Leukocyte- and Platelet-Rich Fibrin versus Commercially Available Fibrin Sealants in Elective Cranial Surgery: A Cost-Minimization Analysis.

BACKGROUND: Previous findings from a clinical trial demonstrated noninferiority of Leukocyte- and platelet-rich fibrin (L-PRF) compared to commercially available fibrin sealants in preventing postoperative cerebrospinal fluid leakage, necessitating intervention. This cost-effectiveness evaluation aims to assess the value-for-money of both techniques for dural closure in supratentorial and infratentorial surgeries. METHODS: Cost-effectiveness was estimated from a health care payer's perspective alongside a randomized clinical trial comprising 328 patients. The analysis focused on clinical and health-related quality of life outcomes, as well as direct medical costs including inpatient costs, imaging and laboratory costs, and outpatient follow up costs up to twelve weeks after surgery. RESULTS: Clinical and health-related quality of life data showed no significant differences between L-PRF (EuroQol five dimensions questionnaire 0.75 ± 0.25, 36-item Short Form Survey 63.93% ± 20.42) and control (EuroQol five dimensions questionnaire 0.72 ± 0.22, 36-item Short Form Survey 60.93% ± 20.78) groups. Pharmaceutical expenses during initial hospitalization were significantly lower in the L-PRF group (€190.4, interquartile range 149.9) than in the control group (€394.4, interquartile range 364.3), while other cost categories did not show any significant differences, resulting in an average cost advantage of €204 per patient favoring L-PRF. CONCLUSIONS: This study demonstrates L-PRF as a cost-effective alternative for commercially available fibrin sealants in dural closure. Implementing L-PRF can lead to substantial cost savings, particularly considering the frequency of these procedures.

Leukocyte- and platelet-rich fibrin in cranial surgery: a single-blinded, prospective, randomized controlled noninferiority trial.

OBJECTIVE: CSF leakage is a major complication after cranial surgery, and although fibrin sealants are widely used for reinforcing dural closure, concerns exist regarding their safety, efficacy, and cost. Leukocyte- and platelet-rich fibrin (L-PRF), an autologous platelet concentrate, is readily available and inexpensive, making it a cost-effective alternative for commercially available fibrin sealants. This study aimed to demonstrate the noninferiority of L-PRF compared with commercially available fibrin sealants in preventing postoperative CSF leakage in supra- and infratentorial cranial surgery, with secondary outcomes focused on CSF leakage risk factors and adverse events. METHODS: In a single-blinded, prospective, randomized controlled interventional trial conducted at a neurosurgery department of a tertiary care center (UZ Leuven, Belgium), patients undergoing elective cranial neurosurgery were randomly assigned to receive either L-PRF (active treatment) or commercially available fibrin sealants (control) for dural closure in a 1:1 ratio. RESULTS: Among 350 included patients, 328 were analyzed for the primary endpoint (44.5% male, mean age 52.3 ± 15.1 years). Six patients (5 in the control group, 1 in the L-PRF group) presented with CSF leakage requiring any intervention (relative risk [RR] 0.20, one-sided 95% CI -∞ to 1.02, p = 0.11), confirming noninferiority. Of these 6 patients, 1 (in the control group) presented with CSF leakage requiring revision surgery. No risk factors for reconstruction failure in combination with L-PRF were identified. RRs for adverse events such as infection (0.72, 95% CI -∞ to 1.96) and meningitis (0.36, 95% CI -∞ to 1.25) favored L-PRF treatment, although L-PRF treatment showed slightly more bleeding events (1.44, 95% CI -∞ to 4.66). CONCLUSIONS: Dural reinforcement with L-PRF proved noninferior to commercially available fibrin sealants, with no safety issues. Introducing L-PRF to standard clinical practice could result in important cost savings due to accessibility and lower cost. Clinical trial registration no.: NCT03812120 (ClinicalTrials.gov).

Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial.

BACKGROUND: Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement. METHODS/DESIGN: This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed. DISCUSSION: With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03910374. Registered on 10 April 2019.

Leukocyte- and platelet-rich fibrin in cranial surgery: study protocol for a prospective, parallel-group, single-blinded randomized controlled non-inferiority trial {1}.

BACKGROUND: CSF leakage is a major complication after cranial surgery, thus, adequate dural closure must be performed. Commercially available fibrin sealants are currently considered the gold standard for dural closure, but problems have been reported regarding safety, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) as an alternative to commercially available fibrin sealants. METHODS/DESIGN: This single-blinded, prospective randomized controlled interventional trial aims to demonstrate the non-inferiority of L-PRF compared to commercially available fibrin sealants for dural closure. This trial will include patients undergoing cranial neurosurgery (supratentorial and infratentorial) with intentional opening of the dura. Patients are randomized in a 1:1 fashion comparing L-PRF to commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage within 12 weeks after surgery. Secondary endpoints are complications such as bleeding or wound infections. Additionally, a cost-effectiveness analysis is performed. DISCUSSION: With this trial, we will evaluate the safety and efficiency of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03812120. Registered on 22 January 2019.

The incidence of postoperative cerebrospinal fluid leakage after elective cranial surgery: a systematic review.

Cerebrospinal fluid (CSF) leakage is a major complication after elective neurosurgical procedures. The aim of this systematic literature review is to summarize the incidence rates of postoperative cerebrospinal fluid leakage for neurosurgical procedures, classified by surgical approach. The Pubmed, Cochrane, Embase, and Web of Science databases were searched for studies reporting the outcome of patients undergoing elective neurosurgical procedures. The number of patients, surgical approach, and indication for surgery were recorded for each study. Outcomes related to CSF leakage such as clinical manifestation and treatment were reported as well. One hundred and thirteen studies were included, reporting 94,695 cases. Overall, CSF leaks were present in 3.8% of cases. Skull base surgery had the highest rate of CSF leakage with 6.2%. CSF leakage occurred in 5.9% of anterior skull base procedures, 6.4% of middle fossa, and 5.2% of transpetrosal surgeries. 5.8% of reported infratentorial procedures were complicated by CSF leakage versus 2.9% of supratentorial surgeries. CSF leakage remains a common serious adverse event after cranial surgery. There exists a need for standardized procedures to reduce the incidence of postoperative CSF leakage, as this serious adverse event may lead to increased health care costs.

Mechanical and structural properties of leukocyte- and platelet-rich fibrin membranes: An in vitro study on the impact of anticoagulant therapy.

OBJECTIVE AND BACKGROUND: Little is known about structural and mechanical properties of leukocyte- and platelet-rich fibrin (L-PRF) membranes and even less about the influence of antithrombotic drugs on L-PRF. The aim of this in vitro study is therefore to investigate mechanical properties, fibrin structure and cell content of L-PRF membranes and the impact of anticoagulant therapy on L-PRF. METHODS: Blood samples were obtained from 12 volunteers and supplemented with either no, 1.25 IU, 2.5 IU, 5 IU, or 10 IU enoxaparin. L-PRF membranes were characterized with tensile testing, scanning electron microscopy, and measurement of platelets and leukocytes. Control and enoxaparin-supplemented L-PRF membranes were compared. RESULTS: At 10 IU enoxaparin, no L-PRF membranes could be generated, whereas the low doses of 1.25 and 2.5 IU had no influence on L-PRF properties. The mechanical properties, fibrin networks, and number of platelets and leukocytes of 5 IU supplemented membranes were unlike the control membranes, but were not found to be significantly different because of limited sampling and inter- and intra-variability. CONCLUSION: Low doses of the anticoagulant enoxaparin do not affect mechanical properties, fibrin network, nor cellular content of L-PRF, whereas high doses impair L-PRF generation.