Vox Sanguinis (2006) 91, 88–90

© 2006 Blackwell Publishing

SHORT REPORT DOI: 10.1111/j.1423-0410.2006.00784.x

Successful treatment of premature rupture of membranes

Blackwell Publishing Ltd

after genetic amniocentesis by intra-amniotic injection of

platelets and cryoprecipitate (amniopatch): a case report
S. Sipurzynski-Budraß,1 S. Macher,1 M. Haeusler2 & G. Lanzer1
1
Department of Blood Group Serology and Transfusion Medicine, Medical University Graz, Austria
2
Department of Gynaecology and Obstetrics, Medical University Graz, Austria

Background and Objectives Iatrogenic premature rupture of membranes (PROM) occurs

Received: 22 December 2005,
revised 15 March 2006,
accepted 31 March 2006,
published online 8 May 2006
in approximately 1% of patients after genetic amniocentesis. If membranes do not seal
spontaneously, fluid leakage through the vagina may cause infection and pregnancy
loss. Intra-amniotic infusion of a platelet concentrate followed by a cryoprecipitate
(amniopatch) is a possible therapeutic approach to restore the amnio-corial link and
to facilitate the amniotic repair process.
Materials and Methods The autologeous platelet concentrate was produced by apheresis
(MCS+, Haemonetics) and contained a total amount of 48 × 109 platelets in a volume
of 30 ml. The concentration of fibrinogen in our cryoprecipitate (20 ml) was 680 mg/dl.
An amniocentesis was performed to apply the amniopatch. The platelet concentrate was
administered first followed by the cryoprecipitate.
Results We report the successful treatment of a 38-year-old woman with ruptured
membranes after genetic amniocentesis in the 16th gestational week. Ten days after
placement of the amniopatch we found a complete closure of the rupture, and in the
36th week of gestation the patient delivered a healthy infant by Caesarean section.
Conclusions Intra-amniotic injection of platelets and cryoprecipitate was a successful
and safe therapy for PROM in this patient. Knowledge of the site of rupture is not
necessary for the amniopatch, as platelets seem to find their way to the defect and seal
it. We consider that amniopatch therapy for iatrogenic PROM is a possible therapeutic
alternative for prolonging and preserving pregnancy and improving the fetal outcome.
Key words: amniopatch, genetic amniocentesis, iatrogenic PROM, intra-amniotic
infusion.

Spontaneous rupture usually occurs in the lower uterine

Introduction
The natural history of premature rupture of membranes (PROM)
differs between spontaneous and iatrogenic cases [1]. The overall
perinatal mortality is 60%, and nearly one-third of these
deaths occur in utero because of infection and pulmonary
hypoplasia. Surviving infants may suffer from blindness, chronic
lung disease and cerebral palsy [1–4].
Correspondence: S. Sipurzynski-Budraß, Department for Blood Group
Serology and Transfusion Medicine, Medical University of Graz,
Auenbruggerplatz 3, A-8036 Graz, Austria
E-mail: sabine.sipurzynski@klinikum-graz.at
segment and is, in the majority of cases, the final result of an
undetected infection; hence, treatment with intra-amniotic
infusion of platelets and cryoprecipate is unsuccessful [1,4–6].
Iatrogenic PROM, however, is evoked in ≈ 1% of cases by
genetic amniocentesis, in 4% by amniodrainages, in 6% by
fetoscopic laser procedures for twin-to-twin transfusion
syndrome and in 30–50% of cases by more complex fetoscopic
procedures [1], and may be caused by membrane detachment
and dissection of the extra-amniotic space by amniotic fluid,
without an infectious background.
Successul prolongation of the pregnancy is complicated by
the fact that iatrogenic PROM typically occurs during early

88

pregnancy. Because of the avascular nature of the fetal
membranes, the amnion is incapable of inducing platelet
activation, fibrin deposition and wound healing [3,4].
However, as an infectious background is absent in iatrogenic
PROM, the artificial administration of platelets and cryo-
precipitate may help to seal the membrane [2].
We report the successful treatment of iatrogenic PROM
in a patient after genetic amniocentesis at 16 weeks of
gestation.
Case history
A 38-year-old woman, gravida 1, para 0, had undergone a
genetic amniocentesis at 16 weeks of gestation. PROM was
diagnosed 4 weeks later by ultrasound and was confirmed
by examination, using a sterile speculum, showing vaginal
pooling of fluid, and by a positive insulin-like growth
factor binding protein-1 (IGFBP-1) test result (i.e. posi-
tivity of IGFBP-1 in vaginal fluid; actimProm; Medix
Biochemica, Kauniaininen, Finland). It is probable that the
membranes had ruptured much earlier, and that fluid loss
had been misinterpreted by the patient as a weakness of
the bladder. Treatment started with a regimen of bed rest,
prophylactic antibiotics, and daily monitoring of inflamma-
tion parameters and temperature. The patient continued to
have fluid leakage, but oligohydramnios, usually defined
as an amniotic fluid index of < 5 cm or a maximum vertical
pocket of < 2 cm, remained discrete (fluid index 5·4 cm,
maximum vertical pocket 2·4 cm), and the fetus developed
well. Although it was probably too late to prevent fetal
lung hypoplasia, amniopatch placement was performed,
without any complication, at 26 weeks of gestation to
avoid infection and intrauterine growth restriction and
because the patient was afraid of a poor outcome for a
successful pregnancy without any intervention. Fluid
leakage persisted for several days following the procedure,
but had stopped by day 10, as confirmed by vaginal fluid
testing. Complete closure of the membranes was diagnosed
and controlled by weekly ultrasound and by examination
using a sterile speculum. Pregnancy continued uneventfully,
with a normal amount of amniotic fluid (maximum
vertical pocket increasing to 7·6 cm). At 36 weeks of gesta-
tion, a healthy male infant was delivered by Caesarean
section.
Methods
Preparation of platelet concentrate
The autologous platelet concentrate (PC) was produced by
plateletpheresis using the MCS plus® blood cell separator
(Haemonetics Corp., Braintree, MA). The patient platelet
precount, of 230 × 103/µl, was used for programming the
device. We collected 145 × 109/µl autologous platelets in a
© 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 91, 88–90
Treatment of premature rupture of membranes by amniopatch 89
volume of 90 ml by processing 1100 ml of blood in 35 min
(two cycles). The total platelet count of the PC produced was
1·44 × 1011. Leucocyte depletion of the PC was performed,
after collection, by inline filtration using gravity. Thereafter,
the PC was stored under agitation of 60 cycles/min at 20–
24 °C until intra-amniotic application. According to the
dose recommended in the literature [1,2,4], we used one-
third of the PC for the amniopatch (i.e. 0·48 × 1011 platelets
in a volume of 30 ml).
Preparation of cryoprecipitate
The day before application, 200 ml of fresh-frozen plasma
(Octaplas®; Octapharma Pharmazeutica,Vienna, Austria) was
slowly thawed at a temperature of 2 °C followed by centri-
fugation (4 °C, 3000 g, 30 min), after which 150 ml of
supernatant was removed. The fibrinogen concentration in
the remaining 50 ml of supernatant was 680 mg/dl. The
cryoprecipitate was stored at −80 °C until required.
Application of the amniopatch
An amniocentesis was performed to inject the amniopatch.
After rewarming to 37 °C, the PC (30 ml) was administered
first, followed by 20 ml of cryoprecipitate via a 22-gauge
needle, directed into an available pocket of amniotic fluid.
Results and Conclusions
Intra-amniotic injection of platelets and cryoprecipitate
was found to be a successful and safe therapy for PROM in
this patient. There were no side-effects or complications during
autologous plateletpheresis and application of the amniopatch.
Preliminary experience has shown that patients with
iatrogenic PROM, occurring between 16 and 24 weeks of
gestation, and without clinical evidence of intra-amniotic
infection, are considered eligible for amniopatch therapy. In
those patients, therapy is successful in ≈ 50% [2,4], although
the precise mechanism of amniopatch treatment is unknown.
Investigations have shown that knowledge of the site of
rupture is not necessary, and that the platelets seem to find
their way to the defect and seal it [3,6]. Furthermore, it is
believed that platelet activation at the site of rupture and
fibrin formation initiate the healing process [2,3]. Some
severe cases have been reported of fetal bradycardia and
hypotension with spontaneous fetal demise following an
amniopatch procedure, probably caused by activation of a
large number of platelets with secretion of vaso-active
substances [1–3]. The development of fibrinous bands
constricting an extremity or the umbilical cord of the fetus is
a further possible risk of amniopatch, but only described as
a complication in twin-to-twin transfusion syndrome patients
with iatrogenic detached membranes [7]. On the other
90 S. Sipurzynski-Budraß et al.
hand, PROM, before 24 weeks of gestation, has a predicted
perinatal mortality of ≈ 90%, and other therapeutic approaches,
such as amnio-infusion of saline solution repeated at
regular intervals or processed by a permanent transcervical
catheter, are complicated by a high risk of amniotic
infection [4].
Although the perinatal outcome in pregnancies with PROM
after genetic amniocentesis is significantly better compared
with pregnancies complicated by spontaneous PROM, rupture
of membranes after genetic amniocentesis is such an
uncommon occurrence that information concerning
pregnancy outcomes is limited [8]. Therefore, we consider
that, according to the literature and to our experience, amni-
opatch therapy for iatrogenic PROM without spontaneous
closure in early pregnancy is a possible therapeutic alterna-
tive for prolonging and preserving pregnancy and improving
the fetal outcome.
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© 2006 Blackwell Publishing Ltd. Vox Sanguinis (2006) 91, 88–90