Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely, angiogenesis, immune control, circulating stem cells trapping, and wound-covering epithelialization. All of the known clinical applications of PRF highlight an accelerated tissue cicatrization due to the development of effective neovascularization, accelerated wound closing with fast cicatricial tissue remodelling, and nearly total absence of infectious events. This initial research therefore makes it possible to plan several future PRF applications, including plastic and bone surgery, provided that the real effects are evaluated both impartially and rigorously.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.     

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part V: histologic evaluations of PRF effects on bone allograft maturation in sinus lift.

OBJECTIVE: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. The use of platelet gel to improve bone regeneration is a recent technique in implantology. However, the biologic properties and real effects of such products remain controversial. In this article, we therefore attempt to evaluate the potential of PRF in combination with freeze-dried bone allograft (FDBA) (Phoenix; TBF, France) to enhance bone regeneration in sinus floor elevation. STUDY DESIGN: Nine sinus floor augmentations were performed. In 6 sites, PRF was added to FDBA particles (test group), and in 3 sites FDBA without PRF was used (control group). Four months later for the test group and 8 months later for the control group, bone specimens were harvested from the augmented region during the implant insertion procedure. These specimens were treated for histologic analysis. RESULTS: Histologic evaluations reveal the presence of residual bone surrounded by newly formed bone and connective tissue. After 4 months of healing time, histologic maturation of the test group appears to be identical to that of the control group after a period of 8 months. Moreover, the quantities of newly formed bone were equivalent between the 2 protocols. CONCLUSIONS: Sinus floor augmentation with FDBA and PRF leads to a reduction of healing time prior to implant placement. From a histologic point of view, this healing time could be reduced to 4 months, but large-scale studies are still necessary to validate these first results.     

Platelet-rich fibrin (PRF) in implant dentistry in combination with new bone regenerative technique in elderly patients

IntroductionSome studies have demonstrated that platelet rich fibrin (PRF) is a healing biomaterial with a great potential for bone and soft tissue regeneration, without any inflammatory reactions and may be used alone or in combination with bone grafts, promoting hemostasis, bone growth, and maturation. PRF appears as a natural and satisfactory aid in bone regenerative surgery in elderly patients with favorable results and low risks.AimThis study wants to demonstrate how PRF in association with a new split crest augmentation technique can be a great aid in implant rehabilitation, especially in the elderly patients, when bone regeneration is required.Materials and methodsTen patients were treated in this study, five following the flapless split crest new procedure and other five patients following traditional procedure without split crest as control. Five patients with an average age between 50 and 60 years were selected to be operated with a split crest flapless modified technique in order to optimize the regenerative conditions with a bone augmentation and implant insertion in one single stage procedure. For all the patients autologous PRF has been used to fill the split crest gap or simply as regenerative material. Orthopantomography, intraoral radiography and CT DentaScan/CT Cone beam were performed for every patient before the treatment and at follow-up time exeption made for CT.ResultsAll cases were successful, there were no problems at surgery time, at post-operative and at osteointegration periods. All implants achieved osteointegration. These results were obtained by accurately managing immediate and late post operative period in all of the operated cases. Mean difference for height bone loss between the two groups of patients was 2.4 mm at T1 and 2.2 mm at T3.DiscussionThe rationale of this split crest flapless modified technique is to obtain a proper buccal cortex expansion preserving its vascular supply avoiding periosteal elevation for better cortical bone nourishing. Moreover, advantages are reported related to the use of PRF. The effectiveness of PRF is shown in promoting the healing of surgical wounds, it has, in fact, platelet growth factors that can improve the vascularisation of the surgical site, promoting neoangiogenesis. Furthermore, by simply changing the settings of the centrifuge, it is possible to obtain a normal gelling if it has to be used as regenerative and stimulating material, or more consistent substance to be used as a filler in the split crest gap.ConclusionsThe main advantages in using the platelet-rich fibrin are healing and bone regenerative properties in combination with its complete resorption after surgery, thus avoiding a second surgery time, important factor in the elderly patients. Currently, it is a minimally invasive technique with low risks and satisfactory clinical results such preventing complications or implant failure particularly in elderly patients for age related conditions.     

Platelet-rich plasma and platelet gel: a review

Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and platelet-poor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many well-designed scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, platelet-rich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented.     

CROWNWeb--the evolution of kidney data management (Part I)

The Centers for Medicare & Medicaid Services is developing a Web-based application, Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb), which is designed to facilitate data entry, updating, and retrieval for dialysis facilities nationwide. Part 1 of this three-part series outlines the history of end-stage renal disease and Medicare, and covers the rapid growth of ESRD data management as well as other events that require progression to an online data collection and management system.     

Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology. (1992)

This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells "at risk," these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis. Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl-, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH. In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interfers with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++. A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++.     

Anesthesia and cardiac electrophysiology (Part I)

Cardiac arrhythmias are a common complication of surgery and anesthesia. They are more likely to occur in patients with heart disease and the presence of a transitory imbalance can supply the underlying substrate for reentry, triggered activity, or abnormal automaticity. The physiologic impact of a given arrhythmia depends on its duration, on ventricular response, and on the underlying cardiac disease. Optimal management of arrhythmias in the anesthetized patient will depend on knowledge of the trigger mechanisms, the effects of anesthetic drugs on cardiac electrophysiology, and situations that favor arrhythmias. The anesthesiologist must cope with a plethora of problems related to the patient's clinical state and the trauma of surgical manipulation. Experience with electrocardiography and the application of various devices (pacemakers, cardioverters, implantable defibrillators) and knowledge of the pharmacodynamics and pharmacokinetics of new intravenous drugs will be essential for patient management. The purpose of the present review is to provide the anesthesiologist with an overview of current views on the diagnosis and management of arrhythmias during anesthesia.     

Platelet parameters. Part I. Platelet counts and mean platelet volume in normal and pregnant subjects

Platelet counts and mean platelet volume (MPV) were studied in 564 normal subjects and 297 pregnant women using a Coulter Model S-Plus electronic counter. The reproducibility of these measurements both intra- and inter-sample was documented. The mean platelet count in the normal group was 283 x 10(9)/l while the mean MPV was 9.32 fl. An inverse correlation between platelet volume and platelet number was documented (r = -0.38; P less than 0.0001). By interval analysis, this inverse relationship was shown to be non-linear. In the pregnant subjects there appeared to be a progressive decrease in platelet count with advancing gestation; this reached a significant level when the first and third trimesters were compared with each other (P less than 0.05). The MPV was unchanged. The fact that the platelet count decreased in proportion to the red cell count suggested that a common factor, such as haemodilution, was in part responsible. There was again an inverse relationship between MPV and platelet number (r = -0.39; P less than 0.0001) shown to be non-linear by interval analysis.     

Pro- and anticonvulsant effects of anesthetics (Part I)

Many inhaled anesthetics and intravenous analgesics have been alleged to produce both proconvulsant and anticonvulsant activity in humans. The reasons for these contrasting actions on the CNS are poorly understood at the present time. However, biologic variability plays an important role in determining individual patient's responses to anesthetic and analgesic drugs. In addition, variations in the responsiveness of inhibitory and excitatory neurons to the central depressant effects of these drugs could also explain these apparently conflicting data. Depending on the brain concentration, centrally active drugs may produce differing effects on the CNS inhibitory and excitatory neurotransmitter systems. The availability of increasingly powerful magnetic resonance imaging techniques to provide noninvasive information about tissue chemistry (e.g., neurotransmitters and citric acid cycle metabolites) and positron emission tomography to noninvasively evaluate CNS drug-receptor interactions should lead to a more in-depth understanding of the in vivo effects of anesthetics and analgesics on the CNS. In the second part of this review article, we discuss the pro- and anticonvulsant effects of the sedative-hypnotics, local anesthetics, and other anesthetic adjuvant drugs.     

Renal vascular resistance changes following thrombin-induced intravascular coagulation: role of platelet and fibrin emboli.

The renal vasculature in the dog reacts to thrombin-induced intravascular coagulation with increasedd resistance. A constant rate infusion of 75 NIHu thrombin/kg b.w. reduced renal blood flow by approximately 55% in 30 min. Renal blood flow had almost regained preinfusion values within 30 min after the end of the infusion. Marked reduction in renal blood flow was not associated with increment of renal regional radioactivity in dogs pretreated with Cr-51 labeled platelets. The renal a-v difference in platelet counts did not contrast with other regions subjected to identical doses of thrombin. It is therefore unlikely that the flow changes are caused by vascular blockage by platelets. The flow decrease was accompanied by increase renal radioactivity in dogs pretreated with I-125 fibrinogen. This may imply renal accumulation of fibrin with obstruction to flow. Substantial renal blood flow reduction occurred with no or insignificant consumption of fibrinogen or changes in renal radioactivity after defibrinogenation. It is concluded that thrombin also induces a humoral vasoconstriction in the kidney.