Hi Brenda

Thank you for your question, and apologies for the delay. I asked our advisory panel members, it seems none of us has had a chance to try Actigraft yet. If your clinic has tried it out, wonder what your experience has been.I was curious about the fundamentals of the mechanism of action and did some research on it. There were a few pilot, non randomized studies using Actigraft for chronic wounds, and most were supported by the manufacturer (this could lead to bias), so evidence supporting its use is still of low certainty.[1-3] There is one more non randomized trial sponsored by the manufacturer recently completed in Oct of 2020 listed on ClinicalTrials.gov, but results don't seem to be out yet. As an activated whole blood clot, it is proposed that the autologous clot tissue creates a scaffold that releases growth factors and cytokines over several days, and it is also proposed that the stroma may serve as a matrix to facilitate migration of cells and promote healing.[4] The mechanism of action makes sense, but it'd be interesting to see the clinical outcomes once more clinical trials (preferably non-sponsored randomized controlled trials) are completed. 

A few of us wondered how blood clot compared with platelet rich plasma (PRP) products for wounds. Although we couldn't find a clinical study on it, there was an experimental study comparing platelet-rich fibrin and blood clot on animal tendons that concluded that platelet-rich fibrin constructs have increased concentrations of the growth factor TGF-β1 and are capable of increasing tendon cell proliferation over time when compared with blood clot.[5] There has been many clinical trials (including RCTs) supporting the use of PRP for chronic wounds, more specifically DFU.[6] PRP differs from blood clots in the sense that the resulting PRP product has high platelet concentrations (≥ 1,000K/µL) compared to normal blood serum.[7] PRP products may have other components such as leukocytes, fibrin, etc. Like Actigraft, PRP products are also prepared at the point of care by drawing blood from the patient. Unlike Actigraft, PRP products usually require a centrifuge sold by the manufacturer to separate the plasma. The proposed mechanism of action for PRP is the gradual release of platelet derived growth factors in the wound bed. Brands used for wound care include Nuo’s Aurix and 3C Patch® System. Reimbursement-wise, according to the manufacturer, for Actigraft, Q4100 may be appropriate to report the ActiGraft® Autologous Whole Blood Matrix when usedin skin substitute application procedures, and application codes are HCPCS codes C5271 – C5278 (low cost). PRP's HCPCS is G0460.  In December 2020, CMS proposed to cover application of autologous PRP for the treatment of chronic non-healing DFU.[8] CMS is proposing that coverage of autologous PRP for the treatment of all other chronic non-healing wounds be determined by local Medicare Administrative Contractors (MACs). Public comments have been favorable and a final determination should be published soon.[6] My personal experience preparing PRP was that it was an easy procedure. Here you can see other clinician's experience with PRP in chronic wounds. https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=300&NcaName=Autologous+Blood-Derived+Products+for+Chronic+Non-Healing+Wounds&ExpandComments=y&CommentPeriod=0&NCDId=217&bc=AAAAAAAAACAA&#Results' target='_blank'>https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=300&NcaName=Autologous+Blood-Derived+Products+for+Chronic+Non-Healing+Wounds&ExpandComments=y&CommentPeriod=0&NCDId=217&bc=AAAAAAAAACAA&#Results Other colleagues her might have experience with that as well. 
Of note, adjunctive treatments are usually indicated for "healable" chronic wounds that fail to heal despite 4-6 weeks of optimal clinical care (including management of underlying conditions and comorbidities that might impede healing)  

Thanks, and keep us posted!

1.Uso de una matriz autóloga en el tratamiento de úlceras de pie diabético, con espectroscopia de infrarrojo cercano y medidor de pH dérmico. https://pubmed.ncbi.nlm.nih.gov/33249991/
2.Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study. https://pubmed.ncbi.nlm.nih.gov/27701127/
3. Safety and Efficacy of an Autologous Blood Clot Product in the Management of Texas 1A or 2A Neuropathic Diabetic Foot Ulcers: A Prospective, Multicenter, Open Label Pilot Study. https://pubmed.ncbi.nlm.nih.gov/29718812/
4. Proposed Mechanism of Action of Topically Applied Autologous Blood Clot Tissue: A Quintessential Cellular and Tissue Based Therapy https://pubmed.ncbi.nlm.nih.gov/33052392/
5. Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-β1 and increase tendon cell proliferation over time when compared to blood clots: a comparative in vitro analysis. https://pubmed.ncbi.nlm.nih.gov/20825593/
6. IWGDF Editorial Board. IWGDF Practical guidelines on the prevention and management of diabetic foot disease: Diabetes Metab Res Rev.  2020;36(S1):e3266. https://iwgdfguidelines.org/wp-content/uploads/2019/05/01-IWGDF-practical-guidelines-2019.pdf
7. CMS public comments on PRP https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=300&NcaName=Autologous+Blood-Derived+Products+for+Chronic+Non-Healing+Wounds&ExpandComments=y&CommentPeriod=0&NCDId=217&bc=AAAAAAAAACAA&#Results' target='_blank'>https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=300&NcaName=Autologous+Blood-Derived+Products+for+Chronic+Non-Healing+Wounds&ExpandComments=y&CommentPeriod=0&NCDId=217&bc=AAAAAAAAACAA&#Results
8. Proposed Decision Memo for Autologous Blood-Derived Products for Chronic Non-Healing Wounds (CAG-00190R4) https://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=300

Thank-you Elaine, for the very complete and well-researched reply. I will share with the two providers who wish to use Actigraft on two patients who should be "healable", but just aren't moving. I remember back in the 90's, when I first started applying NPWT to wounds, the only evidence out there was sponsored by KCI. I understand the bias concern. PRP is an interesting option, but I know we won't be purchasing a centrifuge. Thanks again.