The Safety and Effectiveness of Orthobiologic Injections for Discogenic Chronic Low Back Pain: A Multicenter Prospective, Crossover, Randomized Controlled Trial with 12 Months Follow-up.

BACKGROUND: Chronic low back pain is one of the most common causes of disability, affecting more than 600 million people worldwide with major social and economic costs. Current treatment options include conservative, surgical, and minimally invasive interventional treatment approaches. Novel therapeutic treatment options continue to develop, targeting the biological cascades involved in the degenerative processes to prevent invasive spinal surgical procedures. Both intradiscal platelet-rich plasma (PRP) and bone marrow concentrate (BMC) applications have been introduced as promising regenerative treatment procedures. OBJECTIVES: The primary objective of this study is to assess the safety and effectiveness of an orthobiologic intradiscal injection, PRP or BMC, when compared to control patients. The secondary objectives are to measure: patient satisfaction and incidence of hospitalization, emergency room visit and spine surgery at predetermined follow-up intervals. STUDY DESIGN: A multicenter, prospective, crossover, randomized, controlled trial. SETTING: Comprehensive Spine and Sports Center and participating centers. METHODS: Forty patients were randomized into saline trigger point injection, intradiscal PRP, or BMC. Follow-up was 1, 3, 6, and 12 months posttreatment. Placebo patients were randomized to PRP and BMC injection if < 50% decrease in numeric rating scale (NRS) scores in 3 months, while PRP and BMC patients to the other active group if < 50% decrease in NRS scores in 6 months. RESULTS: Both PRP and BMC demonstrated statistically significant improvement in pain and function. All the placebo patients reported < 50% pain relief and crossed to the active arm. None of the patients had any adverse effects, hospitalization, or surgery up to 12 months posttreatment. LIMITATIONS: The limitations of our study were the small number of patients and open-label nature of the study. CONCLUSION: This is the only human lumbar disc study that evaluates both PRP and BMC in the same study and compares it to placebo. PRP and BMC were found to be superior to placebo in improving pain and function; however, larger randomized clinical trials are needed to answer further questions on the comparative effectiveness of various biologics as well as to identify outcome differences specific to disc pathology.

Angiogenesis and Tissue Repair Depend on Platelet Dosing and Bioformulation Strategies Following Orthobiological Platelet-Rich Plasma Procedures: A Narrative Review.

Angiogenesis is the formation of new blood vessel from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells; an overexpression of inflammatory mediators; such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1); the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases; and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma (PRP)) improve tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets, with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or regeneration. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue repair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis, other than a general one-size-fits-all statement that "PRP has angiogenic capabilities". Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

Basic Science of Autologous Orthobiologics: Part 1. Platelet-Rich Plasma.

In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, such as blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate, and adipose tissue concentrate, respectively. In this article, we will emphasize and discuss the physiological variability of autologous PRP bioformulations regarding their effectivity in tissue repair. Furthermore, recent developments concerning platelet dosing, potentially effecting immunomodulation, and pain killing will be described.

Basic Science of Autologous Orthobiologics: Part 2. Mesenchymal Stem Cells.

In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, like blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC), respectively. In this article, we emphasize and discuss the physiologic variability of autologous prepared BMC and ATC for the delivery of mesenchymal stem cells to support tissue repair processes.

Basic Science of Allograft Orthobiologics.

Orthobiologic procedures are based on altering the microenvironment of musculoskeletal tissues to induce an anti-inflammatory effect and reduce pain, promote healing of these tissues, or provide mechanical support. Allograft tissues have these inherent qualities and can be used as such. This could provide patients whose own autologous tissues may be compromised or have contraindications to harvesting an alternative to treat their orthopedic conditions. Although these allograft therapies are promising, they lack high-quality clinical studies and regulatory guidelines currently limit their use.

Modifying Orthobiological PRP Therapies Are Imperative for the Advancement of Treatment Outcomes in Musculoskeletal Pathologies.

Autologous biological cellular preparations have materialized as a growing area of medical advancement in interventional (orthopedic) practices and surgical interventions to provide an optimal tissue healing environment, particularly in tissues where standard healing is disrupted and repair and ultimately restoration of function is at risk. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues to prepare point of care platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC). Orthobiological preparations are biological materials comprised of a wide variety of cell populations, cytokines, growth factors, molecules, and signaling cells. They can modulate and influence many other resident cells after they have been administered in specific diseased microenvironments. Jointly, the various orthobiological cell preparations are proficient to counteract persistent inflammation, respond to catabolic reactions, and reinstate tissue homeostasis. Ultimately, precisely delivered orthobiologics with a proper dose and bioformulation will contribute to tissue repair. Progress has been made in understanding orthobiological technologies where the safety and relatively easy manipulation of orthobiological treatment tools has been demonstrated in clinical applications. Although more positive than negative patient outcome results have been registered in the literature, definitive and accepted standards to prepare specific cellular orthobiologics are still lacking. To promote significant and consistent clinical outcomes, we will present a review of methods for implementing dosing strategies, using bioformulations tailored to the pathoanatomic process of the tissue, and adopting variable preparation and injection volume policies. By optimizing the dose and specificity of orthobiologics, local cellular synergistic behavior will increase, potentially leading to better pain killing effects, effective immunomodulation, control of inflammation, and (neo) angiogenesis, ultimately contributing to functionally restored body movement patterns.

Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 2 Years: A Prospective Randomized Trial.

BACKGROUND: Autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC) are being used clinically as therapeutic agents for the treatment of knee osteoarthritis. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the efficacy of BMC and PRP on pain and function in patients with knee osteoarthritis up to 24 months after injection. It was hypothesized that patients receiving BMC would have better sustained outcomes than those receiving PRP. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 90 participants aged between 18 and 80 years with symptomatic knee osteoarthritis (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaire before and 1, 3, 6, 9, 12, 18, and 24 months after a single intra-articular injection of leukocyte-rich PRP or BMC. A linear mixed-effects model was performed to quantify the effects over time and the difference between the groups. This model has the random effect for time to assess the extent in which the change over time differs from one person to another. RESULTS: An overall 84 patients completed questionnaires from baseline to 12 months; however, 17 patients (n = 9; PRP group) were lost to follow-up at 18 months and 25 (n = 13; PRP group) at 24 months. There were no statistically significant differences in IKDC (P = .909; 95% CI, -6.26 to 7.03) or WOMAC (P = .789; 95% CI, -6.26 to 4.77) scores over time between the groups. Both groups had significantly improved IKDC (P < .001; 95% CI, 0.275-0.596) and WOMAC (P = .001; 95% CI, -0.41 to -0.13) scores from baseline to 24 months after the injection. These improvements plateaued at 3 months and were sustained for 24 months after the injection, with no difference between PRP and BMC at any time point. CONCLUSIONS: For the treatment of osteoarthritis, PRP and BMC performed similarly out to 24 months. BMC was not superior to PRP. REGISTRATION: NCT03289416 (ClincalTrials.gov identifier).

Platelet Rich Plasma in Orthopedic Surgical Medicine.

There is a global interest in optimizing post-surgical tissue repair strategies, leading to better patient outcomes and fewer complications, most ideally with reduced overall cost. In this regard, in recent years, the interest in autologous biological treatments in orthopedic surgery and sports medicine has increased greatly, and the addition of platelet-rich plasma (PRP) to the surgical armamentarium is of particular note. Unfortunately, the number of PRP preparation devices has also grown immensely over the recent decades, raising meaningful concern for the considerable variation in the qualities of currently available PRP preparations. The lack of consensus on the standardization of PRP preparation and of agreement on condition specific PRP formulations is largely responsible for the sometimes contradictory outcomes in the literature. Furthermore, the full potential of PRP technology, the concept of individualized treatment protocols based on bioformulation options, and platelet dosing, angiogenesis, and antimicrobial and painkilling effects of PRP relevant to orthopedic surgery have rarely been addressed. In this review, we will discuss recent developments regarding PRP preparations and potential therapeutic effects. Additionally, we present a synopsis of several published data regarding PRP applications in orthopedic surgery for treating tendon injuries, inducing bone repair, strengthening spinal fusion outcomes, and supporting major joint replacements.

Role of Mechanical Loading for Platelet-Rich Plasma-Treated Achilles Tendinopathy.

There is no consensus on the optimal rehabilitation protocol after platelet-rich plasma (PRP) treatment for tendinopathy despite basic science studies showing the critical role of mechanical loading in the restoration of tendon structure and function posttreatment. In this article, we will review tendon mechanobiology, platelet biology, and review levels I and II Achilles tendon clinical studies paying particular attention to the role of mechanical loading in rehabilitation of injured tendons. Animal studies emphasize the synergistic effect of mechanical tendon loading and PRP to treat tendon injury while clinical studies described minimal details on loading protocols.

Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial.

BACKGROUND: Approximately 47 million people in the United States have been diagnosed with arthritis. Autologous platelet-rich plasma (PRP) injections have been documented to alleviate symptoms related to knee osteoarthritis (OA) in randomized controlled trials, systematic reviews, and meta-analyses. Autologous bone marrow aspirate concentrate (BMC) injections have also emerged as a treatment option for knee OA, with a limited clinical evidence base. PURPOSE: To compare the efficacy of BMC to PRP for the treatment of knee OA regarding pain and function at multiple time points up to 12 months after an injection. We hypothesized that BMC will be more effective in improving outcomes in patients with knee OA. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 90 participants aged between 18 and 80 years with symptomatic knee OA (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaires before and 1, 3, 6, 9, and 12 months after a single intra-articular injection of leukocyte-rich PRP or BMC. RESULTS: There were no statistically significant differences in baseline IKDC or WOMAC scores between the 2 groups. All IKDC and WOMAC scores for both the PRP and BMC groups significantly improved from baseline to 1 month after the injection (P < .001). These improvements were sustained for 12 months after the injection, with no difference between PRP and BMC at any time point. CONCLUSION: Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. Autologous PRP and BMC showed promising clinical potential as therapeutic agents for the treatment of OA, and while PRP has strong clinical evidence to support its efficacy, BMC has limited support. This study did not prove BMC to be superior to PRP, providing guidance to clinicians treating OA. It is possible that the results were affected by patients knowing that there was no control group. REGISTRATION: NCT03289416 (ClinicalTrials.gov identifier).

Proteomic analysis of platelet-rich and platelet-poor plasma.

BACKGROUND: Autologous blood products, such as platelet-rich plasma (PRP) are commercial products broadly used to accelerate healing of tissues after injuries. However, their content is not standardized and significantly varies in composition, which may lead to differences in clinical efficacy. Also, the underlying molecular mechanisms for therapeutic effects are not well understood. PURPOSE: A proteomic study was performed to compare the composition of low leukocyte PRP, platelet poor plasma (PPP), and blood plasma. Pathway analysis of the proteomic data was performed to evaluate differences between plasma formulations at the molecular level. Low abundance regulatory proteins in plasma were identified and quantified as well as cellular pathways regulated by those proteins. METHODS: Quantitative proteomic analysis, using multiplexed isotopically labeled tags (TMT labeling) and label-free tandem mass spectrometry, was performed on plasma, low leukocyte PRP, and PPP. Plasma formulations were derived from two blood donors (one donor per experiment). Pathway analysis of the proteomic data identified the major differences between formulations. RESULTS: Nearly 600 proteins were detected in three types of blood plasma formulations in two experiments. Identified proteins showed more than 50% overlap between plasma formulations. Detected proteins represented more than 100 canonical pathways, as was identified by pathway analysis. The major pathways and regulatory molecules were linked to inflammation. CONCLUSION: Three types of plasma formulations were compared in two proteomic experiments. The most represented pathways, such as Acute Phase Response, Coagulation, or System of the Complement, had many proteins in common in both experiments. In both experiments plasma sample sets had the same direction of biochemical pathway changes: up- or down-regulation. The most represented biochemical pathways are linked to inflammation.

Optimizing the safety of intradiscal platelet-rich plasma: an in vitro study with Cutibacterium acnes.

Aim: The most common risk associated with intradiscal injection of platelet-rich plasma (PRP) is discitis with Cutibacterium acnes. It is hypothesized that antimicrobial activity of PRP can be enhanced through inclusion of leukocytes or antibiotics in the injectate. Materials & methods: Multiple PRP preparations of varying platelet and leukocyte counts were co-cultured with C. acnes with or without cefazolin, with viable bacterial colony counts being recovered at 0, 4, 24 and 48 hours post-inoculation. Results: A direct correlation between C. acnes recovery and granulocyte counts were observed. Conclusion: We observed the greatest antimicrobial activity with the leukocyte-rich, high platelet PRP preparation combined with an antibiotic in the injectate. However, cefazolin did not completely clear the bacteria in this assay.

Assessing clinical implications and perspectives of the pathophysiological effects of erythrocytes and plasma free hemoglobin in autologous biologics for use in musculoskeletal regenerative medicine therapies. A review.

Autologous biologics, defined as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMC), are cell-based therapy treatment options in regenerative medicine practices, and have been increasingly used in orthopedics, sports medicine, and spinal disorders. These biological products are produced at point-of-care; thereby, avoiding expensive and cumbersome culturing and expansion techniques. Numerous commercial PRP and BMC systems are available but reports and knowledge of bio-cellular formulations produced by these systems are limited. This limited information hinders evaluating clinical and research outcomes and thus making conclusions about their biological effectiveness. Some of their important cellular and protein properties have not been characterized, which is critical for understanding the mechanisms of actions involved in tissue regenerative processes. The presence and role of red blood cells (RBCs) in any biologic has not been addressed extensively. Furthermore, some of the pathophysiological effects and phenomena related to RBCs have not been studied. A lack of a complete understanding of all of the biological components and their functional consequences hampers the development of clinical standards for any biological preparation. This paper aims to review the clinical implications and pathophysiological effects of RBCs in PRP and BMC; emphasizes hemolysis, eryptosis, and the release of macrophage inhibitory factor; and explains several effects on the microenvironment, such as inflammation, oxidative stress, vasoconstriction, and impaired cell metabolism.

Platelet-Rich Plasma as a Treatment for Androgenetic Alopecia.

BACKGROUND: Platelet-rich plasma (PRP) treatment may encourage hair growth by promoting cellular maturation, differentiation, and proliferation. OBJECTIVE: The objective of this study was to evaluate the effectiveness of PRP as a treatment for androgenetic alopecia (AGA). MATERIALS AND METHODS: A literature search combined with meta-analysis was used to calculate the overall standardized mean difference (SMD) in hair density in patients treated with PRP injections in comparison with baseline and placebo treatment. Chi squared analysis and Fisher exact test were used to investigate variation in protocols. RESULTS: The overall SMD in hair density was 0.58 (95% confidence interval [CI]: 0.35-0.80) and 0.51 (95% CI: 0.23-0.80, p < .0004) in favor of PRP treatment when compared with baseline and placebo treatment, respectively. CONCLUSION: Platelet-rich plasma is beneficial in the treatment of AGA. It is recommended that 3 monthly sessions of PRP (once monthly ×3 treatments) be used followed by a 3- to 6-month maintenance period.

Autologous pure platelet-rich plasma injections for facial skin rejuvenation: Biometric instrumental evaluations and patient-reported outcomes to support antiaging effects.

BACKGROUND: During skin aging, a degeneration of connective tissue and decrease in hyaluronic acid polymers occur. Since platelet-rich plasma (PRP) contains growth factors and various cytokines, it was hypothesized that it could play a role in fibroblast activation and type I collagen expression in human fibroblasts. OBJECTIVES: This study was performed to assess the efficacy of autologous PRP injections for facial skin rejuvenation, measured by biometric instrumental evaluations and patient-reported outcomes. PATIENTS AND METHODS: Patients signed an informed consent form. The EmCyte PurePRP® system technology was used to produce neutrophil-poor PurePRP. The efficacy of the procedures was assessed by biometric parameters, and a patient outcome a self-assessment questionnaire on each visit and at 6-month follow-up. RESULTS: Eleven volunteers were included in the study, receiving 3 PurePRP® treatments. A significant decrease in brown spot counts and area (P < 0.05) was seen after 3 months. Wrinkle count and volume were significantly reduced (P < 0.05 for total wrinkle appearance). Skin firmness parameters were significantly improved. Skin redness was significantly improved after 169 days post-therapy for both the nasolabial and malar areas. A decrease in SLEB thickness was already noted at 2 months after the first injection, with an increase in SLEB density (P < 0.05 for both parameters), without affecting subcutaneous fat thickness. Self-assessment at 6-month follow-up revealed an average satisfaction score of >90%. CONCLUSIONS: A series of 3 PurePRP injections at 6-month follow-up resulted in significant skin rejuvenation as demonstrated by biometric parameters and confirmed by patient self-assessment score.

Is the use of autologous platelet-rich plasma gels in gynecologic, cardiac, and general, reconstructive surgery beneficial?

Tissue repair at wound sites begins with clot formation, and subsequently platelet degranulation with the release of platelet growth factors, which are necessary and well-regulated processes to achieve wound healing. Platelet-derived growth factors are biologically active substances that enhance tissue repair mechanisms, such as chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition, and remodeling. This review describes the biological background and results on the topical use of autologous platelet-rich plasma and platelet gel in gynecologic, cardiac, and general surgical procedures, including chronic wound management and soft-tissue injuries.

The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new perspectives.

Platelet concentrates for topical use are innovative tools of regenerative medicine and their effects in various therapeutical situations are hotly debated. Unfortunately, this field of research mainly focused on the platelet growth factors, and the fibrin architecture and the leukocyte content of these products are too often neglected. In the four families of platelet concentrates, 2 families contain significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). The presence of leukocytes has a great impact on the biology of these products, not only because of their immune and antibacterial properties, but also because they are turntables of the wound healing process and the local factor regulation. In this article, the various kinds of leukocytes present in a platelet concentrate are described (particularly the various populations of granulocytes and lymphocytes), and we insist on the large diversity of factors and pathways that these cells can use to defend the wound site against infections and to regulate the healing process. Finally, the impact of these cells in the healing properties of the L-PRP and L-PRF is also discussed: if antimicrobial properties were already pointed out, effects in the regulation of cell proliferation and differentiation were also hypothesized. Leukocytes are key actors of many platelet concentrates, and a better understanding of their effects is an important issue for the development of these technologies.

In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes.

In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

Autologous platelet gel in total knee arthroplasty: a prospective randomized study.

PURPOSE: Total knee arthroplasty (TKA) is often associated with major postoperative blood loss, postoperative pain, and impaired wound healing. The application of autologous platelet gel (APG), prepared from the buffy coat of a unit of autologous blood, has been advocated to improve haemostasis after surgery, to decrease perioperative blood loss, diminish postoperative pain and to enhance the wound healing process. This randomized controlled pilot study was developed to assess the effects of APG after total knee arthroplasty on blood loss, wound healing, pain, range of motion, and hospital stay. METHOD: A prospective, randomized observer blind controlled trial was performed. Forty patients with only osteoarthritis of the knee were scheduled to have a TKA, and they were randomized into two groups. Patients in the treatment group were all treated with the application of autologous platelet gel after the prosthesis was implanted. Patients in the control group were treated with the same protocol but no APG was used. RESULTS: Preoperative and postoperative Hb levels showed no significant difference and allogenic blood transfusions were not given in either group. Haematomas were significantly larger in the control group than in the platelet gel group (P = 0.03). The pain score at rest was higher in the control group on the 3rd day (P = 0.04). Wound healing disturbances were seen in four patients in the control group and in no patients in the APG group (n.s.). Range of motion of the knee was similar postoperatively. Hospital stay was 6.2 days in the APG and 7.5 days in the control group (n.s.). CONCLUSION: In this prospective randomized pilot study on APG in total knee arthroplasty, differences in favour of the use of platelet gel were found, but these were subjective evaluations, marginal in effect, or did not reach statistical significance. The use of drains might have decreased the concentration of delivered platelets and may have diminished the effect. However, in this study, a statistically significant clinically important effect in favour of platelet gel application was not found. Further studies with larger numbers of patients, and without the use of drains, are warranted to investigate the possible benefits of autologous platelet gel in total knee arthroplasty.

Dutch perfusion incident survey.

BACKGROUND: Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. METHODS: An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. RESULTS: The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. CONCLUSIONS: In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended.