Severe bleeding after haemorrhoidal banding in a haemophilia patient treated with emicizumab

Abstract

Hermans et al. have provided us with an excellent summary and review of patients treated with emicizumab who underwent elective procedures and their outcomes. The vast majority of procedures reviewed were dental or orthopaedic in nature.1 We recently cared for patient undergoing rubber band ligation of haemorrhoids, an otherwise simple and commonly done procedure, that nonetheless presented unique challenges given the unpredictable timing of the bleeding risk. The patient, a 44yearold man with severe haemophilia A without inhibitors, had been in our practice since 2006. He had a history of treated hepatitis C and had wellcontrolled HIV infection with undetectable viral loads. Through the years, he received treatment with a variety of factor VIII products, first with monoclonal antibody purified and later with recombinant preparations. Until 2020, he would treat himself ‘on demand’. He would mostly monitor his left ankle as the main target joint, which remained intermittently symptomatic with ondemand treatment. He tolerated procedures in the past, such as an ankle synovectomy and elbow surgeries with with proper factor replacement and without complications. In September 2020, he agreed to transition his treatment to emicizumab. After the initial loading doses, he selftreated with a subcutaneous dose of 6 mg/kg every 4 weeks with excellent control of bleeding and joint pain. Prior to the event described here, the patient claimed his ankle pains resolved and he had no haemorrhagic events. He remained adherent to the prescribed therapy and was instructed to use a factor VIII preparation in case of clinically relevant bleeding episodes. Four months after the start of emicizumab treatment, our patient underwent haemorrhoidal band ligation, but, unfortunately, there was no preoperative consultation with haematology. He had recombinant human factor VIII (rhFVIII) at his disposal, and had been instructed to use it as needed, as this was considered a procedure at low risk for bleeding. Two weeks after the haemorrhoidal banding procedure, our patient developed rectal bleeding. Prior to the hospitalization, the patient treated himself with rhFVIII infusions when he noticed some early breakthrough bleeding, but this rapidly progressed to a more severe haemorrhage. When the patient was seen in the emergency department, he had evidence of hypovolemia with a blood pressure of 96/66 mm Hg and a heart rate of 116 beats/minute, and a haemoglobin of 8.1 g/dL. He received a transfusion of 2 units of packed red blood cells, and 3800 units of rhFVIII and intravenous tranexamic acid until haemostasis was achieved. He required norepinephrine and vasopressin for 12 hours. A limited coagulation assessment was done by the emergency staff before consultation with haematology was done. This included a shortened aPTT at 21 s (normal range: 26.2– 372 s) and a normal prothrombin time. An aPTTbased plasma factor VIII level was not done, based on the emicizumab manufacturer s recommendation. Emicizumab concentration (Stago or r2 Diagnostics assays) measurements were not available. The patient responded well to the treatment, and a flexible sigmoidoscopy, done emergently, revealed 1 cm rectal ulcer. He recovered after 2 days of hospitalization. The case in point presented us with a couple of interesting points for discussion. The first point is whether there is a significantly increased risk for rubber band ligation of haemorrhoidal disease in haemophilia patients. Major bleeding after haemorrhoidal treatment is generally considered a rare complication. When there is bleeding, it frequently occurs 10– 14 days after the procedure, as it occurred in this case. It is thought that this is due to the sloughing of the ligated skin. There are, however, several case reports of patients having lifethreatening bleeding on acetylsalicylic acid.2 We are not aware of specific instructions on how to deal with banding in the setting of haemophilia patients treated with emicizumab that would address the issue of the unpredictability of the time of bleeding risk. The second point has to do with the need to have a proper discussion between patient, surgeon and haematologist regarding haemorrhoidal treatment selection, monitoring of risk and understanding of the mechanism of action of emicizumab. In particular, it is desirable that patients treated with emicizumab are counselled about the need to seek both routine and emergency care where a specialized treating physician will have access to specialized laboratory testing, including chromogenic assays for FVIII and emicizumab concentration tests.3 This case illustrates that while emicizumab provides excellent control of chronic bleeding and quality of life in patients like the one described above, the surgical haemostatic challenge of an apparently simple procedure like haemorrhoidal banding still requires close collaboration between surgery and haematology with a clear understanding of the peak moments of risk, and coordination with the haemostasis laboratory so that proper monitoring can be arranged.