Figure 18.1
The arm is sterilely prepped for the venipuncture
Figure 18.2
The blood sample is obtained
Figure 18.3
15 cc of blood is collected
Figure 18.4
Sample centrifuged for 5 min at 1500 rpm
Figure 18.5
Platelet-containing plasma (yellow fluid) extracted from centrifuged blood sample
Outcome
The patient participated in our postoperative protocol , which consists of a sling and pendulum exercises for the first 6 weeks postoperatively followed by active range of motion, and then strengthening which begins 3 months postoperatively. Six months after surgery the patient reported no pain, had normal range of motion and strength, and had returned to his usual activities including golf.
Literature Review
The healing process following rotator cuff repair is governed by a complex amalgam of biomechanical factors that has been widely studied. The rotator cuff enthesis consists of tendons, fibrocartilage, mineralized fibrocartilage (Sharpey’s fibers), and lamellar bone [1]. The repair provides mechanical stability to protect and promote healing at the tendon-bone interface. The principles for healing of rotator cuff repair are twofold: (1) obtaining structural stability by achieving strong fixation while restoring the anatomic surface of the rotator cuff tendon footprint and (2) minimizing gap formation and failure of the construct by promoting and maintaining mechanical stability while the healing occurs [2]. While the outcomes after rotator cuff repair are typically good, with more than 80% regaining (normal or full) function, re-rupture rates are about 25% and can be as high as 42% [3]. Therefore, we believe that everything that can be done to promote healing should be done.
There are many factors that affect healing after rotator cuff repair ranging from patient factors, tear characteristics, soft-tissue structural problems, and repair technique and implants. Recently there has also been interest in the biology of the healing response. The biologic approach aims to optimize soft-tissue healing to improve clinical outcomes [4]. One method utilizes PRP to curb the inflammation response and supplement tendon-bone healing with growth factors.
Over the past few years, the advances in the biomechanical repair constructs of rotator cuff tear may have peaked, stimulating a growing interest in biological aids to rotator cuff healing. The biologic factors recently studied to enhance soft-tissue healing and regeneration have mainly focused on growth factors, stem cells, and PRP.
Growth factors are molecules involved in the modulation of cell growth during the signal cascade of inflammation. Their influence is paramount in the inflammatory phase of tendon healing [5]. The molecules involved include fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-?), transforming growth factor-beta (TGF-?), and insulin-like growth factor-1 (IGF-1) [6]. These growth factors are produced in great majority by fibroblast and inflammatory cells such as leukocytes and platelets [7]. During the inflammatory and repair phase of tendon healing, platelets aggregate at the site of soft-tissue injury and release an extensive amount of growth factors prompting cell migration and differentiation at the site of injury [8]. Platelets provide a colossal amount of autogenous growth factors. PRP is easy to harvest from blood and is therefore one of the most commonly used biological aids in rotator cuff repair.
PRP has been shown to decrease inflammation through inhibition of molecules such as interleukin 1B and to promote healing through modulation of TGF-B production [5, 9]. PRP is a fraction of whole blood containing very high platelet concentrations (150,000–350,000), which on activation release various growth factors. The preparation consists of obtaining whole blood from the patient with a venipuncture followed by centrifugation to concentrate the platelets. The centrifugation also concentrates growth factors above physiologic level that can then be sterilely injected at the site of the tendon-bone repair. The growth factors present in the concentrate may stimulate cell proliferation and provide a temporary matrix that fills defects in the repair and serve as a matrix for cell migration and tissue remodeling [10].
There are different classification systems to describe the final PRP concentrate. The scientific community has not adopted a universal classification system, which has led to heterogeneity in the way PRP has been described. One of the classifications contains four categories: (1) pure PRP (P-PRP) with a low content of leukocytes, (2) leukocyte-rich PRP (L-PRP) with a high content of leukocytes, (3) pure platelet-rich fibrin (P-PRF), and (4) leukocyte-rich platelet-rich fibrin (L-PRF), with a high content of leukocytes and a high-density fibrin network [11]. The role of leukocytes in the PRP is still the subject of debate as some studies have found it to have a role in the anabolic process of collagen synthesis while other studies have found it to be catabolic [10, 12, 13]. A second classification system has been described with two categories, (1) presence or (2) absence of leukocytes, and further subclassified with (a) PRP-activated, ex vivo activation with thrombin and calcium, or (b) PRP-inactivated, in vivo activation by endogenous collagen [11, 14]. Lastly, our preference is the PAW classification that is based on three factors: [1] the absolute number of platelets, [2] the type of platelet activation, and [3] the presence or absence of white cells [15].
There are different methods of PRP delivery . Currently PRP can be administered as a liquid, in a gel or in a matrix scaffold. The liquid form of PRP can be activated by endogenous methods such as by simple agitation of platelets during centrifugation or by compression of platelets during needle delivery. Endogenous activation also has a potential for slower aggregation of platelets and release of growth factors by allowing contact with type 1 collagen in the rotator cuff tendon to operate as the activator, thereby providing a natural release pattern [16]. The liquid form can be directly administered to the tendon-bone interface of the rotator cuff repair during arthroscopic surgery or simply injected through the arthroscopic portal after evacuation of the intra-articular and subacromial fluid.
The PRP gel and matrix scaffold entail exogenous activation of platelets with the use of calcium chloride and thrombin. The scaffold may better keep the PRP in place at the repair site and possibly to create a more sustained release over the span of several days [15].
Several prospective comparative studies have examined the clinical and structural outcomes with PRP in rotator cuff repair; however the results have been conflicting. Warth et al. performed a systematic review of all level I and II studies comparing clinical and structural outcomes after rotator cuff repair with or without PRP [17]. There was no statistical differences in overall gain in outcome scores or re-tear found, but they noticed a significant gain in shoulder Constant score when PRP was applied at the tendon-bone interface compared to application on top of the repaired tendon. Most of the included studies were powered to detect large differences in outcome scores only. Other studies have indicated that there may be a decrease in re-tear rate with PRP; however, they were unable to show differences in clinical outcomes [18–20]. In a meta-analysis of 13 studies which also included a cost-effectiveness analysis, Vavken et al. found a significant reduction in re-tear rates with PRP; however, this benefit was not cost effective [21]. Another meta-analysis of eight randomized controlled studies comparing rotator cuff repair with and without PRP found no statistical difference in re-tear rates and clinical outcomes [22]. Other systematic reviews have had similar results [23–25]. Furthermore, a Cochrane review by Moraes et al. pooled 19 studies with 1088 participants on the use of PRP in not only rotator cuff but also 5 other tendon pathologies. They found no significant improvement in functional outcomes and insufficient evidence to support the use of PRP in clinical practice [26].
Hsu et al. reported that successful use of PRP varies depending on the preparation method, composition, medical condition of patient, anatomical location, and tissue type [27]. But heterogeneity of the different studies hampers comparison. There are differences in the number of doses administered and the PRP preparation including different volumes of autologous blood collected, speed and time of centrifugation, activating agent and leukocyte concentrations, final volume of PRP, and final concentration of platelets and growth factors. There are also differences in the time between PRP preparation and administration including preoperative, intraoperative, and postoperative administration. The method of administration whether image guided, arthroscopic guided, direct vision, or no guidance varies. Lastly the surgical techniques have varied between single- and double-row repairs and the postoperative rehabilitation protocols are not the same [26, 28].
Overall, studies do not support the clinical use of PRP in rotator cuff repair [29–31] but some data supports its use in a subset of patients. There may be a decrease in re-tear rates among patients treated for small- and medium-size rotator cuff [32, 33]. In a meta-analysis of five studies with 303 patients, Cai et al. found a significant difference in failure of small- to moderate-size rotator cuff repairs when PRP was not used [34]. Chahal et al., in a meta-analysis of five studies including two randomized and three nonrandomized clinical trials of 261 patients, found no difference in rotator cuff re-tear rate and functional outcomes [35]. However, in a stratified sub-analysis , they found a significant reduction in re-tears in those with PRP. In those with massive rotator cuff tears, Antuna et al. found that 28 patients had no significant difference in repairs regardless if they received PRP or not [36]. Bergeson et al. found that outcomes of patients with a combination of advance age, severe tear size, and fatty infiltration were not influenced by an inclusion of PRP scaffold with rotator cuff repair [30].
The use of PRP in rotator cuff tendinopathy has also been studied. Carr et al. studied PRP in patients undergoing arthroscopic acromioplasty for chronic rotator cuff tendinopathy in 60 patients [37]. They found no effect of PRP on clinic outcomes in this patient population. These findings are supported by another randomized controlled trial evaluating chronic rotator cuff tendinopathy, which found a limited role for PRP administration in the short term [38].
PRP can be administered preoperatively, intraoperatively, or postoperatively. It is still unclear which method yields the best effect on soft-tissue healing at the tendon-bone interface. In a review of seven meta-analyses, Saltzman et al. found that PRP injection at the time of arthroscopic intervention does not affect re-tear rate or affect functional outcome. However, there was a trend in reducing re-tear rates in a PRP scaffold construct when it was applied at tendon-bone interface, in a double-row repair, and with small- and medium-sized rotator cuff tears [39]. Furthermore, in 53 patients, Randelli et al. found a significant improvement in early functional outcomes in the intraoperative PRP-treated rotator cuff repair as compared to the control group [40].
The effect of the PRP in the postoperative phase has also been studied. Wang et al. studied 60 arthroscopic supraspinatus tendon repairs with administration of PRP at postoperative days 7 and 12 [41] and found that two distinct image-guided PRP administrations in the postoperative period did not improve early tendon-bone healing or functional recovery. As the biological effects of the growth factors in PRP on reducing inflammatory markers have been well documented [5, 9], a decrease in inflammation following the surgical procedure could potentially decrease the patient’s postoperative pain. Hak et al. conducted a double-blinded placebo study that demonstrated no conclusive effect of PRP in decreasing postoperative pain after arthroscopic rotator cuff repair in a 6-week postoperative period [42]. However, Randelli et al. studied 53 patients and found improvement in pain scores at 3, 7 14, and 30 postoperative days [40].