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Platelet-dependent thrombin generation is a helpful tool to assess ex vivo the interaction between platelets and plasma coagulation factors in the initiation, amplification, and inhibition of thrombin generation (TG). This review article discusses the most relevant available data on the clinical applications of fluorogenic TG, the most widely used TG assay, performed in the presence of platelets, i.e., in platelet-rich plasma. With respect to prothrombotic states, arterial hypertension and obesity were the most prominent cardiovascular conditions linked to increased platelet-dependent TG. In addition, platelet-associated hypercoagulability, assessed by the TG assay, has been shown in individuals with active cancer. In terms of bleeding, platelet-dependent TG has been applied to assess bleeding risk in individuals with hemophilia, von Willebrand disease, and Glanzmann thrombasthenia as well as in subjects with other congenital or acquired coagulation factor deficiencies. In addition to risk prediction, a role of the TG assay has been suggested in monitoring antiplatelet therapy in prothrombotic conditions and replacement therapy in bleeding diathesis. Finally, for the routine clinical use and as a biomarker of disease development and progression, better standardization and clinical validation of platelet-dependent TG are still needed.

Purpose: The use of biologic agents is emerging in bone regeneration procedures due to their ability to increase cellular events in wound healing and therefore to obtain more predictable outcomes. Hence, the aim of the present study was to critically evaluate the methodology of systematic reviews investigating biologic agents in promoting bone formation and implant site development. Materials and Methods: A literature search for systematic reviews with and without meta-analyses was performed in Medline, Embase, and the Cochrane database, as well as in journals with high impact factors in periodontics and implant dentistry. Titles, abstracts, and full-text articles were analyzed for potential inclusion. Three guidelines-AMSTAR, R-AMSTAR, and the checklist proposed by Glenny et al-were utilized to analyze their methodologic quality. Two calibrated reviewers performed all data extraction and appraisal. Cohen's kappa coefficients were calculated to appraise the interexaminer agreement. Results: A total of 12 systematic reviews, 3 with meta-analyses, were evaluated. Platelet-rich derivatives and BMP-2 were the most widely studied biologic agents and sinus augmentation was the most common procedure evaluated. The R-AMSTAR mean score was 28 (range 14-38) and none of the systematic reviews analyzed met all of the items. In the AMSTAR checklist, the mean score was 5.75 (range 2-9) and the only item met by all the systematic reviews was the a priori design. The Glenny et al checklist mean score was 8.6 (range 4-13) and two items, "focused question" and "to identify all relevant studies," were met by all systematic reviews. Conclusion: Systematic reviews on biologic agents to promote bone formation at implant site development demonstrate substantial methodologic variability. Therefore, caution must be exercised when interpreting their findings.

Purpose. This study evaluated the efficacy of 50% autologous serum eye drops in ocular surface diseases not improved by conventional therapy.Methods. We analyzed two groups: (1) acute eye pathologies (e.g., chemical burns) and (2) chronic eye pathologies (e.g., recurrent corneal erosion, neurotropic keratitis, and keratoconjunctivitis sicca). The patients were treated for surface instability after conventional therapy. The patients received therapy 5 times a day until stabilization of the framework; they then reduced therapy to 3 times a day for at least 3 months. We analyzed the best corrected visual acuity, epithelial defects, inflammation, corneal opacity, and corneal neovascularization. We also analyzed symptoms such as tearing, burning, sense of foreign body or sand, photophobia, blurred vision, and difficulty opening the eyelids.Results. We enrolled 15 eyes in group 1 and 11 eyes in group 2. The average therapy period was 16 ± 5.86 weeks in group 1 and 30.54 ± 20.33 weeks in group 2. The epithelial defects all resolved. Signs and symptoms improved in both groups. In group 2, the defect recurred after the suspension of therapy in 2 (18%) patients; in group 1, no defects recurred.Conclusions. Autologous serum eye drops effectively stabilize and improve signs and symptoms in eyes previously treated with conventional therapy.

Purpose To assess the histology and biomechanics of repair cartilage after microfractures with and without repeated local injections of platelet concentrate for the treatment of full-thickness focal chondral defects of the knee. Methods A full-thickness chondral lesion on the medial femoral condyle was created in 30 sheep and treated with microfractures. Animals were divided into 2 groups, according to postoperative treatment: in group 1 we performed 5 weekly injections of autologous conditioned plasma, whereas group 2 did not undergo further treatments. Animals were killed at 3, 6, and 12 months after treatment. Macroscopic, histologic, and biomechanical evaluations were performed. Differences between groups at each time interval and differences over time within groups were analyzed for each outcome. Significance was set at P Results Group 1 showed significantly better macroscopic, histologic, and biomechanical results than group 2 at each time interval. Analysis of time effect within groups showed that in group 1, quality of repair tissue significantly improved from 3 to 6 months after treatment and remained stable over time for all the outcomes; in group 2 a significant histologic and mechanical deterioration was observed between 6 and 12 months' follow-up. Conclusions Five repeated local injections of autologous conditioned plasma after microfractures in the treatment of full-thickness cartilage injuries promoted a better and more durable reparative response than isolated microfractures, although they did not produce hyaline cartilage. Clinical Relevance Periodical intra-articular injections of platelet concentrate after microfractures may improve cartilage repair and prevent further degenerative changes.

Objective The aim of the present study was to evaluate the use of previously frozen, thawed platelet gel supplementation to accelerate the healing of long bone nonunions treated by external fixation. Design Prospective case series with historical controls. Setting University Hospital. Patients Twenty patients affected by tibial, humeral, or forearm atrophic nonunions were treated by percutaneous stabilization with unilateral external fixators and injection of autologous platelet gel. The healing time was compared to the result obtained in a historical control group treated without platelet gel supplementation. Main outcome measurements Consolidation rate and radiographic healing time of nonunions in the 2 groups were assessed by independent blinded observers. The nonunion was judged to be healed when bridging callus formation on both radiographic views was observed on at least 3 of 4 cortices. Results The healing rate of nonunion was 90% (18/20) in platelet gel cases and 85% (17/20) in controls, respectively (P = 0.633). The mean time until radiographic consolidation in nonunions supplemented with platelet gel (147 +/- 63 days) was not different to the result in the control group (153 +/- 61 days; P = 0.784). Analyzing the mean healing time for separate segments, no differences were noted between study and control group-that is, tibia: 112 +/- 43 and 130 +/- 5 days, respectively (P = 0.382); humerus, 225 +/- 36 and 202 +/- 70 days, respectively (P = 0.530). Conclusion The present study failed to show the clinical usefulness of isolated percutaneous platelet gel supplementation in long bone nonunions treated by external fixation; however, caution should be exercised in interpreting this result because the actual numbers are small and the statistical power is limited.

Background: The therapeutic use of autologously prepared, platelet-leukocyte-enriched gel (PLG) is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. The effectiveness of this procedure lies in the delivery of a wide range of platelet growth factors mimicking the physiologic wound healing and reparative tissue processes. Despite an increase in PLG applications, the structures and kinetics of this autogenously derived biologic material have not been observed.Methods: A review of the most recent literature was performed to evaluate the use of PLG in various surgical disciplines.Results: The review showed that the application of PLG has been extended to various surgical disciplines including orthopedics, cardiac surgery, plastic and maxillofacial surgery, and recently also endoscopic surgery.Conclusion: This review demonstrates the usefulness of PLG in a wide range of clinical applications for improvement of healing after surgical procedures.

Platelet components have found successful clinical utilization to initiate or to accelerate tissue-repair mechanisms. However, the molecular pathways by which platelet factors contribute to tissue regeneration have not been fully elucidated. We have studied the effect of thrombin-activated platelets (TAPs) on cell growth in vivo and in cultured cell systems. Application of TAPs to ulcerative skin lesions of diabetic patients induced local activation of ERK1/2 and Akt/PKB. Moreover, when applied to cultured human skin fibroblasts, TAPs promoted cell growth and DNA synthesis and activated platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF)-1 receptor tyrosine kinases. PDGF was released by TAPs and rapidly achieved a plateau. At variance, the release of IGF-1 was mainly provided by the TAPs-stimulated fibroblasts and progressively increased up to 48 h. The PDGF-R blocker Ag1296 reduced the activation of Akt/PKB and, at a lesser extent, of ERK1/2. Conversely, inhibition of IGF-1 signaling by Ag1024 and expression of a dominant-negative IGF-1R mutant selectively reduced the stimulation of ERK1/2 by TAPs and fibroblast-released factors, with minor changes of Akt/PKB activity. Thus, platelet factors promote fibroblast growth by acutely activating Akt/PKB and ERK1/2. Sustained activation of ERK1/2, however, requires autocrine production of IGF-1 by TAPs-stimulated fibroblasts.