Microfibrillar collagen products are available in a variety of forms (powder, sheets, loaded syringes for endoscopic placement) and are applied with pressure directly to the bleeding site. Collagen (Instat, Helistat) is supplied as a sponge, whereas microfibrillar collagen (Avitene, Superstat, Actifoam, Helitene, Hemopad, Novacol) is a tenacious powder or sheet. Microfibrillar collagen, like porcine gelatin and ORC, is absorbed by the body over time.
No studies have evaluated microfibrillar collagen in gynecologic surgery, although case reports of successful application to sites of uterine perforation after dilation and curettage and to bleeding sites after vaginal or laparoscopic hysterectomy have been published.3,4
New products are largely unproven
Class-III devices require significantly more study before safety and efficacy can be demonstrated. The two types of products presented here—topical thrombin and tissue sealants—remain largely unproven.
Topical thrombin
This class of products has been available for more than 20 years. As a liquid (Thrombogen), topical thrombin can be supplied in a syringe and sprayed onto oozing sites. A liquid combination of collagen gelatin matrix and bovine thrombin (FloSeal) provides a structure on which clots can form; triggers topical conversion of fibrinogen to fibrin; and activates the clotting cascade. It was approved for use in 1999. CoStasis and Vitagel are similar products, approved in 2000 and 2006, respectively, that add plasma obtained from the patient at the beginning of the surgical procedure.
Thrombin and ORC don’t mix. The acidity of ORC inactivates thrombin; therefore, ORC products should not be used with any product containing bovine or human thrombin.
The theoretical advantage of products that use patients’ plasma is the addition of autologous clotting factors and platelets to the bovine collagen and thrombin mixture. Preliminary studies have shown:
- a reduction in postoperative pain in 20 orthopedic surgery patients randomized to platelet gel, compared with what was seen in 20 women in the control group5
- a reduction in the rate of sternal wound infection in cardiac surgery patients (0.3% with the gel; 1.8% without it)6
- a potentially shorter healing time when platelet gel is applied to surgical wounds.7
The facts. Labeling for topical thrombin specifically states that it is not for use in cases of infection or for postpartum hemorrhage or menorrhagia. Studies of topical thrombin products have used the time to cessation of bleeding as their primary effectiveness end-point. In practical terms, however, studies have demonstrated no reduction in the need for transfusion or chest tube drainage in re-operative cardiac surgery patients.8
Disadvantages of topical thrombin include the cost of the product (including the cost of a plasma-collection device) and the need for operating room staff to collect and combine the product for use. Topical thrombin also exposes the patient to the risk of antibody formation (see Bovine thrombin can trigger risky antibodies), catastrophic bleeding, and, even, death.
Bovine thrombin can trigger risky antibodies
Products that contain bovine thrombin have some safety issues with regard to their antigenic reactivity. Patients may develop antibodies to the bovine product that cross-react with human thrombin and factor Va. Associated with all products that contain bovine thrombin is a black box warning that states that the product may be associated with severe bleeding, thrombosis, and, rarely, death, because of antibody formation.
In one case report, a very complicated patient who required systemic anticoagulation for a mechanical aortic valve underwent hysterectomy, with topical thrombin administered at the end of the procedure in an effort to avert postoperative hemorrhage.1 She developed antibodies to the bovine thrombin, which caused significant and severe coagulation defects.
No clinical studies have assessed these products in gynecologic surgery.
Reference
1. Sharma JB, Malhotra M, Pundir P. Laparoscopic oxidized cellulose (Surgicel) application for small uterine perforations. Int J Gynaecol Obstet. 2003;83:271-275.
This last set of products has been approved for use in cardiopulmonary bypass procedures, in patients who have splenic injury, and to close a colostomy. They are “tissue glues” that also have hemostatic properties.
Tisseel is a combination of human thrombin, human “sealer protein” (fibrinogen), and aprotinin, a synthetic inhibitor of fibrinolysis that prevents premature degradation of a clot once it has formed. In clinical studies, this product has reduced the need for splenectomy in patients who have bleeding that is difficult to control.
Disadvantages of tissue-sealing products. These products have not been studied in gynecologic patients. They have the significant disadvantage of containing products derived from pooled human plasma. Although precautions have been taken to reduce transmission of infectious disease, viral transmission may occur. Anaphylaxis is an additional risk.