The study pooled data from 4 clinical trials to gain insight into surgical outcomes in this complex population.
Emicizumab can be an effective treatment strategy for hemophilia A prophylaxis, but surgical outcomes for patients on prophylactic emicizumab have not been well-researched. A study published in the journal Blood Advances pooled data from 4 clinical trials to gain insight into surgical outcomes in this population.
Both major and minor surgeries are common for patients with hemophilia A, and these patients are at a greater risk of complications such as bleeding, poor healing, and infection. Hemostatic treatment such as factor VIII (FVIII) replacement or activated prothrombin complex concentrate (aPCC) bypassing agents is an important perioperative strategy, and surgery is especially challenging in those with FVIII inhibitors who do not respond to FVIII replacement. However, it is still possible and can be safe with proper precautions.
“As a result of years of experience of surgeries being performed on patients with hemophilia A with the use of FVIII and bypassing agents to achieve hemostasis, although there is no uniform approach to perioperative management, there now exists a wealth of expert guidance, and even major surgeries can be safely performed on patients with hemophilia A with or without FVIII inhibitors,” the authors wrote.
Emicizumab, a more recently approved bispecific humanized monoclonal antibody for bleeding prevention, is currently recommended as prophylaxis for patients with or without FVIII inhibition in hemophilia A. The HAVEN 1-4 clinical trials (NCT02622321, NCT02795767, NCT02847637, NCT03020160) showed emicizumab to be safe and effective in adults, adolescents, and children with hemophilia A, but there are limited data on emicizumab prophylaxis in patients undergoing minor or major surgeries. “Such data would be of great clinical interest and may inform development of surgical guidelines in the future,” the authors noted.
Of the 399 patients who received emicizumab in the trials, 126 (31.6%) had at least 1 surgery, and 43 (10.8%) had 2 or more. A total of 69 patients (55.6%) who were receiving emicizumab had FVIII inhibitors at the time of study entry. The median age of patients at surgery was 33 years, and the median exposure to emicizumab ahead of surgery was 278 days.
There were 233 surgeries during the trials, including 215 minor and 18 major procedures. Of the minor surgeries, 141 (65.6%) were done without additional prophylaxis, and 121 of the surgeries done without additional prophylaxis (85.8%) were not associated with post-operative bleeding incidents. The number of doses of FVIII or bypassing agents in patients with bleeds after minor surgery was typically low, which suggests the incidents could be controlled quickly and effectively.
Major surgeries were mostly managed with additional prophylactic factor concentrate, which was used in 15 of the 18 major surgeries (83.3%). Of the major surgeries overall, 12 (80%) were not associated with bleeds during or after surgery. None of the surgeries led to death, thrombosis, thrombotic microangiopathy, or FVIII inhibitor development in the trials.
Overall, the pooled data show that surgery can be performed safely in patients who are on emicizumab prophylaxis for hemophilia A.
“Data on surgical experience in patients with hemophilia A on emicizumab continues to grow, and the results concur with those presented here: minor and major surgeries can be performed safely in patients with hemophilia A with or without FVIII inhibitors,” the authors wrote. “To date, there has only been a single prospective clinical trial published, with evidence mainly coming from reviews of medical records and observational studies.”
A notable limitation is that the HAVEN trials were not designed to analyze surgical outcomes and did not have surgical end points. Individuals with major planned surgeries were also excluded from the studies, limiting both the amount of data on major surgeries and the generalizability of the findings in real-world settings.
Future research could help add evidence to the pool and assist in the formation of surgical guidelines for patients with hemophilia A on emicizumab prophylaxis.
Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood Adv. Published online August 8, 2022. doi:10.1182/bloodadvances.2022007458