Understanding Platelets and Their Role in Regeneration
Platelets or thrombocytes are small, disc shaped blood components without nuclei that are derived from the cytoplasm of bone marrow megakaryocytes. These types of cell fragments are known for their clotting effect but are now recognized as main contributors in inflammation, immunity and tissue repair and regeneration. The therapeutic utilization of platelets is in all fields of medicine, dentistry, aesthetics and veterinary applications.
Applications of Platelet-Rich Plasma in Medicine
- Orthopedics: Tendinopathy, osteoarthritis, ligamentous injuries, soft tissue injuries, and many more.
- Dermatology and Aesthetics: Skin rejuvenation, anti-aging, hair restoration, scar revision, sexual wellness and erectile dysfunction.
- Dentistry: Bone graft enhancement, periodontal regeneration.
- Plastic Surgery: Wound healing and fat graft survival.
- Veterinary: Wound healing, ligamentous injuries, osteoarthritis
Platelet Production and Life Cycle
Platelets are formed through a process called thrombopoiesis. In this action, the megakaryocytes extend projections into the bone marrow sinusoids and these projections shear off into circulating platelets. Therefore, the primary site of platelet production is the bone marrow with secondary sites of production in the lung.
The lifespan of a platelet is 7-10 days and after this period they are removed through the spleen and liver.
Thrombopoietin, primarily synthesized by the liver, regulates the megakaryocyte maturation and platelet production.
Platelet Composition and Granules
Platelets are cytoplasmic fragments and do not contain nuclei for replication. However, they are diverse organelles and storage granules with multiple functions in clotting and regeneration of tissues.
Alpha Granules and Their Function
These are the most abundant granule contained on the platelet.
Containing multiple growth factors (PDGF, TGF-B, VEGF, EGF, IGF-1) adhesion molecules (P-selectin, Fibrinogen, Fibronectin)
Function: Promote tissue repair, angiogenesis and cell proliferation.
- PDGF: Stimulates mitogenesis, angiogenesis and macrophage recruitment.
- VEGF: Promotes endothelial proliferation and vascularization.
- EGF and IGF-1: Enhance epithelial cell proliferation and matrix synthesis.
- TGF-B: Regulates inflammation and fibroblastic activity.
Dense Granules
These granules carry ADP, ATP, calcium and serotonin.
Function: Amplify platelet aggregation and recruit additional platelets and other cells to injury site.
Lysosomes/Lambda Granules
These granules carry proteolytic enzymes, and these participate in degradation of damaged tissues and remodeling during healing.
Mechanism of Action of Platelets in Healing
Upon vascular disruption, platelets are activated through exposure to subendothelial collagen and Von Willebrand Factor. This triggers a cascade:
- Adhesion: Platelets adhere to the injury site via GPiib receptors.
- Activation: Shape changes, granules secretion, and synthesis of thromboxane A2.
- Aggregation: Fibrinogen bridges between receptors GPiib receptors and promote a plug formation.
Once hemostasis is complete, platelets then begin the modulation of repair:
- Inflammation: Release of cytokines and the interaction with leukocytes.
- Immune modulation: Interaction of Toll like receptors and cytokines.
- Tissue regeneration: Growth factor release supports cell migration, proliferation and angiogenesis.
There is no longer a debate in medical forums, that platelets are instrumental in clotting and subsequent tissue repair. Therefore, concentrated platelets placed in an area of tissue damage should stimulate and enhance the rebuilding of this tissue.
Defining Platelet-Rich Plasma (PRP)
Platelet Rich Plasma is an autologous concentration of blood derived platelets, rich in cytokines, growth factors and bioactive proteins. Platelet Rich Plasma is widely used in regenerative medicine due to its autologous nature, its anti-inflammatory and anti-infective properties and the high concentration of bioactive molecules that promote healing. However, with no central standardization of PRP, there is confusion concerning accurate quantification and reporting of platelet concentration. This has led to some studies questioning the efficacy of the treatment with platelet rich plasma.
Total Platelets in the Human Body
- Average adult blood volume = 5L (5,000 milliliters)
- Platelet Count is approximately 200 million per milliliter (150,000 to 400,000 per microliter of blood)
- Total Platelets in the body = 200 million x 5000 milliliters = 1 trillion platelets
Platelet Quantification in PRP
There are two ways of reporting the total amount of platelets in a sample of platelet rich plasma:
- Platelets per microliter: this is the standard unit in hematology, normal range is approximately 150,000-400,000 platelets per microliter.
- Platelets per milliliter: this is a derived unit since 1 milliliter = 1000 microliter
1,000,000 platelets microliter equals 1,000,000,000 platelets per milliliter or 1 billion platelets per milliliter.
1-microliter is 1 millionth of a liter
1-milliliter is 1 thousandth of a liter
For example, a PRP sample with 1.5 million/microliters = 1.5 billion platelets / milliliters
Therapeutic Concentration Goals for PRP
Platelet Rich Plasma aims to concentrate platelets 3–7 times above baseline. A therapeutic PRP sample may contain:
- 1–2 million platelets per microliter or
- 1–2 billion platelets per milliliter
Total platelets per injection for example:
- 1.5 million/microliter X 1000 X 5mL = 7.5 billion platelets
Therapeutic Dosage per Literature
- Marx et al proposed that a minimum of 1 million platelets/microliter is necessary for a regenerative effect.
- Giusti et al found that 1.5 million platelets/microliter is optimal for angiogenesis and in concentrations above 2.5 million/microliter endothelial proliferation was inhibited. This indicates a bell-shaped curve dose response for platelet concentration and regenerative potential.
- Fitzpatrick demonstrated that higher doses (5–10 billion total platelets) improved patients in hair restoration in androgenetic alopecia.
Based on these and many other studies, the therapeutic dose of platelet rich plasma for regenerative therapy lies typically between 2–10 billion platelets per injection depending on the tissue and pathology being treated. (equivalent to 2–10 million platelets per microliter)
Clarifying Platelet Count Reporting: Millions vs Billions
Author’s Note: There has been much confusion about the concentration of different platelet rich plasma kits and concentration devices. Some companies report billions of platelets and some report millions of platelets. As evidenced above, both companies are saying the same thing as far as the number of platelets. The difference is the number reported in microliters or milliliters.
However, as noted with the bell-shaped curve concerning platelet concentration, too little may not be effective, too high a concentration will be detrimental to the regenerative process. The regenerative potential of platelet rich plasma is now well documented in the worldwide scientific literature, whether it is reported in millions or billions of platelets.
Studies
- Platelet Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020
Int J Mol Sci 2020 Oct 21;21(20):7794 PMID 33096812 - Platelet Rich Plasma: Evidence to Support Its Use
J Oral Maxillofac Surg 2004 Apr;62(4): 489-96 PMID 15085519 - Platelet Rich Plasma in Dermatology: Cellular and Molecular Mechanisms of Action
Biomedicines 2023 Dec 19;12(1):7 PMID 38275368 - Revitalizing Hair Growth: A New Regimen Utilizing Growth Factor Concentrate for Hair Loss Treatment
Cureus 2024 Jun 28;16(6): e63354 PMID 39070330
Juventix Regenerative Medical Products and Solutions
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are designed for safety, sterility and effectiveness. Our Kits are FDA cleared and scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes that are critical for the regenerative process.
LED Platelet Activation Without Chemicals
Juventix Regenerative Medical offers a patented LED Activator to activate the platelets and begin the regenerative process. This activation is a critical step in the release of growth factors, cytokines and bioactive proteins from the granules that are contained on the platelets and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen. This mode of activation by LED light provides sustained growth factor release versus older methods of activation while adhering to the minimal manipulation standards of the FDA.
Advanced Bio-Incubator for PRF Transformation
Juventix Regenerative Medical supplies a patented Bio-Incubator to transform the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called the “second generation of platelet products” has different cytokines and growth factors than the original platelet rich plasma. These different cytokines provide an anti-inflammatory microenvironment and can be used confidently in inflammatory conditions.
Complete Regenerative Product Line for Clinicians
Juventix Regenerative Medical has a vast array of products, devices and services tailored for the medical, aesthetic and regenerative professionals. Platelet Rich Plasma Kits, LED Activators and Bio Incubators are a few of the many devices that offer the latest in the treatment of soft tissue, ligamentous and joint injuries.
Juventix: Enhancing Outcomes and Patient Satisfaction
With our premier line of products and support from our experienced staff, Juventix Regenerative Medical is poised to aid and professional in enhancing clinical outcomes while increasing patient satisfaction.
RESTORE, REVIVE, REGENERATE — JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
