The management of pregnancy for a woman with bilateral Klippel-Trenaunay syndrome: A case report

Abstract

Klippel-Trenaunay syndrome is rare. It is diagnosed in childhood and the gender distribution is almost equal. A challenge arises in pregnancy, as several risks are significantly elevated, such as hemorrhage, bleeding of the varicosities, and life-threatening thromboembolic events. Due to the rarity of the condition, there is limited literature and guidelines regarding management of pregnancy for these patients. This report describes a successful pregnancy outcome in a 34-year-old primigravida with Klippel-Trenaunay syndrome. The aim is to contribute to the limited literature pertaining to this condition and emphasize the role of meticulous planning of antenatal care and birth, to help formulate clinical guidelines in the management of pregnancy in Klippel-Trenaunay syndrome. Multidisciplinary comprehensive clinical evaluation, involving obstetricians, vascular surgeons, a thrombosis team, anesthesiologists, intensivists, radiologists and intervention radiologists, along with the use of ultrasound and magnetic resonance imaging, aids in identifying the extent of disease and to individualize management.

Highlights

• •For patients with Klippel–Trenaunay syndrome (KTS), pregnancy carries high thrombotic and hemorrhagic risks.
• •Anticoagulation management for pregnant patients with KTS requires individualised assessment.
• •Vascular mapping with magnetic resonance imaging is crucial for delivery planning with these patients.
• •Multidisciplinary team care enables safe pregnancy and delivery outcomes.
• •Elective cesarean section may reduce hemorrhagic risk where there are pelvic vascular malformations.

1. Introduction

Maurice Klippel and Paul Trénaunay in 1900 first described a rare congenital syndrome characterised by vascular malformation of the capillary, venous and lymphatic vessels, with hypertrophy of both soft and skeletal tissues. The reported incidence of Klipple- Trenaunay syndrome (KTS) is 2–5 in 100,000 births [1]. Hence there is paucity of literature in the optimal management of pregnant patients with KTS. A multidisciplinary (MDT) combined with an imaging-guided approach enables safe pregnancy and delivery in women with KTS despite their significantly elevated vascular risks. The challenge in management is to strike a fine balance between the risks of hemorrhage versus thromboembolic events as these haematological complications worsen in pregnancy [2]. This report describes a successful pregnancy outcome in a 34-year-old primigravida with Klippel-Trenaunay syndrome. The aim is to contribute to the limited literature pertaining to this condition, to emphasize the role of meticulous planning of antenatal care and birth, and to help formulate clinical guidelines in the management of pregnancy in KTS.

2. Case Presentation

A 34-year-old nulliparous woman, diagnosed with bilateral Klippel-Trenaunay syndrome (KTS) and with a history of chronic deep vein thrombosis (DVT) of the right popliteal vein and superficial femoral vein, was referred by the vascular team for pre-conceptional counselling. She had been followed prior to conception by the vascular surgeons and thrombosis/hematology team. She had bilateral limb hypertrophy (right more than left), varicose veins and capillary malformation/naevi, and was on conservative symptomatic management. As her D-dimer was significantly elevated she had been on rivaroxaban 10 mg oral tablet daily for over a year.

During her visit to the pre-conceptional clinic, she was counselled in detail regarding the possible implications of the syndrome in pregnancy, which included worsening of thromboembolic and hemorrhagic complications. Her concerns were addressed and she was reassured that it is a somatic mutation that causes the congenital disorder and is not passed to the offspring. Drug safety profile was reviewed, and she was switched from rivaroxaban to a low molecular weight heparin (LMWH), enoxaparin 40 mg (administered subcutaneously). She was advised to continue aspirin and to start folic acid.

The patient had had sclerotherapy and fasciotomy performed at 10 years of age. She had experienced pain over the capillary malformation region in the right thigh and on two occasions, a month apart, and CO₂ laser treatment was performed. In addition, she underwent a hemorrhoidectomy and lateral anal sphincterotomy seven years before the pre-conceptual counselling, during which she developed peri-operative hemorrhage requiring transfusion of blood and blood products.

She was booked in early pregnancy and was on close follow-up throughout. Her antenatal period was uneventful.

The mode of delivery was discussed with her, and she was scheduled for elective cesarean section at 36+ weeks of gestation, under general anesthesia. This plan was made following a meeting of the MDT, involving radiologist, vascular team, hematologist and anesthetist. The decision was based on a detailed review of the magnetic resonance imaging (MRI) of her abdomen and pelvis, which outlined the vascular distribution in those areas.

On examination, she was of average build. She had an uneven gait due to right-sided lower-limb hypertrophy. Port-wine pigmentation could be appreciated on the lateral aspect of both thighs and the right side of the abdomen from right flank to the groin, sparing the umbilicus and not extending to the midline (Fig. 1, Fig. 2). The right foot had a varus deformity, and multiple surgical scars were noted in the right leg.

Fig. 1.

Image depicting the capillary malformation and hypertrophy of the affected lower limb.

Fig. 2.

Image of the gravid abdomen with port-wine stain and capillary malformation.

The symphysiofundal height corresponded to 36 weeks of gestation; the uterus was relaxed with cephalic presentation, with good fetal heart rate on auscultation.

On examination of the perineum, varicosities were noted in the clitoris; however, the vagina looked normal, with no visible varicosities.

Booking labs including serology screen, full blood count, coagulation profile and serial pregnancy ultrasound were within normal limits.

Ultrasound evaluation abdominally and vaginally was performed but was inconclusive, which prompted further assessment with MRI. The MRI of the abdomen and pelvis were done for vascular mapping. Large venous channels extending from the suprapubic region deep into the pelvis and perineum and right inguinal region were seen (Fig. 3, Fig. 4). The infraumbilical region at the midline to the level of the pubic symphysis did not contain any major veins. Anterior to the level of pubic symphysis there were few collaterals extending to the perineum right inguinal region and a plexus of large vascular collateral extending to the level of left labia/ vulvar region.

Fig. 3.

Axial T2 fat-saturated images of the pelvis. Multiple right pelvic wall/lower abdominal wall and right gluteal enlarged venous collaterals noted (arrowheads). Large plexus of veins was also noted at the perineum/vulvar region (arrow).

Fig. 4.

Axial T2 fat-saturated images of the pelvis. Multiple right pelvic wall/lower anterior abdominal wall and right gluteal enlarged venous collaterals noted (arrowheads). Large plexus of veins was also noted along anterolateral aspects of the uterus and pelvic side walls (arrow).

The mode of delivery was discussed by the MDT after reviewing the MRI findings. The patient was involved in decision-making, and a cesarean section was scheduled, given that the patient had multiple abnormal vascular collaterals in the pelvis and perineum, increasing her risk of traumatic post-partum hemorrhage during vaginal birth. This would have been difficult to manage as an emergency had the patient presented in advanced labour.

Perioperative planning included insertion of central venous access and arterial lines, arrangement for cell saver and alerting the blood bank for activating the massive blood transfusion protocol if needed in anticipation of hemorrhage. The decision to proceed with general anesthesia was based on the possibility of abnormal neuraxial vascularity in cases of KTS which could potentially result in hemorrhage with the use of regional anesthesia. Vascular surgeons were available on site for vessel identification and control of bleeding. The interventional radiologist was also informed in case embolisation was needed. Mechanical DVT prophylaxis in the form of a pneumatic compression device was used perioperatively.

Under general anesthesia, an infraumbilical midline incision was made. No significant vessels were encountered. Prominent tortuous vessels on the parietal peritoneum towards the right side were noted. The bladder base had a few engorged vessels. Lower segment cesarean section was done and a male baby weighing 2365 g with good APGAR scores was delivered. The estimated blood loss was 400 ml. The uterus, both tubes and ovaries looked normal.

The patient had an uneventful postoperative period and was discharged with a follow-up appointment. She was counselled regarding contraception. At 3-month follow-up, the patient and her baby were doing well. She was switched back to rivaroxaban 10 mg from LMWH as she had chosen to stop breastfeeding by then.

3. Discussion

Historically, KTS was referred to as a disease of naevus vasculosus osteohyper-trophicus. The diagnostic triad is that of vascular malformations and/or varicosities, and hypertrophy of the bone or soft tissues in one or more extremity. Despite being typically sporadic, KTS has been observed in families without following Mendelian inheritance, implying a multifactorial basis [3]. However, there is lack of robust literature because the disease is rare, with fewer than 100 cases reported worldwide [4].

The venous malformations and hypercoagulable states in pregnancy contribute to heightened risk of deep vein thrombosis (DVT) and pulmonary embolism. Pregnant patients with KTS have a significant risk of worsening symptoms, due to increased circulating blood volume, changes in hormone levels, and venous obstruction by the enlarged uterus [2]. Furthermore, the capillary malformations and venous congestion present in the syndrome itself increase risk of thrombosis [5]. Prenatal counselling, antenatal care, use of thromboprophylaxis, and mode of delivery for these women need meticulous planning (Table 1).

Table 1.

List of challenges in pregnancy and their management in Klippel-Trenaunay syndrome.

Period of pregnancy	Challenges	Management
Pre-conceptional period	•Counselling regarding the possible risks like worsening of thromboembolic and hemorrhagic complications.	•Judicious use of anticoagulation during pregnancy and switching oral medications to injectable low molecular weight heparin. •Though KTS is a congenital disorder it is due to somatic mutation and it is not passed to the offspring. •Rivaroxaban was switched to enoxaparin 40 mg and aspirin was continued •Drug safety profile was reviewed
Antenatal	•Early prenatal care •Close follow-up throughout her antenatal period •Individualize the mode of delivery	•Identification and correction of anemia •Clinical assessment for extent of disease •Serial fetal growth surveillance •Vascular mapping using appropriate imaging techniques •MDT meeting, involving radiologist, vascular team, hematologist and anesthetist.
Intrapartum	•Perioperative planning •Techniques to minimise blood loss •DVT prophylaxis	•Consent for Cesarean section, uterine artery/ internal iliac artery ligation explaining the risk of life saving hysterectomy •Alert Ot team and blood bank •To minimise blood loss techniques •Consider use of tranexamic acid •Arrange cell saver •Central venous access •HDU bed •Incision and techniques to avoid vascular injuries •Avoid regional anesthesia •Mechanical DVT prophylaxis •Avoid unnecessary use of drains as it may cause inadvertent injury to the abdominal vasculature
Post natal	•Time to restart thromboprophylaxis •Contraception •Follow-up	•Restarting LMWH after 12–24 h after delivery and considering oral anticoagulation if mother chooses not to breastfeed. •Contraception advice •Follow-up after 4–6 weeks with multidisciplinary team

* KTS = Klippel-Trenaunay Syndrome, MDT = multidisciplinary team, DVT = deep vein thrombosis, HDU = high dependency unit, LMWH low molecular weight heparin.

Antenatally an increased risk of fetal growth restriction has been frequently reported [6]. Prenatal diagnosis of KTS is possible and increasingly reported, especially when limb hypertrophy or vascular anomalies are detected via fetal imaging. Colour Doppler ultrasound plays a key role in identifying both fetal and maternal vascular features that may affect delivery [7]. Limb hypertrophy or multi-loculated cystic lesions at the level of the thorax abdominal wall or limbs can be easily identified by fetal colour Doppler flow.

Regarding use of thromboprophylaxis, there are no prospective data and it should be discussed and individualised. Pharmacological thromboprophylaxis strategies in KTS need further investigation, and risks of having a significant bleeding versus thromboembolic events must be taken carefully into consideration. However, the most frequently observed complication during pregnancy in women with KTS is DVT, both during and after childbirth. If a patient has had a thrombo-embolic event in the past, therapeutic coagulation is indicated [8]. Antithrombotic stockings are generally advised.

Neuro-axial vascular anomalies can significantly increase the risk of complications of regional anesthesia [9]. Early detection of vascular malformations such as posterior cutaneous hemangiomas or epidural and subdural anomalies allows clinicians to tailor anaesthetic techniques and avoid high-risk areas, ultimately improving outcomes and minimizing neurological injury.

Decision on mode of delivery in such cases is challenging. There was a successful pregnancy outcome in the present case, with delivery by elective cesarean section without any vascular complications. Although there are limited reports on successful labor induction and alternative delivery approaches, in the present case MRI showed large vascular collateral extending from suprapubic region deep into the pelvis and perineum and right inguinal region.

Vascular malformations in KTS are typically segmental, meaning they follow embryonic developmental patterns and do not cross the midline of the body [10]. This was evident in the present case, and the patient was planned for a midline abdominal incision for cesarean, anda careful approach to delivery planning with vascular surgery team. This case report is comparable to others, such as the successful pregnancy outcome reported by Silva et al. [11].

Risk assessment and anticipation of massive hemorrhage, use of intra-operative autologous blood recovery, activation of massive transfusion protocol, intra-operative vascular surgery team with advanced perioperative strategies can be life-saving and contribute to better outcomes. This report highlights the importance of individualised antenatal care and a multidisciplinary approach. Currently, there is limited literature and a lack of evidence-based practice guideline in the management of pregnancy in KTS. Considering the high-risk nature of this condition, women with KTS previously feared conception. However, in the present case meticulous planning helped overcome the challenges of KTS during pregnancy. Regarding the mode of delivery, reports suggest elective cesarean section is to be preferred, especially in cases involving deep pelvic and vulvovaginal varicosities and vascular malformations, as in the present case, further supporting this delivery method as a suitable choice for pregnant patients with KTS who have extensive pelvic and perineal vascularity [11]. Furthermore, vascular mapping by clinical examination and advanced imaging techniques like MRI can guide optimal management [12].

4. Conclusion

The successful outcome of this patient highlights the importance of a co-ordinated, MDT approach in managing complex syndromes of KTS during pregnancy. The involvement of obstetricians, neonatologists, anesthesiologists, intensivists, blood bank specialists and vascular surgeons, along with the judicious use of prophylactic anticoagulation during pregnancy and the postpartum period, was instrumental in ensuring maternal and fetal well-being. This case underscores the value of pro-active planning and collaborative care in achieving optimal results for high-risk pregnancies.

Contributors

Meenakshi Menon R and Richa Sasmita Tirkey contributed to contributed to patient care, drafting the manuscript and undertaking the literature review.

Edwin Stephen, Ahlam Al Hinai, Aaisha Al Balushi, Bashair Al Siyabi, Dina Al Balushi, Khalifa Al Wahaibi, Ibrahim Abdelhady, Bader Al Rawahi, Yarab Al Bulushi, Azza Al Abri, and Kusuma Helemani contributed to patient care and revising the article critically for important intellectual content.

Nihal Al Riyami contributed to patient care, editing and revising the article critically for important intellectual content.

All authors approved the final submitted manuscript.

Patient consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Provenance and peer review

This article was not commissioned and was peer reviewed.

Funding

No specific grant from funding agencies in the public, commercial, or not-for-profit sectors supported the publication of this case report.

Declaration of competing interest

The authors declare that they have no competing interest regarding the publication of this case report.