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33 Blood Conservation andManagement inCardiac Surgery
https://t.me/medicina_free
Fig. 33.3 Pyramid of therapy in coagulopathic patients. (Modied
from Görlinger [31]). The sequence of hemostatic therapeutic interven­tions starts from the bottom of the pyramid and then continues to the top until hemostasis is achieved. Cai, ionized calcium; FFP, fresh frozen plasma; FVIII, coagulation factor VIII/von Willebrand factor concen­trate; FXIII, coagulation factor XIII concentrate; Hb, hemoglobin; PCC, prothrombin complex concentrate; rFVIIa, activated recombinant factor VII; Tc, core temperature [31, 32]
recently, the role of brinogen therapy has been assessed by consensus in a subcommittee of the European Association of Cardiothoracic Anesthesiology. The recommendations
341
include testing and correction of hypobrinogenemia but also recognize the paucity of data to endorse the routine use of brinogen concentrate [
36]. A recent noninferiority study
(FIBRES) of brinogen concentrate versus cryoprecipitate for the management of symptomatic hypobrinogenemia (dened as <150–200mg/dL) demonstrated that concentrates are noninferior to cryoprecipitate administration [37]. Fibrinogen levels necessary to counter coagulopathy have yet to be determined, but hypobrinogenemia as dened by <150–200 mg/dL in the setting of coagulopathic bleeding should be considered as a corrective measure to minimize other allogeneic blood products or riskier prothrombotic concentrates, such as PCCs or rVIIa [38].
The use of platelets in cardiac surgery should be lim-
9
ited to severe thrombocytopenia (<50×10
/L) or in the setting of concomitant antiplatelet drug use with evidence of bleeding [11]. The prothrombin complex concentrate (PCCs) are three- or four-factor preparations that include vitamin K-dependent coagulation factors (II, IX, X, VII) and varying concentrations of protein C, protein S, and antithrombin. The evidence for administration of these agents or fresh frozen plasma (FFP) involve bleeding with deciency of vitamin K-dependent coagulation factors. There is no evidence to support the use of recombinant factor seven (rFVIIa) in cardiac surgery at this time. Its use should be used in uncontrolled bleeding refractory to other measures only.
Cardiac surgical patients are at high risk for the com­plications of allogeneic transfusion given the massive assault on the coagulation cascade as a result of systemic heparinization, preoperative comorbidities (anemia, kid­ney disease), perioperative medical therapy targeting platelet function or the coagulation system, hypother­mia, ischemia, and the proinflammatory response that occurs in response to a surgical stress. While much work is needed to determine optimal management of these patients, there is consensus on a framework of manage­ment that involves a large, multidisciplinary team. The perioperative physician should be apprised of the recom­mendations to provide optimal care for these patients. Figure33.4 provides an overview of the entire periopera­tive period, wherein monitoring, interrogation, and inter­vention are needed to limit unnecessary transfusion and provide evidence- based care.
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B. A. Moore and P. O. McConville
Fig. 33.4 Hemostatic monitoring throughout the perioperative period
and possible treatment modalities. ACT, activated clotting time; CPB, cardiopulmonary bypass; DAPT, dual antiplatelet therapy; DDAVP, desmopressin; EACA, e-aminocaproic acid; EPO, erythropoietin; FFP, fresh frozen plasma; i.v., intravenous; MiECC, minimally invasive
References
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2. Stover EP, Siegel LC, Parks R, Levin J, Body SC, Maddi R, etal. Variability in transfusion practice for coronary artery bypass sur­gery persists despite national consensus guidelines: a 24- institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology. 1998;88(2):327–33.
3. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559–67.
4. Society of Thoracic Surgeons Blood Conservation Guideline Task F, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944–82.
5. Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, etal. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med. 2006;34(6):1608–16.
6. Koch CG, Li L, Duncan AI, Mihaljevic T, Loop FD, Starr NJ, etal. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg. 2006;81(5):1650–7.
7. Hogan M, Klein AA, Richards T.The impact of anaemia and intra­venous iron replacement therapy on outcomes in cardiac surgery. Eur J Cardiothorac Surg. 2015;47(2):218–26.
8. Harker LA, Malpass TW, Branson HE, Hessel EA 2nd, Slichter SJ.Mechanism of abnormal bleeding in patients undergoing car­diopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood. 1980;56(5):824–34.
9. Edmunds LH Jr. Inammatory response to cardiopulmonary bypass. Ann Thorac Surg. 1998;66(5 Suppl):S12–6; discussion S25-8.
extracorporeal circulation circuit; PCC, prothrombin complex concen­trate; PRBC, packed red blood cells. (Modied from Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic S etal. [
10. Kaplan JA, Augoustides JGT, Manecke GR, Maus T, Reich DL. Kaplan’s cardiac anesthesia: for cardiac and noncardiac surgery 7th Edition. Elsevier 2017.
11. Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic S, the European Association of Cardiothoracic A, Boer C, Meesters MI, Milojevic M, Benedetto U, etal. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018;32(1):88–120.
12. Lazar HL.The use of preoperative aspirin in cardiac surgery: the ruling on the eld stands. J Card Surg. 2017;32(12):775–6.
13. Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, etal. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58(24):e123–210.
14. Liu H, Li J, Chen M, Yang T, Ruan Z, Su J, etal. A meta-analysis of randomized and observational studies: aspirin protects from cardiac surgery-associated acute kidney injury. Heart Surg Forum. 2019;22(4):E301–E7.
15. Mangano DT, Multicenter Study of Perioperative Ischemia Research G.Aspirin and mortality from coronary bypass surgery. N Engl J Med. 2002;347(17):1309–17.
16. Terwindt LE, Karlas AA, Eberl S, Wijnberge M, Driessen AHG, Veelo DP, et al. Patient blood management in the car­diac surgical setting: an updated overview. Transfus Apher Sci. 2019;58(4):397–407.
17. Hofmann B, Kaufmann C, Stiller M, Neitzel T, Wienke A, Silber RE, etal. Positive impact of retrograde autologous priming in adult patients undergoing cardiac surgery: a randomized clinical trial. J Cardiothorac Surg. 2018;13(1):50.
18. Rosengart TK, DeBois W, O’Hara M, Helm R, Gomez M, Lang SJ, etal. Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfu-
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sion requirements. J Thorac Cardiovasc Surg. 1998;115(2):426–38; discussion 38–9.
19. Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, etal. Off-pump or on-pump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366(16):1489–97.
20. Diegeler A, Borgermann J, Kappert U, Breuer M, Boning A, Ursulescu A, et al. Off-pump versus on-pump coronary­artery bypass grafting in elderly patients. N Engl J Med. 2013;368(13):1189–98.
21. Hallowell P, Bland JH, Buckley MJ, Lowenstein E.Transfusion of fresh autologous blood in open-heart surgery. A method for reducing bank blood requirements. J Thorac Cardiovasc Surg. 1972;64(6):941–8.
22. Lawson NW, Ochsner JL, Mills NL, Leonard GL.The use of hemo­dilution and fresh autologous blood in open-heart surgery. Anesth Analg. 1974;53(5):672–83.
23. Jarnagin WR, Gonen M, Maithel SK, Fong Y, D’Angelica MI, Dematteo RP, et al. A prospective randomized trial of acute nor­movolemic hemodilution compared to standard intraoperative man­agement in patients undergoing major hepatic resection. Ann Surg. 2008;248(3):360–9.
24. Henderson RA, Mazzef MA, Strauss ER, Williams B, Wipi C, Dawood M, et al. Impact of intraoperative high-volume autolo­gous blood collection on allogeneic transfusion during and after cardiac surgery: a propensity score matched analysis. Transfusion. 2019;59(6):2023–9.
25. Barile L, Fominskiy E, Di Tomasso N, Alpizar Castro LE, Landoni G, De Luca M, etal. Acute normovolemic hemodilution reduces allogeneic red blood cell transfusion in cardiac surgery: a system­atic review and meta-analysis of randomized trials. Anesth Analg. 2017;124(3):743–52.
26. Licker M, Sierra J, Kalangos A, Panos A, Diaper J, Ellenberger C.Cardioprotective effects of acute normovolemic hemodilution in patients with severe aortic stenosis undergoing valve replacement. Transfusion. 2007;47(2):341–50.
27. Harke H, Tanger D, Furst-Denzer S, Paoachrysanthou C, Bernhard A.Effect of a preoperative separation of platelets on the postop­erative blood loss subsequent to extracorporeal circulation in open heart surgery (author’s transl). Anaesthesist. 1977;26(2):64–71.
28. Zhou SF, Estrera AL, Loubser P, Ignacio C, Panthayi S, Miller C 3rd, etal. Autologous platelet-rich plasma reduces transfusions dur-
ing ascending aortic arch repair: a prospective, randomized, con­trolled trial. Ann Thorac Surg. 2015;99(4):1282–90.
29. Bai SJ, Zeng B, Zhang L, Huang Z. Autologous platelet-rich plasmapheresis in cardiovascular surgery: a narrative review. J Cardiothorac Vasc Anesth. 2020;34(6):1614–21.
30. von Heymann C, Sander M, Foer A, Heinemann A, Spiess B, Braun J, et al. The impact of an hematocrit of 20% during normother­mic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome--a randomized controlled study [ISRCTN35655335]. Crit Care. 2006;10(2):R58.
31. Görlinger K.Coagulation management during liver transplantation. Hamostaseologie. 2006;26(3 Suppl 1):S64–76.
32. Görlinger K, Shore-Lesserson L, Dirkmann D, Hanke AA, Rahe­Meyer N, Tanaka KA.Management of hemorrhage in cardiothoracic surgery. J Cardiothorac Vasc Anesth. 2013;27(4 Suppl):S20–34.
33. Karlsson M, Ternstrom L, Hyllner M, Baghaei F, Nilsson S, Jeppsson A. Plasma brinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospec­tive observational study. Transfusion. 2008;48(10):2152–8.
34. Karkouti K, McCluskey SA, Syed S, Pazaratz C, Poonawala H, Crowther MA.The inuence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery: a prospective observational study. Anesth Analg. 2010;110(6):1533–40.
35. Li JY, Gong J, Zhu F, Moodie J, Newitt A, Uruthiramoorthy L, etal. Fibrinogen concentrate in cardiovascular surgery: a meta-analysis of randomized controlled trials. Anesth Analg. 2018;127(3):612–21.
36. Erdoes G, Koster A, Meesters MI, Ortmann E, Bolliger D, Baryshnikova E, etal. The role of brinogen and brinogen con­centrate in cardiac surgery: an international consensus statement from the Haemostasis and Transfusion Scientic Subcommittee of the European Association of Cardiothoracic Anaesthesiology. Anaesthesia. 2019;74(12):1589–600.
37. Callum J, Farkouh ME, Scales DC, Heddle NM, Crowther M, Rao V, etal. Effect of brinogen concentrate vs cryoprecipitate on blood component transfusion after cardiac surgery: the bres randomized clinical trial. JAMA. 2019;322:1–11.
38. Ranucci M, Pistuddi V, Baryshnikova E, Colella D, Bianchi P.Fibrinogen levels after cardiac surgical procedures: association with postoperative bleeding, trigger values, and target values. Ann Thorac Surg. 2016;102(1):78–85.
Platelet-Rich Plasma: Not forAthletes Only
https://t.me/medicina_free
RyanT.Gualtier, LuisChabla-Penael, andAnuraghTrikha
34
Platelet Rich Plasma (PRP) is increased concentration of autologous platelet suspended in small amount of plasma pro­duced by centrifugation of patient’s own blood. Use of PRP has been widely studied in bone and tendon tissue healing and reconstruction [1]. Platelets contains alpha granules which are important source of anabolic growth factors including bro­blast growth factors (FGF), bone morphogenic proteins (BMP), transformation growth factor beta-1 (TGF-β1), plate­let-derived grown factor (PDGF), basic broblast grown fac­tor (BFGF), vascular endothelial grown factor (VEGF), epidermal grown factor, insulin-like growth factor, and several others [2]. In fact, PRP is known to contain more than 1,500 bioactive proteins [1]. These factors are important for biologi­cal processes including wound healing, inhibiting inamma­tion and pain, chemotaxis, neovascularization, synthesis of extracellular matrix, and scar formation which aides in improvement in soft tissue healing, vascularization of grafts and bone [3]. Normal platelet ranges between 150,000 and 350,000 μ/L. PRP contains four to six times concentration greater than whole blood. Improvement in bone and soft tissue healing properties have been demonstrated with concentration of platelets of 1,000,000 μ/L, which is the concentration of platelets in commercial platelet systems [2].
There are four different types of PRP variations which give each commercial system its unique properties, includ­ing leukocyte-rich PRP (LR-PRP), pure PRP, or leukocyte­poor PRP (LP-PRP), platelet-rich brin, and leukocyte-and- platelet- rich brin. LP-PRP increases anti­inammatory mediators including IL-4 and IL-10, whereas LR-PRP signicantly increases proinammatory markers including TNF-alpha, IL-6, INF-gamma, and IL-1-beta and metalloproteinases which antagonize the anabolic cytokines within platelets [2].
R. T. Gualtier (*) · L. Chabla-Penael · A. Trikha New York University School of Medicine, Department of Anesthesiology, Perioperative Care, and Pain Medicine, New York, NY, USA e-mail: Ryan.gualtier@nyulangone.org
Commercial PRP systems use different methods to collect platelets concentrate layer. Generally, whole blood is mixed with anticoagulation factors and centrifuged to obtain plate­lets. The centrifugation process separates whole blood to RBC layer, platelet-poor plasma layer, and “buffy coat” layer containing platelets with or without leukocytes. The platelet concentrate layer is isolated using various processing tech­niques. These platelets can then be either directly injected into the patient or activated via different compounds that leads to degranulation and release of growth factors [2].
The current clinical review shows abundant high-quality evidence of use of LP-PRP for osteoarthritis (OA) of the knee and LR-PRP for lateral epicondylitis. Moderate high­quality evidence supports the use of LR-PRP injection for patellar tendinopathy and LP-PRP for donor site pain in patellar tendon graft BTB (bone-tendon-bone) ACL recon­struction and plantar fasciitis [1]. At this time, the following diagnoses do not have high-quality evidence available; how­ever, small clinical trials have shown promising results. These include rotator cuff tendinopathy, osteoarthritis of the hip, donor site pain in ACL reconstruction with patellar ten­don autograft, and high ankle sprains.
Osteoarthritis oftheKnee
Osteoarthritis is a disease of synovial joints caused by failure in repair of joint damage resulting in alteration of joint struc­tures. It is the most common musculoskeletal disorder lead­ing to functional decline, mobility limitations, and disability of aging population. The most common clinical manifesta­tion of osteoarthritis is joint pain. 240 million people suffer from osteoarthritis globally. Current nonsurgical treatment modalities include physiotherapy, analgesia, nonsteroidal anti-inammatory drugs, and intra-articular injections, such as hyaluronic acid, corticosteroids, or ozone, with the pur­pose of reducing symptoms and improving joint function [4]. In vitro and exvivo studies have provided the foundation for
© Springer Nature Switzerland AG 2021 C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
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this interest, and positive effects of PRP have been observed, including chondrogenic differentiation of pluripotent mesen­chymal cells with expression of cartilage specic genes, chondrocyte proliferation, increased extracellular matrix production, and inhibition of catabolic pathways [5]. Despite the prevalence, no FDA-approved disease- modifying osteo­arthritis drugs currently exist to prevent, slow, or halt knee osteoarthritis [6].
Abundant high-quality evidence supports the use of LP-PRP intra-articular injection for osteoarthritis of the knee. Shen etal. [4] performed a meta-analysis of 14 ran­domized clinical trials comprising 1423 individuals between 2011 and 2016 to compare intra-articular PRP injections to various controls including saline placebo, hyaluronic acid, ozone, and corticosteroids. Compared with control, PRP injections signicantly reduced WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain sub­scores at 3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP signicantly improved WOMAC physical function sub-scores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also signi­cantly improved total WOMAC scores at 3, 6, and 12months (all p<0.001). PRP did not signicantly increase the risk of post-injection adverse events (RR, 1.40 [95% CI, 0.80–2.45],
2
I
=59%, p=0.24). Subgroup analysis further showed that PRP is more efcacious in patients with mild-to-moderate osteoarthritis [2].
Lucia etal. [7] performed a narrative review of the meta­analysis and systemic reviews in 2019, and according to the narrators, at present, results from RCTs seem to favor PRP use over other intra-articular treatments to improve pain scales in the short and medium term (6–12months), but the overall level of evidence is low. They concluded that this is likely the result of a lack of standardization of PRP prod­ucts, scarceness of high-quality RCTs not showing high risks of bias, and poor patient stratication for inclusion in the RCTs.
A meta-analysis by Riboh etal. [5] included six random­ized controlled trials and three prospective comparative stud­ies with a total of 1055 patients. Injection of LP-PRP resulted in signicantly better WOMAC scores than did injection of hyaluronic acid (mean difference, 21.14; 95% CI, −39.63 to 2.65) or placebo (mean difference, 17.84; 95% CI,
34.95 to 0.73). No difference was observed in LR-PRP. SUCRA (surface under the cumulative ranking) analysis showed that LP-PRP was the highest ranked treat­ment for both measures of clinical efcacy using the International Knee Documentation Committee (IKDC) sub­jective score and WOMAC score. This is likely due to the biological basis of LP-PRP and LR-PRP as mentioned in the Introduction section. Thus, intra-articular LP-PRP may be the preferred preparation for the treatment of knee osteoar­thritis symptoms [2].
Lateral Epicondylitis
Lateral epicondylitis, also known as tennis elbow, affects 1–3% of adults each year. It often affects the dominant arm in patients with high demand of gripping or repetitive wrist movements. Individuals between the ages of 35 and 50years are at high risk. Elbow tenderness and pain with resisted wrist extension are common manifestations of lat­eral epicondylar tendinopathy. Overuse and repetitive microtraumas of wrist extensor tendons are believed to be the mechanism of injury of lateral epicondylitis. The lesion starts as a tear in the extensor tendon leading to abnormal microvascular response. It is commonly associated with functional disorder and pain of the elbow joint. Initial interventions include rest, activity or equipment modica­tion, nonsteroidal anti- inammatory medication, bracing, and physical therapy. If these treatments fail to improve the pain and tenderness, second-line treatments such as cortisone injections, prolotherapy, autologous blood injec­tions, PRP injections, and needling of the extensor tendon origin have been recommended. If patients continue to report pain and dysfunction despite these measures, sur­gery is then considered [8]. Abundant high-quality evi­dence supports the use of LR-PRP injection for lateral epicondylitis who have failed to respond to conservative treatments [2].
Mishra etal. [8] evaluated 230 patients in a large multi­center double-blinded prospective randomized controlled trial. All the patients had at least 3months of symptoms and failed conservative therapy. The patients were randomly divided into PRP treatment and active control, and all patients had their extensor tendon needled with and without PRP, respectively. No statically signicant difference was found at 12 weeks in this study. However, at 24 weeks, the PRP­treated patients reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group (P=0.019). 29.1% of the PRP-treated patients reported sig­nicant elbow tenderness versus 54.0% in the control group (P=0.009). Success rates for patients with 24weeks of fol­low- up were 83.9% in the PRP group compared with 68.3% in the control group (P=0.037).
Gosens etal. [9, 10] conducted a double-blind random­ized controlled trial with a 2-year follow-up to determine effectiveness of LR-PRP compared with corticosteroid injec­tion in patients with chronic lateral epicondylitis. The pri­mary analysis included visual analog scale (VAS) pain scores and disabilities of the arm, shoulder, and hand (DASH) out­come scores. When baseline VAS and DASH scores were compared with the scores at 1year follow-up, VAS was suc­cessful and statistically signicant in PRP as compared to corticosteroid (73% vs. 49%, P< 0.001), as well as DASH when compared to corticosteroid (73% vs. 51%, p=0.005). When baseline VAS and DASH scores were compared with
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the scores at a 2-year follow-up, both groups signicantly improved over time. However, the DASH scores of the corti­costeroid group returned to baseline levels, while those of the PRP group signicantly improved.
Rotator Cu Tendinopathies
Rotator cuff tendinopathies are one of the most common rea­sons why patients present with shoulder pain and disability. In fact, it’s not only athletes who suffer from rotator cuff tears, but they can happen to anyone with routine daily activ­ities or with overuse. An estimated 50% of patients present­ing with shoulder pain may be diagnosed with rotator cuff tendinopathy, including supraspinatus partial thickness tears and tendonosis [11]. The goal of the treating physician is to reduce patients’ pain and, by doing so, hopefully improve function. Unfortunately, many patients are refractory to these conservative therapies, which include rest, multimodal pain regimen, physical therapy, and corticosteroid injections, and surgery becomes the only viable option. Due to the relative avascular nature of tendons, their regenerative potential is limited; however, there is some clinical evidence that PRP may help revascularize the area of injury and promote healing. Several RCTs have investigated whether PRP can be utilized for improving pain and functional outcomes in rota­tor cuff pathology.
In a placebo-controlled double-blind randomized clinical trial by Kesikburun etal. [12], a total of 40 patients were enrolled, with [12] history of shoulder pain for >3months during overhead-throwing activities [1], MRI ndings of rotator cuff tear, and [11] minimum of 50% reduction in shoulder pain with administration of anesthetic injection. Patients received 5ml of PRP or 5ml of saline via ultra­sound-guided injection into the subacromial space. In addi­tion, all patients underwent a 6-week standard exercise program. Outcomes were measured via the Western Ontario Rotator Cuff (WORC) Index, Shoulder Pain and Disability Index (SPADI), VAS, and shoulder pain with Neer Test at 3, 6, 12, and 24weeks, as well as 1year after injection. At the 1-year follow- up, PRP was found to be no more effective in improving quality of life, pain, disability, and shoulder ROM than placebo patients who were treated with physical therapy.
Rha etal. [2] went on to compare the effects of PRP with those of dry needling on shoulder pain and function in patients with rotator cuff disease. 39 patients with supraspi­natus tendon lesions less than 1.0 cm, but not a complete tear, were included. Half of the group received two dry­needling procedures, and the other half received two PRP injections to the affected shoulder at 4-week intervals utiliz­ing ultrasound guidance. SPADI, passive ROM, and a physi­cian rating scale at 6months follow-up were used to measure
outcomes. The clinical effect of PRP was found to be supe­rior to dry needling at 6months.
In another study by Shams etal. [11], a similar outcome was reached in regard to PRP vs corticosteroid for the treat­ment of symptomatic rotator cuff tears. 40 patients with symptomatic rotator cuff tears were assessed pre-injection, 6 weeks, and 3 and 6 months after injection utilizing the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Constant-Murley Score (CMS), Simple Shoulder Test (SST), and Visual Analog Scale (VAS) for pain. Both injection groups showed statisti­cal signicance with outcomes over time compared to those pre-injection. At 12weeks, there was also a statistically sig­nicant difference between the PRP and corticosteroid group, in favor of PRP, although there was no signicance after 6months. Therefore, the group summarized that sub­acromial PRP may be considered a good alternative to corti­costeroid injections in those with a contraindication to corticosteroid administration.
Osteoarthritis oftheHip
Osteoarthritis (OA) of the hip has not been studied as exten­sively as OA of the knee; however, little evidence of its ef­cacy does exist. OA is a slowly evolving process, which typically is characterized by pain, stiffness, and decreased range of motion. Overall, roughly 40% of those over 65years old may suffer from OA of the hip or knee [13]. The preva­lence of hip OA alone may account for 7–25% in white patients over 55years [11]. OA is brought on by biomechani­cal and biochemical factors which leads to cartilage disrup­tion and bone hypertrophy. Within the knee or hip joint, proinammatory cytokines and proteinases interfere with the normal production of hyaluronic acid (HA), which results in a signicantly reduced molecular weight and viscoelasticity leading to degradation of articular cartilage and joint func­tion [14]. As the joints affected by OA have a lower than normal concentration of HA, any exogenous administration of HA should increase the synovial uid viscosity, leading to improved shock absorption and lubricating capabilities. In addition, HA is known to stimulate the body’s own endoge­nous HA synthesis via CD44 receptor binding [15].
The current non-operative treatment modalities for OA of the hip include both non-pharmacologic and pharmacologi­cal therapies aimed at reducing pain, stiffness, and disability. Intra-articular corticosteroid injections tend to temporarily reduce pain and improve function [16], however do not change the natural progression of the disease and may also have negative effect on hip structures [17].
There have been four major RCTs comparing PRP to hyaluronic acid for OA of the hip. Battaglia etal. [5] looked to compare clinical efcacy of PRP vs HA at 12months of
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follow-up in patients with hip OA. 100 patients with chronic unilateral hip OA were enrolled and randomly assigned PRP or HA via ultrasound-guided injection. Patients were evalu­ated at 1, 3, 6, and 12months using visual analog scale and Harris Hip Score (HHS). At the 1- and 3-month follow-up, both groups showed overall improvement. At 6 and 12months, there was a slight worsening, however no statisti­cal difference between HA and PRP.In conclusion, the study noted PRP injections to be efcacious in terms of functional improvement and pain reduction, but not superior to HA at 12months’ follow-up.
Di Sante etal. also compared the efcacy of HA vs PRP with ultrasound-guided intra-articular injection [18]. They looked at 43 patients with unilateral severe hip OA.Patients were randomly assigned to receive HA or PRP and received three injections in total (one per week). Patients were evalu­ated at baseline, week 4, and week 16. Primary outcomes were measured with VAS and WOMAC. Results revealed that compared to baseline, the PRP-treated VAS scores were signicantly decreased at 4 weeks, but not at 16 weeks, which indicates an early effect on pain that was not sustained at a longer-term follow-up. In contrary, the HA group had a signicant decrease in both VAS and WOMAC values between baseline and 16weeks.
In an RTC performed by Dallari etal. [14], ultrasound­guided injection of PRP and hyaluronic acid was per­formed separately and in combination for hip osteoarthritis. The primary outcome measure was a change in pain inten­sity as assessed by VAS at 2, 6, and 12months. Other mea­sures included WOMAC and concentration of growth factors in PRP and their correlation with clinical outcomes. A total of 111 patients were randomly assigned to receive three weekly injections of either PRP (44 patients), PRP+HA (31 patients), or HA (36 patients). At all follow­ups, PRP had the lowest VAS scores. The results indicated the intra-articular PRP injections do offer signicant clini­cal improvement in patients with hip OA without relative side effects.
Doria etal. [13] also performed a prospective controlled double-blinded RCT on 80 patients with symptomatic early hip OA.The measures included WOMAC, VAS, and Harris Hip Score, which were evaluated before and at 6 and 12months post-treatment. Both groups showed a signicant improvement from baseline at both endpoints; however, PRP did not offer signicantly better results compared to HA in patients with moderate OA.
Although data is limited in regard to PRP for intra­articular injections for hip osteoarthritis, it does show some promising results with pain reduction and improved function by patient-reported scores. Several studies do show PRP with an earlier onset to pain reduction compared to HA; however there is no statistical difference as time goes on, particularly at 12months post-injection. More high-quality
studies are necessary to see whether PRP can be utilized as a modality for delaying hip surgery due to OA.
Anterior Cruciate Ligament Tears
Anterior cruciate ligament (ACL) tears are one of the most common sports medicine-related injuries, which makes ACL reconstructive surgery one of the most frequently performed procedures in the eld [19]. Majority of these patients are young and athletic, with high expectations of recovering from their injury and returning to the sport. Although most of the current surgical techniques can provide satisfactory results, it’s not 100% guaranteed, and not all patients are able to regain their pre-injury activity level. Clinical results may be shaped not only by the type of graft used but even factors such as pre-injury knee laxity. Due to the nature of these injuries and the expectations by the patients, most research is looking into ways to improve ACL healing, reduce failure rate, and improve on recovery times. PRP is one of these sought-after approaches that are being looked at more closely as a potential therapeutic agent.
A prospective randomized trial performed by Vogrin etal. [20] concluded that platelet gel produced from autologous platelet-rich plasma and applied locally demonstrated a signi­cantly higher level of vascularization in the osteoligamentous interface in 4–6weeks (0.33±0.09) in PG-treated group than the control group (0.16±0.09, p< 0.001). An observational study performed by Sanchez et al. [21] evaluated the gross morphologies of the grafts on second-look arthroscopy in 37 volunteers who underwent either conventional (control group, n=15) or platelet-rich plasma preparation rich in growth fac­tors assisted (n=22) ACL reconstruction with an autogenous hamstring. Biopsy specimen was evaluated by the use of Ligament Tissue Maturity Index to assess the histologic changes during the 6- to 24-month postoperative period of graft maturation. It was found that newly formed connective tissue, resembling synovial-like tissue, enveloped the treated graft in
77.3% of the PRGF-treated grafts and 40% of the controls.
Systematic literature review by Di Matteo et al. [22] showed that the only advantage of PRP is related to a better graft maturation over time, without clear benecial effects in terms of clinical outcome, bone-graft integration, and pre­vention of bony tunnel enlargement. Recent literature review by Riediger etal. [23] concluded that the research failed to show signicant clinical benet of using biologics like PRP and therefore does not support the routine use in ACLR. However, there is some evidence that use of PRP may promote graft harvest site healing, graft maturation and reduce tunnel widening in the short term. A prospective, ran­domized, and double- blinded clinical study by Seijas etal. [24] evaluated the donor site anterior knee pain in “patellar graft” or “bone- tendon- bone” (BTB) autograft ACL recon-
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struction with the application of autologous plasma rich in growth factors (PRGF). PRGF group showed decreased donor site pain in comparison to the control group, with sig­nicant differences in the rst two postoperative months of follow-up. The current study does not show clinical effect of PRP on graft integration or maturation, but limited studies have shown positive results in decreasing patellar tendon donor site pain.
Patellar Tendinopathy
Patellar tendinopathy is a common cause of pain among ath­letes, known as “jumper’s knee.” It has been associated with activities involving jumping, more specically repetitive jumping. Patellar tendinopathy is not an inammatory disor­der; it’s a degenerative disorder. Tendinosis occurs with pro­gressive degeneration of the tendinous tissue and inability for repair.
Risk factors associated with patellar tendinopathy include high body mass index, large abdominal circumference, limb­length discrepancy, at foot arch, weak quadriceps, and low exibility of both quadriceps and hamstring muscles. However, tendinopathy does not occur in all people with the same type of activity; therefore there must be both intrinsic and extrinsic factors.
Patellar tendinopathy can cause pain that is debilitating and impede with a patient’s mobility. Patients usually pres­ent with pain over the proximal and distal part of the patella tendon. Patients will report pain of the proximal tendon when the knee is exed and report pain of the distal tendon when the knee is extended. A provocative test is the single leg squat test, which causes increased load on the patellar tendon. Ultrasound and MRI are useful imaging for diagno­sis. Common differential diagnosis includes patellofemoral pain syndrome, fat-pad syndrome, meniscal tears, cartilage lesions, and referred pain.
Common treatment modalities include eccentric exer­cises, extracorporeal shock wave therapy, steroid injections, sclerosing agents, and hyaluronic acid. The last resort is sur­gery. There is interest in PRP.PRP has a high concentration of growth factors, which can help stop the degeneration of the tendon. These growth factors work on tenocytes, cells that maintain homeostasis in tendons. Some of these growth factors include platelet-derived growth factor, vascular endo­thelial growth factor, epidermal growth factor, and insulin­like growth factor. They promote proliferation, cell differentiation, chemotaxis, and angiogenesis. However, there is conicting evidence to support PRP over other modalities for patellar tendinopathy.
There have been several studies looking at PRP for patel­lar tendinopathy. They have looked at PRP vs saline, PRP vs dry needling, PRP vs extracorporeal shock wave therapy, and
PRP vs steroids. Some studies have shown that PRP is supe­rior over other modalities, and some studies have not. A study conducted by Scott etal. [17] showed that PRP was not more effective than saline for the improvement of patellar tendinopathy symptoms. His study looked at both LR-PRP and LP-PRP.The study occurred over 3 sites, with a sample size of 20 patients in each arm, followed over 12weeks. There was no statistical difference, but he noted that the LR-PRP arm at both 6weeks and 12weeks had an increase in pain. They hypothesized that this was due to the introduc­tion of WBC, which increased the inammatory process. The study was limited by the sample size and the lack of standardization of physical therapy, and the patients were mostly young adults to middle-aged males.
PRP may be effective over dry needling. A study con­ducted by Dragoo etal. [15] showed that PRP plus dry nee­dling was superior over dry needling alone. He showed an acceleration in recovery but that over time the effects were decreased. Notable in this study was that the PRP group reported signicant decrease in pain and an improvement in symptoms and function. PRP may also be more effective over extracorporeal shock wave therapy (ESWT). Vetrano etal. [25] looked at a total of 43 patients that were compa­rable in age, sex, and level of sport participation. He fol­lowed the patients over 1 year. At both 6 months and 12months, there was an improvement in pain and function. The researchers noted that the improvement of tendinopathy with PRP might be possible because they did not inject PRP with local anesthetics. However, previous investigations have shown that both ESWT and PRP increase the number of tenocytes and production of collagen type I and type III, which are needed for tendon repair.
The discrepancies in the studies can be attributed to the preparation of PRP and with the amount of PRP injected into the tendon. Amounts have ranged from 3mL to 5mL.Moreover, there is a lack of standardization on how PRP is prepared. Another question that has yet to be answered is the frequency of injections. Most studies have looked at single injections, with an average follow-up of 1year. These patients may ben­et from repeat injections in lieu of a single injection.
Plantar Fasciitis
Plantar fasciitis is a common cause of heel pain, affecting people of different lifestyles. It can be caused by overuse from prolonged standing and running. Risk factors include high arch, leg length discrepancy, obesity, sedentary life­styles, and tightness of the Achilles tendon and intrinsic foot muscles. Like patellar tendinopathy, it is a chronic process of degeneration and not believed to be secondary to acute inammation. Plantar fasciitis is diagnosed through physical exam and history. Patients will report heel pain, tightness in
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the morning, and improvement of pain after ambulation. However, toward the end of the day, there may be increased pain. On physical exam, it will be noted that the patient usu­ally guards the foot that is affected. Pressure on the medial plantar calcaneal region will cause a sharp and stabbing pain. Imaging is not necessary to diagnose plantar fasciitis. But both ultrasound and MRI are the best modalities.
Plantar fasciitis is treated conservatively. This includes rest, acetaminophen, nonsteroidal anti-inammatory drugs, massage, and modication of activity. If there is no improve­ment, or little improvement with physical therapy, other modalities are recommended. These include percutaneous needling, steroid injection, anterior night splint, and Botox. The use of PRP for plantar fasciitis seems appealing and is being used more.
A study by Sherpy etal. [26] showed that PRP vs steroid injection had comparable results. Patients in both groups improved clinically. Patients that received steroid injection had better outcome with ultrasound evaluation, with a decrease in thickness, and the fascia became more hyper­echoic. Monto etal. [27] showed that PRP was superior to steroid injections for severe chronic plantar fasciitis. He studied patients over 24months and showed that patient’s function initially improved with steroid injections, and then there was a decline. With PRP there was a steady increase in function, the maximum function at 3months, which stayed stable until 24months. It should be noted that most studies looking at PRP injections usually use a volume of 3–5mL; Monto etal. [27] used 9 mL. It is uncertain if the volume contributed to a positive effect. But it can be hypothesized that with increased volume, there are more growth factors released that aid in the repair of the damaged collagen. Research conducted by Jain etal. also showed the PRP was more benecial over steroid injections, highlighting that the effects of PRP were longer-lasting than steroids.
A meta-analysis by Yang et al. [28] showed that PRP does not have a short-term benet on functional status or pain, but it has a better long-term effect. The reason why PRP may not have a short-term effect is because the growth factors in PRP need time for the regenerative process. The advantage of PRP compared to steroids is that there is less risk for abscesses, osteomyelitis, fat pad atrophy, and plan­tar fascia tears.
In contrast to steroid injections, Kim etal. [29] looked at PRP vs dextrose prolotherapy (DP). He took 11 patients and injected them with dextrose prolotherapy, a total of 2 injec­tions. Ten patients were injected with PRP, in a series of two injections. He found that there was an improvement in both pain and function that was sustained over 6 months, and there was no difference between DP and PRP.His study was limited by the small sample size, and there was no placebo. Therefore, there are an abundance of studies looking at PRP
for PF, with conicting efcacy. However, PRP may be more appealing with less risk of side effects when compared to steroids. Moreover, patients may need more than one injec­tion of PRP.
Conclusion
PRP shows promise in treating several musculoskeletal dis­eases. PRP works by releasing factors that are important for wound healing, inhibiting inammation and pain, chemo­taxis, neovascularization, synthesis of extracellular matrix, and scar formation, which aids in soft tissue healing. There are several studies looking at PRP for osteoarthritis of the knee, lateral epicondylitis, ACL reconstruction, rotator cuff tendinopathy, osteoarthritis of the hip, patella tendinopathy, and planter fasciitis. These studies have demonstrated that PRP may be an alternative treatment and may avoid some side effects of common treatments, i.e., steroid injections. However, there is no consensus into which PRP variation is better and which preparation process is superior. Larger studies and standardization of PRP processing may be mov­ing forward.
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