Uterine arteriovenous malformation: a case report with proposal for pathogenesis

Abstract

Uterine arteriovenous malformation (UAM) is a rare medical condition. Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients. Here, we present one elderly woman with uncommon UAM. We first discuss our experience regarding the diagnoses and treatments of UAM and then propose a hypothesis for the pathogenesis of UAM.

Introduction

Uterine arteriovenous malformation is an abnormal connection between the uterine arterial branches and the uterine venous plexus, with extremely low incidence. UAM can be classified into either congenital or acquired types. The incidence of congenital UAM is extremely low. This type of UAM is likely formed as part of the normal differentiation of primitive vascular structures at the embryonic stage and can be accompanied by vascular malformations of adjacent pelvic or remote organs. The acquired type is often secondary to trauma, infection, or develops after uterine surgery, including curettage, cesarean section, and abortion.

Even though UAM can cause abnormal and life-threatening uterine hemorrhage, there is no consensus on the clinical guideline on its treatments, most likely due to its low incidence, unknown etiology, and distinct fertility demands by different patients.

In this paper, we report an elderly patient with huge uterine arteriovenous malformation. This patient has no high risk factors of arteriovenous fistula in conventional cognition, and because of the older onset age, the possibility of simple congenital arteriovenous fistula is rare. We share this case in order to provide reference for the diagnosis and treatment of uterine arteriovenous fistula in the future, and then propose a hypothesis for the pathogenesis of UAM.

Case presentation

A 64-year-old woman (gravida 5, para 4, abortus 1) presented to our hospital due to progressively worsening abnormal vaginal bleeding over the past month. She received tubal ligation more than 25 years ago and denied any other history of pelvic or abdominal surgery. Her laboratory test showed a low hemoglobin level of 82 g/L. The patient reported dizziness, and her physical strength and spirit were worse than when she had not experienced abnormal uterine bleeding. Physical examination showed that the conjunctiva of the eyelid was pale, but her heart rate and blood pressure were still in the normal range. Color Doppler ultrasonography showed honeycomb-like diffusely dilated blood vessels within the myometrium. Color Doppler flow imaging (CDFI) examination demonstrated rich internal blood flow signals, which was consistent with arteriovenous fistula. The vessels in the left para-uterine area were expanded to approximately 8.8 X 4.8 X 3.8 cm and spread upward to the left iliac fossa (Fig. 1). Abdominal computed tomography angiography (CTA) showed bilateral markedly tortuous and dilated uterine arteries that were distributed in both sides of the uterine body, with more prominent vessels in the left side. The left uterine artery showed a local tumor-like expansion to a maximum cross-sectional area of approximately 1.8 X 1.6 cm. In the early arterial phase, the left uterine body also demonstrated venous structures, which were twisted and widened (Fig. 2). We observed the formation of labyrinthine vascular clusters at the end of the vascular structure, which appeared to be connected to the adjacent uterine artery.

Fig. 1

Honeycomb-like blood vessels within the myometrium were diffusely dilated. In the color Doppler flow images, the internal vessels had rich blood flow signals. The arteriovenous fistula spectrum was explored. The vessels in the left para-uterine area were expanded (about 8.8 X 4.8 X 3.8 cm) and extended upward toward the left iliac fossa. The arteriovenous fistula spectrum was again explored

Fig. 2

Computed tomography angiography showed bilateral obviously tortuous and dilated uterine arteries, which were distributed to both sides of the uterine body, with more prominent features in the left side. The left uterine artery displayed a local tumor-like expansion, with a maximum cross-section area of approximately 1.8 X 1.6 cm. The left uterine vein appeared early in the arterial phase and was tortuous and dilated

After ruling out surgical contraindications, we performed a bilateral uterine arteriography and embolization. Digital subtraction angiography (DSA) revealed that the left uterine artery was obviously enlarged and tortuous. The drainage veins were also significantly dilated. Convoluted vessels could be observed in the middle segment of the artery. In addition, we also noticed a twisted right uterine artery, which could be an early sign of the development of dilated veins. Fluoroscopic-guided uterine artery embolization (UAE) was performed several times during the operation until reduced blood flow, with functionally delayed veins, was visualized under the uterine arteriography (Fig. 3). After embolization, ultrasonography showed no obvious blood flow signal at the spring ring (Fig. 4). We further performed a hysterectomy plus bilateral appendectomy. During the surgery, we found that the size of her uterus was enlarged to mimic a 3-month pregnant uterus, with diffuse varicose veins on the surface. An earth-worm like vascular plexus could be seen in the broad and main ligaments and spread to the iliac vascular areas in the bilateral peri-uterine regions. These vascular structures were deep into the pelvic floor, particularly on the left side. The veins had significant expansions in the bilateral adnexal areas (Fig. 5). There was also a large number of obviously visible dilated communicating vessels branched from the peri-uterine arteries and veins, with implanted spring rings and thromboses (Fig. 6). After the operation, the patient's general condition improved, anemia gradually improved, and there was no obvious vaginal bleeding after the operation. However, the patient did not have regular follow-up after the operation and was eventually lost.

Fig. 3

a and b show bilateral markedly tortuous and dilated uterine arteries, which were distributed to both sides of the uterine body, with more prominent features in the left side. c is the image after embolization

Fig. 4

Convoluted and expanded tubular structures were found in both sides of the uterine bodies. An internal exploration of the tubular structures and the frequency spectrum of high-speed and low-resistance arteries and veins showed that the blood-supply artery came from the internal iliac artery branch. Multiple hyperechoic areas were identified in the left side of the uterine body (suggesting the spring ring), followed by a comet-tail sign with no obvious blood-flow signal found at the spring ring

Fig. 5

Diffuse varicose veins were noticed on the uterine surface. An earth-worm-like vascular plexus could be seen in the broad ligament and main ligament of the bilateral peri-uterine regions, which spread to the iliac vascular areas in both sides and deep to the pelvic floor; this was more prominent in the left side

Fig. 6

Uterine blood vessels showed many vascular communicating branches visible to the naked eye in the peri-uterine area

This patient had a large lesion, where the vessels in the left para-uterine area were expanded (about 8.8 × 4.8 × 3.8 cm) and extended upward toward the left iliac fossa. The patient was diagnosed at an advanced age without obvious inducement, which is rare in other cases [1]. When selecting the treatment method, we first considered adopting UAE because the patient was older and generally in relatively poor condition. The first assessment revealed that the patient is less likely to tolerate open surgery, for the reason that when patients are older, accompanied by anemia, and without special treatment such as UAE, there may be more intraoperative bleeding and higher risks. In addition, since the patient was postmenopausal, oral administration of estrogen and progesterone drugs may increase the possibility of endometrial lesions and breast lesions, so estrogen and progesterone drugs were not the first choice for treatment. If UAE can stop uterine bleeding, UAE can obtain the maximum benefit with the least trauma. Follow-up observation can be done after the operation. Even if the bleeding cannot be completely stopped, UAE can reduce the amount of bleeding to a certain extent, block the blood supply vessels and reduce the risk of intraoperative bleeding for the next surgical treatment. After UAE failed to completely stop uterine bleeding, we adopted a total uterus plus bilateral appendectomy treatment plan.

Review

Arteriovenous malformations can occur in every organ, particularly in the lungs and brain [2]. UAM, an abnormal connection between the uterine arterial branches and the uterine venous plexus, is rare; it was first reported by Dubreuil and Loubat in 1926 [3]. O’Brien et al. reported that the incidence of UAM was approximately 4.5% [4,5,6], although the actual incidence rate might be much higher than the reported data. With the development of diagnostic technologies and more advanced examinations performed in women, the incidence could be gradually increasing.

In general, the etiology of UAM can be classified into either congenital or acquired types. The incidence of congenital UAM is extremely low. This type of UAM is likely formed as part of the normal differentiation of primitive vascular structures at the embryonic stage and can be accompanied by vascular malformations of adjacent pelvic or remote organs. The acquired type is often secondary to trauma, infection, or develops after uterine surgery, including curettage, cesarean section, and abortion. Uterine tumors, such as trophoblastic tumors that could infiltrate blood vessel walls and create arteriovenous communications, may also lead to UAM [7, 8]. In addition, it has been reported that the uterine suturing during a laparoscopically assisted myomectomy might also cause abnormal connections between arteries and veins, with subsequent UAM developments.

In the report of nearly 120 cases of UAM published in recent ten years, we found that the vast majority of patients diagnosed with uterine or pelvic arteriovenous malformation and showing related symptoms were women in the reproductive period, and only five patients were in post-menopause period. Moreover, women in the reproductive period have recently undergone pelvic and abdominal operations before diagnosis, such as induced abortion and curettage. In contrast, our patients has been menopausal for many years and have not received pelvic and abdominal surgery for nearly 25 years, which obviously does not meet the common manifestations of UAM. Therefore, the study and analysis of this special case can help us to better understand and summarize the causes of UAM and make treatment decisions.The exact causes for the formation and progression of UAM remain unknown at the present time. Considering these previous publications and the lesson from our present case, we propose a hypothesis to explain the pathogenesis of UAM as follows.

Uterine arteries and veins are connected by blood vessels as a sequence of arterioles-capillaries-venules-small veins. When one or several small veins that converge into the uterine vein become blocked due to trauma, infection, surgery, or tumor infiltration, the blood can still flow into the uterine vein by other similar small veins through the interwoven capillary network. The extra blood flow and the increased intravascular pressure can then dilate the capillary network and small veins. When the compensatory blood vessels are overloaded and refluxes for a prolonged length of time, vascular structures can be altered. The diameters of the capillaries, arteries, and veins may be enlarged to look like arterioles or venules, which form direct anastomoses between arteries and veins and finally results in arteriovenous malformations. In addition, under the stress and possible subsequent thrombosis, the fibroblasts, endothelial cells, and smooth muscle cells can be over-activated to play an important role in the formation of a fistula. Compared with normal blood vessels, thickened arteriovenous anastomotic branches can locate closely to the endometrium, which is prone to various stimulations and injuries with abnormal uterine bleeding. The amount of bleeding may be related to the extent of the arteriovenous fistula. Since an arteriovenous fistula is commonly thin-walled and is muscle-free, with extremely poor elasticity, its bleeding is difficult to control (Fig. 7).

Fig. 7

a Normal capillary network. b Veins were blocked by embolism, tumor, or other causes. c The capillary network became congested and swollen. d Uterine arteriovenous malformations

Currently, there is no consensus on a clinical guideline to treat UAM. In clinical practice, we often rely on a patient’s symptoms, signs, age, and fertility requirements; and comprehensively evaluate the hemodynamics of the lesion to formulate treatment plans. Treatment plans can include expectant management, medication, UAE, or hysterectomy. Our patient was treated with UAE, but the effect was unsatisfactory, as she still had uterine bleeding and anemia.

We consider that the reasons for UAE failure were as follows. The arteriovenous fistula contains a large amount of blood accumulated in the vessels. UAE therapy can play a favorable therapeutic role in unruptured blood vessels. After successful UAE therapy, blood flow can sharply decline in the arteriovenous fistula. The abnormally dilated vascular anastomotic branches can gradually close and become more organized. The risk of massive bleeding is reduced. If the fistula is ruptured, embolization of the uterine artery can markedly reduce the amount of active bleeding, but the stagnant blood in an anastomotic branch can keep flowing continuously. If the vascular wound persists, there is still the risk of sudden massive bleeding after the UAE therapy. In our patient, even after the UAE therapy, a large number of communicating dilated vascular branches were visible to the naked eye in the peri-uterine region. The implant coils and thromboses could not completely block the bloodstream. This might explain the reason why the interventional therapy did not reach the optimal outcome. In addition, interventional surgery is expensive and may bring great economic burden to patients. Therefore, UAE therapy may not be the first choice in the treatment of UAM patients with active bleeding. Some studies reported to induce uterine contractions and squeeze the ruptured blood vessels to stop the bleeding. This method could be attempted to reach temporary hemostasis prior to other treatments in selected patients. A follow-up definitive treatment is required to achieve a long-term curative effect.

Conclusion

To summarize, in this article, we report a case of UAM, which showed abnormal uterine bleeding after menopause. After UAE, it failed, and finally it was treated by open hysterectomy and bilateral appendectomy. Although there is no consensus on the clinical treatment and diagnosis of UAM, clinicians should rule out the possibility of UAM in women with acute abnormal uterine bleeding. When selecting the treatment strategy, many factors, including age, fertility requirement, and lesion size and extent, should be considered comprehensively [9, 10]. Although UAE can be an effective treatment method, various other methods should also be considered to select the best treatment option and maximize the therapeutic outcomes and minimize the complications.