PRP for Surgeries: Are You Using Bovine Thrombin?

Dr. C asks:
When using PRP [Platelet Rich Plasma] for surgeries, are you using bovine thrombin to coagulate the platelets? I have heard that there can be a medical issue using bovine thrombin in human subjects, but I don’t know what that problem is and whether the use of the thrombin to coagulate the PRP can cause any damage. Has anybody experienced any problems when using this technique? Should I be concerned about the dangers of this technique?

21 thoughts on “PRP for Surgeries: Are You Using Bovine Thrombin?

  1. Dr. C
    You may want to compare PRP with PRF for several reasons.
    Lack of chemical additives.
    Lack of animal derived products.
    Ease of use.
    Versatility.
    Effective for longer period of time.

  2. Have been using PRP for about 10 years…without any issues, including the use of Bovine thrombin. Do any double blind, split mouth studies exist comparing PRP with PRF? I’ve been in practice for 28 years and remember how some patients suffered before we began using PRP…so I’m sold on its use. I don’t want to reinvent the wheel unless PRF confers more verifiable benefits than PRP.

  3. The basic advantage of PRF lies in ease and simplicity of its handling of blood sample, just a spin and you are ready with the product.

  4. More research is coming out on prf showing sustained release of tissue growth factors including mineralization, not just early soft tissue healing like prp.
    Here is one such article:
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology Volume 108, Number 5, November 2009 p 707

  5. PRP with bovine thrombin has no adverse effect and the results are fantastic.Have been using bovine thrombin only .PRF ease to handle is only a way to avoid preparation of PRP.The effect on healing with PRP is much better than PRF.

  6. Why should anybody use bovine products?

    In those products you could have something from animals inside. I am sure that there are risks for patients.

    Membranes from pics for augmentation for example????

    And products from a cow belongs into a soup of course.

    That´s the point!

  7. Here in Rio, we have a Biochemist, that comes to our office to perform the PRP process, but He does NOT use Bovine Thombin in his process.

    His process was developed after years of clinical experience in performing this procedure and microscopic observation of the resulting material. This process is based on a fractioned separation, by means of centrifugation of the patients venous blood on a previously calibrated centrifuge that has been tested, by means of several platelet counts at diferent times and RPM combinations, performed during the process, to obtain the time and RPM necessary to obtain the purest fraction possible of platelets and plasma, which he pipets successively from one tube to another, until the material is obtained.

    Clinical results are outstanding and it provides a tremendous cost savings in terms of biomaterial. For example; To perform a bilateral sinus augmentation, we utilize only 2 grams of HA biomaterial, dissolved in PRP, which stays in place and seals any perforations that might exist in the sinus membrane, since it is placed in a viscous soup like gelatinous state. He controls this geling time by maintainig the vessel containing the mixture in an ice water bath. He can also fabricate flat membranes and plugs, much as in the PRF process.

    This is not a simple procedure, that may be delegated to a Dental Assistant, so having a trained Bichemist in your office performing the process, while you perform the surgery is definitely a plus to utilizing this process, which here costs on average U$ 150.00.

    Unfortunately, we do not have the facilities, nor the resources for testing, but I believe that by totaly avoiding any bovine material, superior clinical results are obtaned, due to the absence of foreign animal protein, besides eliminating the possibility of a prion infection.

  8. What you have just described is, essentially, Platelet Rich Fibrin. The use of thrombin is required when using PRP to help release the growth factors from alpha granules within the platelets. The problem with PRP, as admitted by Robert Marx, is that this sudden release of all of the growth factors from the platelets is available for approximately 7-14 hours. After that, the effect of these cytokines dramatically diminishes. Having the platelets within a non-thrombinized fibrin mesh, along with leukocytes, releases PDGF, VEGF, TGFb, and thrombospondin over 7-14 DAYS, precisely when angiogenesis is peaking and bone growth begins. For me, PRF is superior to PRP and PRGF because there is actually an INCREASE in cytokine release at the most important time during wound healing. PRF also allows me to fabricate autologous membranes that can be sutured in place and will increase the biotype of tissue. Alternatively, I can fabricate plugs for extraction sites and can use PRF in extraction/immediate implant sites to graft the space between implant and facial plate (no bone graft needed). Additionally, after purchasing the centrifuge and PRF box, the cost per use is under $5 US. For me, it is an investment that makes sense both financially and biologically.
    RJM

  9. When using a PRF membrane is primary closure a must? Or can you leave the PRF membrane slightly exposed without any negative effects on the underlying graft material? I dont know how thick the membranes wind up being, but it seems like your supposed to place 4 or even 6 membranes in some cases.

  10. You can leave the PRF membrane exposed. If there is a large defect, layer 2-3 membranes over the site to prevent premature dehisence. If the defect is small, just take a single membrane and fold it over. Your site should be fully epithelialized in 7-10 days.

  11. When fabricating the PRF membrane, what is the “liquid” left at the bottom of the PRF box? Is it PPP? What can this be used for?

  12. By definition, any fluid that does not contain platelets is platelet-poor-plasma (PPP). While it does not contain any significant numbers of platelets or leukocytes, it does contain measureable amounts of growth factors. We will use the serum at the base of the box to rehydrate our graft materials and stimulate osteogenesis. Nothing in the L-PRF process is wasted.
    RJM

  13. There is a black box warning for the repeat use of bovine thrombin. This issue documented in the literature.
    The only alternative seems to be indicated below. I have used bovine thrombin wt the harvest system over a significant number of surgeries with no problems. The reduction of post op complications and patient po prn is significantly reduced.
    Two Pharmaceutical Companies To Market New Recombinant Thrombin Product

    Bayer HealthCare entered into a “co-promotion agreement,” with ZymoGenetics, Inc., a biopharmaceutical company headquartered in Seattle, to develop and commercialize rThrombin, a new drug candidate. The product, which is pending approval by the U.S. Food and Administration (FDA), is a recombinant form (engineered through DNA technology) of thrombin, a coagulation protein. Currently, the only thrombin therapy available in the U.S. is Thrombin-JMI®, manufactured by King Pharmaceuticals, a bovine-derived product made from cow blood.

    Thrombin helps the blood clot by converting fibrinogen, a protein manufactured by the liver, to fibrin. Fibrin is an elastic protein that forms into a network of interlocking chains that make up the foundation of the clot. The new thrombin product is being developed “as an aid to controlling bleeding during surgery,” according to the June 19, 2007 press release. Thrombin is used in more than one million surgeries in the U.S annually.

    ZymoGenetics is positioning rThrombin as a safe, effective alternative to plasma-based thrombin, which can potentially cause the formation of inhibitory antibodies to bovine thrombin, and other safety concerns associated with an animal-derived blood product.

    Bayer HealthCare will provide sales and marketing expertise for the first three years following the official launch of rThrombin. The Leverkusen, Germany-based company will be responsible for clinical trials and regulatory approvals necessary for product approval in all countries outside the U.S. Bayer will commercialize rThrombin in all non-U.S. countries.

  14. Thanks for this great discussion. If anyone is still reading this, I am in the midst of rationalizing continued use of PRP/bovine thrombin or switch to PRF.
    I have purchased the PRP apparatus years ago.PRP gives a PRF fraction.PRF can be coagulated from the PRP spin down by using thrombin to coagulate it.I read this is not the same form as the “PRF” system. The PRF system is obviously much less expensive and not an issue to buy.
    I have gone through the learning curve of blood draw using a 19g needle (hydrate patient heavily).
    Dr. Miller’s answer is most persuading as to bone matrix/woven bone time line.

    The issue I ask at courses but never seem to get a straight answer: What IS the problem with bovine thrombin? I found the answers via medical journal articles. To keep it very simple, antigenicity happens in 30% of first case usage and 90% of second case usage in all patients. This means that, if the patient has medical surgery ie heart surgery, kidney, hemodialysis etc, the next sensitization could cause coagulopathies and/or anaphylactic death. Many in the medical profession feel that bovine thrombin needs to be used only for medical use and that dental use does not warrant the possible risks. Coagulopathies means the patients INR will either go up or down dramatically post thrombin use. This could mean thrombosis embolism or internal bleeding of a surgical wound. The thrombin suddenly does not act thrombin-like. There are 100 cases only in the literature. With more use there will be more cases. It is like the latex surge of allergies. The point is that, eventhough it is entirely unlikely, do I want to be the first DDS to have a patient die from thrombin reaction. This is NOT being dramatic. It is an ethical issue now that I know the consequences. I have used the bovine/PRP for years but now I know the parameters I have to choose from. I am very interested in the rhThrombin and will follow that coming to market. In the mean time, I really can’t afford the possible risks and future risks to my career or my patients lives. Those who say it is unlikely to happen: remember the “next sensitization” will most likely be in a hospital setting and there are trained MD’s to take care of the issue whether simple or life threatening. If you were given a consent form by your dentist that listed the risk of PRP use and thrombin as a possible sensitization that could cause future severe medical complications, would you want it? Any comments appreciated.

  15. DO NOT USE bovine thrombin:
    1. It can create an antigencic reaction in the patient, so if they ever have a serious surgery where the thrombin is needed, they will be allergic to it.
    2. Bovine thrombin immediately activates the platelets, causing the growth factors, etc to be released too soon to help with the effect you want.

    PRF, obtained using the Salvin Centrifuge and Supplies, is the best way to get a thrombin, platelet-enriched clot that you can use for anything.

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