Differential diagnosis of uterine vascular anomalies: Uterine pseudoaneurysm as a cause of massive hemorrhage

Abstract

In this article, we comment on the paper by Kakinuma et al published recently. We focus specifically on the diagnosis of uterine pseudoaneurysm, but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms. Uterine artery pseudoaneurysm is a complication of both surgical gynecological and non-traumatic procedures. Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm. Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures, being the most frequent after cesarean or vaginal deliveries, curettage and even during pregnancy. However, there are several cases described unrelated to pregnancy, such as after conization, hysteroscopic surgery or laparoscopic myomectomy. Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment. However, there are other uterine vascular anomalies that may be the cause of severe hemorrhage, which must be taken into account in the differential diagnosis. Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.

Key Words: Uterine artery pseudoaneurysm; Vascular anomaly; Uterine vascular malformation; Massive hemorrhage; Postpartum hemorrhage; Angiography; Uterine embolization; Transarterial embolization

Core Tip: Uterine pseudoaneurysm can develop after delivery but there are several cases unrelated to pregnancy and obstetricians, such as conization, hysteroscopic surgery or laparoscopic myomectomy and gynecologists and radiologists should be aware of it. There are another uterine vascular anomalies that also may cause life-threatening hemorrhage, so awareness and suspicion is essential for early diagnosis and treatment. Doppler ultrasound is used for initial diagnosis, and magnetic resonance imaging and computed tomography angiography are valuable methods to confirm the presence of the anomaly.

TO THE EDITOR

Uterine artery pseudoaneurysm (UAP) is an acquired vascular lesion with an extraluminal collection of blood with turbulent flow, communicating the original vessel through a defect in the arterial wall. This anomaly can develop after vascular trauma during cesarean section or after gynecological procedures[1]. There are also cases described after vaginal delivery or abortion and during pregnancy[2,3]. The classification system of the International Society for the Study of Vascular Anomalies divides them into vascular malformations (VMs) and vascular tumors[4], mainly depending on the presence of increased endothelial cell turnover. VMs are structural anomalies of the venous, arterial, capillary or lymphatic systems and they do not have increased endothelial cell turnover, whereas vascular tumors arise from the abnormal growth of blood vessels.

UAP has been described as a very rare condition, but the reality is that incidence may reach 3-6/1000 deliveries-although it depends on the sources consulted, incidence varies from 2-3 to 3-6/1000 and 5-6/1000 cases of postpartum hemorrhage[5]. UAP may result from damage in the wall of the uterine artery branches so blood escapes and dissects adjacent tissues and a perivascular collection connected with the parent vessel is formed. The blood in the pseudoaneurysm is contained by fibrin or platelet crosslinks. Extraluminal turbulent blood flow can lead to enlargement of the UAP and therefore there is a risk of hemorrhage as a result of the rupture. There is a UAP that communicates with the uterine cavity and causes genital bleeding, but there is another type of UAP that does not communicate, so a hematoma outside the uterus may be formed and cause hydronephrosis.

CLINICAL CONSIDERATIONS

UAP has been described as a very uncommon condition, but its incidence may be much higher than previously considered, so based on its incidence it should not be classified as very rare. The fact is that most cases are described in the context of postpartum hemorrhage after cesarean[6,7] or vaginal deliveries[8]. However, several case reports of UAP are described in the literature after gynecological procedures such as conization[9,10], curettage or laparoscopy for myomectomy[11], hysterectomy or deep endometriosis[12,13]. Recently, massive haematuria as a clinical presentation of UAP has been published[14]. Hemorrhage may be the consequence of the rupture of the UAP. UAP can also be asymptomatic or it can lead to thrombosis. Risk of rupture may be correlated to the size of the UAP and the intramural pressure but it is difficult to predict whether a UAP will rupture.

Initial management begins with clinical suspicion of a UAP or vascular anomaly by obstetricians, gynecologists and radiologists. In the context of a secondary postpartum hemorrhage, infection or retained products of conception must be evaluated. Following assessment is usually based on Doppler ultrasound that may reveal an intrauterine mass and the blood shows a swirling flow. This to-and-fro pattern is pathognomonic of a pseudoaneurysm[15,16] and it is the consequence of blood flow into the pseudoaneurysm. After this suspicion, magnetic resonance imaging (MRI) can show a pseudoaneurysm sac-like structure within the uterus and computed tomography angiography (CTA) is valuable to confirm the presence of UAP showing a narrow connection with the uterine artery.

Management includes, in most cases, angiography for a definitive diagnosis and consequent embolization[17,18]. Embolization is routinely used worldwide in the field of vascular diseases and becomes the first therapeutic option for UAP when the patient remains hemodynamically stable. It is particularly important that an interventional radiologist be available in these cases or to have the possibility of transferring the patient to a center with possibility of performing angiography[19]. Unilateral embolization may be enough to control bleeding but sometimes bilateral embolization may be necessary due to redistribution from the opposite side uterine artery if bleeding persists. CTA can identify the bleeding site, and embolization could even be repeated if necessary. In addition, it is a fertility sparing procedure. If CTA cannot be performed, either because the patient is unstable or it is not technically available, surgery for uterine or internal iliac artery ligation or even hysterectomy may be necessary to control massive hemorrhage.

Assessment of extravasation of the ruptured UAP using contrast-enhanced ultrasonography during uterine balloon tamponade has been described in the literature[20]. The balloon produces direct compression at the bleeding point of the pseudoaneurysm, leading to coagulation at the rupture point and may be useful to locate the bleeding site at the bedside. The treatment strategy for an unruptured UAP merits further investigation. There is no consensus on whether it should be treated prophylactically or whether a watchful waiting strategy should be adopted. Both changes in the size of the pseudoaneurysm and the treatment resources available are factors involved in the indication for treatment. The feasibility of emergency uterine artery embolization if bleeding occurs is a decisive factor in treatment decision making. However, UAP is not the only possible diagnosis when a vascular anomaly is suspected. In fact, the majority of vascular anomalies can cause severe hemorrhage so a differential diagnosis must be carried out when other causes of secondary postpartum hemorrhage have been ruled out (Table 1).

Table 1 Uterine vascular anomalies.

Characteristics	Uterine pseudoaneurysm	Arteriovenous malformation	Arteriovenous fistula	Uterine hemangioma
Patient history	Vascular malformation; gynecological procedures: Curettage, conization, hysterectomy, and laparoscopy	Vascular malformation; congenital, acquired: Curettage, uterine surgery	Vascular malformation; previous uterine trauma	Vascular tumour; congenital: Associated to syndromes; acquired: Pregnancy/delivery
Signs and symptoms	Pain, fever, genital bleeding/hydronephrosis (depending on type)	Miscarriages, menorrhagia	Irregular uterine bleeding/massive hemorrhage; pelvic, vaginal, rectal, pain	Pain, vaginal hemorrhage
Risks	Rupture (hemorrhage)	Vaginal or intra-abdominal hemorrhage	Catastrophic hemorrhage	Postpartum hemorrhage, DIC
Diagnosis	Doppler US, CT, MRI	Doppler US, CT, MRI; gold standard: Angiography	Doppler US, CT or MRI	CT, MRI, angiography
Management	-	Conservative vs surgical intervention or embolization	Endovascular or open surgery	Vaginal delivery is preferred
Treatment	Angiography and uterine artery embolization	Embolization	Embolization of the communication (communicating artery?)	Conservative: Excision, embolization; surgery: Hysterectomy

US: Ultrasound; CT: Computed tomography; MRI: Magnetic resonance imaging; DIC: Disseminated intravascular coagulation.

Uterine hemangioma, which is a vascular tumor, and uterine arteriovenous malformation (UAVM) and arteriovenous fistula (AVF), apart from UAP, are VMs that can enlarge during pregnancy and can cause life-threatening, uterine hemorrhage. The rupture of congested vessels or the inability of thin-walled and dilated vessels to contract properly may cause hemorrhage. Congenital uterine hemangioma is associated with some hereditary diseases or syndromes but most published cases refer to acquired hemangioma. It is known to have many heterogenous clinical symptoms including vaginal hemorrhage, abdominal pain and others in the context of obstetric complications. Pregnant women are at risk of suffering postpartum hemorrhage and disseminated intravascular coagulation. Hormonal or physical changes of the uterine structure during pregnancy or delivery have been considered as etiologies that affect these preexisting lesions involving abnormal and excessive generation of thrombin and fibrin in the proliferative endothelium within the hemangioma.

Computed tomography and MRI can lead to the diagnosis, although the definitive diagnosis is histological. Several conservative measures have been proposed as possible treatments: Local excision, cauterization, radiation, suture ligation, cryotherapy, excision, laser photocoagulation and radiation therapy. If conservative treatment fails, hysterectomy may be considered. AVF is uncommon but may cause irregular and also life-threatening uterine hemorrhage secondary to a massive uterine bleeding. Uterine AVF occurs as a consequence of previous uterine trauma such as curettage and prior pelvic surgery[3]. The most common are aortocaval fistula, followed by ilio-iliac and aortoiliac fistula. Pulsatile pelvic mass or abnormal vascularity in the lower genital track can be identified on clinical examination of the patient. The major presenting symptoms reported are throbbing pelvic, leg, vaginal or rectal pain, menorrhagia, and dyspareunia. High output cardiac failure is reported in nearly 20% of cases.

UAVM is a rare condition and is classified as either congenital or acquired. Abnormality of vascular structures in the embryologic development produces congenital UAVMs, and usually have multiple feeding arteries and draining veins and an intervening nidus. Patients with UAVMs usually experience miscarriages or recurrent menorrhagia. Acquired UAVMs are usually traumatic, resulting from direct trauma, uterine surgery, prior dilation and curettage or therapeutic abortion. Transvaginal color duplex sonography examination may show multiple large, tortuous and dilated anterior myometrial vessels, with turbulent and high velocity arterial flow and static veins showing venous flow inside, in association with a normal endometrium. Uterine artery embolization is often considered a first-line uterine-sparing treatment for symptomatic uterine UAVMs.

The initial diagnosis of AVF and UAVMs, as in the case of a pseudoaneurysm, starts with a suspicion of a vascular anomaly. Ultrasound is used for the initial estimation, and CTA and MRI are valuable, non-invasive imaging methods. They are complementary methods to digital angiography, providing good compatibility with it to support the diagnosis and treatment. Angiography is used both for diagnosis and following embolization if it is indicated. Timely diagnosis is crucial to provide appropriate treatment for alleviating complications.

Venous malformations are the most common VM. These anomalous veins undergo gradual stretching and expansion of the lumen over time due to endothelial cellular abnormalities and severe deficiency of the smooth muscle layer[3]. The malformed veins become distended with dependency or increased venous pressure. Clinical manifestations include pelvic congestion syndrome as a result of ovarian vein insufficiency. Patients with extended venous malformation may develop intralesional coagulopathy resulting in systemic coagulopathy. MRI is used for diagnosis, and treatment is endovascular ablation. Placental chorioangioma is the most common benign tumor of the placenta[3]. Tumors under 5 cm in size usually remain asymptomatic and they infrequently produce obstetric complications. A hypo or hyperechoic well-circumscribed placental mass is the common ultrasound finding of chorioangioma. If maternal condition worsens or late onset complications with viable fetus occur, terminating the pregnancy should be considered. Prenatal intervention maybe be necessary if severe complications occur before the fetus is viable, to extend the gestation.

CONCLUSION

Several uterine vascular anomalies can produce, if rupture occurs, life-treatening hemorrhage. Diagnosis starts with the suspicion of a vascular anomaly when other causes of bleeding after gynecological or obstetrics procedures have been ruled out. There are several cases of uterine pseudoaneurysms described not only related to pregnancy but also to another procedures such as conization, curettage or laparoscopy for myomectomy, hysterectomy or deep endometriosis. Doppler ultrasound and MRI are valuable methods for diagnosis and CTA may confirm the presence of vascular anomaly and embolization can be performed as first therapeutic option.