Current applications of platelet gels in facial plastic surgery

The response of living tissue to injury is a central component in the planning of all surgical procedures. The wound-healing process is typically divided into three phases (inflammatory, proliferative, and remodeling) and is a complex process in which a multitude of cellular and humoral components interact to restore a wound defect. Platelets and their released cytokines and growth factors are pivotal in the modulation of this entire process. Although several techniques may be used to achieve hemostasis after initial injury, few initiate and actually accelerate tissue regeneration. Both platelet gel and fibrin glue are effective hemostatic agents. Platelet gels, unlike fibrin glue, have a high concentration of platelets that release the bioactive proteins and growth factors necessary to initiate and accelerate tissue repair and regeneration. In particular, two growth factors that play a major role in platelet gels are platelet-derived growth factor, a powerful chemoattractant, and transforming growth factor beta, which significantly increases and stimulates the deposition of extracellular matrix. In creating a platelet gel, autologous blood is centrifuged to produce a concentrate high in both platelets and plasma. This concentrate can be applied to wounds, providing hemostasis, adhesion, and enhanced wound healing. Recent techniques for the autologous concentrating process have been streamlined, and now platelet gels are clinically accessible to most physicians. Platelet gels have global applications in surgery and are especially useful for the soft tissue and bony reconstructions encountered in facial plastic and reconstructive surgery. In these applications, their use has been associated with a decrease in operative time, necessity for drains and pressure dressings, and incidence of complications. When applied to bony reconstruction it provides adhesion for the consolidation of cancellous bone and comminuted fracture segments.     

The role of platelet-rich plasma in foot and ankle surgery

Platelet-rich plasma (PRP), derived from autologous blood, is defined as a volume of plasma that has a platelet concentration that typically is five times greater (approximately 1,000,000/microl) than physiologic levels. PRP serves as a reservoir of critical growth factors, including platelet-derived growth factor, transforming growth factor-beta, and insulin-like growth factor-I. Although there is an abundance of literature pertaining to dental applications, this article highlights the use of PRP in orthopedic applications, ranging from PRP preparation to in vitro and in vivo studies to clinical research.     

Bioactivity and stability of endogenous fibrogenic factors in platelet-rich fibrin

Platelet‐rich fibrin (PRF^®) is an autologous fibrin sealant (FS) enriched with a platelet concentrate (>1,000,000 platelets/μL) produced by the automated Vivostat^® system and used to enhance wound healing. The effects of PRF were compared with supernatant from thrombin‐activated platelet concentrate, recombinant human platelet‐derived growth factor (rhPDGF) isoforms, and a homologous FS in cultured normal human dermal fibroblasts. Also, the release of selected endogenous growth factors from PRF and their stability against proteolytic degradation were studied. The proliferative effect of PRF exceeded that of FS and rhPDGF‐BB, although it was lower than thrombin‐activated platelet concentrate possibly due to sustained growth factor release from platelets in PRF. Anti‐PDGF antibody blocked the mitogenic effect of rhPDGF‐BB but not that of PRF in growth‐arrested fibroblasts. PRF promoted secretion of carboxyterminal propeptide of type I collagen into conditioned medium while rhPDGF‐AB had no significant effect on collagen biosynthesis. Limited proteolysis of PDGF‐AB and no proteolysis of transforming growth factor‐β1 (TGF‐β1) in PRF were observed with trypsin treatment, whereas rhPDGF‐AB and rhTGF‐β1 in bovine serum albumin, matching the total protein concentration of PRF, were almost completely degraded after 24 hours at 37 °C. To conclude, PRF provides sustained release and protection against proteolytic degradation of endogenous fibrogenic factors important for wound healing.     

Heparin‐Conjugated Poly(Lactic‐Co‐Glycolic Acid) Nanospheres Enhance Large‐Wound Healing by Delivering Growth Factors in Platelet‐Rich Plasma

Platelet‐rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long‐term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin‐conjugated poly(lactic‐co‐glycolic acid) nanospheres (HCPNs) can provide long‐term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long‐term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet‐derived growth factor‐BB (PDGF‐BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG‐PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full‐thickness skin wound treatment in mice with FG‐HCPN‐PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG‐HCPN or FG‐PRP. The enhanced wound healing using FG‐HCPN‐PRP may be due to the prolonged release not only of PDGF‐BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site.     

Freeze-dried platelet-rich plasma shows beneficial healing properties in chronic wounds

Fresh platelet concentrates are used in many centers to treat recalcitrant wounds. To extend the therapeutic shelf-life of platelets, we analyzed the wound-healing effects of fresh-frozen and freeze-dried (FD) platelet-rich plasma (PRP) using a diabetic mouse model. Db/db mice with 1.0 cm2 dorsal excisional wounds (n = 15/group) were treated with a single application of FD PRP (1.2 x 10(6) platelets/microL) with or without a stabilization solution, and compared with wounds treated with fresh-frozen, sonicated PRP, and untreated wounds. Granulation tissue area, thickness, and wound size were analyzed 9 days posttreatment. Immunostained sections were quantified for vascularity and proliferation using antiplatelet endothelial cell adhesion molecule I and antiproliferating cell nuclear antigen antibodies. The results showed that all PRP preparations increased granulation tissue formation as assessed by surface coverage, thickness, and angiogenic response, when compared with untreated wounds. In addition, wounds treated with FD PRP, and biochemically stabilized FD PRP, exhibited higher proliferative levels. The possibility to deliver growth factors using platelets, and the potential to extend the shelf-life of platelet concentrates makes freeze-drying methods particularly suitable for enhanced wound care.     

A comparative histologic analysis of tissue-engineered bone using platelet-rich plasma and platelet-enriched fibrin glue.

OBJECTIVE: The aim of this study was to compare the effects of platelet-rich plasma (PRP) and platelet-enriched fibrin glue on bone formation in bone tissue engineering. STUDY DESIGN: PRP was mixed with bone marrow mesenchymal stem cells and bone morphogenetic protein-2 (BMP-2), and the composites were injected into the subcutaneous space on the dorsum of nude mice. On the contralateral side of the dorsum, platelet-enriched fibrin glue/bone marrow mesenchymal stem cells/BMP-2 composites were injected. Bone formation was evaluated after 12 weeks. RESULTS: The volumes of subcutaneous nodules formed in nude mice were 55 +/- 18 microL at the PRP/bone marrow mesenchymal stem cells/BMP-2 sites and 135 +/- 27 microL at the platelet-enriched fibrin glue/bone marrow mesenchymal stem cells/BMP-2 sites. Histomorphometric analysis demonstrated that the nodules contained 14.9 +/- 4.1% newly formed bone when using PRP and 19.8 +/- 3.6% newly formed bone when using platelet-enriched fibrin glue. CONCLUSION: The results indicated that the osteogenic characteristics of platelet-enriched fibrin glue are superior to PRP in bone tissue engineering.     

Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation

The economic, social, and public health burden of chronic ulcers and other compromised wounds is enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis, and tissue sealing. In this study, we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely platelet-rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study, for the first time, shows the kinetics of the viability of platelet-embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The vascular endothelial growth factor released from PRFM was primarily responsible for endothelial mitogenic response via extracellular signal-regulated protein kinase activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers.     

Proliferation and differentiation of human tenocytes in response to platelet rich plasma: an in vitro and in vivo study

Platelet rich plasma (PRP) is the autologous plasma fraction with a platelet-rich cellular component which is enriched with a number of growth factors. Due to its availability and low cost, PRP has become an increasingly popular clinical tool as an alternative source of growth factors for various applications, for example, tendon regeneration but with limited success in clinical trials. The main objective of the current study was to determine whether activated PRP [i.e., platelet rich plasma-clot release (PRCR)] could be used to induce the proliferation and collagen synthesis in human tenocyte in vitro. The advantage of using PRCR is that the platelet-derived bioactive factors are more concentrated and could initiate a more rapid and accelerated healing response than PRP. Our results demonstrated that 10% PRCR treatment accelerated the extent of cell proliferation and collagen production by human tenocytes in vitro. The expression of specific tenocyte markers were similar to conventional fetal bovine serum (FBS)-treated tenocytes implanted in mice within 14 days of implantation in diffusion chambers. Moreover, relatively more collagen fibrils were evident in PRCR-treated tenocytes in vivo as compared to 10% FBS-treated cells. Overall, our feasibility study has indicated that PRCR can induce human tenocyte proliferation and collagen synthesis which could be implemented for future tendon regeneration in reconstructive surgeries.     

Functional assessment of autologous platelet-rich plasma (PRP) after long-term storage at −20 °C without any preservation agent

Background: Platelet-rich plasma (PRP) is increasingly being used in the treatment of chronic wounds, pathologies of the musculoskeletal system, and in cosmetic medicine; however, the preparation of platelet-rich plasma is both time-consuming and requires invasive intervention. Additional costs are introduced if special equipment is used during preparation. The aim of the present study is to test whether autologous platelet-rich plasma (PRP) preserves the feature of growth factor release when stored at ?20?°C after preparation.

Method: Autologous PRP concentrates were prepared using whole blood samples obtained from 20 healthy subjects and divided into three parts to form three groups. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet derived growth factor-AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), transforming growth factor-beta (TGF-β), and P-Selectin levels were immediately analysed in the control group. The other groups were defined as the experimental groups and were stored at ?20?°C and analysed on the 7th and the 14th days. The same growth factors were tested in the experimental groups.

Results: The growth factors (EGF, VEGF, PDGF-AB, IGF-1, TGF-β) and P-selectin levels were significantly decreased in the autologous PRP samples stored at ?20?°C compared to the control group.

Conclusion: The growth factor levels on days 7 and 14 suggest that autologous PRP can be stored at ?20?°C without preservative agents, although in vivo studies are required in order to evaluate the clinical efficacy of the detected growth factor levels.     

PRF促进急性创面愈合的研究进展

伤口愈合很大程度上依赖于机体自身的修复能力,而组织损伤会激活多种细胞分泌生长因子参 与炎症反应过程,调节蛋白质和其他细胞成分的合成、分解,从而促进细胞增殖、基质形成、血管再生 及肉芽形成,达到创面修复的目的。富血小板纤维蛋白（PRF）是第二代血小板浓缩物,与富血小板血 浆（PRP）不同,PRF制备时未加入抗凝剂和其他化学成分,有效避免了过敏反应。PRF富含生长因子, 可持续释放生长因子至少1周以上,同时具有良好的立体纤维蛋白空间结构,可为创面提供理想的细胞支 架,能有效促使细胞迁移和增殖,从而达到促进创面愈合的作用。本文为探究PRF促进急性创面愈合的研 究进展,现就伤口愈合过程、PRF应用于急性伤口愈合时的作用机制作一综述。     

In vitro human cord blood platelet lysate characterisation with potential application in wound healing

Platelets contain abundant growth factors and cytokines that have a positive influence on the migration and proliferation of different cell types by modulating its physiopathological processes. As it is known that human umbilical cord blood platelet lysate (UCB‐PL) contains a supraphysiological concentration of growth factors, in the present study, we investigated its effectiveness in wound‐healing processes. Human UCB‐PL was obtained by the freeze/thaw of platelet concentrate (1.1 × 10⁹ platelets/L), and its effect was evaluated on human or mouse endothelial cells, monocytes, fibroblasts, and keratinocytes in different concentrations. Human UCB‐PL was observed to have high levels of pro‐angiogenic growth factor than peripheral blood platelet‐rich plasma. Among the cell lines, different concentrations of human UCB‐PL were necessary to influence their viability and proliferation. For L929 cells, 5% of total volume was necessary, while for human umbilical vein endothelial cell, it was 10%. Cell migration on monocytes was increased with respect to the positive control, and scratch closure on keratinocytes was increased with respect to serum‐free medium with only 10% of human UCB‐PL. We concluded that the human UCB‐PL may be useful to produce a large amount of standard platelet concentrates sufficient for several clinical‐scale expansions avoiding inter‐individual variability, which can also be used as a functional tool for clinical regenerative application for wound healing.     

Safer circumcision in patients with haemophilia: the use of fibrin glue for local haemostasis

OBJECTIVE: To evaluate the efficacy and the reduced costs of factor concentrates in circumcision by using fibrin glue in patients with haemophilia. PATIENTS AND METHODS: Eleven patients with haemophilia (age range 6-14 years, 10 with haemophilia A, one with haemophilia B) were circumcised using fibrin glue for local haemostasis and to reduce the duration of clotting factor replacement after surgery. Circumcision was carried out under general anaesthesia; the prepuce was incised circumferentially and excised using the Gomco clamp technique. Haemophiliac patients were divided into two groups: in group 1 (four patients, three with haemophilia A and one with haemophilia B) the factor levels were assessed every 8 h and bolus injections of factor repeated during the first 4 days after surgery; in group 2, the seven remaining haemophilia A patients received a postoperative bolus injection and approximately 4 U/kg per hour of factor substitution for the first 2 days after surgery by continuous infusion. Eleven other patients with haemophilia A underwent circumcision using same surgical procedure but were given only factor substitution without fibrin glue, and served as a control group (group 3). RESULTS: None of the patients had significant bleeding or complications. The total costs were significantly reduced, to $8898 per patient in group 1 and $4866 per patient in group 2, when compared with $12875 per patient in group 3 (both P<0.05). CONCLUSION: Fibrin glue is a useful treatment for circumcision in patients with haemophilia; it lessens the need for factor substitution after circumcision and thus reduces the high cost of treatment.     

Platelet rich concentrate: basic science and current clinical applications

Improvements in resuscitation, dissemination of ATLS protocols, and growth of regional and local trauma centers has increased the survivability after severe traumatic injuries. Furthermore, advances in medical management have increased life expectancy and also patients with orthopaedic injuries. While mechanical stabilization has been a hallmark of orthopaedic fracture care, orthobiologics are playing an increasing role in the management of these patients with complex injuries. Platelet-rich concentrate is an autologous concentration of platelets and growth factors, including transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The enhancement of bone and soft tissue healing by the placement of supraphysiologic concentration of autologous platelets at the site of tissue injury or surgery is supported by basic science and clinical studies. Due to the increased concentration and release of these factors, platelet-rich plasma can potentially enhance the recruitment and proliferation of tenocytes, stem cells, and endothelial cells. A better understanding of platelet function and appropriate clinical use is essential in achieving the desired outcomes of platelet-rich concentrate in orthopaedic clinical applications.     

Platelet-rich plasma combined with skin substitute for chronic wound healing: a case report

Contemporary management of chronic wounds focuses on improving natural healing and individualization of treatment. Incorporating multiple therapies has become increasingly common. Of interest are autologous growth factors, which are especially important in chronic wound healing and may contribute to tissue formation and epithelialization. Autologous platelet concentrate or platelet-rich plasma (PRP) is a concentration of at least five autologous growth factors and has been shown to accelerate wound healing and may have infection-fighting properties. Chronic wound healing is complicated by both decreased growth factor availability and infection, making PRP use valuable in these types of wounds. In this report, the use of PRP therapy alone and in combination with a bioengineered skin substitute as a platelet-rich tissue graft in a chronic, non-healing wound is detailed. Over 27 weeks, the patient received multiple therapies in attempts to heal a severe decubitus ulcer of the sacrum. The introduction of PRP therapy at Week 14 led to a 26% reduction in wound depth over 4 weeks. At Week 19, PRP therapy was combined with a powdered skin substitute to create a platelet-rich tissue graft. The combination brought dramatic results, eliminating wound tunneling and reducing the wound dimensions from 6.2 cm long x 6.7 cm wide x 2.7 cm deep to 5.0 cm long x 6.0 cm wide x 1.4 cm deep. The promising observations from this case report indicate that further study on the combining of PRP therapy and skin substitutes is necessary.     

Thrombocytes are effectors of the innate immune system releasing human beta defensin-3

Background

Thrombocyte concentrate i.e. platelet-rich plasma (PRP) has become a popular adjunct for many surgical procedures. It is believed to improve bone and soft tissue healing. Recently antimicrobial effects of the autologous preparation were reported by several groups. In this study we investigated the antimicrobial effect of PRP against gram-negative microbes which frequently cause severe complications in orthopaedic trauma surgery.

Methods

Platelet-rich plasma was produced from liquid preserved thrombocyte concentrates. ELISA, Western blot and immunohistochemistry were preformed to investigate the release and content of platelet concentrates. A radial diffusion assay was used to detect antimicrobial effects of PRP.

Results

We detected the human beta defensin-3 in bactericidal concentrations in platelet preparations by ELISA, Western blot and immunohistochemistry. In antimicrobial testing we demonstrated effective inhibition of Escherichia coli (ATCC 11303), Bacterium megaterium (ATCC 14581), Klebsiella pneumoniae (ATCC 13883), Enterococcus faecalis (ATCC 29212) and Proteus mirabilis (ATCC21100).

Conclusion

With this study we demonstrate antimicrobial action of a popular adjunct for orthopaedic and trauma surgery against gram-positive and gram-negative bacteria. We have identified a possible mechanism of action via the secretion of HBD-3 as a first line defence in contaminated wounds and in elective application of PRP. This finding supports a broader spectrum of clinical indications for an autologous platelet preparation.     

Relationship of cytokine levels and clinical effect on platelet‐rich plasma‐treated lateral epicondylitis

Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet‐rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. A total of 156 patients with LE were randomly divided into group 1, treated with a single injection of 2‐ml autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks’ follow‐up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet‐derived growth factor‐AB (PDGF‐AB), PDGF‐BB, transforming growth factor‐β (TGF‐β), vascular endothelial growth factor, epithelial growth factor, and interleukin‐1 β in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (p < 0.05). PDGF‐AB, PDGF‐BB, and TGF‐β levels were more significantly increased in PRP than in whole blood. TGF‐β level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF‐β level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:913–920, 2018.

     

Platelet rich plasma and fresh frozen bone allograft as enhancement of implant fixation. An experimental study in dogs.

Platelet rich plasma (PRP) is an autologous source of growth factors. By application of PRP around cementless implants alone or in combination with bone allograft chips, early implant fixation and gap healing could be improved. We inserted two porous HA coated titanium implants extraarticularly in each proximal humerus of eight dogs. Each implant was surrounded by a 2.5 mm gap. Four treatments were block randomized to the four gaps in each dog: Treatment 1: empty gap, treatment 2: PRP, treatment 3: fresh frozen bone allograft, treatment 4: fresh frozen bone allograft+PRP. PRP was prepared from each dog prior to operation by isolating the buffycoat from centrifuged blood samples. Platelet count in PRP was increased 670% compared to baseline level. Calcium/thrombin was added to degranulate platelets and form a gel. Three weeks after surgery, push-out test and histomorphometri was performed. After three weeks, the non-allografted implants had poor mechanical properties. Bone grafting significantly increased implant fixation, bone formation in the gap and bone growth on the implant surface. We found no significant effect of PRP alone or mixed with bone allograft on implant fixation or bone formation. In conclusion, we showed the importance of bone allografting on early implant fixation and bone incorporation but we found no effect of PRP. More studies are needed to investigate the effect and possible clinical applications of platelet concentrates which are now being commercialised.     

Endothelial cells incubated with platelet‐rich plasma express PDGF‐B and ICAM‐1 and induce bone marrow stromal cell migration

Platelet‐rich plasma (PRP) is used to accelerate bone repair through the growth factors released by platelets. The purpose of this study was to evaluate if PRP induce human umbilical vein endothelial cells (HUVEC) to express mRNA for osteogenic growth factors and stimulate the migration of bone marrow stromal cell (BMSC). The effects of PRP were compared to those induced by vascular endothelial growth factor‐A (VEGF‐A) or, as a negative control, by platelet poor plasma (PPP). After incubation with PRP, but not with PPP, HUVEC showed an increased expression of mRNA for platelet derived growth factor‐B (PDGF‐B), and this effect was not inhibited by an anti‐VEGF‐A antibody. The migration of BMSC was more stimulated by HUVEC incubated with PRP than by HUVEC incubated with low serum medium or PPP. Besides, PRP increased the expression of intercellular adhesion molecule‐1 (ICAM‐1) and osteoprotegerin, but did not affect the expression either of the receptor activator for nuclear factor κB ligand (RANKL) or of RANK. These findings support the hypothesis that PRP contribute to bone repair by favoring the pro‐osteogenic function of endothelial cells, including the recruitment of osteoblast precursors and the expression of adhesion molecules for monocyte/macrophages, while inhibiting their pro‐osteolytic properties. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1493–1498, 2009     

Comparative study of different biological glues in an experimental model of surgical bleeding in anesthetized rats: Platelet-rich and -poor plasma-based glue with and without aprotinin versus commercial fibrinogen-based glue

The use of fibrin glue in cardiovascular surgery has been associated with decreased operative time, effective control of localized bleeding, and reduced postoperative blood loss. All preparations of fibrin glue mimic the final common pathway of the coagulation cascade in which fibrinogen is converted to fibrin in the presence of thrombin and calcium. The goal of the study was to compare five different types of fibrin glue, with or without aprotinin, on a surgical bleeding model in the rat. In 70 anesthetized Wistar rats, after laparotomy, a 3 cm liver incision was performed. After randomization, seven groups were studied. In the first group, Biocol® was used as a pinpoint application to the bleeding site. Four groups received a fibrin glue obtained from a single human donor plasma using Cell Saver V (Haemonetics). The sealant was applied as a two-component system. The first component of the glue was either platelet-rich-plasma (PRP) or platelet-poor-plasma (PPP). The second component consisted of a mixture of 0.5 ml CaCl 10% with 1000 U of human thrombin, with or without 400KUI of aprotinin (AP). The last two groups, control and aprotinin were treated using saline solution or topical aprotinin respectively. Hemoglobin and hematocrit were measured before surgery and 30 min after application of the glue. The decrease in hemoglobin (Hb) and hematocrit (Hct) was the primary efficacy variable. Before surgery, there was no difference regarding Hb and Hct values between groups. Thirty min after the application of the glue, the decrease in hemoglobin expressed as percent of the control values is only significantly lower in the Biocol group when compared to control. No significant difference was observed with the other groups in comparison to control. The commercial fibrin glue (Biocol) is more efficient than other preparations. This efficacy is likely due to a higher fibrinogen concentration.