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10 Articles in Volume 12, Issue #7
August 2012 Pain Research Updates
Cash Patient: A Clinical Dilemma
Common Opioid-Drug Interactions: What Clinicians Need to Know
Compliance in Pain Patients: Balancing Need to Test With Need to Treat
Cytochrome P450 Testing In High-dose Opioid Patients
Discharging a Patient Suspected of Diversion
Examining the Safety of Joint Injections In Patients on Warfarin
Genomic Medicine
Letters to the Editor from August 2012
Minimally Invasive Spine Surgery— Who Can it Help?

Examining the Safety of Joint Injections In Patients on Warfarin

Many physicians who treat pain have been hesitant to perform invasive procedures on patients who are taking warfarin sodium (Coumadin) due to the potential risk of complications associated with the medications. However, the same patients who are on anticoagulants may also be the ones who would benefit the most from such procedures as joint injections and aspirations.

Warfarin sodium (Coumadin) is the most widely prescribed anticoagulant medication in North America.1 It is commonly used for the treatment and prevention of venous thrombosis, pulmonary embolism, and thromboembolic disorders. It is also used to reduce the risk of death, recurrent myocardial infarction (MI), and thromboembolic events after MI.2 However, according to the Physicians’ Desk Reference, there are a number of contraindications to using warfarin, including procedures with potential for uncontrollable bleeding (Table 1).3

Two of the most common procedures performed in the outpatient setting are joint injections and aspirations.Joint injections (intra-articular injections) are used in the diagnosis and treatment of a number of inflammatory and non-inflammatory joint conditions, such as rheumatoid arthritis, psoriatic arthritis, gout, tendonitis, bursitis, and osteoarthritis. Joint aspiration (arthrocentesis), on the other hand, uses a needle and syringe to collect synovial fluid from a joint capsule. It is commonly used in the diagnosis of gout, arthritis, and synovial infections and therapeutically in the management of joint effusions.4 These procedures are commonly used by multiple medical specialties and carry little risk of complications (Table 2).4-6

It has been suggested that there are increased risks of complications during these procedures in patients on warfarin sodium. However, there are currently very little data assessing the safety of joint injections/aspirations on patients taking warfarin sodium. Studies in the literature have assessed the safety of intramuscular and other injections for patients who are on warfarin sodium.7,8 Most of these studies detailing complications of taking warfarin sodium involved spontaneous hemarthrosis, which was typically both diagnosed and treated via joint aspiration.9-16

A review of three articles that describe studies assessing the safety of joint injection/aspiration for patients taking warfarin sodium found that bleeding complications occurred rarely. In a study conducted by the Mayo Clinic, Thumboo and O’Duffy did a prospective analysis of 32 joint or soft tissue aspirations and injections in patients taking warfarin sodium. Their study had no patient-reported complications of joint or soft tissue hemorrhage and they concluded that this procedure is low risk for hemorrhagic complications.17

In the second study, Salvati et al conducted a prospective analysis of 15 patients on oral anticoagulation (OAC) with a joint effusion. Of the 15 participants, 2 patients had a hemarthrosis seen as a complication of the arthrocentesis. It was noted that these 2 patients had supratherapeutic international normalized ratios (INRs) of 3.8 and 5.0, respectively. This article concluded that anticoagulation should not be an absolute contraindication to arthrocentesis.18

In the last study, Dunn and Turpie reviewed thromboembolic events and complications for patients taking OAC who needed to undergo surgery or invasive procedures. They found that major bleeding while receiving therapeutic OAC was rare for dental procedures (0.2% [4 of 2,014]), arthrocentesis (0.0% [0 of 32]), cataract surgery (0.0% [0 of 203]), and upper endoscopy or colonoscopy with or without biopsy (0.0% [0 of 111]).19

Many physicians hesitate to treat patients on OAC with invasive procedures. We conduced a retrospective study of patients who underwent joint injections/aspirations while concurrently on warfarin sodium, and compared the complication rates to those of a matched-control group who were not on OAC, in the hopes of determining whether such procedures are contraindicated in patients on anticoagulant therapy.

Table: Warfarin sodium: contraindications and adverse effects

Study Design
Study Population
The study included 110 patients who received joint injections/aspiration procedures at the McConnell Spine, Sport, & Joint Center in Columbus, Ohio, between January 2006 and January 2009. The study population was divided into two groups: the study group (61 patients on warfarin, which included 2 men and 8 women who had undergone multiple injections) and the control group (18 men and 31 women). The age of the patients in the study group ranged from 42 to 79 years, with a mean age of 74 years. The age of the patients in the control group ranged from 24 to 88 years, with a mean age of 61 years.

All the patients who received a joint injection/aspiration while concurrently on warfarin sodium had to have their prothrombin time (PT)/INRs recorded within one month of the procedure.

As this was a retrospective study, patient data, including socio-demographics, were recorded and patient-specific injuries and/or complications from the procedures were assessed and charted via follow-up appointment or phone call. The INR was assessed by both chart review as well as accessing the OhioHealth Results Browser online.

Potential negative outcomes from the procedure were collected and could include a primary complication of hemarthrosis (bleeding complication), and additionally: infection (including septic arthritis), tendon rupture, post-injection flare, skin atrophy, fat atrophy, skin hypopigmentation, corticosteroid arthropathy, osteonecrosis, nerve damage, and excessive injection-site bleeding.

Results of the Study
None of the procedures in the study or control groups were associated with patient- or physician-reported joint and/or soft tissue hemorrhage. No incidences of post-procedural infection, tendon rupture, post-injection flare, skin atrophy, osteonecrosis, or nerve damage were reported in the study. One patient in the study group with a target INR reported “feeling ill” the night after the injection, which was not considered to fall under any of the procedural-related complications outlined in this study. One patient in the control group reported refractory pain after the procedure.

Non–procedural-related complications reported for the patients on OAC included eye hemorrhage, gum bleeding, easy bruising, and abdominal bleeding. Most of these complications notably occurred in patients within target and supratherapeutic INRs. Interestingly, the abdominal bleeding was only noted in patients with a subtherapeutic INR.

Areas injected in the study group included 52 knee injections, 30 of which had a therapeutic INR; 5 shoulder injections, 4 of which had a therapeutic INR; 2 hip/trochanteric bursa injections, all of which had a therapeutic INR; and 2 hand injections, all of which had a therapeutic INR. In the control group there were 24 knee injections, 17 shoulder injections, 9 hip/trochanteric bursa injections, and no hand injections (Figure).

Indications for knee injection/aspiration in both groups included osteoarthritis, effusion, knee pain, patellofemoral syndrome, patellar tendonitis, and congenital knee deformity. Indications for shoulder injection/aspiration included bicipital tenosynovitis, subacromial bursitis, shoulder pain, and osteoarthritis. Indications for hip/trochanteric bursa injection/aspiration included osteoarthritis, iliotibial band syndrome, labral tear, hip pain, and greater trochanteric bursitis. Indications for hand injection/aspiration included osteoarthritis and hand pain.

Limitations of the Study
The most restricting limitation the authors had in this study was for recruitment of patients and acquisition of all study-related parameters. Prior to submitting the proposal to the institutional review board, it was thought that a retrospective 3-year collection period would have sufficed to gain adequate power for this study. Based on the premise that patients on warfarin sodium OAC have the same bleeding complication rates as patients not on warfarin sodium OAC, this study had a pre-hoc power analysis to retrospectively examine the data from approximately 266 patients.

For future direction, closely following patients who are on warfarin sodium who present for joint or soft tissue aspiration/injection with concise documentation of their most recent laboratory values, current medications, indications for OAC, and routine documentation of follow-up after the procedure will yield more consistent and accurate results. The use of ultrasound or fluoroscopic guidance for the procedure should also be better noted in future studies.

A longer data collection period to achieve the pre-hoc power analysis of 133 study and 133 control patients would also be recommended, in addition to documenting whether the patients in the study and the control groups were on any other medications known for bleeding-related complications. These include non-steroidal anti-inflammatory drugs, aspirin, clopidogrel, dipyridamole, ticlopidine, cilostazol, or any combination of these medications.20

Table: Joint injection/aspiration: complications and adverse events

Although some of the patients in this study had a supratherapeutic INR, this study did not adequately examine the rate of hemarthroses and other injection-related complications in patients who are supratherapeutic on their OAC treatment. The safety of these procedures on patients whose PT/INR are elevated beyond their therapeutic limit is still unknown. Such procedures should still be approached with caution in these patients and preferably delay the procedure until the patient has therapeutic PT/INR levels.

The rate of subclinical hemarthrosis could not be assessed or determined via this study without joint aspiration, advanced imaging (ie, magnetic resonance imaging), or arthroscopy being performed. Subclinical hemarthroses are typically incidentally found on aspiration or imaging and do not usually cause harm to the patient.21

This study was a retrospective chart review and, therefore, the patient follow up could have been more accurately assessed in a prospective trial where specific complications could be asked about and/or found on examination.

A final study limitation was that this study was conducted at a single facility with two highly skilled sports medicine physicians who perform multiple joint injections on a daily basis. Whether the results from this study can be extrapolated to the general physician population is not known. The complication rate from this study was similar to other published studies.17-19

Due to the inability to collect enough subject data to achieve sufficient power, inferential statistics could not be calculated for this study. The risk of developing an injection/aspiration-related hemarthrosis was 0% in both study groups. The risk of developing other injection/aspiration-related complications was 0% in both the OAC group and the control groups. It could be inferred from this retrospective chart review that there was no difference in the rate of procedural complications for joint and soft tissue injections/aspirations between patients who are on OAC compared to a non-anticoagulated population.

The results from this study can non-authoritatively provide relief to physicians concerned about performing joint and soft-tissue injections/aspirations on their patients who are on warfarin sodium. As long as a patient’s PT/INR is within therapeutic range for their associated condition, this study demonstrates that one can safely perform injections and arthrocentesis without an increased rate of complications compared to the general population. It is the authors’ hope that a more sufficiently powered study can put physicians’ concerns over performing such procedures on these patients to rest.

Figure. Anatomical distribution of injection/aspiration procedures in the study group and controls

In the fields of primary care, sports medicine, rheumatology, orthopedics, and pain management there are several new treatment modalities showing promise for treating acute and chronic musculoskeletal conditions. Therapies such as platelet rich plasma, viscosupplementation, and prolotherapy have shown good success in treating such conditions.22-24 This study may serve as a means to recruit patients currently on warfarin into future trials aiming to prove the efficacy of these modalities. We have shown the safety of patients on OAC receiving intra-articular injections and, therefore, excluding patients on warfarin from these clinical trials is not absolutely necessary.

In the era of evidence-based medicine, this study further adds to the limited literature assessing the safety and complication rates of patients receiving therapeutic and diagnostic injections and aspirations who are on anticoagulation therapy.

Last updated on: October 26, 2012
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