富血小板血浆有助于上踝炎和前交叉韧带修复

《美国整形外科医师协会杂志》发表的一篇文献综述显示，大多数证据支持富血小板血浆(PRP)疗法对肘部肌腱炎和前交叉韧带(ACL)重建的有效性，这增加了保险公司未来将其纳入覆盖范围的可能性(J. Am. Acad. Orthop. Surg. 2013;21:739-48)。

美国西北大学整形外科Wellington Hsu医生及其同事总结认为，临床证据表明，局部注射含有白细胞的PRP或有益于标准非手术治疗难以治愈的慢性肘部上髁炎治疗，不过对其他慢性肌腱病的疗效并不明确。他们还确认，虽然临床结局未见显著差异，但初步临床证据表明，PRP或有益于ACL移植物愈合以及髌腱移植物收获部位的韧带化和成熟过程。

研究者还指出，PRP对于肩袖和跟腱修复的临床研究结果并不确定，因此，在作出明确结论和推荐意见之前尚需进一步研究。同样，PRP对骨软骨病变和膝骨关节炎的疗效也需要进一步研究加以证实。

此外，几乎没有临床证据表明PRP有利于骨骼愈合，现有证据也没有表明PRP单独或作为辅助治疗用于局部骨移植物有效。该综述包括了60多篇PRP研究报告。

PRP是患者血液样本经离心分离得到的血小板富集血浆，富含生长因子或其他有助于组织愈合和再生的成分，治疗时将其注入关节间隙、腱鞘或其他部位。

Hsu医生在声明中指出，PRP最初于上世纪50年代用于皮肤和口腔颌面部疾病治疗，但最近5年对PRP的兴趣超过了这方面的研究，部分原因是一些著名运动员应用PRP恢复损伤。有关PRP的大肆宣传已经超前于科学研究，这也正是保险公司未将其纳入覆盖范围的原因。

然而，患者仅一次注射需要支付1,000多美元，而一个常规疗程需要多次注射。随着对某些适应症的证据逐渐明确，保险公司有望考虑将其纳入覆盖范围。

研究者认为，PRP治疗成功率因PRP制备方法和成分不同而有所差异。目前已有40多个商业化的PRP系统，每次研究结果因所用PRP的制备方法和成分不同而存在差异。此外，PRP剂量应答曲线并非线性，当血小板浓度达到足够高的水平时出现抑制性级联，从而呈现饱和效应。

研究者指出，由于血小板在损伤炎性初期或持续期对愈合的作用最大，部分作者推测PRP注射时间对愈合的影响可能大于血小板数量。

2009年PRP市场值为4,500万美元，预计2016年可增至1.26亿美元。

Hsu医生和其他多数作者报告与Medtronic SofamorDanek等多家PRP设备及产品制造商存在利益关系。

评论：保险覆盖的可能性不大

风湿病专家Norman Gaylis医生在接受本刊采访时称，他对上述结果并不意外，他在临床实践中已成功应用PRP疗法。

他指出：“我们已经发现肘部肌腱炎、跟腱炎、膝骨关节炎以及肩袖撕裂临床应答非常显著，PRP可明确改善膝骨关节炎症状、功能以及减少关节空间损失。”

不过，Gaylis医生并不确定保险公司将来是否会将其纳入覆盖范围。他认为，除非大规模盲法试验结果能够说服他们，否则他们很可能永远不会将其纳入保险范围，因为没有公司能够申请类似PRP这种来自患者本身产品的专利。

据Gaylis医生介绍，多数患者是在接受类固醇注射剂、非甾体抗炎药物(NSAID)及其他保险公司覆盖产品治疗失败后转向PRP治疗。如果患者能够支付得起PRP治疗费用，在疾病早期接受治疗效果更佳。

Gaylis医生称，获得3~6 ml的PRP大约需要35~60 ml血液，PRP注射量取决于治疗面积的大小，膝关节治疗约需6 ml PRP。他在临床实践中，在超声引导下注射PRP，然后通过矫正靴等方法限制关节活动。PRP治疗可能需要4~6周时间才能看到应答，对于部分应答患者给予第2次注射治疗，但对于无应答和完全应答患者可能不需第2次注射。

Gaylis医生在注射PRP前或2周后不会立即使用任何NSAID，他认为这些药物可能抵消期望得到的炎性应答。

Gaylis医生在佛罗里达州阿文图拉拥有一家私人风湿病诊所。他声称在其行医之外与PRP无商业利益关系。

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By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

Most evidence supports the effectiveness of platelet-rich plasma therapy for elbow tendinitis and anterior cruciate ligament reconstruction, raising the possibility that insurance companies might one day cover the procedure for those problems, according to a literature review in the Journal of the American Academy of Orthopaedic Surgeons.

"The clinical evidence suggests that local injection of PRP [platelet-rich plasma] containing [white blood cells] may be beneficial to patients with chronic elbow epicondylitis refractory to standard nonsurgical treatment. However, the results of PRP treatment of other chronic tendinopathies are not as clear," concluded lead author Dr. Wellington Hsu, an orthopedic surgeon at Northwestern University in Chicago, and his coauthors, also orthopedic surgeons. They also determined that "although no significant difference in clinical outcomes has been found, preliminary clinical evidence suggests that PRP may be beneficial during the ligamentization and maturation processes of [anterior cruciate ligament] graft healing as well as that of the patellar tendon graft harvest sites."

However, for rotator cuff and Achilles tendon repairs, "the results of clinical studies are equivocal, and further study is needed before definitive conclusions can be drawn and recommendations can be made." Similarly, "further study is required before conclusions can be made regarding the efficacy of PRP in the management of osteochondral lesions and knee osteoarthritis," they wrote.

"Limited clinical evidence exists demonstrating any beneficial effects from the use of PRP in bone-healing applications. The available evidence indicates that PRP is not efficacious either alone or as an adjunct to local bone graft[s]," the authors wrote. The review included more than 60 PRP studies and publications (J. Am. Acad. Orthop. Surg. 2013;21:739-48).

PRP is created by spinning down a patient’s blood sample to isolate and concentrate platelets; the resulting solution is then injected into their joint spaces, tendon sheaths, or other areas. It’s rich in growth factors and other substances thought to aid tissue healing and regeneration.

PRP was first used in the 1950s for dermatology and oromaxillofacial conditions; "interest in PRP jumped way ahead of the research" during the last 5 years partly because celebrity athletes have been using it to recover from injuries. "The hype around PRP definitely came before the science," which is why insurance companies don’t cover it, Dr. Hsu said in a statement.

Instead, patients sometimes pay more than $1,000 for just one of several injections during a typical treatment course. As evidence builds for some indications, "insurance companies hopefully will consider coverage," he said.

Success varies depending on the preparation method and composition. With more than 40 commercial PRP systems on the market, both preparation method and composition vary from one study to the next, as do protocols. In addition, "the dose-response curve is not linear, and a saturation effect has been described in which an inhibitory cascade ensues once a sufficiently high concentration of platelets is reached," the authors wrote.

"Because platelets can exert the greatest influence on healing during or immediately after the inflammatory phase of injury, some authors have postulated that the timing of the administration of PRP has a greater impact on healing than does the number of platelets," they wrote.

Valued at $45 million in 2009, the PRP market is expected to grow to $126 million by 2016.

Dr. Hsu and most of the other seven authors reported financial ties to companies that make PRP equipment or products, including Medtronic SofamorDanek, Stryker, Terumo Medical, Zimmer, Baxter, Biomet, ThermoGenesis, BioParadox, Smith & Nephew, and DePuy.

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Insurance coverage unlikely

Rheumatologist Norman Gaylis said he isn’t surprised by the findings; he’s had success with platelet-rich plasma at his own practice.

"We’ve seen fairly significant clinical responses in tendinitis of the elbow, Achilles tendinitis, osteoarthritis of the knee, and rotator cuff tears. We’ve seen it definitely improve symptoms and function and reduce loss of joint space in" knee osteoarthritis, he said.

Dr. Gaylis isn’t so sure, though, that insurance companies will ever cover the procedure. The large blinded trials it would take to convince them will probably never be done because there’s no way for a company to patent a natural patient-derived product like PRP.

Most people turn to PRP after failing steroid shots, NSAIDs, and other things their insurance will pay for. For those who can afford it earlier in the disease process, "we get better results," he said.

It takes about 35-60 ml of blood to get 3-6 ml of PRP. The injection volume depends on the area treated; a knee joint might get all 6 ml. Dr. Gaylis said he injects under ultrasound guidance, and limits joint motion afterward with, for instance, an orthopedic boot.

Patients should know it can take 4-6 weeks to notice a response. After that time, Dr. Gaylis might reinject partial responders, but likely skip a second shot in nonresponders and full responders.

"We don’t use any NSAIDs immediately before or for a couple weeks after" an injection. "They may counteract the inflammatory response you are trying to generate," he said.

Dr. Gaylis made his remarks in an interview with this newspaper. He has a private rheumatology practice in Aventura, Fla. He said he has no commercial interests in PRP outside of his own practice.