"Autologous Platelet Rich Plasma” (Platelet Gel)
was developed in the early 1970’s as a by-product of multicomponent
pheresis. Techniques and equipment have dramatically improved through the
1990’s. This is a new procedure which utilizes the patient’s own
(autologous) platelets. Briefly, here’s how the procedure works:
A small amount of whole blood (approximately 50 to 120 milliliters) is
drawn, either pre-operatively or in the Operating Room, into a syringe
containing a citrate-phosphate-dextrose adinine. The blood is then
centrifuged by using a variable-speed centrifuge autotransfusion machine
or portable machine, to separate the buffy coat suspended in plasma above
the red blood cell layer and below the platelet-poor plasma fraction. This
is the platelet concentrate used for Platelet
Gel. Depending on the initial platelet counts, it is common
to achieve platelet counts in excess of over three to five (3-5) times
baseline counts. Other important factors in quality of
Platelet Gel are platelet viability
and percent retained on the procedure. While white cell content increases
125% with selection for lymphocytes and monocytes, the inclusion of
platelets and white cells appears have several beneficial aspects. White
cells confer additional healing cytokines while providing antibacterial
activity.
On activation with thrombin/calcium to form a coagulum, the platelets
interdigitate with the forming fibrin web, developing a gel with
adhesiveness and strength materially greater than the plasma alone.
Thrombin/calcium also causes platelets to immediately release highly
active vasoconstrictors, including beta thromboxane, serotonin and PDGF.
Related Reference Articles to Thrombin:
- Rapaport, S.I., Zivelin, A., Minow, R.A.,
et al. Clinical Significance of Antibodies to Bovine and Human Thrombin
and Factor V After Surgical Use of Bovine Thrombin, Am J. Clin Pathol,
1992; 97:84-96.
- Zehnder, J.L., Leung, LLK., Development
of Antibodies to Thrombin and Factor V with Recurrent Bleeding in a
Patient Exposed to Topical Bovine Thrombin, Blood, 1990;
76:2011-2016.
- Nichols, W.L., Daniels, T.M., Fisher,
P.K., et al, Antibodies to Bovine Thrombin and Coagulation Factor V
Associated with the Surgical Use of Topical Bovine Thrombin or "Glue": A
Frequent Finding, Blood, 1993; 82:59 (abstract).
- Christie, R.J., Carrington, L., Alving,
B., Postoperative Bleeding Induced by Topical Bovine Thrombin: Report of
Two Cases, Surgery, 1997; 121(6):708-710.
In addition, platelets contain many tissue growth
factors. These predominant growth factors are:
- PDGF (Platelet Derived
Growth Factor) - PDGF is a very powerful regulatory growth
factor and a sentinel growth factor that begins nearly all wound
healing. PDGF’s main function is to stimulate cell replication (mitogenesis)
of healing capable stems and premitotic partially differentiated
osteoprogenitor cells which are part of the connective tissue-bone
healing cellular make-up. PDGF also causes replication of endothelial
cells, causing budding of new capillaries (angiogenesis). PDGF exists in
three forms: PDGFaa, PDGFbb,
PDGFab.
- TGF (Transforming Growth
Factor) - TGF regulates proliferation and differentiation of
multiple cell types. TGF found in platelets is subdivided into TGFβ1
and TGFβ2, which
are the more generic connective tissue growing factors involved with
matrix formation influencing osteoblasts to lay down bone matrix through
the process of osteogenesis. Also cells activated by TGFβ1
and TGFβ2 include
fibroblasts, endothelial and osteoprogenitor cells, chondroprogenitor
cells and messenchymal stem cells. A condoroprogenitor cell will further
differentiate and produce the matrix for cartilage. A messenchymal stem
cell stimulated to mitose provides wound healing cells.
Other important growth factors in platelets are:
- EGF (Epidermal Growth
Factor) - EGF is responsible for cell differentiation and
stimulates re-epitheliation, angiogenesis and collangenase activity.
- IGF (Insulin Growth
Factors) - IGF is also important in wound healing, and
stimulates
both proliferation and differentiated function in osteoblasts.
There are over 30 known growth factors to date.
These Platelet Growth Factors:
- Increase tissue vascularity through increased
angiogenesis
- Are chemotactic for monocytes, macrophages, and
fibroblasts
- Enhance collagen synthesis
- Increase the rate of epitheal and granulation
tissue production
- Enhance osteogenesis
- The high concentration of leukocytes in the buffy
coat add an antimicrobial
effect, while wound hemostasis and lymphatic sealing provide an
opportunity to
eliminate post-operative drains and reduce pain
- Provides watertight seal for dural closures
- When mixed auto/allograft bone fragments, it
forms a putty-like form ideal
for packing of structural reconstructions
- Provides for an immediate surgical hemostatic
agent that is biocompatible, effective and safe.
Related Reference Articles:
- Scott, John D., Pawson, Tony, Cell
Communication: The Inside Story, Scientific American, 2000;
282:72-79.
- Martin, P., et al, Growth Factors and
Cutaneous Wound Repair, Progress in Growth Factor Research, 1992;
4:25-44.
- Hom, David B., Maisel, Robert H.,
Angiogenic Growth Factors: Their Effects and Potential in Soft Tissue
Wound Healing, Ann Otol Rhinol Laryngol, 1992; 101:349-354.
- Herndon, D., et al, Growth Factors Local
and Systemic, Archives of Surgery, 1993; 128:1227-1233.
- Lind, et al, Growth Factors: Possible
New Clinical Tools, Acta Orthop Scand, 1996; 67(4): 407-417.
- Roberts, et al, Physiological Actions
and Clinical Applications of Transforming Growth Factor-beta (TGF-beta),
Growth Factors, 1993; 8:1-9.
- Slater, Micheal, et al, Involvement of
Platelets in Stimulating Osteogenic Activity, Journal of Orthapaedic
Research, 1995; 13:655-663.
- Hannon, Timothy J., Autologous Platelet
Gel, 1999; 1-13.
- Harrison, P., Cramer, E.M., Platelet
a-Granules, Blood Reviews, 1993; 7:52-62.
- Lozano, Teresa, Broumand, Vistaub, Marx,
Robert E., Evaluation of Risk with the use of Bovine Thrombin in the
Clot Initiation of Platelet Rich Plasma, 1998; 1-2.
- Funheer, R., Pietersz, R.N.I., Korte,
D., Gouwerok, C.W.N., Dekker, W.J.A., Reesink, H.W., Platelet activation
during preparation of platelet concentrates: a comparison of the
platelet-rich plasma and the buffy coat methods, Transfusion,
1990; 634-638.
- Ernesto, C., Clinical Review 35: Growth
Factors and their Potential Clinical Value, J. Clin Endocrinology
Metabol., 1992; 75:1-4.
- Lynch, S.E., Colvin, R.B., Antoniades,
H.N., Growth Factors in Wound Healing: Single and Synergistic Effect on
Partial Thickness Porcine Skin Wounds, J. Clin Invest, 1989; 84:640-646.
- Zimmermann, R., Jakubietz, R., Jakubietz,
M., Strasser, E., Schlegel, A., Wiltfang, J., Eckstein, R., Different
Preparation Methods to Obtain Platelet Components as a Source of Growth
Factors for Local Application, Transfusion AABB, Volume 41,
October 2001, 1217-1223.
- Editorial: Topical Platelet Growth
Factor Therapy: Of Lotions and Potions, Transfusion AABB, Volume
41, October 2001, 1186-1189.
Autologous Platelet Gel:
- is safe
- is non-toxic to tissue
- is autologous
- is easily prepared
- is readily available
- is cost effective
- promotes a firm seal in minutes
- is reabsorbed by the body in days to a few short
weeks
- promotes local tissue growth and repair
Autologous Platelet
Gel is the Perfect Operating Sealant!
Autologous Platelet Rich Plasma
(Platelet Gel), on activation with thrombin/calcium, is a fibrin tissue
adhesive, having hemostatic and tissue sealing properties, but differs
from fibrin tissue adhesives (Fibrin Glue) in its ability to improve wound
healing and enhance osteogenesis.
Current Wound Sealants
Cyanoacrylates have been used in
the closure of tension-free wounds, but are limited in clinical
applications. The acrylic plastic cyanoacrylates are biodegradable and
bacteriostatic, and use of these short chain methyl- and
ethylcyanoacrylates can result to severe histotoxic responses (neural
toxicity). When longer chain butyl- and isobutylcyanoacrylates are
utilized, there is an increase in inflammatory responses and foreign body
giant cell reactions. When neovascularization is compromised through
mechanical blockage, normal wound healing is affected. Recently, topical
applications of octylcyanoacrylates have been used and reported in
clinical studies. They have limited usage, and are for external use only.
Fibrin Glue - Some of the first
applications of Fibrin Glue are reported by Matras in Vienna. Fibrin
tissue adhesives (Fibrin Glue) involve thrombin activation of concentrated
fibrinogen with the presence of Factor XIII, the plasma proteins
Fibronectin and cold-insoluable Globulin, Aprotinin and Calcium Chloride.
The commercial preparation of Fibrin
Glue involves cryoprecipitation of Fibrinogen from single donor or pooled
homologous human blood by adding calcium and thrombin at the time of
usage. A fibrin clot is produced.
Commercial preparations currently under
the brand name Tissel™ (Baxter AG, Deerfield, IL) use purified clotting
factors derived from pooled homologous human blood products. They have
been virally inactivated by heat vaporization or solvent detergent
methods. These preparations contain high concentrations of fibrinogen
(70-140 mg/ml). Also Fibronectin, Factor XIII and antifibrinolytics may
be included.
Also a fibrin sealant, Hemaseal© has
been licensed for use in the United States. In addition, autologous
cryoprecipitated fibrinogen preparations have been employed in the United
States.
Related Reference Articles:
-
Touriumi, D.M., Raslan,
W.F., Friedman, M., Tardy, M.E., Variable Histotoxicity of Histoacryl
When Used In A Subcutaneous Site, Arch Oto. He N Surgery, 1990;
277:1527-1530.
-
Bruck, H.G., Fibrin Tissue
Adhesion And It's Use In Rhtidectomy, Aesth Plast Surg, 1982;
6:197.
-
Matras, H., Zur Nahtlosen
Interfaszikularen Nervetransplantation in Tierexpieriment, Wien
Medical Wochenschreibe, 1992; 122:517.
-
Quinn, J., Wells, G.,
Sutcliffe, T., et al, A Randomized Trial Comparing Octylcyanoacrylate
Tissue Adhesive and Sutures in the Management of Lacerations, JAMA,
1997; 277:1527-1530.
-
Revocation of Fibrinogen
License, FDA Drug Bulletin, 1978; 8:15.
-
Wilson, S.M., Dell, P.,
Donegan, E.A., HIV Transmission Following The Use Of Cryoprecipitated
Fibrinogen and Gel/Adhesive, Transfusion, 1991; 31s:51s.
-
Oz, M.C. Jeevanandam, V.,
Smith, C.R., Autologous Fibrin Glue From Intraoperatively Collected
Platelet-Rich Plasma, Ann Thor Surgery, 1992; 53:530-531.
-
Man, Daniel, Posker, Harvey,
Winland-Brown, Jill E., The Use of Autologous Platelet-Rich Plasma
(Platelet Gel) and Autologous Platelet-Poor Plasma (Fibrin Glue) in
Cosmetic Surgery, Plastic and Reconstructive Surgery, 2001;
229-239.
-
Sierra, D.H., Fibrin Sealant
Adhesive Systems: A Review Of Their Chemistry, Material Properties and
Clinical Applications, J Biomat Applicat, 1993; 7:309-352.
-
Tawes, R.L., Sydorak, G.R.,
DuVall, T.B., et al, Autologous Fibrin Glue: The Last Step In Operative
Hemostasis, Am J Surg, 1994; 168:120-122.
-
Brittberg, M.,
Sjogien-Jansson, E., Lindahl, A., Peterson, L., Influence Of Fibrin
Sealant (Tissel™) On Osteochondral Defect Repair In The Rabbit Knee,
Biomaterials, 1997; 18(3):235-242.
-
Siriex, D., Chemla, E.,
Catier, Y., et al, Comparative Study Of Different Biological Glues In An
Experimental Model Of Surgical Bleeding In Anesthetized Rats:
Platelet-Rich and -Poor Plasma-Based Glue With and Without Aprotinin
Versus Commercial Fibrinogen-Based Glue, Ann Vasc Surg, 1998;
12(4):311-316.
-
Oz, M.C., et al, Autologous
Fibrin Flue From Intraoperatively Collected Platelet-Rich Plasma,
Annals of Thoracic Surgery, 1992; 53:530-531.
-
Gibble, J.W., et al, Fibrin
Glue: The Perfect Operative Sealant?, Transfusion, 1990;
30:741-747.
-
Hartman, A.R., et al,
Autologous Whole Plasma Fibrin Gel - Intraoperative Procurement, Arch
Surgery, 1992; 127:357-359.
-
Radosevich, M., et al,
Fibrin Sealant: Scientific Rationale, Production Methods, Properties,
and Current Clinical Use, Vox Sang, 1997; 72:133-134.
-
Dhall, T.Z., et al, Fibrin
Network Structure: Modification by Platelets, Thromb Haemostas,
1983; 49:42-46.
-
Dulchavsky, Scott A., et al,
Autologous Fibrin Gel: Bactericidal Properties in Contaminated Hepatic
Injury, The Journal of Trauma, 1991; 31:991-994.
-
McGill, Victoria, et al, Use
of Fibrin Sealant in Thermal Injury, Journal of Burn Care &
Rehabilitation, 1997, 18:429-434.
-
Byrne, D.J., et al, Effect
of Fibrin Glues on the Mechanical Properties of Healing Wounds,
British Journal of Surgery, 1991; 78:841-843.
-
Blackstone, Michael O.,
Fibrin Glue for Bleeding Peptic Ulcers, The Lancet, 1997,
350:679.
-
Kram, Harry B., Fibrin Glue
Achieves Hemostasis in Patients with Coagulation Disorders, Arch
Surgery, 1989; 124:385-387.
-
Holcomb, John. B., et al,
Implications of New Dry Fibrin Sealant Technology for Trauma Surgery,
Surgical Clinics of North America, 1997; 77:943-952.
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NewsEdge, Repair of Chronic
Anorectal Fistulae Using Commercial Fibrin Sealant, Arch Surg,
2000; 135:166-169.
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Cintron, Jose R., Commercial
Fibrin Sealant Safe and Effective Treatment for Anorectal Fistulae,
Arch Surg, 2000; 135:166-169.
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Marx, Robert E. D.D.S., Kevy,
Sherwin V., M.D., Jacobson, May S., PhD, Platelet Concentrate
Preparation in the Office Setting: A Comparison of Manual and Automated
Devices, July-September 2001.
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Marx, Robert E. D.D.S., Kevy,
Sherwin V., M.D., Jacobson, May S., PhD, Platelet Concentrate
Preparation in the Office Setting: A Comparison of Manual and Automated
Devices, Update March 2002.
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Marx, Robert E., D.D.S.,
Platelet-Rich Plasma (PRP): What Is PRP and What Is Not PRP?; Implant
Dentistry, Vol. 10 No. 4 2001.
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