Ehlers-Danlos syndrome (EDS) is a rare (1:5000-1:25,000 births) and heterogeneous group of inherited connective tissue disorders caused by a defect in the synthesis of collagen, and its clinical presentation ranges from an incidental finding to a dramatic life-threatening emergency due to organ perforation or arterial rupture.[1, 2] Surgical procedures in these patients are challenging because of the high risk of poor healing, bleeding, and anastomotic disruption due to extreme tissue fragility.[2-4]

We present a case of liver transplantation (LT) in a patient with EDS type II. This 39-year-old woman presented with end-stage liver disease secondary to nonalcoholic steatohepatitis and a Model for End-Stage Liver Disease score of 38. She was diagnosed with EDS type II at the age of 2 years. Manifestations of EDS include skin atrophy, easy bruising, pectus excavatum, mitral valve prolapse, temporomandibular joint disorder, and history of miscarriage.

The patient was listed for transplantation, and her surgery was scheduled when an appropriate organ became available. After induction with general anesthesia, percutaneous internal jugular central venous and femoral arterial lines were placed for vascular access and pressure monitoring. A bilateral subcostal incision was used, but surgical exposure was difficult because of her pectus excavatum. During the dissection of the hepatic hilum, a right hemothorax was noted and treated with a thoracostomy tube. The hepatectomy, allograft implantation, and reperfusion were uneventful. Gentle manipulation and atraumatic handling were used to dissect the recipient's hepatic artery, and to prevent excessive traction, we used a donor-derived arterial jump graft for the arterial anastomosis, which was first sewn to the recipient's proper hepatic artery. At that point, an extensive retroperitoneal hematoma was seen in the right flank and pelvic area. Femoral bleeding from the arterial line insertion was suspected, and it was confirmed by groin exploration. The arterial defect was closed with pledgeted stitches. The operation was completed, and the patient was taken to the intensive care unit in stable condition.

On postoperative day (POD) 5, the patient experienced abdominal pain and fever. Exploratory laparotomy revealed a 2-mm small bowel perforation. No obvious cause was identified, although traction from the mechanical retractor during LT was suspected. A 2-layer small bowel repair was performed. On POD 10, she developed a partial wound dehiscence that was managed with a wound vacuum-assisted closure device and daily dressing changes. The patient recovered well and was able to be discharged on POD 19. On POD 24, the patient returned with spontaneous right hand edema and pain with no apparent cause. Magnetic resonance imaging showed soft-tissue edema suggestive of an abscess. The patient underwent hand exploration. A partially cloudy fluid collection was encountered and drained, and the patient was treated with antibiotics, but cultures were negative. Twenty-two months after LT, she was in good health, and her liver allograft function was normal.

To our knowledge, this is the first report of LT performed in a recipient with EDS. EDS is classified into 6 types according to the phenotypic manifestations, but it presents extreme clinical variability and locus heterogeneity.[5] Classic EDS, an autosomal dominant transmitted disease that include types I and II, is the most common variation and is diagnosed on the basis of 3 major clinical criteria: joint hypermobility, widened atrophic scarring (tissue fragility), and skin hyperextensibility.[1] Type I includes severe skin involvement caused by mutations in collagen V α1 and collagen V α2 genes, which code for collagen V, and in collagen I α2, which codes for collagen I. Type II lacks the collagen I α2 gene mutation and has a less severe manifestation.[6] Types I and II compose a clinical continuum with different grades of clinical presentation.[1, 4]

EDS type III is characterized by joint hypermobility, whereas EDS type IV (or vascular EDS) has a collagen III α1 gene mutation that affects the synthesis of collagen III[1, 7] and can present major complications such as aneurysms, pseudoaneurysms, and dissections of major arteries and/or spontaneous vascular or visceral rupture.[2-4] Because of the difficulty in managing fragile tissues, surgical procedures in patients with EDS type IV are associated with high rates of complications, including severe postoperative bleeding (37%), re-exploration (20%), and late graft anastomotic complications (40%).[8]

Although EDS type IV is associated with the most serious complications and a significantly increased risk of death, vascular or visceral disease can present in different types of EDS patients.[2] On the basis of the available literature, one could infer that the risk for surgery is high in patients with EDS type IV, intermediate in patients with type I or II, and low in patients with type III.

Easy bruising is produced by a deficiency of normal perivascular collagen because coagulation is usually normal in EDS.[7] Disruptions of the endothelium integrity, as occur during vascular line insertion, can result in significant bleeding, sometimes out of proportion to the grade of the injury. Because of the uncertainty about the grade of vascular fragility, a cutdown, open access, and repair should be considered in patients with a history of previous vascular complications, when large-bore devices are used or severe coagulopathy is present.[2]

Ideally, the surgeon should be aware of the diagnosis of EDS before any procedure, although the patient is aware of the diagnosis in <30% of cases.[2, 8] In surgery, gentle, atraumatic, and delicate handling of tissues is mandatory to prevent vascular tears, intimal dissection, and peri-adventitial hematomas. The use of soft, protected arterial clamps or balloon occlusion is preferable to the use of standard vascular clamps. Retractors should be placed carefully to prevent damage to the adjacent bowel or mesentery, and the anastomosis should be tensionless.[8] In our case, a graft for the arterial anastomosis was first sewn to the recipient's hepatic artery to prevent excessive traction. The anastomosis may be reinforced with Teflon felt strips or pledgeted sutures. Autologous grafts are contraindicated if vascular reconstruction is required.[2] The postoperative course can be complicated by common findings in EDS such as chronic fatigue, muscle weakness,[9] and skin dehiscence.[1-3]

Few if any medical options exist to lessen the surgical risk. Celiprolol, a β1-adrenoceptor antagonist with β2-adrenoceptor agonist action, has shown a benefit in preventing vascular complications in patients with EDS type IV,[10] and it could be an option for preventing postoperative vascular complications.

  • Humberto E. Bohorquez, M.D.

  • Daniel Gomez, M.D.

  • Ari J. Cohen, M.D.

  • David S. Bruce, M.D.

  • Ian C. Carmody, M.D.

  • Trevor W. Reichman, M.D., Ph.D.

  • George E. Loss, M.D., Ph.D.

  • Multi-Organ Transplant Institute

  • Ochsner Clinic Foundation

  • New Orleans, LA


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