Key words
twin pregnancy - placenta praevia - placenta percreta - renal failure
Schlüsselwörter
Mehrlingsschwangerschaft - Placenta praevia - Placenta percreta - Niereninsuffizienz
Introduction
We report here on an unusual case of placenta percreta. Placentation disorders (placenta
accreta, increta, and percreta) occur in around 2 % of all births [1]. The incidence of placenta percreta reported in the literature ranges between 1 : 7000
[2] and 1 : 2500 [3] pregnancies. Due to increasing numbers of C-sections, however, over the last few
years the incidence appears to be on the rise.
After a diagnosis of placenta percreta has been made ante partum, there are four main
approaches for clinical management:
-
C-section with hysterectomy
-
Planned in situ retention of the placenta percreta with embolisation of the uterine
artery
-
Planned in situ retention of the placenta percreta with subsequent methotrexate therapy
-
Planned in situ retention of the placenta percreta with expectant management and close
monitoring
The main criterion for conservative management of placenta percreta is the wish of
the patient to have more children [1]. Moreover, in cases of placenta percreta with invasion of the bladder, conservative
management results in fewer operative complications, such as fistula formation or
injury to the ureter, both of which are associated with high maternal morbidity [3]. Complications of conservative management of placenta percreta described in the
literature include bleeding, infection (endometritis, wound infection, peritonitis,
pyelonephritis, uterine necrosis), sepsis and septic shock, fistula formation, thrombosis,
pulmonary embolism, pulmonary oedema, and the side-effects of methotrexate therapy
[3]. Acute renal failure has only been described in one case with methotrexate injection
into the umbilical cord and was considered an acute side-effect of methotrexate therapy
[3]. In a systematic review done in 2011, the course in 434 patients with placenta accreta,
increta, and percreta treated with conservative therapy was investigated. Severe vaginal
bleeding occurred in 53 % of cases and sepsis in 6 %; the secondary hysterectomy rate
was 19 % (6 % in patients treated with methotrexate), and maternal mortality was 0.3 %
(0–4 %). 67 % of patients managed conservatively became pregnant again [1].
Case Report
A 22-year-old gravida II, para I, with a previous history of secondary C-section and
repeat pregnancy in rapid succession, presented with a dichorial diamniotic twin pregnancy
and was diagnosed with placenta praevia totalis in the 21st gestational week (GW).
The patient was admitted to our hospital in the 24 + 1 GW with acute vaginal bleeding.
In addition to placenta praevia totalis, sonographic imaging was suspicious for placenta
percreta of the 1st twin with the placenta of the 2nd twin immediately adjacent on
the uterine wall ([Fig. 1]). This suspicion was confirmed by cystoscopy. During the patientʼs stay in hospital,
various modes of delivery including C-section followed by hysterectomy or retention
of the placenta percreta in situ followed by methotrexate therapy were discussed with
the patient and her partner. Based on the overall combination of findings they opted
to leave the placenta percreta in situ with subsequent methotrexate
therapy.
Fig. 1 Sonographic imaging of placenta praevia totalis et percreta in our patient.
After the recurrence of vaginal bleeding and the onset of labour, secondary C-section
was performed in the 27 + 2 GW and the twin placenta were left in situ. As the placenta
of the 2nd twin was directly adjacent to the placenta percreta, it was considered
too risky to remove the 2nd placenta. Two preterm infants were delivered, in differing
stages of growth. Both adapted well and continued to develop according to their stage
of maturation. The patient received 2 units of packed red blood cells perioperatively
together with prophylactic antibiosis consisting of cefuroxime administered intravenously.
On the 1st postoperative day, methotrexate therapy with the dosage tailored to the
patientʼs weight (76 mg = 50 mg/m2 median BSA) was initiated. Different therapy regimes for methotrexate dosages and
application to treat placenta percreta have been described in the literature [2], [4], [5]. The above dosage chosen by us and the application interval had previously been
used successfully in another patient with placenta percreta treated in our hospital
and corresponded to dosages given in the British therapy guidelines for the conservative
management of tubal pregnancy [6]. On the 13th postoperative day, the patient was discharged home in good general
health with further monitoring done on an outpatient basis.
The patient continued to receive a weekly application of methotrexate at the dosages
described above; each after routine laboratory investigations such as complete blood
count, CRP, and creatinine levels. The patient received a total of 8 × 76 mg doses
of methotrexate administered intramuscularly. Throughout this period, levels of β-HCG
were controlled regularly and the patient was monitored with regular sonograms. Initially,
vascularisation of the placenta praevia and percreta regressed well, but as levels
of β-HCG in serum stagnated, vascularisation began to increase again ([Table 1]).
Table 1 Course of laboratory findings during methotrexate therapy.
|
2011-04-21
|
2011-04-28
|
2011-05-05
|
2011-05-12
|
2011-05-19
|
2011-05-26
|
2011-06-03
|
2011-06-10
|
|
Hb (g/dl)
|
9.2
|
7.0
|
10.5
|
10.1
|
10.0
|
10.7
|
11.4
|
10.7
|
|
Quick (%)
|
100
|
> 110
|
|
|
|
|
|
|
|
PTT (s)
|
31
|
29
|
|
|
|
|
|
|
|
CRP (mg/dl)
|
16.5
|
3.7
|
1.3
|
1.8
|
|
2.3
|
2.5
|
1.8
|
|
Crea (mg/dl)
|
0.7
|
0.6
|
|
|
0.4
|
0.6
|
0.6
|
0.7
|
|
β-HCG (IU/l)
|
60 212
|
22 155
|
20 975
|
7 612
|
3 893
|
1 422
|
649
|
674
|
The patient was readmitted to hospital 4 days after the last administration of methotrexate
with moderate vaginal bleeding and impaired coagulation (Quickʼs value: 56 %, partial
thromboplastin time [PTT]: 36 s). After a brief time in the intensive care unit where
the bleeding was stopped and coagulation parameters improved, the patient was initially
transferred to the general ward again, and conservative management of the placenta
percreta still appeared possible. Three days later, however, there was strong clinical
deterioration with renal failure necessitating dialysis (creatinine increase from
0.5 mg/dl on admission to 3.4 mg/dl after a few days), and incipient pulmonary oedema.
The patient also presented with intermittent accompanying symptoms such as diarrhoea,
vomiting, icterus, and pancytopenia. After the patient was stabilised in the intensive
care unit, secondary hysterectomy was performed with reconstruction of the bladder.
Intraoperatively, the patient
required mass transfusion and the administration of coagulation factors. Two days
after the operation, the patient was transferred to the nephrological intensive care
unit for further treatment. Due to the pulmonary oedema she required ventilation for
10 more days. She continued to be anuric and required dialysis.
Subsequently, comprehensive differential diagnostics were done. Based on the accompanying
gastrointestinal symptoms described above and the pancytopenia, there was an initial
suspicion that the acute renal failure was a consequence of methotrexate intoxication.
But the serum methotrexate levels were already below the detection limit a few days
after administration of the last dose; moreover, the overall low dosages administered
(one tenth of the dosage administered in tumour therapies) and subsequent unremarkable
bone marrow aspiration militated against an overdose of methotrexate. Hypovolaemic
shock as the cause of acute renal failure appeared unlikely, as vaginal bleeding was
quickly stopped after admission to hospital, and the patientʼs vital parameters remained
unremarkable until she required intubation. Sepsis was excluded based on the constantly
stable CRP levels and negative procalcitonin. Haemolytic-uraemic syndrome (HUS) was
excluded because of the rapid
increase in thrombocytes after the administration of thrombocyte concentrates and
the too low numbers of schistocytes; similarly, EHEC and hantavirus serology found
no pathogens. Massive preeclampsia was also discussed as a possible cause but was
excluded from the differential diagnosis due to the fact that the patientʼs blood
pressure remained normal, she had no proteinuria and the sFlt/PlGF ratio was unremarkable.
Further diagnostic imaging finally showed bilateral necrosis of the renal cortex on
MRT as the cause of the existing renal failure. Based on laboratory findings, which
showed a fibrinogen level of < 50 at the time of the dramatic clinical deterioration,
the assumption was that pronounced disseminated intravasal coagulation was the cause
of the bilateral renal cortical damage. This was most probably triggered by a massive
accumulation of trophoblastic tissue from the twin placentas remaining in situ at
the time of the recurrence of vaginal bleeding. It is known that extensive necrosis
of the renal cortex can occur as a result of a thrombosis of the interlobular artery
and the afferent vessels, particularly after an endotoxic shock (in our case through
the accumulation of trophoblasts) with disseminated intravasal coagulation [7]. As this pathomechanism appeared to be the most plausible one, the nephrologists
in attendance decided against
performing invasive renal biopsy.
One year after renal failure the patient permanently requires dialysis and is on the
list for kidney transplantation.
Discussion
A case like the one presented here of placenta percreta with bilateral renal cortical
damage and subsequent chronic renal failure has not been previously described in the
literature. We therefore suggest that careful evaluation and detailed diagnostics
are important if placenta percreta is left in situ. The infiltration of adjacent organs,
the wish of the mother to have more children, and the special course in cases with
twin placentas with large amounts of trophoblastic material are all important points
to watch. If conservative management is chosen post partum, frequent and regular sonographic
monitoring together with monitoring of coagulation parameters and renal function is
required.
