the factor VIII level 쐌 factor substitution only on demand

쐌 early sonography of the brain

쐌 no intramuscularly application of drugs

쐌 CAVE: bleeding risk of the mother

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weighing 1200g. Factor VIII measured directly after birth was surprisingly low (0.03 IU ml ^-1 ). Sonography of the brain showed intraventricular hemorrhage °I. Therefore the patient was substituted 1 hour after birth with 50 U plasma derived factor VIII concentrate/kg body weight. Due to respiratory problems, the patient had to be ven- tilated by CPAP. He was consecutively substituted every 12 hours for the first 11 days. The IVH did not worsen and no other bleedings were observed with factor VIII levels of 60-180% 30 minutes after substitution and 22-60% before substituti- on. Factor VIII replacement therapy was then continued with 30-50 U/kg once daily until week 5. No operations were necessary and any invasive procedure (i.e. correc- tion of feeding tube, blood drawing) was done after substitution. Apart from the mild respiratory problems the only other complication was hemorrhagic enteroco- litis, which did improve spontaneously after discontinuation of oral feeding. After the stop of factor substitutions, factor VIII levels dropped to 0.03 IU ml ^–1 again (Fig. 1). No factor VIII inhibitor was observed after 35 exposure days. Factor VIII levels were controlled every day for the first week, then approximately every two to three days. At day 27 recovery (96%) and half-life (6 hrs) were measured (Fig. 2).

Due to low plasma volume more repeated measurements were considered unethi- cal, but the data collected showed longer half life during the first days of life. Re- exposure to factor VIII in the sixth month of life after a minor trauma did not lead to the development of an inhibitor. 12 month after birth the factor VIII level increa- sed to 0.09 IU ml ^-1 , probably due to maturation of the liver. Genetics of the grand- father and the patient are still unknown, but the rise of factor VIII levels indicates that the boy might only suffer from mild hemophilia, despite the lower factor VIII levels during the first 9 months of life.

Management of a Premature Infant below 1500 g with Hemophilia A 117

0 5 10 15 20 25

11.

04. 03 13.

04. 03 15.

04. 03 17.

04. 03 19.

04. 03 21.

04. 03 23.

04. 03 25.

04. 03 27.

04. 03 29.

04. 03 01.

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03 Once daily substitution with 50 U (total) ( ~ 50 – 30 E/ kg KG)

Colitis

Factor VIII before substitution [%]

Fig. 1. Course of factor VIII levels after day 11. The boy was substituted once daily with 50 U

factor VIII concentrate (~ 50-30 U/kg body weight) for the time indicated, the decrease of pre-

substitution factor levels after the colitis is caused by the increase in body weight.

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Conclusion

The very benign course of our case report shows that early substitution in a pre- mature infant with hemophilia A can prevent bleeding complications despite low post partum factor levels. Obviously this observation is limited by the fortunate lack of common complications in premature infants below 1500 g, such as the often necessary operations. In concordance with the publication by Gale et al. we report good recovery (96%) but shortened half-life (6 hrs) of the factor VIII concentrate, but both swayed considerably particularly at the beginning of the therapy. The low post partum factor VIII levels increased during the first year of life. Close coopera- tion between obstetricians, neonatologists and the pediatric hemophilia centre was essential for the successful treatment of our patient.

References

1. Giangrande, PLF. Pregnancy in Women with inherited bleeding disorders in: Treatment of Haemopilia, No. 29, Feb 2003

2. Kulkarni R, Lusher J. Perinatal management of newborns with hemophilia, B J Haematol (2001) 112:264-2743. Gale, RF. et al. Management of a premature infant with moderate haemophilia A using recombinant factor VIII, Haemophilia. (1998), 4:850-853

118 C. Bidlingmaier et al.

0 2 0 4 0 6 0 8 0 1 0 0 1 2 0

0 2 4 6 7 9 1 1 1 3 1 5 1 7 1 9 2 1 2 3 2 4

Hours after substitution

Factor VIII [%]

Half-time

Fig. 2. Half-life of factor VIII after substitution of 40 U/kg at day 27 (~ 6 hrs)