Abstract
Objective
To assess the effects of platelet-rich plasma (PRP) injection among patients with thumb carpometacarpal (CMC) joint osteoarthritis (OA).
Design
Retrospective chart review with follow-up questionnaires/surveys. Post-procedure, patients were sent standardized, automatically-generated follow-up questionnaires, and contacted for a survey regarding patient-reported outcomes.
Setting
Single institution (tertiary care hospital) outpatient clinic from 2015 to 2020.
Participants
Nineteen adult patients (9 women; average age 65.0 [±6.3 years]) who received a PRP injection for OA of 1 or both thumb CMCs (N=19).
Interventions
Platelet-rich plasma injection.
Main Outcome Measures
Outcome measures included symptom improvement (subjective, visual analog scale), duration of benefit, subsequent procedures, satisfaction, and side effects/adverse events. Cellular composition of whole blood and PRP injectate (platelets, erythrocytes, leukocytes, neutrophils, lymphocytes, and monocytes) were analyzed.
Results
Subjects reported moderate or excellent symptom improvement in 68.8% of injected joints and were moderately or very satisfied with 68.8% of the procedures. Mean patient-reported duration of benefit was 15.6 months (±19.5) months (mean duration of follow-up: 32.4 [±18.1] months). There were no major complications attributed to the procedures, but 1 patient was diagnosed with presumed unrelated lymphoma 2 weeks post-procedure. PRP mean platelet concentration was 1787.77 (±687.14) × 109/L, resulting in a mean platelet concentration factor of 8.80 (±4.19) times baseline and mean platelet dose of 1881 × 106. Other PRP cell concentration factors were erythrocytes, 0.02; neutrophils, 0.14; lymphocytes, 3.76; and monocytes, 3.29.
Conclusions
PRP injection appears to be a safe and potentially effective treatment option for pain related to first CMC OA. Further study is needed to optimize treatment protocols and better understand which patients are most likely to benefit.
KEYWORDS: Biological products, Blood platelets, Hand, Intra-articular injections, Rehabilitation, Retrospective studies
The thumb (first) carpometacarpal (CMC) joint is 1 of the most common areas affected by osteoarthritis (OA).1, 2, 3 The prevalence ranges from 15% to 36% in women and 5% to 11% in men.1 It can be functionally debilitating,3,4 with symptoms including pain, weakness, deformity, instability, and decreased range of motion.5, 6, 7, 8
Common nonsurgical treatment options for management of this condition include oral and topical NSAIDs, hand therapy, activity modifications, splinting, and intra-articular injections. Injections have traditionally consisted of corticosteroids demonstrating variable efficacy and viscosupplementation with conflicting results.9, 10, 11 Surgical options include trapeziectomy with ligament reconstruction and tendon interposition, fusion, and less commonly, implant arthroplasty.4
Platelet-rich plasma (PRP) is an emerging treatment option for various musculoskeletal conditions, including osteoarthritis.12, 13, 14 PRP is defined as plasma with platelet concentrations greater than whole blood. In practice, PRP is generally autologous and created by centrifuging a patient's whole blood.15,16 It is hypothesized that PRP stimulates recruitment, proliferation, and differentiation of regenerative cells via release of various growth factors,17 such as platelet-derived growth factor-AB and -BB, transforming growth factor-β1, insulin-like growth factor-1, fibroblast growth factor-basic, epidermal growth factor, vascular endothelial growth factor, and interleukin (IL)-12.18 The platelets in PRP have anti-inflammatory properties with modulators including IL-1 receptor antagonist, soluble tumor necrosis factor receptor I and II, IL-4, IL-10, IL-13, and interferon gamma.19
Although PRP has been used clinically for the past several decades and studied in a variety of musculoskeletal conditions, variable extraction methods, cell and cytokine compositions, and lack of standardized PRP reporting has made interpretation and comparison of studies difficult.20 Consequently, the optimum parameters for PRP production and administration remain unclear. For these reasons, there has been a call for the standardization of PRP in clinical use.20
Despite the prevalence of thumb CMC OA, little research has been published regarding the utility of PRP injection. To our knowledge, there are only a few studies in the literature, totaling a small number of patients with first CMC OA treated with PRP, highlighting a need for further investigation with larger samples sizes.1,2,7
The primary aims of this study were to (1) assess outcomes of PRP injection in patients with thumb CMC OA and (2) characterize the cellular composition of the PRP injected. The secondary aim was to describe the procedural technique used at our institution.
Methods
Setting and design
This was a single institution retrospective case series study. Following Institutional Review Board approval, we performed a retrospective electronic medical record (EMR) chart review identifying patients who received PRP injection for thumb CMC OA. This study conforms to the provisions of the Declaration of Helsinki. Patients provided informed consent and their anonymity was preserved throughout the study process. Patients seen in physical medicine and rehabilitation, orthopedic surgery hand, and sports medicine clinics from 2015 to 2020 were eligible for inclusion. Further EMR search parameters and inclusion criteria consisted of patients with thumb CMC OA who received a PRP injection. Patient records were reviewed independently by 2 authors (I.H. and M.B.), and any discrepancies were decided upon by the senior author, a non-surgical hand specialist (J.B.). OA severity was graded via available plain films. Each joint was graded initially by the primary author (I.H.) and confirmed by the senior author (J.B.). The Eaton classification system was used, with I being mild and IV being severe.21
Primary outcomes
Primary outcomes measured included patient-reported outcomes after injection as well as cellular composition of whole blood and PRP. Patient outcomes were based on chart review and follow-up surveys. Patients were sent standardized, automatically generated follow-up questionnaires via the EMR which included established measures such as Visual Analog Scale (VAS) pain scores and Quick Disabilities of Arm, Shoulder, and Hand (qDASH) scores.22 Patients were also contacted via telephone for a follow-up survey which included questions related to amount of patient-reported symptom relief after injection, satisfaction with the procedure, duration of benefit, and complications/adverse effects. Composition analysis of whole blood and PRP included platelets, erythrocytes, leukocytes, neutrophils, lymphocytes, and monocytes.
Secondary outcomes
We also assessed patient population and demographics, and techniques involved with blood draw, processing, and injection. We recorded age, sex, and thumb CMC OA severity (Eaton classification) for each patient in the cohort. Variables surrounding the blood draw and processing techniques that were analyzed included the venipuncture site, whole blood volume, centrifuge type, hematocrit setting, and PRP volume produced. Regarding the injection technique, we recorded the following: volume of PRP injected into the CMC joint, local anesthesia amount/type used, needle gauge, approach, use of ultrasound guidance, ultrasound transducer characteristics, and needle view in relation to ultrasound transducer.
Data analysis
Descriptive data, including means (SDs) for continuous data and frequencies for categorical data, were calculated. Data were analyzed with IBM SPSS Statistics Version 25 software (IBM Corp, Armonk, NY, USA).
Results
Population
Our EMR review search resulted in 119 patients that were identified as potential candidates for inclusion. After a manual chart review of these eligible patients, we identified 19 different patients, resulting in 33 thumb CMC joints that were injected with PRP (table 1). The remaining 100 patients with history of thumb CMC OA were excluded as they received PRP injections in body regions rather than the first CMC joint. Patient age ranged from 40 to 74 with a mean of 65.0 (±6.3) years old. There were a total of 6 different clinicians within our institution, all physical medicine and rehabilitation physicians, who administered these injections.
Table 1.
Demographics of patients (n=19) who received platelet-rich plasma injection(s) (n=33) for thumb carpometacarpal joint osteoarthritis
| Demographic | Mean (SD) | n (%) | |
|---|---|---|---|
| Age, y | 65.0 (6.3) | ||
| Sex | Men | 10 (53) | |
| Women | 9 (47) | ||
| BMI | 27.0 (5.7) | ||
| Injection laterality | Right | 18 (55) | |
| Left | 15 (45) | ||
| Osteoarthritis severity (Eaton classification) | 1 | 0 (0) | |
| 2 | 7 (21) | ||
| 3 | 18 (55) | ||
| 4 | 8 (24) |
Abbreviation: BMI, body mass index.
Severity of osteoarthritis
There were no grade 1 (0.0%), 7 grade II (21.2%), 18 grade III (54.6%), and 8 grade IV (24.2%) Eaton classifications.
Blood draw/processing
Venipuncture and platelet-rich plasma production
Whole blood was obtained with venipuncture on the day of the procedure and combined with ACD-A. Mean volume of blood drawn was 116.3 (±41.8) mL. PRP volume produced ranged from 0.8 to 7.3 mL, with a mean of 3.6 (±1.5) mL. More blood was drawn in cases involving concurrent injection of other body regions. Of the 33 procedures, 24 venipunctures were documented from the antecubital vein and 1 from the femoral vein. The remaining 8 that were undocumented were presumed to be from the antecubital vein as is standard practice at our institution. All blood samples were processed with the Arthrex Angel Systema, according to the manufacturer recommendations. A 1% hematocrit setting was used for all cases.
Peri-procedural and injection details
To avoid potential interference with PRP mechanisms, all patients were instructed to avoid non-steroidal anti-inflammatory medications at least 1 week prior to and 1 week following the procedure. Patients were advised to avoid vigorous activity with the injected hand for 1 week, followed by gradual return to activities of daily living. No platelet activators were used in any of the procedures. All blood samples were kept at room temperature under ambient lighting and were processed and injected in a procedure room during the same clinic visit that day.
Biologic characteristics
Of the 33 cases, 27 (81.8%) had samples of whole blood and PRP sent for cellular analysis (complete blood count) at our institution's hematopathology laboratory on the same day of the procedure (table 2). Analysis of these samples showed a mean platelet concentration of 216.8 (±46.6) × 109/L in whole blood, and 1787.8 (±687.1) × 109/L in PRP, resulting in a mean platelet concentration factor of 8.8 (±4.2). Mean platelet dose injected into the first CMC joint was 1881 (±894.33) × 106 cells. Mean erythrocyte concentration was 4581.54 (±314.03) × 109/L in whole blood, and 113.46 (±67.02) × 109/L in PRP, resulting in a mean erythrocyte concentration factor ratio of 0.02 (±0.02). Mean neutrophil concentration was 3.54 (±1.07) × 109/L in whole blood, and 0.47 (±0.90) × 109/L in PRP, resulting in a mean neutrophil concentration factor of 0.14 (±0.26). Other PRP cell concentration factors were total leukocytes, 1.42 (±0.88); lymphocytes, 3.76 (±2.29); and monocytes, 3.29 (±1.98). Therefore, the PRP used in this cohort was depleted in erythrocytes and neutrophils but enriched in lymphocytes and monocytes.
Table 2.
Cell composition of whole blood and platelet-rich plasma in patients receiving injections
| Cell Type | Concentration in Whole Blood (× 109/L) | Concentration in PRP (× 109/L) | Concentration Factor (Ratio of PRP/Whole Blood) | Cell Dose in PRP Injected Into Joint (× 106) |
|---|---|---|---|---|
| Platelets | 216.77±46.62 (88.00-282.00) |
1787.77±687.14 (442.00-2943.00) |
8.80±4.19 (1.83-19.07) |
1881.78±894.33 (295.50-4414.50) |
| Erythrocytes | 4581.54±314.03 (4210.00-5280.00) |
113.46±67.02 (20.00-240.00) |
0.02±0.02 (0.01-0.05) |
102.97±70.06 (7.50-300.00) |
| Leukocytes | 5.85±1.25 (3.80-8.30) |
7.89±4.66 (1.20-18.40) |
1.42±0.88 (0.16-3.41) |
7.84±5.38 (0.11-27.60) |
| Neutrophils | 3.54±1.07 (1.61-5.45) |
0.47±0.90 (0.00-3.51) |
0.14±0.26 (0.00-1.01) |
0.35±0.33 (0.00-0.96) |
| Lymphocytes | 1.62±0.43 (1.00-2.54) |
5.70±3.29 (0.92-16.39) |
3.76±2.29 (0.48-9.69) |
6.41±4.62 (0.09-24.59) |
| Monocytes | 0.52±0.15 (0.30-0.80) |
1.67±1.07 (0.14-3.60) |
3.29±1.98 (0.28-7.32) |
1.65±1.06 (0.02-3.60) |
NOTE. Data expressed in mean ± SD (range).
Injection technique
The amount of PRP injected into the CMC joint ranged from 0.25 to 2.0 mL, with a mean of 1.1 (±0.4) mL (table 3). All 33 injections were performed under ultrasound guidance, with the use of either high frequency standard or small footprint linear (ie, “hockey stick”) transducers. Lidocaine (1%) local anesthetic was used at the skin in 28 of the procedures (84.9%), with a mean volume of 0.9 (±0.7) mL. Needle gauge size ranged from 22 to 30, with the most common being a 27 gauge (45.5%). Transducer orientation was long axis relative to the first metacarpal (perpendicular over the joint) in 28 of the 33 injections (84.9%) with the remaining in short axis relative to the first metacarpal (long axis with the joint). Regarding needle orientation in relation to the ultrasound transducer, 31 of the 33 injections (93.9%) were reported as out-of-plane in relation to the transducer, and 2 (6.1%) as a combination of in-plane and out-of-plane.
Table 3.
Description of technique used for platelet-rich plasma injections
| Injection Technique | Mean (SD) | n (%) | |
|---|---|---|---|
| Skin (local) anesthesia type | Lidocaine | 28 (85) | |
| Local anesthesia volume (mL) | 0.86 (0.65) | ||
| Ultrasound transducer orientation (in relation to metacarpal) | Long axis | 28 (85) | |
| Short axis | 5 (15) | ||
| Needle gauge | 27 | 15 (45) | |
| 30 | 9 (27) | ||
| 25 | 7 (21) | ||
| Needle orientation | Out-of-plane | 31 (94) | |
| Combined in- and out-of-plane | 2 (6) | ||
| PRP injected volume (mL) | 1.07 (0.40) |
NOTE. Data expressed in mean ± SD or n (%).
Patient outcomes
Follow-up data were based on chart review (VAS and qDASH) and patient telephone survey responses (table 4). The number of responses on electronic follow-up questionnaires regarding VAS and qDASH scores ranged from 7 responses (out of 19 patients) at baseline to as low as 2 responses (out of 19 patients) at 12 months, depending on whether patients answered certain aspects of the questionnaires. Based on these responses, mean VAS pain scores at rest and activity were 4.3 and 5.6 pre-injection (7 responses), and 3.3 and 2.3 at 12 months post-injection (4 responses). Mean qDASH scores improved from 28.6 pre-injection (5 responses) to 52.3 at 12 months post-injection (2 responses).
Table 4.
Follow-up outcome data based on survey responses in patients (n=18) who underwent platelet-rich plasma injections (n=32) for thumb carpometacarpal joint osteoarthritis
| Survey Question | Response | n (%) |
|---|---|---|
| How would you rate your improvement after the procedure? | None | 7 (22) |
| Mild | 3 (9) | |
| Moderate | 11 (34) | |
| Excellent | 11 (34) | |
| How would you rate your current symptoms? | None | 6 (19) |
| Mild | 12 (38) | |
| Moderate | 11 (34) | |
| Severe | 3 (9) | |
| Have you had any additional procedures since the injection? | PRP | 4 (13) |
| Corticosteroid | 6 (19) | |
| Surgery | 3 (9) | |
| How satisfied were you with the procedure? | Very unsatisfied | 6 (19) |
| Mostly unsatisfied | 0 (0) | |
| Neutral | 4 (13) | |
| Mostly satisfied | 9 (28) | |
| Very satisfied | 13 (41) | |
| Would you recommend the procedure to a friend or family member? | Yes | 13 (72) |
| No | 5 (28) |
Given the limited response rate with the VAS pain and qDASH electronic questionnaires, patients were contacted via telephone for follow-up survey, resulting in additional follow-up data for 18 of 19 patients (32 of the 33 joints injected). One patient could not be reached despite multiple attempts. Mean time from initial injection to telephone survey response was 32.4 (±18.1) months. There were no major complications noted. There were 3 complications/side effects reported. Two of these consisted of a patient reporting increased bilateral thumb pain that resolved within 4 weeks after receiving bilateral injections. One patient reported right axillary swelling that was first noticed approximately 2 weeks after bilateral thumb injections, leading to medical workup of the eventual diagnosis of low-grade diffuse follicular B-cell non-Hodgkin lymphoma.
Of the 32 joints (18 patients) for which follow-up questionnaire data were obtained, joint symptom improvement after injection was rated as follows: 7 joints were rated as “no improvement” (21.9%), 3 mild (9.4%), 11 moderate (34.4%), and 11 excellent (34.4%). Mean patient-reported duration of benefit was 15.6 months (±19.5) months. Joint symptom ratings at the time of follow-up survey responses were as follows: 6 joints were rated as “not currently symptomatic” (18.8%), 12 as mild (37.5%), 11 as moderate (34.4%), and 3 as severe (9.4%). Thirteen of the 32 injected joints (40.6%) received further intervention. Four joints (12.5%) underwent repeat PRP injection (mean 11.0 months after initial PRP injection), and 6 (18.8%) underwent subsequent corticosteroid injection (mean 7.0 months after initial PRP injection). 3 joints (9.4%) [(2 patients (11.1%)] underwent surgical intervention (mean 11.7 months after initial PRP injection). Regarding patient satisfaction, 6 injections were rated as “very unsatisfied” (18.8%), 0 “mostly unsatisfied” (0.0%), 4 “neutral” (12.5%), 9 “mostly satisfied” (28.1%), and 13 “very satisfied” (40.6%). Thirteen of 18 patients (72.2%) responded “yes” when asked whether they would recommend this procedure to a friend or family member. In terms of OA severity, 4 of the 7 grade II joints (57.1%), 13 of the 17 grade III (76.5%), and 5 of the 8 grade IV (62.5%) were rated as moderately or excellently improved.
Discussion
Emerging evidence suggests that PRP injection is an effective treatment option to improve pain and function in knee OA.12,13 However, there remains limited evidence for PRP in the treatment of OA elsewhere in the body, including common and debilitating OA of the thumb CMC joint. This retrospective study was designed to provide a descriptive analysis of PRP injection for thumb CMC OA. Our results indicate that PRP injection, using a PRP with minimal erythrocytes and neutrophils, is a relatively safe and potentially effective treatment for thumb CMC arthritis in most of patients treated (68.8% of injected joints rated improvement either moderate or excellent). Patients reported relatively long duration of therapeutic effects (mean 15.6 months) with high patient satisfaction (68.8% rated as mostly or very satisfied with their procedure).
Loibl et al performed a non-comparative pilot study investigating fluoroscopic-guided leukocyte-reduced PRP injection into the thumb CMC joint on a population of 10 patients.7 This series received 2 consecutive PRP injections 4 weeks apart and was followed over a period of 6 months. Follow-up demonstrated statistically significant improvement in VAS (mean 6.2 pre-injection to 5.4 post-injection) and Mayo Wrist scores at 6 months. There were no adverse events reported, and the investigators concluded that PRP for first CMC OA was a safe conservative treatment modality. Our study differed from the Loibl et al study in the use of ultrasound guidance and a single injection. In addition, Loibl et al used an Arthrex ACP system, which has been demonstrated to provide lower platelet concentrations compared with PRP.23 PRP cellular characteristics in their series were presumed based on a previous study rather than directly measured.
Malahias et al performed a prospective randomized controlled trial in 33 patients comparing 2 consecutive thumb CMC intra-articular PRP injections (n=16) to methylprednisolone/lidocaine injections (n=17).1 They found a statistically significant improvement in VAS, qDASH, and patient satisfaction in the PRP group compared with methylprednisolone/lidocaine (median VAS scores improved from 7.5 to 2.0 in the PRP group from pre-injection to 12 months post-injection, and 7.0 to 6.5 in the methylprednisolone/lidocaine group). They concluded that PRP may achieve a lasting effect of up to 12 months for those with early to moderate thumb CMC arthritis. Similar to Loibl et al and unlike in our current study, Malahias et al performed 2 consecutive injections. Based on a prior study demonstrating decreased effect of corticosteroid injection for advanced stages of thumb CMC OA,24 they decided to exclude those with stage IV OA. However, because of the differing mechanisms of PRP vs corticosteroid, and given that 62.5% of the joints with grade IV OA severity in our study were given improvement rating of moderate to excellent, we would argue that this assumption may be premature.
Medina-Porqueres et al described a case presentation of PRP injection for grade II CMC OA in a professional pianist, along with a review of the literature.2 In their described case, 3 PRP injections at 1-week intervals were performed without image guidance, which has been shown to be less accurate compared with using image guidance.25 The patient reported high satisfaction with return to prior high-level function. No PRP composition/analysis were provided.
Sward et al reported on a series of patients with various thumb CMC OA severity who underwent 2 fluoroscopically-guided injections of PRP using the Arthrex ACP system 3-4 weeks apart. At three-month follow-up, they found no significant improvements in reported pain, PRWHE score, grip strength, or key pinch. The contrast in outcomes between this study and our investigation may be explained by the difference of PRP product. The Arthrex ACP system has been shown to produce relatively low platelet PRP (concentration factors of 1-2 ×) in several studies,23 which is much lower than the mean concentration factor of 8.8 in our study.
One patient in our study noted axillary swelling 2 weeks after his injection and was later diagnosed with low-grade diffuse follicular B-cell non-Hodgkin lymphoma. He underwent surgical resection and immunotherapy and is currently in remission. To our knowledge, there are no studies in the literature to date that have identified an association between PRP injection and lymphoma. Given the previous safety record of PRP in the literature and the short time frame between the injection and the patient's lymphoma diagnosis in this case, we think the diagnosis was likely unrelated. Nevertheless, PRP injection has been shown to cause a transient rise in systemic growth factors (eg, IGF-1), so there has been some theoretical concern about PRP injection triggering growth of latent cancer cells.26 Larger studies of PRP are needed to conclusively demonstrate whether or not there is an association of PRP with cancer.
Strengths and limitations
This is 1 of the first studies examining the effect of PRP injection on thumb CMC OA, suggesting that a single ultrasound-guided injection may be a viable, relatively long-lasting treatment for an otherwise debilitating condition with few options. The analysis of the PRP cellular composition in this study provides data on the treatment response that may be expected using a relatively high-platelet PRP product with minimal erythrocytes and neutrophils.
The major limitations of this study were the small sample size, retrospective and uncontrolled design, and low follow-up response on established patient-reported outcome measures such as qDASH and VAS pain scores. Our numbers were likely insufficient to determine whether there was a relation between PRP cellular composition (eg, platelet concentration factor or dose) and patient outcomes. Although our sample size was small, other studies investigating PRP injection for thumb CMC OA have reported on patient populations of 1, 10, 16, and 21 patients.1,2,7,27 The retrospective nature of this study meant it was limited to a chart review. The poor response rate to electronic established questionnaires (VAS pain and qDASH) prompted us to obtain follow-up data via post-hoc phone survey responses, introducing the potential for recall bias.
High-quality, randomized controlled trials investigating PRP injections for thumb CMC OA are still needed. These should report on established patient reported outcomes, pinch/grip strength, and thumb range of motion both pre- and post-injection at various points in time extending out to 1 or more years. In addition, PRP characteristics (cell composition at a minimum) of each individual injection should be performed to contribute to the body of data correlating these PRP characteristics with patient outcomes.
Conclusions
PRP injection appears to be a safe and potentially effective treatment option for pain related to thumb CMC OA. There is a paucity of studies on this emerging treatment for a common and debilitating condition. This study suggests that a single, ultrasound-guided injection of erythrocyte/neutrophil-poor PRP can provide worthwhile pain relief for a heterogenous group of patients with thumb CMC OA. Further study is needed to optimize treatment protocols and better understand which patients are most likely to benefit.
Suppliers
-
a.
Arthrex Angel System; Arthrex Inc.
Acknowledgments
This work was supported by the authors’ efforts and all patients’ willingness to participate. No funding was required.
Footnotes
List of abbreviations: CMC, carpometacarpal; EMR, electronic medical record; IL, interleukin; OA, osteoarthritis; PRP, platelet-rich plasma; qDASH, Quick Disabilities of Arm, Shoulder, and Hand; VAS, visual analog scale
Disclosures: none.
References
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