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Blood plasma is the acellular liquid matrix of whole blood, constituting approximately 55% of total blood volume. It is an aqueous solution of water (~92% by volume), proteins, electrolytes, dissolved gases, nutrients, hormones, and signalling molecules that serves simultaneously as the transport medium of the circulatory system and as the biochemically active environment in which blood cells – erythrocytes, leukocytes, and platelets – are suspended.

Composition

Plasma proteins constitute the most clinically relevant fraction of plasma for regenerative treatment purposes, and fall into three primary categories:

Albumin – the most abundant plasma protein (~60% of total plasma protein), primarily responsible for maintaining oncotic pressure and acting as a carrier molecule for hormones, fatty acids, and drugs. In the context of PRP and iPRF preparation, albumin remains present in the plasma fraction but is not a primary therapeutic component.

Globulins – include immunoglobulins (antibodies), transport proteins such as transferrin and ceruloplasmin, and complement proteins. Alpha and beta globulins carry lipids, hormones, and metal ions; gamma globulins constitute the humoral immune response.

Fibrinogen – the soluble precursor to fibrin, present in plasma at approximately 2–4 g/L. On activation by thrombin – released from platelets during the coagulation cascade – fibrinogen polymerises into fibrin, forming the structural scaffold of a clot and the three-dimensional fibrin matrix of iPRF. Fibrinogen remains present in the plasma fraction of all blood-derived preparations, but its activation state differs by protocol. In PRP and iPRF, the plasma fraction remains liquid and injectable – fibrinogen is retained in its soluble form and does not polymerise during preparation. In PRF preparations – where no anticoagulant is used – fibrinogen converts to fibrin during centrifugation, producing the gel or membrane structure that releases growth factors over a sustained period. Fibrinogen concentration is a meaningful variable in PRF quality specifically, as it directly determines the structural integrity of the resulting fibrin matrix.

Beyond proteins, plasma carries electrolytes (sodium, potassium, calcium, bicarbonate) that maintain pH and osmotic balance; glucose and other nutrients; dissolved oxygen and carbon dioxide; and a broad range of growth factors, cytokines, and hormones at baseline physiological concentrations – distinct from and lower than the concentrated growth factor content of platelet-derived secretions released upon activation.

Plasma in Blood Separation

When whole blood is centrifuged, the components separate by density. Erythrocytes (densest) pellet at the base; the buffy coat – platelets and leukocytes – forms a thin intermediate layer; and plasma occupies the upper fraction. The specific plasma volume and platelet concentration collected depends on centrifugation speed and duration:

• PRP preparation concentrates platelets within a plasma fraction, typically achieving 3–8× baseline platelet concentration depending on protocol. The plasma component carries the growth factors released upon platelet activation alongside the fibrinogen and other proteins of the plasma fraction itself.
• iPRF preparation uses lower centrifugation speeds that preserve the leukocyte fraction alongside platelets within the plasma – the leukocyte content contributes additional growth factors and immunomodulatory signals, and the unactivated fibrinogen in the plasma fraction forms the fibrin matrix when calcium chloride is added post-centrifugation.

In both cases, the plasma is not merely a carrier for platelet-derived growth factors – it is itself a biochemically active medium containing baseline concentrations of IGF-1, TGF-β1, VEGF, and PDGF that contribute to the treatment effect at concentrations below but additive to the platelet-derived burst.