Extended Half-life Products Prevent Surgery Bleeds in Hemophilia A, B

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Extended half-life (EHL) blood-clotting factor products are safe and effective at preventing bleeds during minor and major surgeries in people with hemophilia, according to a real-world study in Nordic countries.

While dosing recommendations in the perioperative period, or the period around surgery, vary across Nordic hemophilia treatment centers for EHL products, pre-surgery clotting factor doses for both major and minor surgeries were close to those recommended in the Nordic Hemophilia Council guidelines for major surgeries.

These findings support the use of EHL products for both hemophilia A and B patients during surgery and may help inform treatment guidelines, the researchers noted.

The study, “Surgical outcomes in patients with haemophilia A or B receiving extended half-life recombinant factor VIII and IX Fc fusion proteins: Real-world experience in the Nordic countries,” was published in the journal Haemophilia.

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Hemophilia is caused by defective or missing blood clotting factors, impairing the body’s ability to prevent excessive bleeding. The type of hemophilia depends on the faulty clotting factor: factor VIII (FVIII) in the case of hemophilia A and factor IX (FIX) in the case of hemophilia B.

Due to their high risk of bleeding during and after surgery, treatment guidelines recommend the use of replacement therapy in the perioperative period — starting immediately before surgery up until recovery.

As the name suggests, replacement therapy delivers the missing clotting factor for that specific type of hemophilia. Treatment can be delivered through bolus dosing, involving repeated injections at regular intervals, or continuous into-the-vein infusion.

Compared with standard half-life clotting factor concentrates, EHL products take longer to be broken down by the body, meaning they work for longer periods of time after being infused into the bloodstream.

“This presents the potential for reduced factor consumption and injection frequency during surgery,” the researchers wrote.

In Europe, EHL products are available as Elocta (recombinant FVIII fusion protein; Eloctate in the U.S.) for hemophilia A and Alprolix (recombinant FIX fusion protein) for hemophilia B.

While these therapies have been shown to be effective for perioperative management in clinical trials, real-world reports to date did not consistently provide details on dosage and patient outcomes.

They also involved “various regions of the world with a wide range of treatment standards,” making it “difficult to apply these learnings to inform clinical practice with EHL products in Nordic Countries,” the researchers wrote.

Nordic Hemophilia Council guidelines recommend that the same principles for standard half-life products use in surgery should be applied to EHL products, but “there is currently a lack of alignment between Nordic haemophilia treatment centres (HTCs) regarding dosing recommendations,” the researchers wrote.

As such, characterization of real-world use of EHL products during surgery in Nordic countries “can be used to generate more data to inform treatment guidelines,” they wrote.

Now, a team of researchers from Norway, Sweden, and Finland retrospectively analyzed clotting factor dosing and surgical outcomes of 20 hemophilia A and B patients treated with EHL products for perioperative management at four Nordic HTCs.

Results showed that 25 surgeries (five patients had two surgeries) were performed between April 1, 2017, and Nov. 30, 2019. These included 19 surgeries (11 minor and eight major) in people with severe hemophilia A and six surgeries (four minor and two major) in patients with mild-to-severe hemophilia B.

Patients’ mean age at the time of surgery was 34.5 years, and eight surgeries (32%), all minor, were performed in children. All surgeries, most commonly orthopedic, were managed with bolus dosing except one minor hemophilia A surgery.

Median pre-surgery Elocta doses were 48 IU/kg (range, 35–57 IU/kg) for major surgeries and 50 IU/kg (range, 24–79 IU/kg) for minor surgeries. Pre-surgery Alprolix doses were 50 IU/kg and 20 IU/kg for the two major surgeries (in one patient) and 47 IU/kg (range, 40–71 IU/kg) for minor surgeries.

The team noted that received doses were generally close to those recommended for major surgeries in the Nordic Hemophilia Council guidelines (50 IU/kg for FVIII and 60–70 IU/kg for FIX) and that available post-dose FVIII levels for all major surgeries were within the recommended target range (70–100 IU/dl).

Also, total factor consumption for both EHL products “varied considerably within surgical classifications, especially for major surgeries in patients with severe [hemophilia A],” the researchers wrote.

“This may be partially explained due to the greater bleeding risk associated with orthopaedic surgeries of the lower extremities (e.g. hip and knee arthroplasty) compared with the upper extremities (e.g., elbow arthroplasty), but also highlights the need for consensus recommendations,” they wrote.

Tranexamic acid, an antifibrinolytic, was used in all major and in 87% of minor surgeries. Antifibrinolytics are medications that promote blood clotting and are commonly used in hemophilia patients undergoing surgery.

In nearly all (96%) surgeries, bleeding control both during and after surgery were rated as at least good/excellent by the physician or surgeon, with bleeds occurring in only three (12%) surgeries (one major and two minor). All three cases needed additional bolus injections after surgery.

No patient needed preventive treatment against blood clots or blood transfusions, and no adverse events were reported.

“The Nordic experience suggests that [EHL products] can be used safely and effectively for peri-operative [bleeding control] in patients with [hemophilia A and B], but further research and follow-up discussions are needed to develop local dosing guidelines,” the researchers concluded.