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FAQ: C-PET Canine Platelet Enhancement Therapy

Platelets

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Scientific Background for Canine Therapy

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What are platelets?

Platelets are a cell-like component of blood and are primarily responsible for the development of clots. Platelets also contain a remarkable array of growth factors involved in healing. The list includes platelet-derived growth factors (PDGF), ß-thromboglobulin, fibroblast growth factor, insulin-like growth factor 1, epidermal growth factor, and vascular endothelial growth factor. These growth factors are primarily responsible for the recruitment and differentiation of progenitor cells; promoting angiogenesis, new tissue growth, and replenishing the extracellular matrix.    

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How long has platelet therapy been around?

Platelet therapy has been used since the early 1970’s in periodontics for the treatment of severe gingivitis and in maxillofacial surgery to build bone mass in the jaw in preparation for dental implants. Since then, the use of platelets from a patient’s own blood has been employed in the treatment of tendon and ligament damage, popularized recently by televised reports of its use in professional athletes.

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Are there any other names for platelet therapy?

The most common name for platelet therapy is ‘platelet rich plasma’, or PRP.

It’s worth noting that the term ‘PRP’ has two uses in the medical literature. Traditionally, PRP is used by the blood banking industry to describe a whole blood product that has been processed into platelets and plasma and destined for transfusion. Platelets in this product are only concentrated to levels about twice that found in circulating whole blood. This is not the ‘PRP’ used in platelet therapy.

The ‘PRP’ used as a platelet therapy in dentistry, orthopedics and sports medicine, etc, is a product that concentrates platelets 3 to 8+ times above the levels found in whole blood. These products are produced by centrifugation or, as is the case with C-PET, by filtration, and can include white and red blood cells along with the platelets and plasma. Many of the fields that use platelet therapy have started to use terms other than ‘PRP’, and some of the evolving terms include ‘platelet concentrate’, ‘platelet preparation’, and concentrated platelet product (CPP).

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What is in a platelet therapy?

Most platelet therapies are milieus of cells, cell-parts, and plasma constituents. While there is no agreement on what the best product composition is for any given indication, the one thing all platelet therapies have in common is the concentration of platelets.

Platelets: Current evidence suggests that platelet concentrations at least 3 times above naturally occurring levels provide effective treatments. There is some evidence to suggest that extreme concentrations, roughly 10x or more, may be less effective in some applications. It is important to note that preparations with equal platelet concentrations can differ in the amount of growth factors they deliver depending on the activation status of the platelets. C-PET produces a 3-4x non-activated platelet preparation.

White blood cells (WBCs): Some platelet preparations contain WBCs, and those that do sometimes concentrate WBCs to levels higher than that found in circulating whole blood. There is a growing body of evidence that platelet gels reduce the risk of post-operative infections, particularly in thoracic surgery1, and it is possible the WBC’s in these preparations contribute to the response. Others argue that WBC could be detrimental, releasing cytokines that could exacerbate inflammation. However, WBCs are also the primary source of interleuken-1 receptor antagonist protein2, a potent anti-inflammatory, and the protein used in IRAP™ therapy. C-PET produces a preparation with approximately a 2x concentration of WBCs

Red blood cells (RBCs): Very few, if any, platelet preparations actually concentrate RBCs, but many preparations contain them. Most clinicians are not bothered by the presence of RBCs, but some prefer that they are removed, believing that RBCs can contribute to pain at the site of injection. Sporadic reports of pain at the site of injection using preparations that do not contain RBCs suggest the incidents may be related to the citrated anti-coagulant, an agent with a low, but well documented, incidence of causing pain in blood draws and injections. On the flip side of the RBC discussion, some have argued that the ADP in RBCs may help mediate a sustained release of platelet growth factors at the site of injection. C-PET produces a preparation with an approximately 15% hematocrit.

Optional agonists to assist in fibrin-clot formation: Most platelet preparations can be modified to include fibrin-clots, but the decision to do so is application specific. For instance in bone reconstruction, surgeons prefer platelet preparations that are thick enough to mold into the treatment site and stay there. Some platelet therapies offer proprietary agonists for these applications that add to the structure of the preparation, such as modified bone chips or calcium matrices. For obvious reasons, these structural modifications are not recommended for intra-articular, -ligament, or -tendon injections. The C-PET kit does not include an optional fibrin-clot forming agonist, nor has it been characterized for fibrin-clot forming applications.

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What is the difference between C-PET and other types of platelet therapy?

Simplicty: With C-PET there are no power requirements, no centrifuges, and no service contracts. The system is small, portable, quick, and easy to use.

Filter based preparation: Standard methods of preparing platelet therapy require centrifuges that expose platelets to forces several thousand times the force of gravity. In some products, these forces can cause the premature release of platelet growth factors before they can be administered as a therapy. Pall’s C-PET is the only platelet therapy method that uses filtration technology to gently capture and recover platelets. Our studies have shown that this process is so innocuous that the platelets prepared by C-PET are no more activated than the levels naturally found in circulating blood.

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Risk

What are the risks?

In the 60 dogs treated with C-PET in our pilot study to date, no adverse reactions have been reported. In addition, the use of our filter-based platelet therapy in horses for ligament damage exceeds 2,500 cases without a single untoward incident related to administering the platelet therapy

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Expectations of Outcome

What is the likelihood of success of the treatment?

Our pilot data suggests that dogs under the age of 10 with significant lameness show the best response, with 91% of them experiencing a clinically compelling improvement in lameness when rated by both dog owners and vets alike. For more information on our ongoing pilot study, see our product performance page.

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How did you assess efficacy in your pilot study?

Canine patients in our pilot study were evaluated pre- and 3 months post-treatment using the Hudson Visual Analog Score (VAS) questionnaire, an assessment tool correlated with force plate kinetics3. Using vet enrollment data from the pilot program, we found that improvements greater that 2 points on the 10 point VAS scale for the first client treated strongly correlated with a vet’s likelihood to stay enrolled in the program. We define this 2 point threshold as a ‘compelling improvement’ and use it as a benchmark to differentiate between small, but statistically significant, improvements and meaningful improvements.

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How long does it last?

We are continuing to monitor progress over time. The first dogs treated in the C-PET pilot program have retained benefit for over 1 year and counting.

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Do patients need more than one treatment?

There may be value in providing an additional treatment but this has not been studied yet. We are currently evaluating the use of multiple treatments for dogs over the age of 10, a population that was less responsive to a single injection of the therapy in our pilot study.

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Treatment

What’s the procedure?

The animal is sedated or anesthetized, blood is drawn and filtered to trap the platelets, and then the platelets are recovered by reverse flow using a proprietary elution solution. Thereafter, a needle is inserted in the affected joint, synovial fluid aspirated to confirm the location, and the therapy is administered until resistance in the joint is felt. The volume administered can range from 1 to 5 mL depending upon the dog, the joint, and the extent of disease.

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How long does it take?

For an experienced clinician, the entire procedure typically takes 30 to 40 minutes. The component parts include sedation (5 minutes, anesthesia takes longer), blood draw (5 minutes), filtration and recovery (15 minutes) followed by location of the joint, aspiration and injection (5 minutes).

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Recovery

Is there a specific post treatment regimen?

Some veterinarians ask their client owners to restrict the dogs to leash walking for the first day or two; thereafter, they can resume unrestricted behavior pleasing to the animal. Animals should not be forced to run for the first week or two.

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How will the patient feel right after the treatment?

Some dogs have displayed discomfort that can be treated with ice for the first 20 minutes post-procedure. If needed, an oral analgesics may be used the first day or two after the treatment.

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How long does it take to recover from the treatment and see benefit?

Most owners report seeing benefits within the first few days. A handful of owners reported a mild to moderate relapse of symptoms approximately 2 weeks after treatment before seeing a sustained benefit from the treatment.

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More Questions?

Contract Pall Animal Health’s veterinary help line - 516-462-3991

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1Khalafi, R., et al. Topical application of autologous blood products during surgical closure following coronary artery bypass graft. European Journal of Cardio-thoracic Surgery, 34 (2008) 360-364.
2Arend WP.Interleukin-1 receptor antagonist. Adv Immunol. 1993;54:167-227. PMID: 9597123
3 Hudson et al. Assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. Am J Vet Res. 2004 Dec;65(12):1634-43.