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As recurrent rotator cuff tears following repair remain a significant problem, improving healing potential using biologic adjuvants, including concentrated bone marrow aspirate (cBMA), platelet-rich plasma (PRP), or subacromial bursa tissue (SBT), has become increasingly popular in recent years. In an attempt to combine the benefits of these various biologic adjuvants and maximize the healing potential of the repaired tendon, an arthroscopic rotator cuff repair technique biologically augmented with autologous SBT, cBMA, PRP, platelet-poor plasma (PPP), and bovine thrombin has been developed. The created clot is used as a biologic scaffold for sufficient delivery, and it is stabilized using bovine thrombin in order to ensure maximum stability and retainment of the applied biologic augments at the repair site. Classifications I: shoulder; II: rotator cuff., Technique Video Video 1 Arthroscopic rotator cuff repair augmented with autologous subacromial bursa tissue, concentrated bone marrow aspirate, platelet-rich plasma, platelet-poor plasma, and bovine thrombin.

Ultrasound-guided thrombin injection (UGTI) is often the first-line treatment for iatrogenic post-catheterization pseudoaneurysms (psA). There are also first reports of the use of biologically derived tissue glues (TG) instead of sole thrombin especially when UGTI was unsuccessful or in case of psA recurrence. Previously, we have established that a late to early velocity index (LEVI) 0.2 and they underwent UGTI. The injection set containing human thrombin and fibrinogen was used for UGTGI. Bovine thrombin was used for UGTI. The success rate was 100% and no psA recurrence was detected during a 2-week follow-up. It was significantly better when compared to the expected recurrence rates based on our previous 14 years of experience (0% vs. 13%, p = 0.01). All complications (10% in the UGTGI group and 15% in the UGTI group) were mild and transient and included clinical symptoms of paresthesia, numbness, tingling, or pain. Their rates were comparable to the rates we previously reported. No significant differences in other characteristics were observed. The approach to choose the first-line treatment method for iatrogenic psA based on LEVI is encouraging. It may increase the success rate and avoid unnecessary repetition of the procedure, without increasing complication rate while keeping costs of the procedure reasonable.

Turbidity analysis is widely used as a quantitative technique in hereditary dysfibrinogenemia. We aimed to compare several coagulation triggers in hereditary dysfibrinogenemia and control plasmas. We included 20 patients with hereditary dysfibrinogenemia, 19 with hotspot mutations Aα Arg35His (n = 9), Aα Arg35Cys (n = 2), γ Arg301His (n = 6), γ Arg301Cys (n = 2), and one with Aα Phe27Tyr, and a commercial pooled normal plasma. Fibrin polymerization was activated by bovine or human thrombin or tissue factor (TF), in the presence or absence of tissue type plasminogen activator. The lag time (min), slope (mOD/s), maximum absorbance (MaxAbs, mOD), and area under the curve (AUCp, OD s) were calculated from the fibrin polymerization curves and the time for 50% clot degradation (T50, min), AUCf (OD s) and the overall fibrinolytic potential from fibrinolysis curves. The lag time was significantly shorter and AUC increased in Aα Arg35His patients with bovine thrombin as compared with human thrombin. The MaxAbs and AUCp were significantly higher in γArg301His patients with bovine thrombin compared with human thrombin. Fibrin polymerization parameters of patients' samples were closer to those of control when assessed with TF compared with both human and bovine thrombin. T50 and overall fibrinolytic potential were similar in all samples regardless of the coagulation trigger used, however, with TF the AUCf of Aα Arg35His and γ Arg301His groups were significantly decreased compared with control. Bovine and human thrombin cannot be used equally for studying fibrin polymerization in hotspot hereditary dysfibrinogenemia or control plasmas.

Development of acquired factor V (FV) inhibitor is a rare coagulation disorder. Production of heteroantibodies against bovine FV, a contaminant in fibrin tissue adhesives, is a common cause of this condition in the field of surgery. The development of recombinant thrombin eliminated contamination of bovine FV, and infrequent use of bovine thrombin has decreased the risk of FV inhibitor development. Here, we report the case of a 43-year-old man who had marked prolongation of prothrombin time and activated partial thromboplastin time after surgery. Mixing coagulation studies with normal plasma and patient’s plasma suggested the presence of an inhibitor. Clotting factor assays revealed that FV activity decreased to

The specialty of thoracic and cardiovascular surgery (TCV) has developed rapidly during the second half of the twentieth century. For this purpose, fibrin sealant is gaining increased popularity as a surgical tissue adhesive. Many of the major thoracic and cardiovascular surgical centers in the country have mechanisms for obtaining concentrated sources of human fibrinogen and Factor XIII required with bovine thrombin and calcium for the formation of fibrin tissue adhesive. Making fibrin sealant easily and rapidly available to thoracic and cardiovascular surgeons at the University of Virginia Health Sciences Center has fostered a variety of new application methods. Fibrin sealant can also be employed to reduce leakage of other body fluids in TCV. The issue of tissue fibrosis in response to fibrin sealant application has been evaluated and, at least in situations where sealant is used without antifibrinolytics, does not appear to be clinically significant.

The aim of this case report was to evaluate the efficacy of a new platelet-rich plasma preparation and its regenerative capacity of bone periapical tissue for the treatment of a very compromised endodontic treated tooth, with a periapical lesion of 1.5 cm in diameter, using a pure platelet concentrate. This is made without the use of anticoagulant or any type of activator, e.g., bovine thrombin, calcium chloride. For this reason, it has been called “Pure”; it is the B.P.F.C.® Bio-Plasma® with Pure Growth Factors (BioPlasma®) designed and developed by Dr. Raffaello Viganò. The patient has read and signed a written consent form. The study protocol was approved by the Ethics Committee for Human Studies, University of Varese. X-ray at 2 and 6 months and 4 years after endodontic surgery demonstrated the success of the treatment.

Clinicians have increasingly applied platelet-rich plasma (PRP) for wound healing treatments. Topical treatments commonly require biochemical agents such as bovine thrombin to activate PRP ex vivo for clotting and growth factor release to facilitate healing upon application to the wound of interest. Recent studies have explored electrical stimulation as an alternative to bovine thrombin for PRP activation due to the former's cost, workflow complexity and potentially significant side effects; however, both approaches require separating the PRP from whole blood (WB) prior to activation. Eliminating the separation (typically centrifugation) step would reduce the cost and duration of the clinical procedure, which may be critical in trauma and surgical applications. We hypothesize that electric pulses (EPs) can release growth factors from WB, as they do from PRP, without requiring centrifugation of WB into PRP. A pilot study for two donors demonstrates the potential for EP stimulated growth factor release from WB. This motivates future experiments assessing EP parameter optimization for WB activation and in vivo studies to determine the clinical benefits for topical treatments and, especially, for injections in orthopedic applications that already utilize non-treated/non-activated WB.

In blepharoplasty and facelift procedures, different methods may be used to reduce postoperative complications and the need for draining, including the use of complete haemostatic, quilting sutures, heterologous glue, compressive dressing, and tissue sealants. Different types of surgical adhesives have emerged as alternatives capable of fixing and guaranteeing adhesion of tissue. Among these, biological sealants (or fibrin sealants) are produced by recurring to a combination of material from a pool of known donors and bovine thrombin, whereas platelet-rich plasma (PRP) glue is an autologous preparation obtained from the patient’s own blood and which acts as a growth-factor reservoir during treatment.

Introduction: Although more than 100 operative procedures have been described for the treat- ment of patellar instability, there is no single univer- sally successful procedure. For the most patients with lateral patellar instability medial patellofemoral liga- ment (MPFL) reefing is recommended. When we per- form MPFL reefing we are not aware of the quality and strength of the MPFL tissue. In the presence of recur- rent patellar instability, the quality and strength of MPFL tissue is often compromised and it disturbs pa- tellar stability after MPFL reefing. Biomedicine devel- opment, recognizing the ligament healing process show us that autologous blood products, particularly PRP can enhance healing in soft tissue injuries. Purpose: The purpose of this study was to deter- mine the potential effect of Plasma preparation rich in growth factors on patellar stability after MPFL reefing. Material and methods: Plasma preparation rich in growth factors was produced from a unit of autolo- gous whole blood using Arthrex ACP double syringe system.Platelet gel was prepared by adding bovine thrombin and 10% solution of calcium chloride.The platelet gel was applied locally into the place where su- turing of the MPFL was performed. In this prospective, randomized and double blind study12 patients were in- cluded:6 patients in the PG group who received plate- let gel and 6 patients in the control group who were not treated with platelet gel. Patellar stability was evalua- ted before surgery and 3 months after surgery with Ax- ial stress radiographs. Results: The calculated 3 month improvement was 12.67 ± 2.51 in the control group and 17.33 ± 1.52 in the PG group, (p = 0.064). Although there was greater improvement in patellar stability in PG group compar- ing to the control group, the difference was not statisti- cally significant (p > 0.05). The main reason for this was probably the small number of patients included in the study. Conclusion: Results showed that growth factors from the plasma preparation rich in growth factors ha- ve positive effect on patellar stability after MPFL reef- ing.We believe that they stimulate and accelerate phys- iological healing and reparative tissue processes in li- gament healing. More studies should be made, including more patients, if we want to get more relevant results.

Objective To compare clotting efficiency of platelet-rich plasma (PRP) and concentrated platelet-poor plasma (cPPP) to citrated whole blood after activation by autologous thrombin, bovine thrombin, or calcium chloride (CaCl2). Study Design Experimental study. Animals Healthy adult horses (n = 6). Methods PRP and cPPP were prepared by commercial devices. Using thromboelastography, clotting variables were compared after activation of citrated autologous blood, PRP, and cPPP by autologous thrombin, bovine thrombin, or CaCl2, respectively. Results PRP had the greatest clot strength and quickest clot rate, whereas cPPP had the weakest clot strength, slowest clot rate, and longest clot initiation time. Bovine thrombin resulted in the shortest clot initiation time, quickest clot rate, and was similar to CaCl2 for greatest clot strength. CaCl2 also resulted in the longest clot initiation time and time to reach maximum clot strength. Autologous thrombin resulted in the lowest clot strength. Conclusion When combined with either bovine thrombin or CaCl2, PRP provided the best combinations for clinical use. Autologous thrombin was suboptimal, but could be an autologous alternative for clinical application. As prepared here, cPPP had inefficient clotting, but may be sufficient for plasma spray indications.

Over the past decade, platelet-rich plasma (PRP), a platelet-concentrated plasma fraction, has been widely investigated and applied to regenerative medicine. The clinical utility of PRP is supported by evidence that PRP contains high concentrations of platelet-related growth factors and normal concentrations of plasma-derived fibrinogen, both of which contribute synergistically to the regenerative process. Additionally, its superior cost-efficacy versus conventional therapies is attractive to many clinicians. However, current disadvantages of PRP include a relatively complicated preparation procedure and variable operator-dependent efficacy. An additional disadvantage is the use of bovine thrombin, an animal-derived biological, as a coagulant. Many of these disadvantages are overcome by recent advances in preparation procedures and devices; for example, Joseph Choukroun simplified the platelet-rich fibrin preparation procedure and improved handling efficiency without the aid of animal-derived factors. With advancements in cell processing technology, there has been a general shift in cell therapy from autologous to allogeneic treatment; however, autologous PRP therapy will not easily be replaced by allogeneic treatment in the near future. Therefore, to provide more predictable regenerative therapy outcomes using autologous PRP, further investigations should address developing a standardized procedure for PRP preparation to augment its efficacy and potency, independent of donor variability. We would then propose that operators and clinicians prepare PRP according to the standardized protocol and to carefully evaluate the clinical scenario (i.e., recipient factors comprising skeletal defects) to determine which factor(s) should be added to PRP preparations. This careful approach will lead to improved clinical outcomes for patients.

Platelet-rich fibrin (PRF) is a stringently autologous fibrin matrix containing a large quantity of platelets (thrombocytes) and leukocyte cytokines. PRF is an upcoming newer treatment modality used to augment healing process and has been in clinical use over the last decade within many disciplines, such as peri-implant defects, periodontal defects, exclusively as grafting material, in treatment of alopecia, orthopedic, oral-maxillofacial and cardiac surgery, and plastic and cosmetic surgeries. Choukroun in 2001 (France) and his coassociates were among the inventors for use of PRF in any reconstructive surgery to encourage and enhance the bone healing. PRF is found better than the previously used PRP (platelet-rich plasma) as it is easier to prepare and apply, cheaper, and there is no need to add bovine thrombin or anticoagulant in it. Thus in the current setup, it is proving to be benevolent to the surgical reconstructive dentistry.

Diabetic foot ulcers are one of the most important causes of lower limb amputations worldwide. The conventional treatments of diabetic foot ulcers are costly and often require patients to be hospitalized for long periods of time, thus representing a huge burden on any health care system. The use of autologous platelet-rich plasma (PRP), which is rich in multiple growth factors, may bear some similarities to the natural wound healing process. Nonetheless, few studies on human subjects have so far addressed the efficacy of PRP as a novel and minimally invasive treatment. Today, there is only 1 approved and available system to separate PRP from a patient's own blood in order to be used in diabetic ulcers. This system incorporates bovine thrombin for activation of PRP gel and may be applied by many healthcare providers without the need for extensive special training. In this report, a patient with extensive diabetic foot ulcers, non-responsive to other treatment modalities, was successfully treated by PRP.

Reducing blood loss during primary total knee arthroplasty (TKA) can improve outcomes by reducing transfusion requirements and wound complications. We examined the use of bovine thrombin to augment hemostasis during primary TKA. A double-blinded randomized trial was performed with 80 primary TKA patients. Half received intraarticular bovine thrombin at the time of wound closure, and half did not. Hemoglobin levels in the study group did decline less than the control group, but no statistically significant difference was found in rates of transfusion, drain outputs, length of stay, or Knee Society scores. This agent does appear to slightly reduce blood loss, but routine use is not cost effective. Thrombin may be considered for patients who would benefit more from greater blood conservation.

SummaryObjective: To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants.Methods: Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet ly-sates (PL) over time.Results: Growth factor concentrations were significantly lower in plasma and higher for all PRG supernatants. Platelet lysates contained a significantly lower concentration of PDGF-BB than PRG supernatants and a significantly higher concentration of TGF-β1 than PRG supernatants. Clots from PRP activated with sodium salts were more stable over time and had significant growth factor release, whereas CC produced gross salt deposition. Significant correlations were noticed for platelet with leukocyte concentrations in PRP (rs: 0.76), platelet counts in PRP with TGF-β1 concentrations in PRG supernatants (rs: 0.86), platelet counts in PRP with PDGF-BB concentrations in PRG super-natants (rs: 0.78), leukocyte counts in PRP with TGF-β1 concentrations in PRG supernatants (rs: 0.76), and PDGF-BB concentrations with activating substances (rs: 0.72).Clinical significance: Calcium gluconate was the better substance to induce PRP activation. It induced growth factor release free from calcium precipitates in the clots. Use of BT alone or combined with calcium salts was not advantageous for growth factor release.

Investigations of endogenous blood-derived growth factors have increased in the past two decades. The initial protocols for blood concentrates, such as platelet-rich-plasma, utilized anticoagulants followed by bovine thrombin to catalyze fibrin polymerization. Subsequently, platelet-rich-fibrin (PRF) protocol was developed to eliminate anticoagulants and thrombin. The PRF production was described in a vertical rotor centrifuge with an angle of ~33°. Many commercial enterprises have attempted to replicate this protocol with a multitude of different centrifuges. These attempts have utilized revolutions per minute (RPM) to develop their protocol to generate PRF. However, RPM is a variable parameter, as it depends on the design and radius of the centrifuge. The separation of blood components is highly dependent on the relative centrifugal force (RCF) generated, which is based on the applied centrifugal force, expressed as multiples of earth's gravitation (g) field. RCF is a function of the acceleration due to the gravity of the earth, g = 9.81 m/s2 RCF, not RPM, is the key factor for the sedimentation of the cells and proteins within blood concentrates. RCF is determined using the maximum centrifuge radius for calculation. The initial PRF was generated by applying an RCF of 700 ×g. Accordingly, so far, a large number of studies existing about PRF are not comparable, as they were technically prepared with different RCFs. In addition, due to the nonstandardized measurement methods, in some published studies, incorrect RCF values are published as the authors did not know how to calculate the RCF correctly. This is the case for a widespread blood concentrate called leukocyte-PRF, which is commercially available. Recently, we introduced the low-speed centrifugation concept (LSCC) for the production for solid and liquid PRF matrices. This concept is based on the above-mentioned initial PRF protocols, which represents a relatively high RCF. It shows that a systematic reduction of 700 ×g to 44 ×g can significantly increase the cells and growth factors within the same blood concentrates. The LSCC concept was established initially for a fixed rotor centrifuge with a radius of ~110 mm. The present narrative review highlights the necessity of standardization in the generation of blood concentrates, which utilizes RCF, rather than commercial protocols.

The occurrence of an inhibitor against coagulation factor V (FV) is a rare but challenging condition, which may span from asymptomatic laboratory abnormalities to potentially life-threatening bleeding. The onset of FV inhibitors has been associated most frequently in the past with the patients' exposure to topical bovine thrombin administered during surgery procedures. However, since this preparation is no longer used, in this systematic review we have only focused on non-bovine thrombin-related FV inhibitor cases.

Factor V and thrombin inhibitors may develop following exposure to bovine thrombin preparations. In patient populations where exposure to bovine thrombin is common, such as children undergoing cardiovascular surgery, the development of such inhibitors should be considered in the evaluation of prolonged prothrombin times. We present three cases of children developing factor V and thrombin inhibitors following repeated exposure during cardiac surgical procedures.

Purpose To review topical bovine thrombin spontaneous adverse event (AE) reports that were forwarded to the US Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS) between January 1986 and December 2006. Methods Forty-one spontaneous AE reports were summarized for reported AE profile and chronological reporting patterns. Each AE report was adjudicated by a hematologist for the topical bovine thrombin product that was given and the AE(s) that were reported. AEs were grouped as allergic, coagulopathy/bleeding, and all other AEs combined. Grouped AE serial analyses were carried out using successive 3-year time increments between 1986 (the year an AE report was first noted for a bovine thrombin product) and 2006 (the first full year that was available at the time of initiation of the data summary). Main outcome measures The primary outcome measures were every 3-year trend lines for all-AE reports, all reporters, and topical bovine thrombin brand mentions for 2 AE groups of interest (allergic events and coagulopathy/bleeding events). Results The all-AE spontaneous reporter trend showed a downward appearance for AE reporting activity that started in 1995–1998 and continued through 2004–2006. The all-AE reports trend showed two potential safety signals that could be identified serially: (1) a prominent 1989–1991 peak that was attributable to allergic events (in particular, anaphylaxis), and (2) a small 1995–2000 broad peak that was attributable in part to coagulopathy/bleeding events. Allergic events were predominantly reported with products approved prior to 1995, were not temporally associated with prior medical literature case reports, and continued to be forwarded to the FDA at low levels up to the end of this study in 2006. Coagulopathy/bleeding events were reported only with products approved prior to 1995, were temporally associated with medical literature case reports, and were not forwarded to the FDA after 2000. Conclusions Overall, spontaneous AE reporting for topical bovine thrombin occurs at very low levels, and appears to have been decreasing since 1995. The serial reporting patterns for topical bovine thrombin are best explained as a strong safety signal for allergic events with ongoing, low level reporting, and a weak safety signal for coagulopathy/bleeding events that ceased on or before 2000. Although this descriptive trend analysis cannot measure associations or causation, the coagulopathy/bleeding signal may have been prompted by multiple, antecedent published case reports. The subsequent diminishment of signal attributed to thrombin likewise may coincide with lack of such reporting in larger follow-up clinical trials or, alternatively, in the introduction and growing market share of thrombin brands of greater purity. Currently marketed topical bovine thrombin formulations are rarely volunteered as possible causes of adverse events. Copyright © 2009 John Wiley & Sons, Ltd.