Chapter 16 Biological Therapies in Canine Sports Medicine 405which may mitigate inflammation and initiate
anabolic processes and tissue regeneration.
Many different growth factors are contained
in these alpha‐granules, but those most com‑
monly cited to facilitate tissue healing include
vascular endothelial growth factor (VEGF),
platelet‐derived growth factors (PDGF), and
transforming growth factor beta (TGF‐β).
Several of the applications for which PRP have
been used, but not necessarily demonstrated to
be efficacious, include injection into injured
tendons, muscles, and ligaments, placement in
fractures to facilitate bone healing, and intra‐
articular injection for symptomatic management
of osteoarthritis.
Characteristics
Concentration of platelets is typically the charac‑
teristic of PRP that is most scrutinized. However,
eliminating erythrocytes is also a potential goal
of PRP preparation because erythrocytes are
inflammatory stimuli when extravascular, and
have been shown to significantly increase cell
death of human fibroblast‐like synoviocytes
in vitro (Braun et al., 2014). In addition, some
investigators contend that removal of leukocytes
is also a desired objective of PRP preparation
because the concentrations of inflammatory
cytokines correlates with leukocyte concentra‑
tion in human PRP (Sundman et al., 2011). The
ideal PRP may be a function of platelet, eryth‑
rocyte, and leukocyte concentrations (or their
ratio), and the optimal PRP likely varies for dif‑
ferent medical conditions (Arnoczky & Shebani‐
Rad, 2013). As a result, clinicians should know
the characteristics of the PRP they use and the
evidence supporting the use of that particular
type of PRP for a specific ailment. Classification
systems have been devised to categorize the
numerous different PRP compositions to enable
comparison and summary of the evidence sup‑
porting their clinical use. These classification
systems are based on the cellular composition of
the PRP (platelets, leukocytes, erythrocytes) and
if or how platelets in the PRP are intentionally
activated (DeLong et al., 2012; Dohan Ehrenfest
et al., 2014).
The goal of PRP therapy is to provide anabolic
growth factors. This requires platelet activation,
fusion of the alpha‐granule with the external
platelet membrane, and release of the growth
factors into the extracellular environment. One
mechanism of in vivo platelet activation is
contact and interaction with collagen, which is a
common component of musculoskeletal tis‑
sues. Accordingly, PRP is often injected with‑
out intentional exogenous activation, in which
case the clinician depends on activation to
occur in vivo at the site of tissue injury. This
practice may allow a more extended release of
growth factors if activation occurs over time
in vivo (Harrison et al., 2011; Arnoczky &
Shebani‐Rad, 2013). However, suboptimal acti‑
vation could occur in vivo. As a result, some
authors recommend that intentional exogenous
activation be performed prior to PRP application
to assure that platelets are activated. Numerous
studies using human, equine, and canine PRPs
have compared different activators including
soluble collagen, calcium‐based products, and
thrombin (Fufa et al., 2008; Harrison et al.,
2011; Silva et al., 2012; Textor & Tablin, 2012).
There are some differences among studies
but all demonstrate that use of these substances
increases platelet activation and growth factor
release in comparison to samples that are not
activated. As a result, an additional compo‑
nent of PRP classification schemes is what, if
any, intentional exogenous activation has been
performed.
Although not part of classification schemes,
the volume of blood used in PRP preparation
and the volume of PRP are relevant when
comparing different PRP products and systems.
The volume of blood used in PRP preparation is
germane because acquisition of larger volumes
of blood from small dogs can be unappealing,
and hence preparation of an effective PRP with
a smaller blood volume is desirable. However,
having the ability to process a large volume of
blood is also appealing because the easiest way
to prepare PRP with a high concentration of
platelets is to begin with more platelets, which
is achieved by using a larger volume of blood.
In turn, consideration of both the minimum
and maximum volumes of blood that can be
processed is pertinent to PRP preparation.
Similarly, the final volume of PRP and total
number of platelets in the PRP should be quan‑
tified rather than just evaluating the final plate‑
let concentration. A PRP with a high platelet
concentration, but a small volume of PRP, may