Platelet-rich plasma injections for the treatment of refractory Achilles tendinopathy: results at 4 years

Background

Chronic Achilles tendinopathy is responsible for a severe reduction in physical performance and persistent pain. There is currently a number of therapeutic options and the local administration of growth factors is an emerging treatment strategy. In particular, platelet-rich plasma (PRP) is a widely used way to provide a local regenerative stimulus for tendon healing. The aim of this study was to document the mid-term results obtained after treating recalcitrant Achilles tendinopathy with injections of high concentrate, leucocyte-rich PRP.

Materials and methods

Twenty-seven patients (mean age: 44.6 years; 22 men and 5 women) affected by chronic mid-portion Achilles tendinopathy (7 bilateral, for a total of 34 tendons), refractory to previous treatments, were enrolled. Patients were treated with three ultrasound-guided intra-tendinous injections of PRP at 2-week intervals. Patients were prospectively evaluated at baseline, and then at 2, 6, and up to a mean of 54.1 months of follow-up (minimum 30 months), using the following tools: Blanzina, VISA-A, EQ-VAS for general health, and Tegner scores.

Results

The VISA-A score showed a significant improvement: the baseline score of 49.9±18.1 increased to 62.9±19.8 at 2 months (p=0.002), with a further improvement at 6 months (84.3±17.1, p<0.0005), and stable results at 4.5 years (90.0±13.9). The EQ-VAS score also showed a similar positive trend. An evaluation of the activity level confirmed these findings, showing a significant improvement in the Tegner score over time (p=0.017 for the final evaluation). The longer duration of symptoms before treatment was associated with a slower return to sport (p=0.041).

Discussion

PRP injections produced good overall results for the treatment of chronic recalcitrant Achilles tendinopathy with a stable outcome up to a medium-term follow-up. Longer symptom duration was related with a more difficult return to sporting activity.     

Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.     

The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: A retrospective analysis of the FEATHER study

Introduction

Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5 mg (Pras-5), and prasugrel 10 mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups.

Materials and Methods

Aspirin-treated patients with stable coronary artery disease (N = 72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20 μM ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed.

Results

Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p < 0.01).

Conclusions

Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel.     

Platelet gels

Platelet gels (PG) are blood-derived biomaterials that are generally obtained through the activation of a platelet-rich plasma or a platelet concentrate by thrombin or calcium chloride, resulting in the simultaneous conversion of fibrinogen into a fibrin gel and in the generation of a platelet releasate rich in a physiological cocktail of growth factors. To reinforce the physical strength of the fibrin network, a fibrinogen-rich fraction – generally cryoprecipitate – can be added to the platelet fraction prior to activation, resulting in the generation of platelet fibrin glue (PFG). PG and PFG, prepared from single donations, either autologous or allogeneic, are increasingly used, alone or in combination with grafting materials, in various field of regenerative medicine where the presence of growth factors is expected to stimulate the healing of soft or hard tissues. Being obtained from human blood, they are physiological and biodegradable preparations and do not induce tissue necrosis. So far, the viral safety of most allogeneic PG and PFG relies on donors selection and donation testing, as is the case for all non-virally inactivated blood components for transfusion. Major fields of clinical applications of PG and PFG in osseous tissue regeneration include maxillo-facial surgery, implantology, reconstructive and plastic surgery. Platelet gels are also used for enhancing the healing of soft tissues, most particularly recalcitrant lower extremity ulcers of various aetiologies, and burns. Newer promising indications include the treatment of osteo-arthritis and joint inflammation, and the repair of musculoskeletal tissue lesions in sports medicine. Autologous PG and PFG are mostly ‘home-made’ single-donor preparations prepared using medical devices. They suffer from the variability in donor characteristics and in isolation procedures of the platelet fraction. Clinical application methods are not standardized. Variability in autologous product characteristics is high, and optimal content of growth factors is unknown, confusing the analysis of product efficacy. The evidence of clinical benefits of these products based on controlled clinical studies is lacking in most indications, although many case studies do support an objective benefit in soft and probably hard tissues healing. Improvement in the standardization and formulation of PG and PFG is a mandatory step forward for improving the reliability and the predictability of clinical outcomes of these interesting blood preparations.     

Platelet‐rich plasma protects rotator cuff‐derived cells from the deleterious effects of triamcinolone acetonide

Triamcinolone acetonide (TA) injections are widely used to treat enthesopathy, but they may induce adverse effects such as tendon impairment and rupture. Platelet‐rich plasma (PRP) is a blood fraction containing high platelet concentrations and various growth factors that play a role in tissue repair processes. The purpose of this study is to investigate whether TA has deleterious effects on human rotator cuff‐derived cells, and if PRP can protect these cells from the effects of TA. Human rotator cuff‐derived cells were cultured with and without TA and PRP, and the culture without any additive served as the control. Cell morphology was assessed at days 7 and 21. Cell viability was evaluated at days 1, 7, 14, and 21 by a water‐soluble tetrazolium salt assay. Induction of apoptosis was measured by immunofluorescence staining and flow cytometry at day 7. Induction of cleaved caspase‐3 was measured by immunofluorescence staining at day 7. The cells cultured with TA had a flattened and polygonal shape at day 7. The cells cultured with both TA and PRP were similar in appearance to control cells. Exposure to TA also significantly decreased cell viability, but cell viability did not decrease when PRP was added along with TA. The number of apoptotic cells increased with TA exposure, while addition of PRP prevented cell apoptosis. In conclusion, the deleterious effect of TA was prevented by PRP, which can be used as a protective agent for patients receiving local TA injections. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 976–982, 2013     

富血小板血浆对大鼠游离脂肪移植物存活的作用

目的 探讨富血小板血浆(platelet rich plasma,PRP)对游离脂肪移植物存活的作用.方法 采用自身配对设计,获取Wistar大鼠脂肪组织和PRP,于24只Wistar大鼠背部分别注射以下3组脂肪移植物:A组为空白对照组;B组为PRP未激活组;C组为PRP激活组.术后1、2、3个月各处死8只大鼠,分别获取3组移植物标本,进行形态学和组织学观察,标本行HE染色,于光镜下观察脂肪组织存活情况,并进行病理学分析.结果 形态学结果显示,术后1个月C组移植物直径明显大于A组(P＜0.05),而移植物体积比较,3组间差异均无统计学意义(P＞0.05).组织学结果显示,术后1个月,C组小血管密度明显高于A组(P＜0.05),术后3个月,C组炎性反应明显轻于A组和B组(P＜0.05),而其他病理观察指标:脂肪组织完整性、纤维化程度及囊腔空泡形成,在各时间段3组间差异均无统计学意义(P＞0.05).结论 在Wistar大鼠模型上PRP对游离脂肪移植物的存活无明显促进作用.