First Case of Laparoscopic Mini-Gastric Bypass for the Treatment of Morbid Obesity in Severe Haemophilia A

Bariatric surgery is continuously growing with more than half a million procedures performed yearly worldwide.[1] Its safety regarding morbidity and mortality and its effectiveness regarding long-term weight loss have been demonstrated repeatedly. Among the most common procedures, the bypass procedures such as Roux-en-Y gastric bypass (RYGB) or mini-gastric bypass (MGB) seem to be superior to sleeve gastrectomy (SG) concerning remission of metabolic comorbidities, especially type 2 diabetes mellitus (T2DM).[2] [3] [4]

According to the current literature, the average surgeon (including the bariatric surgeon) will—from a statistical point of view—encounter a haemophiliac patient only once during his surgical career.[5] In experienced institutions, no differences could be found in the outcome of haemophiliac patients undergoing various surgical procedures compared with patients without impaired hemostasis.[6] [7]

Nevertheless, bariatric surgery is challenging in patients with haemophilia, and to the best of our knowledge, except one case of SG in haemophilia B, no cases of gastric bypass in haemophiliac patients have been reported in the literature so far.[8]

Herein, we report on a 40-year-old male patient suffering from both severe haemophilia A (factor VIII activity below 1%, normal range: 70–150%) and obesity since childhood. When he came to our centre at the age of 14 years, prophylaxis was started. He suffered from inactive hepatitis B and C, but there was no HIV infection. At the age of 25 years, he already weighed 100 kg (BMI: 35.0 kg/m²), and there was a further increase of 16 kg within 6 years to a peak weight of 116 kg (BMI: 40.6 kg/m²); at the time of initial presentation to the bariatric centre, the BMI was 38.2 kg/m² (109 kg, 1.70 m). His annual bleeding rate was three bleedings per year. He repeatedly suffered from multiple haemarthrosis of both knee, elbow, and ankle joints, resulting in an endoprosthesis of the right knee joint in 2015. Other obesity-related comorbidities were T2DM (baseline HbA1c: 10.5%), hypertension, and reflux disease. After various unsuccessful conservative weight loss treatments, including a multidisciplinary program over 6 months, he was approved for bariatric surgery by his health care insurance and scheduled for laparoscopic MGB in November 2016. MGB was favoured over SG for expected better outcome on T2DM, and over RYGB because the single anastomosis would be easily accessible in case of a bleeding event.

A five-trocar laparoscopic approach was applied, starting with the creation of a long and narrow gastric pouch (calibrated by a 10-mm bougie) approximately 3 cm below the angulus up to the angle of His. The remnant stomach and a 180-cm-long biliopancreatic limb were bypassed by performing an antecolic end-to-side gastroenterostomy ([Fig. 1]). The staple lines were completely reinforced with titanium clips for additional haemostasis. The 60-minute-long procedure was completed by a toluidine blue test to prove tightness of the anastomosis and placement of a drain for 1 day. The operative technique has been described by our group in detail earlier.[9]

Fig. 1 Mini-gastric bypass was performed by creation of a long and narrow gastric pouch and a single gastroenterostomy 180 cm distal to the ligament of Treitz.

On the evening before the operation, 26 IU/kg bw (body weight) rFVIII was applied intravenously. Therapy with 1 g tranexamic acid every 8 hours was started and continued until day 4. On the operation day, the total FVIII consumption was 105 IU/kg bw (divided into three doses). On the first postoperative day, the total FVIII dose was reduced to 85 IU/kg bw (divided into two doses), and on the second postoperative day, the total FVIII consumption was 59 IU/kg bw (divided into two doses). Twelve-hour trough levels of FVIII activity ranged from 85 to 100%. From day 7 on, replacement therapy was continued initially with 42 IU/kg bw (divided into two doses). Thereafter, to guarantee wound healing, the dose was tapered over 4 weeks.

The peri- and postoperative course was uneventful. No bleeding complications occurred. The patient was discharged after 5 days and received 5,000 IU (international units) dalteparin daily for thromboprophylaxis.

At 3-month follow-up, he already lost 18.6 kg (total body weight loss [TBWL]: 17.1%, excess weight loss [EWL]: 49.5%). Hypertension medication was completely stopped, while diabetic medication could be reduced to metformin only (HbA1c: 7%). His physical activity improved remarkably, as he was able to perform physical training thrice a week. At 6-month follow-up, weight loss increased to 26.9 kg (TBWL: 24.7%, EWL: 71.5%). HbA1c dropped to 5.9%, and so metformin medication was stopped. Proton pump inhibitors (PPI) medication could be abandoned, as reflux symptoms had stopped completely. At 9-month follow-up, weight loss was 27.4 kg, TBWL was 25.1%, and EWL was 72.9%. One year after the operation, weight loss stabilized at 29 kg, resulting in 26.6% TBWL and 77.1% EWL ([Fig. 2]). The BMI at 1-year follow-up thus decreased to 28 kg/m², while the comorbidities of T2DM and hypertension continued to be in complete remission. Laboratory exams demonstrated normal levels for micronutrients including folic acid, B vitamins, zinc, parathormone, albumin, iron, and ferritin (without iron substitution).

Fig. 2 Pre- and postoperative BMI, total body weight loss (TBWL), and excess weight loss (EWL) at 3, 6, 9, and 12 months of follow-up.

Prior to surgery, prophylaxis was performed with three injections of a rFVIII concentrate with prolonged half-life per week: 2 × 2,000 IU (19 IU/kg bw) and 1 × 3,000 IU (28 IU/kg bw). FVIII trough levels after injection of 2,000 IU were 18% after 24 hours and 4.2% after 48 hours. Seventy-two-hour FVIII trough level after injection of 3,000 IU was 3.3%. Nine months after surgery, prophylaxis was continued with 2 × 2,000 IU (25 IU/kg bw) and 1 × 3,000 IU (37 IU/kg bw). FVIII trough levels after injection of 2,000 IU were 35% after 24 hours and 11.8% after 48 hours, and 72-hour FVIII trough level after injection of 3,000 IU was 4.7%. With a postoperative weight loss of 25%, we saw an increase of FVIII trough levels of 100% after 24 and 48 hours, and of 40% after 72 hours.

Before switching to a FVIII concentrate with extended half-life, the patient has been on a prophylactic regimen with daily injections of 2,000 IU of rFVIII concentrate (17 IU/kg bw) due to arthropathy. Treatment with rFVIII concentrate with extended half-life led to a reduction of injection frequency (three vs. seven injections) and to a reduction of FVIII consumption (7,000 vs. 14,000 IU/week) with comparable FVIII activities.

After bariatric surgery, the patient experienced a reduction in the annual joint bleeding rate from 2 bleedings in the year before surgery to 0.5 bleedings per year leading to a pharmacoeconomic benefit.

A further reduction of FVIII dosage was not considered because of underlying arthropathy and increased physical activity in consequence to weight loss after surgery.

To the best of our knowledge, we are able to report about the first gastric bypass procedure in an obese, haemophilia A patient and have shown that laparoscopic MGB can be successfully performed with very good results regarding weight loss and control of comorbidities. A close collaboration between specialized centres for bariatric surgery as well as for haemophilia was essential for an uneventful intra- and postoperative outcome without elevated risk despite the severe haemophilia. Further studies are necessary to evaluate the influence of body composition and pharmacokinetics for dosing.

Informed Consent

Informed consent was collected from the patient for this study.

Authors' Contribution

A.P. and K.P.R. operated on the patient, performed the surgical follow-up and wrote the article. G.G. and S.H. were responsible for the factor VIII administration/monitoring and wrote the section on FVIII administration. P.L. and J.D. wrote parts of the article and revised it. J.O. made final revisions and contributed the rFVIII.

• References

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