Subinvolution of placental sites (SPSs) is a rare but a potentially fatal cause of secondary postpartum hemorrhage (PPH). Although the combination of abdominal pain and vaginal bleeding has been reported as the main presenting features for SPSs, rarely SPS can present with only abdominal pain without bleeding. This can result in delay or misdiagnosis which in turn can lead to a potentially life-threatening bleeding. The report describes a case of a 29-year-old woman who presented with lower abdominal pain eight days following vaginal delivery. Although the pelvic ultrasound was in keeping with retained product of conception, the histopathology of uterine curetting’s was suggestive of SPS. The case describes a rare case of SPS. The aim of this report is to raise the awareness about SPS & to highlights the importance of considering differential diagnoses in the context of persistent postpartum abdominal pain, in the absence of excessive vaginal bleeding.

Keywords: Sub involution; Placental; Bleeding; Product; Conception; Uterine; Pain

Sub involution of placental site (SPS) or vessel Sub involution of the placental implantation site is rare, but an important cause of secondary postpartum hemorrhage (PPH). SPS can result in considerable life-threatening bleeding leading to significant maternal morbidity and mortality.

SPS is defined as delay or failure of normal physiological involution of the spiral arteries at the uteroplacental site. The exact cause of SPS is unknown, however abnormal fetomaternal immunologic reaction was suggested to be contributing to the development of SPS. The diagnosis is only be made by histopathological examination of the endometrial curetting and/or hysterectomy specimen. However, any delayed PPH along with sonographic findings of low resistance dilated vessels in the myometrium should raise the possibility of SPS.

A 29-year-old, para 2 presented to the emergency department on postpartum day (PPD) 8 with a history of severe lower abdominal pain. She had no history of vaginal bleeding, fever, urinary or bowel symptoms. The delivery was complicated by a primary PPH of 800 ml, caused by uterine atony. Complete placenta and membrane were confirmed at the time of delivery. She had an unremarkable background medical history. On initial assessment, there was severe lower abdominal tenderness but no guarding or rigidity. Episiotomy was healing well. Vital signs were normal.

The initial blood count revealed a normal white cell count (WCC) of 11.8 x 10*9\L with a significantly raised C-reactive protein(CRP) of 100.6 mg/L. Genital bacterial swabs and urine culture were negative. Pelvic Ultrasound performed on PPD 11 revealed a uterus of 13 x 94 x 70 mm in size, the endometrial thickness of 5mm, and a nodular area in the inferior part of the uterus measuring 44 x 15 x 22 mm with no internal blood flow on color Doppler, findings consistent with a retained product of conception (RPOC). Based on this, the initial clinical impression was RPOC with endometritis. Thus, the patient was commenced on IV antibiotics (Cephazolin & metronidazole) along with oral analgesia. There was a noticeable clinical improvement within two days after admission, the pain had reduced and the CRP was down to 15.9 mg\L. However, in light of ultrasound findings of the significant size of suspicious RPOC, the patient underwent ultrasound guided suction evacuation of the uterus & a sample was sent for histopathological examination. Intraoperative ultrasound revealed a gradually distending uterine cavity with blood. To control the bleeding, uterotonics medications (Oxytocin and Ergometrine) were used along with bimanual compression of the uterus & evacuation of blood clots. The estimated intraoperative blood loss was 250 ml. The bleeding settled and the hemodynamic status of the woman remained stable throughout. Postoperative recovery was uneventful, with no further vaginal or abdominal pain reported. She was discharged home on oral antibiotics (Clavulanic acid). The histopathology of the uterine curetting revealed large superficial blood vessels with features of sub involution of placental site. The follow-up reviews, there was no further episodes of abdominal pain or vaginal bleeding [Figure 1].

Figure 1: H+E showing blood vessels with little intervening myometrium and trophoblasticcells in walls of vessels (10x, 40x, and 200x). Immunohistochemistry for pan cytokeratin (MNF-116) and inhibin highlight the trophoblastic cells.

Postpartum hemorrhage (PPH) is a serious obstetric problem and a significant contributor to maternal mortality worldwide. The overall incidence of PPH is about 5-20% of all births, with the highest percentage among developing countries[1,2]. PPH is classified as primary or secondary. Primary PPH occurs in the first 24 hours from delivery, whereas secondary PPH may occur any time between 24 hours to 6 weeks postpartum. Although the frequency of secondary PPH accounts for 1% of all deliveries, it constitutes a danger to a woman’s health, as it occurs after the woman has been discharged home.

Since there is a dearth of clinical information about SPS and a relative increased risk of maternal morbidity and mortality associated with undiagnosed SPS, our aim in this case report is to draw attention to the unusual presenting features of SPS and the management approach required. SPS (also known as vessel sub involution (VSI) of the placental implantation site) is defined as delayed or failure of the normal physiologic involution of the uteroplacental arteries [3].

Normally, the remodelling process of the utero-placental vessels starts in the postpartum period to eliminate all the vessels and prepare the uterus to return to the non-gravid state. In SPS, this process is impaired resulting in the persistence of low resistance high flow dilated uterine vessels leading to postpartum bleeding [4]. SPS was first reported in literatures in 1910 by Kuster, but a clear clinical description of the case was published in 1945 by Rutherford and Herting [5,6]. Although SPS can occur at any time, from one week up to after months or years after delivery, the most common reported presenting time for SPS cases is in the second week after delivery. The exact percentage of SPS out of all secondary PPH cases is unknown, as it often gets misdiagnosed; and for a proper diagnosis to be achieved histopathological examination of uterine curetting is essential.

The exact pathophysiology of SPS is still unknown, however, there are few hypotheses that explain the process of sub involution. Abnormal immune feto maternal interactions are thought to play a role in the pathogenesis of SPS [7]. Andrew et al [8] found that the sub involuted vessels, unlike the involuted ones are deprived of immunoglobulins(IgG, IgM, IgA) and complement proteins (C1q, C3d, C4). Another theory is the inhibition of apoptosis by excessive expression of anti-apoptosis protein bcl-2, which results in the persistence of utero placental arteries in a gestation-like state [9]. The reverse happens in pre-eclampsia, when there is less expression of anti-apoptosis protein resulting in an altered and insufficient utero placental vasculature.

The diagnosis of SPS is primarily made by histopathological examination of either curetting (providing that the placental site has been sampled) or by gross examination of the uterus after hysterectomy. Histological findings of large patent and dilated myometrial vessels that have little intervening stroma and presence of intermediate trophoblastic cells within the wall, with thick and distorted walls and intramural thrombus are diagnostic of SPS [10,11]. Pelvic ultrasound may also be useful in the diagnosis of SPS, with sonographic findings of low resistance uterine vessels mainly in the inner third of the myometrium being suggestive of SPS[12]. Pulse wave Doppler sonography can be used to confirm the presence of an increased area of uterine vascularity with a low resistance waveform which can be an indicator of SPS [13]. Contrast based MRI scans could confirm the vascular prominence of the uterine wall to support a diagnosis of SPS, although these are rarely used in the clinical context [14,15]. Angiography has also been reported to be a possible diagnostic option for SPS. The differential diagnosis of SPS includes retained product of conception (as in our reported case) and arteriovenous malformation (AVM). Although it is difficult to differentiate between these conditions, sonographic findings of echogenic material in the uterine cavity is suggestive of RPOC whereas high flow uterine vessels are consistent with MVA [16].

Management of symptomatic SPS presenting with vaginal bleeding involves prompt resuscitation, use of uterotonic agents to control the bleeding, followed by full diagnostic workup to exclude other causes of secondary PPH. Dilatation and curettage of the uterus, the approach followed in our case, can be performed if ultrasound is inconclusive in terms of SPS. The option of conservative management with uterine tamponade by gauze or Bakery balloons is preferable if a diagnosis of SPS is not made. Uterine artery ligation and hysterectomy are considered additional surgical options for SPS with intractable bleeding [17]. Furthermore, percutaneous uterine artery embolization has been reported in literature as an alternative measure prior to hysterectomy to preserve fertility [16].

A single case of maternal mortality was reported as a result of intractable recurrent vaginal bleeding caused by SPS [18].

SPS is a rare but a significant cause of delayed secondary PPH. It may be misdiagnosed as it can present with only abdominal pain and can coexist or mimic RPOC. Sonographic findings of low resistance dilated thick wall vessels is diagnostic of SPS and the diagnosis can be further confirmed by histopathological examination of curetting material. SPS can be managed conservatively however uterine artery ligation and hysterectomy may be required if bleeding is life threatening.

• Physicians should have a high index of suspicion to consider SPS as a differential diagnosis in all cases of delayed secondary PPH or unresolved abdominal pain postpartum.
• SPS is considered an idiopathic and not an iatrogenic cause of PPH. The exact cause of SPS is unknown, however fetomaternal abnormal immune reaction is postulated. • If conservative management is used, patient follow up is mandatory as SPS can cause recurrent vaginal bleeding and the patient should be strongly instructed to seek medical attention if this occurs.
• Early intervention in SPS is crucial to preserve fertility. Hysterectomy is the gold standard if the bleeding is uncontrolled, but should be the last resort.

Patient consent was obtained.

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