Plasma-derived medicinal products (PDMPs) are manufactured from human plasma by pharmaceutical companies. Plasma is the liquid part of blood collected from voluntary donors through plasmapheresis or by separating it from the other blood components by the use of physical means like a centrifuge. PDMPs play a key, sometimes unique, role in the treatment of many acute and chronic clinical conditions.
Due to the biological origin of PDMPs, their quality and safety reles on strict controls on plasma as well as on the industrial processing (fractionation), including methods of viral elimination and inactivation.
In Italy, the plasma collected and industrially processed comes exclusively from voluntary, anonymous and unpaid donations, mostly from regular donors.
Plasma-derived medicinal products from national plasma and their clinical indications:
Human albumin is a plasma protein produced by the liver, which accounts for about 60% of all plasma proteins. Its concentration in blood ranges between 3.5 and 5 g/decilitres. In most cases, lower albumin levels are due to a reduced production of albumin by the liver. Human albumin is appropriate in the treatment of many hepatic diseases as well as in paracentesis on account of ascites, in spontaneous bacterial peritonitis, in hepatorenal syndrome, in therapeutic plasma exchange and occasionally in other clinical conditions with reduced blood volume.
Immunoglobulins (IGs, Igs) are used in the replacement therapy of immunodeficiencies and in the treatment of autoimmune diseases or systemic inflammatory processes. They are the so-called driver products due to the constant increase in their demand worldwide. Since 2007 soluble IG preparations for subcutaneous/intramuscular (SC/IM) administration have been available in Italy in addition to those for intravenous use (IntraVenous, IV).
IGs, like all other PDMPs, are processed from pools of human plasma; this results in significant idiotypical diversity that grants higher antibody protection to the recipient. The preparations contain structurally and functionally intact IG, with normal half-life and proportions of subclasses: 95% of monomeric IgG, small quantities of dimers, and variable quantities of IgA and IgM.
Antithrombin is a glycoprotein synthesised by the liver present in plasma at a concentration of approximately 150 μg/mL. It is a protease inhibitor belonging to the serpin family or serine protease inhibitors. It is the most powerful natural inhibitor of coagulation and plays a fundamental role in maintaining the balance in the coagulation system.
Antithrombin inactivates all activated coagulation factors except factors V and VIII; indeed, due to its particular affinity for thrombin is also called the heparin “cofactor”. Antithrombin can be used in the treatment of congenital deficiencies of this glycoprotein.
Coagulation Factor VIII concentrates (FVIII) are used in the replacement therapy of haemophilia A, a rare, haemorrhagic, hereditary, recessive and gender-related disease, caused by a deficit of FVIII. Depending on the activity level of FVIII, haemophilia A is classified as severe (FVIII < 1%), moderate (between 1 and 5%) and mild (between 30 and 40%).
Coagulation Factor IX concentrates (FIX) are used in the replacement therapy of haemophilia B, also called “Christmas disease”. It is a rare, haemorrhagic, hereditary, recessive and genderrelated disease, with an estimated prevalence of 2-3/100,000 male subjects, caused by a deficit of FIX. Depending on the level of the FIX activity, haemophilia B is classified as severe (FIX< 1%), moderately severe (between 1 and 5%) and mild (under 5%).
Coagulation factor VII (FVII) is a vitamin K-dependent glycoprotein that triggers the coagulation cascade in blood. The congenital defect linked to the FVII factor is a rare haemorrhagic disorder due to a genetic abnormality of the chromosome. It is an autosomal recessive disease. Replacement therapy is essential for patients with a severe phenotype.
Coagulation factor XIII (FXIII), also known as fibrin-stabilising factor, is used in the replacement therapy of the congenital deficiency of the same protein, an autosomal recessive disease whose prevalence is estimated in about 1/2,000,000. Severe (FXII <1%), moderate (between 1 and 4%) and mild forms (FXIII >5%) are distinguished according to the activity level of FXIII.
Prothrombin Complex Concentrates (CCP) are used to correct acute or temporary deficiency of factors belonging to the prothrombin-related complex. CCP with three or four factors can be produced through appropriate chromatographic techniques. CCP3s contain the factors II (FII), FIX and X (FX), CCP4s contain FII, FVII, FIX, FX with a procoagulant effect, as well as natural and physiological coagulation inhibitors such as protein C, protein S and traces of AT, heparin and vitronectin.
Fibrinogen is one of the most abundant coagulation factors in plasma, which is coverted into fibrin by Thrombin, and is the main component of the coagulation phase. Therefore, fibrin is to be regarded both as a structural protein and a coagulation factor. A fibrinogen deficiency means a lower blood clotting ability leading to an increased tendency to bleed. Fibrinogen is primarily used in the treatment and prophylaxis of haemorrhage caused partially or totally by a severe fibrinogen deficiency.
Legislation
Blood and plasma are invaluable and limited resources with a high ethical significance stemming from the voluntary, responsible and unpaid nature of donations.
In Europe, the plasma and plasma-derived medicinal products system is strictly regulated by a comprehensive European legislation as well as national laws on transfusion activities. Moreover, there are extensive regulations referring to the Community code on medicinal products for human use.