Multidisciplinary approach to Klippel–Trenaunay syndrome: a case report

Abstract

Klippel–Trenaunay syndrome (KTS) is a rare inherited disorder presenting as a triad of capillary malformations (cutaneous hemangiomas), soft tissue hypertrophy, and varicosities. Two out of three signs are enough to make a diagnosis. It is associated with gastrointestinal, hematological, neuro-ophthalmic, dermatological, pulmonary, oro-dental, renal cardiac, and vascular complications. There is no curative treatment for the disease. Complications are currently managed symptomatically and thorough documentation of all signs and symptoms is essential for timely identification and management of potential complications, thereby improving patient outcomes. KTS was diagnosed in a 16-year-old female, with dyspnea and fever associated with hemoptysis and abdominal pain. On physical examination, cutaneous findings and signs of respiratory compromise as well as evidence of vascular disease were observed. After appropriate medical care, the patient was soon discharged from the hospital. Following initial treatment, the patient’s symptoms arbitrarily recurred requiring continued medical management and blood product administration to manage complications resulting from KTS. KTS is a chronic disorder with no cure. Patients with KTS are managed symptomatically and require frequent hospitalizations for the same.

Introduction

Klippel–Trenaunay syndrome (KTS), also known as angio-osteohypertrophic syndrome^[1], is uncommon and has no racial or geographic prevalence. It has an incidence of 2–5/100 000 population^[2] with a mortality rate of approximately 1%^[3]. The clinical triad in it consists of port wine stains, venous tortuosities, and bone & fat hypertrophy. This may also covers pain, swelling, bleeding, superficial thrombophlebitis, and deep vein Thrombosis^[3]. In some cases, patients with congenital vascular disorders like KTS may have associated cardiac anomalies^[4,5] although this is rare.

HIGHLIGHTS

• Rare case presentation: This report presents a unique case of Klippel–Trenaunay syndrome (KTS) in a 16-year-old female, highlighting its severe bleeding manifestations and vascular complications.

• Multisystem involvement: The patient exhibited complex symptoms, including consumptive coagulopathy, recurrent hemorrhagic episodes, and venous malformations, requiring a multidisciplinary approach.

• Advanced diagnostic techniques: MRI, Doppler ultrasound, and colonoscopy played a crucial role in confirming the diagnosis and evaluating the extent of vascular abnormalities.

• Tailored management approach: The treatment plan included supportive care, blood transfusions, compression therapy, and systemic medications to manage symptoms and prevent complications.

• Significance for clinical practice: This case underscores the need for early diagnosis, individualized treatment strategies, and interdisciplinary collaboration in managing complex vascular syndromes like KTS.

Since KTS is known to show rare manifestations and complications as well, we have adapted the treatment approaches in accordance with each patient’s specific symptoms, clinical course in progression, and prognosis^[6,7]. Gastrointestinal involvement is suspected to be present in up to 1–13% of patients with KTS with implications for health-related outcomes. Its severity can be worsened by a pre-existing coagulopathy and/or anemia.

We present the case of a 16-year-old female patient diagnosed with KTS with bleeding manifestations in 2018 with 3 hospitalizations over a year for the same. The patient was thoroughly screened for possible complications and managed appropriately by various departments for the same.

Case presentation

A 16-year-old female with no known comorbidities presented to the hospital in 2018 with chief complaints of shortness of breath, fever with chills and rigor, and bleeding per rectum for 3 days. She also gave a history of nonbilious vomiting which was previously associated with hematemesis. There was no significant history or family history.

Physical Examination

On evaluation, the patient was found to be febrile, pulse was 92 bpm and Blood Pressure was 110/70 mm Hg. The patient was febrile at presentation, with a temperature of 101.2°F (38.4°C), and exhibited chills and rigor suggestive of an underlying infective process. Systemic examination revealed bilateral crepitations and a soft systolic murmur on auscultation. Physical examination showed right lower limb hypertrophy with tortuous venous dilatation and port wine stain (Fig. 1). Dark raised bleeding lesions and multiple verrucous nodules of reddish blue to black color and size of 20 × 15 cm note which were tender to touch were noted on the right lower limb (Fig. 2). There was a history of spontaneous rupture of a lesion over the right gluteus with bleeding. Per rectal examination Indicated lax sphincter tone with multiple papillomatous lesions over the right gluteal region. It was loaded with soft feces and the rectum was found to be normal.

Figure 1.

Right lower limb hypertrophy with tortuous venous dilatation and port wine stain.

Figure 2.

Dark raised bleeding lesions and multiple verrucous nodules.

This case report has been done according to the CARE guidelines 2013 criteria^[8].

Investigations

We performed relevant laboratory investigations and they showed a hemoglobin of 2.3 gm%, hematocrit of 9.8%, INR of 1.77, and potassium of 2.9 mEq/L (Table 1). Ophthalmic evaluation showed visual acuity of 6/ 36 in the left and normal acuity in the other eye. Fundus evaluation showed a hypermetropic optic disc on the left.

Table 1.

The laboratory examination at the time of the first admission

Days since admission	Day 1	Day 2	Day 6	Day 12	Day 18	Day 24
Laboratory investigations
Hemoglobin (Hb)	2.3 gm%	5.4 gm%	5.6 gm%	6.5 gm%	9.5 gm%	7.3 gm%
Hematocrit	9.8%	18.1%	19.6 &	23%	21.2%	26.7%
Platelet count	83OOO /cumm	9000/cum	18 000 /cumm		441 000 /cumm
Total leucocytic count (TLC)	11 000/cumm	8180 /cumm	5800 /cumm		6400/cumm	6400 /cumm
Peripheral blood smear			Microcytic hypochromic with normocytes, few fragmented red blood cells and teardrops		Microcytic, hypochromic with anisocytosis and few macrocytes and normocytes	Normocytic hypochromic
Serology
BSL random			121 mg/dl	164 mg/dl
Liver function test (LFT)
Total protein			6.76 g/dl	7 gm/dl
Albumin (A)			3.13 g/dl	3.29 g/dl
Total bilirubin			1.1 mg/dl	1.21 mg/dl
Direct bilirubin			0.24 mg/dl	0.27 mg/dl
Alanine transaminase			79 IU/L
Coagulation profile
INR	1.77
Plasma fibrinogen (PT-FG)	211
Potassium		3.6 mEq/L	2.9 mEq/L	3.6 mEq/L		3.7 mEq/L
Sodium		134 mEq/L	133 mEq/L	141 mEq/L		135 mEq/L
Renal function test
Blood urea			108 mg/dl	13 mg/dl	13.2 mg/dl
Creatinine		0.7 mg/dl	0.6 mg/dl	0.39 mg/dl	0.32 mg/dl	0.6 mg/dl

Differential diagnosis

Based on the history, clinical findings and laboratory investigations , we considered differential diagnoses of KTS as, congenital lipomatous overgrowth vascular malformation with epidermal nevus and skeletal abnormalities, (diffuse capillary malformation with overgrowth, Beckwith–Wiedemann syndrome and Parkes–Weber syndrome.

Radiological examination

A colonoscopy was done given PR findings and it showed internal hemorrhoids with vascular prominence throughout the colon and rectum. The patient was advised to undergo Magnetic Resonance Imaging of both the lower limbs. It showed right lower limbs with large, mildly longer hypertrophied vessels with T1 hypointense and T2 hyperintense vascular spaces. Linear tortuous lesions were found in the subcutaneous fat planes of the gluteal lesions predominantly in the right lower limb. Similar nodules were noticed in the posterior and anteromedial aspects of the pelvic wall and extending into the labia on the right side. These features were suggestive of slow-flow venous malformations thus indicating KTS. All other veins were normal. Venous Color Doppler was done to confirm the findings. MRI brain Arteriogram/Venogram showed bilateral hypoplastic posterior communicating arteries.

CT was done to rule out pulmonary embolism. Thus, the patient was diagnosed With KTS along presented with bleeding per rectum and severe dimorphic anemia with thrombocytopenia. According to the ISSVA Classification, KTS is categorized under slow-flow vascular malformations, requiring imaging and clinical criteria for confirmation. Ultrasound alone may lead to misdiagnosis, and advanced imaging (MRI, Doppler) is recommended for accurate differentiation.

Treatment and management

The patient was started on supportive management with oxygen support, intravenous fluid and hemodynamic monitoring. The patient was advised to wear compression stockings and maintain good local hygiene for chronic venous insufficiency. Due to the suspicion of Kasabach–Merritt phenomenon (KMP), the dermatology department advised starting systemic corticosteroids if coagulopathy worsened. Hematology advised blood transfusion due to severe anemia (Hb 2.3 g/dL); two units of packed red blood cells were administered. Electrolyte imbalances were corrected, including intravenous potassium supplementation. The patient was closely monitored and discharged on oral iron therapy and multivitamins.

The patient was discharged on medications.

Second admission

She was admitted with anemia and per rectal bleeding. The recorded Hb was 6.5 mg/dl and platelet count was 18 000/cumm, which improved to 8.5 mg/dl on day 18. Additional labs showed normalized TLC (6400/cumm), serum potassium (3.6 mEq/L), and creatinine (0.39 mg/dL). For management two units of packed red blood cells (PRBC), initiated injection tranexamic acid (antifibrinolytic), IV ceftriaxone (suspecting secondary infection), and vitamin B complex supplementation. Ceftriaxone was initiated in response to low-grade fever and suspected secondary infection. After symptomatic improvement, she was discharged with advice on iron-rich diet and regular follow-up.

Third admission

On the third hospitalization, with recurrent GI bleeding and hematemesis, she was diagnosed with consumptive coagulopathy associated with KTS. Light lower limb showed soft tissue hypertrophy, tortuous venous channels, and healed lesions. We transfused one unit PRBC again and managed supportively. Tranexamic acid was prescribed for use in case of minor bleeding. No surgical intervention was required. She was discharged on oral iron, folic acid, and advised referral to hematology-oncology for specialized care.

Follow-up and subsequent presentation

The patient presented again 9 months later with shortness of breath and exercise intolerance, a history of bleeding per rectum for 3 months, and a history of bleeding from the leg. A physical exam revealed a hypertrophied right lower limb with tortuous veins. Investigations revealed microcytic hypochromic anemia and thrombocytopenia, multiple perianal papillomatous lesions, fissures at the noon position, and external hemorrhoids at the 12 o’clock position. The patient underwent two blood transfusions and was started on a regimen of Injection Tranexamic acid and Ceftriaxone supplemented with intravenous Vitamin B complex. The patient was thus discharged upon resolution of symptoms.

The patient was admitted again after 7 months with complaints of bleeding per rectum, fever, hematemesis, melena, and shortness of breath. On evaluation, the patient was found to have a pallor and all other vitals were within normal limits. Systemic examination was unremarkable. Relevant laboratory investigations were done and the patient was diagnosed with a concurrent state of consumptive coagulopathy with KTS. The patient was given a whole red blood cell transfusion and discharged with appropriate medications (Table 2).

Table 2.

Clinical timeline of events and interventions

Timeline for admission	Clinical details	Approximate time point
Presentation at the first reporting	Dyspnea, fever, hemoptysis, rectal bleeding.	Day 0 in OPD
First hospitalization	Severe anemia (Hb 2.3 g/dL), venous malformations identified via imaging, transfused.	Week 1
First discharge	Discharged on compression therapy, local hygiene advice, and oral iron.	Week 2
Second hospitalization	Recurrent per rectal bleeding, transfused 2 units PRBC, treated with ceftriaxone and tranexamic acid.	9 months
Second discharge	Symptom resolution; discharged on supplements.	9 months, 1 week
Third hospitalization	Hematemesis, melena, diagnosed with consumptive coagulopathy, treated supportively.	16 months
Final discharge	Referred to hematology; discharged with symptomatic meds and counseling.	16 months, 1 week

Discussion

KTS is an inherited disorder associated with the overgrowth of vascular malformations due to PIK3CA gene mutation^[9]. KTS can be diagnosed by a triad of cutaneous capillary and venous malformations, soft tissue enlargement, and bony overgrowth and is associated with a range of complications, including thrombosis, coagulopathy, pulmonary embolism, heart failure, and bleeding manifestations^[10,11].

Early identification of cutaneous vascular malformations and correlation with systemic findings is a strength of management. Timely use of MRI and Doppler ultrasound has given the clear picture of this case. These investigations confirmed the diagnosis of KTS by demonstrating characteristic slow-flow venous malformations. The support in the form of blood transfusion was important to reduce mortality in the case of severe anemia. The multidisciplinary involvement with dermatology advising corticosteroids for suspected KMP, and radiology aiding in diagnosis through advanced vascular imaging, was another strength.

Genetic studies have identified PIK3CA gene mutation as a contributing factor to KTS and other disorders within the limb overgrowth spectrum (PROS) as well as genes like RASA 1 and AKT1 providing valuable insights into the molecular mechanisms underlying KTS and PROS. Gene analysis can be applied to patients and their families to identify at-risk individuals^[12]. While KMP is commonly associated with tufted angiomas and Kaposiform Hemangioendothelioma (KHE), cases of consumptive coagulopathy in KTS patients may present with overlapping features. The exact pathophysiological link remains unclear but is believed to be triggered by inflammatory and coagulation activation.

Although gastrointestinal involvement is relatively infrequent, affecting 1–13% of patients, it can lead to significant gastrointestinal hemorrhage, ranging from occult bleeding to life-threatening situations^[13]. The patient presented in our case had internal hemorrhoids as seen on colonoscopy and had several bleeding manifestations in the form of hematemesis. Imaging studies revealed unilateral venous tortuosities, persistent embryonic veins, aberrant venous systems, endolymphatic malformations, cavernomas, aneurysms, and thromboembolism^[14].

KTS is a complex condition that can be detected antenatally by ultrasound detection of cystic lesions or postnatally by the presence of characteristic signs and symptoms. Fetal well-being and delivery planning should be guided by frequent and meticulous ultrasound evaluations, considering gestational age, lesion severity, and potential internal organ involvement. A conservative or surgical treatment strategy can be adopted depending on the stability of the condition. Sclerotherapy, laser therapy, or radiotherapy are potential neonatal interventions^[15].

Our patient demonstrated the potentially severe complications of KTS, which can include anemia, consumptive coagulopathy, and bleeding events like hematemesis and bleeding per rectum. Mortality in patients with KTS can be due to Kasabach–Merritt syndrome (disseminated intravascular coagulation and hemolysis) a severe complication characterized by consumptive coagulopathy, cardiac failure, and pulmonary embolism^[16].

Nonoperative medical management represents the primary therapeutic approach for symptomatic KTS patients. KTS is a vascular malformation syndrome, while KMP is a rare coagulopathy typically seen with vascular tumors such as KHE. In rare cases like ours the KTS is associated with KMP, the venous malformations may trigger KMP features including bleeding required hematological monitoring. Patients could be prescribed compression therapy and limb elevation which constitute the foundational principles for managing limb edema. In the event of developing soft tissue inflammation, initial management should involve analgesics. Management for varicosities can include sclerotherapy or embolization techniques^[17]. The clinical features and course of the disease are diverse, hence treatment should be personalized for the patient^[1].

Despite multiple admission and recurring complaints, the oncology specialist was not consulted making it a limitation of the study. The planning for long term treatment was not considered at the time of first admission making it another limitation. Some test like iron studies, B12 and folate assays, D-Dimer were required but nit performed due to resource limitations.

Throughout her prolonged treatment journey, the patient expressed both physical and emotional exhaustion caused by recurrent bleeding episodes, frequent hospitalizations, and the uncertainty of living with a rare disease. Despite experiencing temporary relief after each discharge, she often felt anxious about potential relapses. The visible hypertrophy and skin lesions also affected her confidence and social interactions, particularly during adolescence. However, she showed resilience and gratitude for the compassionate, multidisciplinary care she received. She emphasized the importance of clear communication, timely support, and psychological encouragement, which helped her cope with the long-term nature of KTS.

Conclusion

This case of KTS in a 16-year-old female, complicated by recurrent gastrointestinal bleeding and consumptive coagulopathy, illustrates the complexity of managing vascular malformation syndromes. The patient’s repeated hospitalizations, need for transfusions, underscore the necessity for early diagnosis, timely referral, and a multidisciplinary care approach. Personalized follow-up and preventive strategies are essential to minimize morbidity in similar presentations. KTS is a chronic disorder with no cure. Patients with KTS are managed symptomatically and require frequent hospitalizations for the same.

Ethical approval

Not required as it is a case report.

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

The authors received no financial support for the research, authorship, or publication of this case report.

Author contributions

S.B., N.S.J., and A.S.: conceptualization, data curation, validation, writing – original draft preparation, writing – review & editing; H.G., T.S., D.M.M., D.S., M.A.M., N.K., C.R.S., and H.A.O.: writing – original draft preparation, writing – review & editing.

Conflicts of interest disclosure

None.

Research registration unique identifying number (UIN)

None.

Guarantor

Hamza Orfali

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

The data that support the findings of this study are available in the study itself.