Autologous Blood Plasma Therapy (Chapter 1)

Whatever the reason might be, the heyday of autohemotherapy lasted no longer than until the middle of the 20th century. After that, its popularity began to decline, and it soon disappeared almost entirely. However, it was immediately replaced by a new treatment concept involving blood components, namely platelet-rich plasma (PRP). The findings from our literature review on this topic suggest that Kingsley first used the term "platelet-rich plasma" (PRP) in 1954 to refer to thrombocyte concentrate during experiments investigating blood coagulation. In the 1960s, this term was mentioned in several scientific publications dedicated to platelet transfusion and various methods of concentrating platelets. However, some authors believe that hematologists coined the term PRP in the 1970s to describe plasma with a platelet count above that of peripheral blood, which was initially used as a transfusion product to maintain hemostasis during surgery, as well as to treat patients with thrombocytopenia. According to others, the history of PRP began with the research of Matras, who studied fibrin glues used to improve skin wound healing in a rat model. A few years later, an upgraded concept for the use of blood extracts was proposed, called the "platelet-fibrinogen-thrombin mixture." In this concept, fibrin glues included a significant concentration of platelets in the final preparation. This procedure was carried out to naturally reinforce the fibrin gel and achieve a combined effect by merging the healing properties of platelets and fibrin. Presumably, these techniques can be regarded as the first platelet-rich plasma gels in the sense that we understand them today. From 1986 to 1990, this approach was confirmed under another name, such as "platelet-derived wound healing factors," and was successfully used to treat skin ulcers, following the principles developed with fibrin glues 15 years earlier by Matras. In 1997, Whitman et al. proposed an autologous alternative to fibrin glue, initially calling it PRP but later changing the name to "platelet gel."

Whichever of the authors mentioned above is correct, it cannot be denied that the 1998 article by Marx et al. became the starting point for the PRP craze and for the concept of platelet growth factors in regenerative medicine.

It should be noted that all products obtained using the above preparation techniques, regardless of their content or structure, were initially called PRP. For better recognition, commercial companies began assigning them individual names.

In 1999, a technique for preparing platelet-rich plasma entered the market under the trade name "plasma rich in growth factors" (PRGF). A year later, Choukroun et al. developed another form of platelet concentrates, which they termed "platelet-rich fibrin" (PRF). A characteristic feature of this preparation was the strong fibrin gel polymerization, and it was labeled as a "second-generation platelet concentrate," since its difference from other PRPs was clear. In 2014, the same author introduced an advanced form of PRF called A-PRF, which was claimed to contain more monocytes.

In 2006, Bielecki et al. proposed PRG (platelet-rich gel), which they defined as a fibrin matrix rich in platelets and leukocytes, more biologically activated than PRP. In the same year, Sacco introduced a new concept of CGF (concentrated growth factors). His technique made it possible to obtain much larger and denser fibrin-rich blocks. In 2008, Everts et al. drew particular attention to the leukocyte component of the platelet concentrate and described its non-activated and activated forms. The non-activated product was called "platelet-leukocyte-rich plasma (P-LRP)," while the activated gel was labeled "platelet-rich-leukocyte gel (PLG)."

Among the concepts introduced in subsequent years, Sohn's "sticky bone" (autologous fibrin glue mixed with bone graft) in 2010 and the technical note on the preparation of i-PRF (injectable platelet-rich fibrin) by Mourão et al. in 2015 deserve special mention.

Scientific breakthroughs and discoveries in this field were reflected in clinical practice: platelet-rich plasma gradually gained popularity among doctors of various specialties as a growing body of research demonstrated that PRP has significant anti-inflammatory, antibacterial, mitogenic, angiogenic, and chemotactic properties. It also stimulates cell proliferation and induces fibroblast activation. Since the mid-1990s, PRP has been used in dentistry and maxillofacial surgery, and later in sports and rehabilitation medicine, orthopedics, dermatology, dermato-cosmetology, trichology, ophthalmology, and other areas of medicine.

Theories on the mechanisms through which autologous plasma exerts its effects, as well as methods of PRP preparation, have evolved, been revised, and supplemented over time. Today, the only undisputed fact is that autologous plasma is an effective and safe treatment for many pathological conditions, producing marked regenerative and reparative effects on various body tissues. However, there is no consensus among researchers and clinicians regarding the definition of PRP, the role of its various components and their proportions, and the methods and techniques for obtaining autologous plasma.

What is platelet-rich plasma? The term refers to a volume of autologous plasma with a platelet concentration well above the baseline. However, authors disagree on the platelet concentration necessary to confer therapeutic properties to the plasma: some believe it should exceed the baseline concentration by 2 to 5 times, while others report that, for example, a 4 to 7-fold excess is necessary for the successful treatment of alopecia. Some studies describe an increase in platelet concentration by as much as 25 times. However, almost all researchers agree that the optimal platelet concentration remains undetermined, and this issue requires further investigation. Contrary to expectations, an increase in platelet concentration does not always lead to better treatment outcomes. In fact, some studies have shown that increasing the platelet concentration by more than 2.5 times can inhibit tissue repair processes.

This is likely why the platelet count of at least 1,000,000 platelets/μl in 5 mL of blood plasma, as proposed by Robert Marx as a working definition of PRP, became a kind of standard.