Our Most Recent Publication on Blood Clots, Anticoagulation, and Knee Arthritis BMC Procedures

New medical technology attains a few predictable levels as it’s adopted by more and more physicians. Because we’ve been performing knee bone marrow concentrate procedures for a very long time and collecting registry data on them, we’re well into the final level. As a result, we just published a peer-reviewed research paper on the risk of a blood clot after a knee bone marrow concentrate procedure and whether that warrants anticoagulation. Let’s dig in.

The Levels of Procedural Adoption

When a new interventional orthobiologics procedure is invented, there are some basic steps that the research goes through:

  1. The Basics: Is it safe? What should be injected? What’s the Right Dose?
  2. Does it work?
  3. Who is a good candidate?
  4. What risks occur at scale? How do you mitigate those risks?

For bone marrow concentrate containing the patient’s stem cells, we began using that to help knee arthritis patients way back in 2005. In fact, the only person on earth to use BMC in knees before us was Phillipe Hernigou in France. However, Dr. Hernigou pursued a bone injection technique while we began with injecting inside the joint and the ligaments/tendons. So for what we do, we’ve been using BMC in knees longer than anyone else on earth. Here’s the research we’ve added on each of those topics above:

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The Basics: Is It Safe? What should be injected? What’s the Right Dose?

Our research group answered these basic questions quite some time ago. On safety, we published the world’s largest orthopedic bone marrow safety paper in 2016 (1). To dial in what should be injected, we compared adding in an adipose (fat) injection with BMC and found that it didn’t add to the outcome versus BMC alone (2). Finally, we published our first dosing paper way back in 2015 finding that we needed a minimum number of nucleated cells to get the best results (3). In addition, we’ve just had a paper that uses an alternate dosing method (CFU-f) accepted for publication just this week.

Does it work?

While our early efficacy study (the one above about adding fat into the joint with BMC) was published in 2014, we eventually followed that up with a randomized controlled trial in 2018 (4). So we can safely say that the specific procedure we use works. Is more research needed? Always.

Who Is a Good Candidate?

The next level is figuring out who is the ideal candidate for the procedure. For knee osteoarthritis, all of our published papers have looked at this and we’ve performed several analyses of our outcome data outside of our published research. The last one was during the pandemic where we looked at hundreds of MRIs based on their features and could discern no trends that firmly placed one patient into the good versus poor candidate bin. Meaning that a patient with severe arthritis did as well as a patient with mild arthritis.

In the end, we did find one key for determining the clinical outcome with about 80% accuracy. To get there, we began to look at the cytokine and growth factor levels in the knee joint and used machine learning to find the best candidates. This is now being turned into a laboratory test with our group partnering with a lab company that is able to easily test these levels in a tiny amount of synovial fluid.

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What risks occur at scale? How do you mitigate those risks?

The final level is tracking not hundreds, not thousands, but tens of thousands of patients over long periods of time to answer questions that require treatment at scale. That’s where our new paper on blood clots and the knee BMC procedure comes in. These are very rare events, such that the average clinic that does many of these procedures might not see a single event in several years of treating hundreds or a thousand or more patients.

What question does our new research answer? Should we be concerned enough about blood clots that we need to place these knee BMC patients on a formal anticoagulation protocol?

Risks at Scale: Blood Clots in Knee Arthritis BMC Procedures

Blood clots fall into the broad category of VTE (Venous Thromboembolism). They can occur at the back of the knee (Deep Vein Thrombosis or DVT) or travel from there to the lung (Pulmonary Embolism or PE). They are so common in knee replacement surgeries that you can reduce the risk for patients by placing them on oral anticoagulant drugs. Meaning the risks caused by the drug of excessive bleeding is less than the overall knee replacement blood clot risk. However, for knee arthritis BMC procedures, nobody has ever had enough data to answer this same question.

We maintain the world’s largest and oldest outcomes and complications dataset. As a result, we finally got to the scale of treating tens of thousands of patients where this rare complication could be detected in enough numbers to determine if the risk of VTE outweighed the risk of the anticoagulant drug.

In our new peer-reviewed publication, the risk of VTE with a knee arthritis BMC procedure was calculated at 0.16% of treated patients or approximately 1 in 639 procedures (5). Given that the risk of serious bleeding caused by anticoagulant drugs is about 3% which is higher than the risk of VTE, our study concluded that physicians should not routinely anticoagulant these patients.

It’s important to note however that this is a general statement. Meaning that any given patient may have specific medical risk factors that markedly increase their VTE risk and as such, the treating physician may believe that it’s important to anticoagulate that patient. For example, there may be genetic factors that make someone’s VTE risk very high.

The upshot? Getting into these level 4 questions about orthobiologic procedures is a key part of allowing these treatments to go mainstream. Thanks to all of our research team who helped the whole field of interventional orthobiologics with this seminal research!



(1) Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop. 2016 Aug;40(8):1755-1765. doi: 10.1007/s00264-016-3162-y. Epub 2016 Mar 30. Erratum in: Int Orthop. 2018 Jan;42(1):223. PMID: 27026621.

(2) Centeno C, Pitts J, Al-Sayegh H, Freeman M. Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. Biomed Res Int. 2014;2014:370621. doi: 10.1155/2014/370621. Epub 2014 Sep 7. PMID: 25276781; PMCID: PMC4170694.

(3) Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord. 2015 Sep 18;16:258. doi: 10.1186/s12891-015-0714-z. PMID: 26385099; PMCID: PMC4575428.

(4) Centeno C, Sheinkop M, Dodson E, Stemper I, Williams C, Hyzy M, Ichim T, Freeman M. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018 Dec 13;16(1):355. doi: 10.1186/s12967-018-1736-8. PMID: 30545387; PMCID: PMC6293635.

(5) Centeno, C.J., Money, B.T., Dodson, E. et al. The rate of venous thromboembolism after knee bone marrow concentrate procedures: should we anticoagulate?. International Orthopaedics (SICOT) (2022). https://doi.org/10.1007/s00264-022-05500-3

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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NOTE: This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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