The application of autologous platelet rich fibrin reduces allogeneic blood transfusions and improves wound healing in total hip arthroplasty

Total hip arthroplasty (THA) is often associated with a considerable amount of
per- and post-operative blood loss, requiring allogeneic blood product
transfusions (ABPTs) (1). The risks of ABPTs have been described extensively
and comprise the whole range of transfusion related as well as human error
related risks (2-5). However, ABPTs in patients undergoing a THA primarily
increase the risk for infections, fluid overload and increased duration of
hospitalization (6,7). Increased awareness of these complications has led to a
continuous search for blood conservation techniques in orthopaedic surgery (8).
Most conservation techniques primarily concentrate on managing blood loss
and/or trying to avoid the transfusion trigger, instead of focussing more on
less surgical bleeding, improved haemostasis and wound healing.
PRF® is manufactured from a small volume of the patients own blood. Treatment
with PRF® involves direct application of concentrated platelets using fibrin as
a carrier and a delivery media to ensure controlled and prolonged release of
platelet growth factors. The high concentration of fibrin binds and protects
several growth factors from proteolytic degradation and protects the sealant
from an early fibrinolysis (11). Platelet growth factors, especially PDGF,
TGF-β and VEGF, have favourable effects on the augmentation of the wound
healing cascade (12,13,14). The use of PRF® has shown an enhanced effect on
fibroblast proliferation in vitro as well as in vivo, where other commercial
fibrin sealants did not have that effect (15).
The treatment with PRF® also involves application of vital white blood cells
(16). Leukocytes also participate in wound healing through production of growth
factors, destruction of bacteria and foreign material and digestive removal of
damaged tissue in the wound, as a function of the myeloperoxidase mechanism of
the granular neutrophils. In the human body, neutrophils are believed to be the
first line of defence against invading micro- organisms. After phagocytosis of
microorganisms neutrophil granules fuse with the phagosome containing the
microorganisms. In azurophilic granules, myeloperoxidase (MPO) is present at a
high concentration.
We believe that the high concentration of vital neutrophils and monocytes
containing MPO are responsible for the supposed antibacterial effect of PRF®.
Research on a formulated enzyme system based on myeloperoxidase has shown a
rapid kill various bacteria, such as MRSA, and antibacterial effects were
better than with antibiotics. Moreover, in vivo testing on rats, showed that
this system was effective in eliminating bacteria in solution and at open
surgical sites (17,18,19) .
The anti-bacterial effect of the myeloperoxidase, released from the neutrophils
and monocytes in the PRF® might not only benefit early outcome but even result
in an
unexpected long term benefit. In this perspective antibiotic treatment has
already proven its value in THA with regard to the drastic reduction of the
revision rate for a-septic loosening and deep infection (20,21). However, it is
suggested that not only in the infected prosthesis but also in the majority of
a-septic loosening cases, bacteria are involved that can only be identified
with more sensitive techniques as PCR (polymerase chain reaction) detection.
Because of its microbicidal properties the application of PRF® might affect the
incidence of both deep infection as a-septic loosening related revisions.
In a recent in vitro study we investigated the microbicidal effect of platelet
gel showing the kill of MSSA within 12 to 18 hours after application, in
contrast with the control group.

The primary objective of this study is to investigate whether application of
PRF® will reduce postoperative wound leakage, the necessity for allogeneic
blood transfusions and the incidence of wound healing disturbances in patients
undergoing unilateral primary THA.
The primary endpoints of this study will be the use of allogeneic blood
products and the incidence of wound healing disturbances.
Secondary objectives of this study are to investigate whether PRF® will reduce
the loss of Red Blood Cell Mass (RBCM), improve primary healing of incision
sites, the incidence of wound infections (superficial or deep) and the use of
pain medication for pain sensations at surgical wound site.
Secondary endpoints will be:
• Difference in RBCM between pre-operative status and the 5th
post- operative day.
• The course of haemoglobin (Hb) value.
• The difference in fluid administration.
• The amount and duration of wound leakage.
• The incidence of wound infections.
• Use of pain medication for surgical site pain.

This investigation is a prospective, randomized study, comparing the use of
allogeneic blood products, the amount and duration of wound leakage and the
incidence of wound healing disturbances in patients with primary osteoarthritis
undergoing a THA. After enrolment, 50% of the patients will be treated with
PRF® (PRF-group) and 50% of the patients will receive conventional treatment
only (control-group).
All patients in the study will be divided into 4 subgroups; patients with
cemented and non-cemented prosthesis and with or without PRF-treatment,
although we don*t expect any differences in outcome with regard to our study
objectives between cemented and non-cemented THA.

Intra-operatively, after spinal anaesthesia has been administered, a volume of
120 ml of whole blood will be collected, through a peripheral line in the
median cubital vein, in a special reservoir called the Preparation Unit. The
Preparation Unit already contains a citrate volume for anti-coagulation. The
preparation unit will be placed in the Processor Unit and after 23 minutes an
autologous PRF-solution is ready to use. The concentration of platelets in
Vivostat® PRF® is approximately 10 times the platelet level of the donor*s
blood. The high amount of platelets is combined with a concentration of fibrin
of approximately 7-10 times over baseline. The syringe containing the Vivostat®
PRF® solution can than be loaded into the Applicator Unit. The PRF® is ready
for application using a spray pen. The residual volume in the Preparation Unit
has to be discarded and can not be infused back into the patient. The system
requires no added thrombin. The PRF® solution polymerises immediately upon
application by a simple pH-change at the tip of the spray
pen.

Theoretically blood is at risk for bacterial contamination at the moment of
drawing blood from the patient to fill the preparation unit. From the
preparation process until the application of the APRF the whole process is
fully automated. Therefore the risk for bacterial contamination is practically
eliminated compared to conventional preparation techniques.
We don't expect any adverse effects of the application of the PRF, because it's
an autologous product.