Recombinant Human Thrombin Controls Bleeding of Most Wounds

CHICAGO — Spray recombinant human thrombin achieved hemostasis within 20 minutes in 91.5% of patients following burn wound excision in a prospective safety study in 71 patients.

Recombinant human thrombin (rThrombin) was also minimally immunogenic, principal investigator Dr. David G. Greenhalgh said at the annual meeting of the American Burn Association (ABA).

One patient had specific, low-titer antibodies to rThrombin at baseline, but no increase in titer post treatment. A second patient developed non-neutralizing antibodies to rThrombin at day 29.

The findings are encouraging because rThrombin was developed as an alternative to bovine plasma-derived thrombin, which has been available since the 1940s, but carries a black box warning about severe bleeding risks associated with potential antibody development, explained Dr. Greenhalgh, professor and chief of burn surgery, University of California, Davis. Roughly 20%-90% of patients treated with topical bovine thrombin develop antibodies to the preparation.

In January 2008, the Food and Drug Administration approved Recothrom, the first and only rThrombin for use as a topical hemostat in combination with an absorbable gelatin sponge. The product is devoid of human or animal plasma proteins, which also minimizes the risk of pathogen transmission, he said.

The current open-label, multiple-site study evaluated the safety of spray rThrombin in 71 patients, aged 2–75 years, who received a partial- or full-thickness autologous sheet or mesh graft following excision of burn wounds covering 1%-4% of their total body surface area. The spray was applied at 5-minute intervals for up to 20 minutes. Sheet grafts were received by 53 patients and mesh grafts by 18.

Hemostasis was achieved without the use of tourniquets or clysis, which makes the 91.5% hemostasis rate even more impressive, because both reduce the rate of bleeding, Dr. Greenhalgh said.

At day 29, one graft was infected and four grafts failed. Other adverse events reported were pain (25 patients), pruritus (18), deep vein thrombosis (1), adult respiratory distress syndrome (1), and GI hemorrhage (1).

There were no study drug discontinuations or deaths in the study, which was sponsored by ZymoGenetics Inc. (Seattle); the company markets rThrombin in the United States as Recothrom.

Session moderator and former ABA president Dr. Glenn D. Warden asked whether immunogenicity might be a concern with repeated use of rThrombin over larger wounds.

Dr. Greenhalgh answered that it would be beneficial to conduct a study to evaluate repeated use, but that he felt better about human recombinant products than bovine plasma-based products because of their reduced risk of viral transfer and antibody development.

When asked if human recombinant products were too costly for regular use, Dr. Greenhalgh said, "It's not something that's going to break the bank … I think it's going to be reasonable, compared to what's available."

Dr. Greenhalgh, who reported no conflicts of interest, said he uses spray rThrombin in combination with tourniquets for excisions on hands or arms and in combination with topical and injected epinephrine and cautery for large tangential excisions on the trunk.

CHICAGO — Spray recombinant human thrombin achieved hemostasis within 20 minutes in 91.5% of patients following burn wound excision in a prospective safety study in 71 patients.

Recombinant human thrombin (rThrombin) was also minimally immunogenic, principal investigator Dr. David G. Greenhalgh said at the annual meeting of the American Burn Association (ABA).

One patient had specific, low-titer antibodies to rThrombin at baseline, but no increase in titer post treatment. A second patient developed non-neutralizing antibodies to rThrombin at day 29.

The findings are encouraging because rThrombin was developed as an alternative to bovine plasma-derived thrombin, which has been available since the 1940s, but carries a black box warning about severe bleeding risks associated with potential antibody development, explained Dr. Greenhalgh, professor and chief of burn surgery, University of California, Davis. Roughly 20%-90% of patients treated with topical bovine thrombin develop antibodies to the preparation.

In January 2008, the Food and Drug Administration approved Recothrom, the first and only rThrombin for use as a topical hemostat in combination with an absorbable gelatin sponge. The product is devoid of human or animal plasma proteins, which also minimizes the risk of pathogen transmission, he said.

The current open-label, multiple-site study evaluated the safety of spray rThrombin in 71 patients, aged 2–75 years, who received a partial- or full-thickness autologous sheet or mesh graft following excision of burn wounds covering 1%-4% of their total body surface area. The spray was applied at 5-minute intervals for up to 20 minutes. Sheet grafts were received by 53 patients and mesh grafts by 18.

Hemostasis was achieved without the use of tourniquets or clysis, which makes the 91.5% hemostasis rate even more impressive, because both reduce the rate of bleeding, Dr. Greenhalgh said.

At day 29, one graft was infected and four grafts failed. Other adverse events reported were pain (25 patients), pruritus (18), deep vein thrombosis (1), adult respiratory distress syndrome (1), and GI hemorrhage (1).

There were no study drug discontinuations or deaths in the study, which was sponsored by ZymoGenetics Inc. (Seattle); the company markets rThrombin in the United States as Recothrom.

Session moderator and former ABA president Dr. Glenn D. Warden asked whether immunogenicity might be a concern with repeated use of rThrombin over larger wounds.

Dr. Greenhalgh answered that it would be beneficial to conduct a study to evaluate repeated use, but that he felt better about human recombinant products than bovine plasma-based products because of their reduced risk of viral transfer and antibody development.

When asked if human recombinant products were too costly for regular use, Dr. Greenhalgh said, "It's not something that's going to break the bank … I think it's going to be reasonable, compared to what's available."

Dr. Greenhalgh, who reported no conflicts of interest, said he uses spray rThrombin in combination with tourniquets for excisions on hands or arms and in combination with topical and injected epinephrine and cautery for large tangential excisions on the trunk.

CHICAGO — Spray recombinant human thrombin achieved hemostasis within 20 minutes in 91.5% of patients following burn wound excision in a prospective safety study in 71 patients.

Recombinant human thrombin (rThrombin) was also minimally immunogenic, principal investigator Dr. David G. Greenhalgh said at the annual meeting of the American Burn Association (ABA).

One patient had specific, low-titer antibodies to rThrombin at baseline, but no increase in titer post treatment. A second patient developed non-neutralizing antibodies to rThrombin at day 29.

The findings are encouraging because rThrombin was developed as an alternative to bovine plasma-derived thrombin, which has been available since the 1940s, but carries a black box warning about severe bleeding risks associated with potential antibody development, explained Dr. Greenhalgh, professor and chief of burn surgery, University of California, Davis. Roughly 20%-90% of patients treated with topical bovine thrombin develop antibodies to the preparation.

In January 2008, the Food and Drug Administration approved Recothrom, the first and only rThrombin for use as a topical hemostat in combination with an absorbable gelatin sponge. The product is devoid of human or animal plasma proteins, which also minimizes the risk of pathogen transmission, he said.

The current open-label, multiple-site study evaluated the safety of spray rThrombin in 71 patients, aged 2–75 years, who received a partial- or full-thickness autologous sheet or mesh graft following excision of burn wounds covering 1%-4% of their total body surface area. The spray was applied at 5-minute intervals for up to 20 minutes. Sheet grafts were received by 53 patients and mesh grafts by 18.

Hemostasis was achieved without the use of tourniquets or clysis, which makes the 91.5% hemostasis rate even more impressive, because both reduce the rate of bleeding, Dr. Greenhalgh said.

At day 29, one graft was infected and four grafts failed. Other adverse events reported were pain (25 patients), pruritus (18), deep vein thrombosis (1), adult respiratory distress syndrome (1), and GI hemorrhage (1).

There were no study drug discontinuations or deaths in the study, which was sponsored by ZymoGenetics Inc. (Seattle); the company markets rThrombin in the United States as Recothrom.

Session moderator and former ABA president Dr. Glenn D. Warden asked whether immunogenicity might be a concern with repeated use of rThrombin over larger wounds.

Dr. Greenhalgh answered that it would be beneficial to conduct a study to evaluate repeated use, but that he felt better about human recombinant products than bovine plasma-based products because of their reduced risk of viral transfer and antibody development.

When asked if human recombinant products were too costly for regular use, Dr. Greenhalgh said, "It's not something that's going to break the bank … I think it's going to be reasonable, compared to what's available."

Dr. Greenhalgh, who reported no conflicts of interest, said he uses spray rThrombin in combination with tourniquets for excisions on hands or arms and in combination with topical and injected epinephrine and cautery for large tangential excisions on the trunk.