Aprotinin is an antifibrinolytic and as such has an inhibitory effect on the cleavage of the protein fibrin (i.e., on fibrinolysis). Because of this property, it is found in tissue adhesives. Indications include operations to create a coronary artery bypass and the very rare alpha2-antiplasmin deficiency, which is genetically determined. Because of potential risks of aprotinin, the drug is approved in Germany only under certain conditions.
What is aprotinin?
Aprotinin is a drug substance from the group of antifibrinolytics. The name of this group of substances comes from the enzyme fibrinolysin, which is better known today as plasmin. In medicine, fibrinolysis also refers to the process of fibrin cleavage by the enzyme plasmin, which is a serine protease. Temporary inhibition of plasmin is possible with aprotinin, among other drugs, because the active ingredient binds reversibly to the enzyme and deactivates it. However, plasmin remains intact and can later become active again. Aprotinin occurs naturally in the lungs of cattle. Pharmacological production of the active ingredient is based on fermentation of that tissue. Subsequently, filtration frees the substance from superfluous components. A special gel serves as an aid in purifying the fermented bovine lung tissue.
Pharmacological action
Aprotinin is found in tissue adhesives. It is also known to medicine as fibrin glue and is used in surgery to seal tissue layers or wound edges. Two components are required, with aprotinin belonging to component 1. Other active ingredients in this component are fibrinogen and factor XIII, whose production is based on the fractionation of human blood plasma. This raw material is also the source of thrombin, which belongs to component 2 of the tissue adhesive and is initially present there in the form of the precursor prothrombin. Component 2 also includes calcium chloride or calcium chloride dihydrate, which provides the required calcium ions. During surgical use, the various active ingredients interact with each other: prothrombin converts to thrombin and thus becomes enzymatically active. It then cleaves the clotting factor fibrinogen into fibrin and activates factor XIII, which in turn weaves the individual fibrinomers into a network that the human body can break down itself. The advantage of this is that the fibrin glue can also bind tissue that would be difficult to reach after stitches have been removed. The function of aprotinin in this context is to inhibit the body’s own enzyme plasmin and slow down its function. Plasmin cleaves fibrin and thus could prematurely release the adhered tissue.
Medical application and use
The use of aprotinin is possible, for example, during surgery to create a coronary artery bypass. Such a bypass is an artificial bypass of the blood vessel. The goal is to allow blood to flow despite a narrowing of the affected coronary artery. The bypass can bypass both an artery and a vein. Medicine also refers to this clinical picture as coronary stenosis, which often occurs in the context of coronary heart disease. However, a bypass is not necessary or possible in every case. Surgical treatment of the stenosis can also include a stent, for example, in which a tube acts as an endoprosthesis in the blood vessel to ensure flow. In the past, physicians also used aprotinin to stop bleeding when increased fibrinolysis (hyperfibrinolysis) underlay this bleeding. Today, however, this approach is no longer common because aprotinin is associated with risks that make its use appropriate only under very specific conditions. However, aprotinin is still indicated in alpha2-antiplasmin deficiency. This is a deficit of the serine protease inhibitor. The inhibitor binds to plasmin, thereby deactivating it. Deficiency may therefore result in primary hyperfibrinolysis. Alpha2-antiplasmin is produced in the correct amount in the liver in healthy individuals. The body can synthesize it itself. Alpha2-antiplasmin deficiency is extremely rare, with only a few cases described, and is based primarily on a corresponding genetic predisposition that is inherited in an autosomal recessive manner.For all indications considered for the use of aprotinin, it is necessary to weigh individual factors that influence the cost-benefit ratio in each case.
Risks and Side Effects
Aprotinin temporarily lost its approval in Germany between 2007 and 2013 because a 2006 study indicated a possible increase in the risk of renal failure. The renewed approval was accompanied by stricter conditions. Hypersensitivity related to bovine proteins is a contraindication to aprotinin use, as the active ingredient is a polypeptide from the bovine organism and originates from the animal’s lungs. Side effects of aprotinin include anaphylactic reactions and various allergic reactions. The latter manifest themselves mainly as itching and pathological skin changes (efflorescences). Bradycardia may occur, in which the heart rate slows and falls below the rough limit of 60 beats per minute, which is the reference for adults. Aprotinin can also trigger bronchospasm. This is manifested by cramping of the bronchial muscles, which may result in an increase in airway resistance. Chills and hypertension (high blood pressure) are also among the undesirable side effects of aprotinin. Furthermore, bruises (hematomas) and edema may form. The latter are characterized by an increased accumulation of fluid in the tissues.
