What is aprotinin injection?
Aprotinin, also known as bovine pancreatic trypsin inhibitor is a protein which affects the way in which blood clots.
It is administered by injection to reduce bleeding during complex surgery as patients who are undergoing open heart surgery and as in liver surgery.
Aprotinin main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use is to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. This reduces the amount of blood transfusion required. Generic aprotinin injections are not yet available.

Chemistry
Aprotinin is a monomeric (single-chain) globular polypeptide derived from bovine lung tissue; it has a molecular weight of 6512 and consists of 16 different amino acids arranged in a chain of 58 amino acid residues.

The stability of the molecule is due to the 3 disulfide bonds linking the 6 cysteine members of the chain (Cys5-Cys55, Cys14-Cys38 and Cys30-Cys51).The lysine (15)-alanine (16) sequence on this strongly basic polypeptide represents the active centre.

Aprotinin is the axiomic member of the protein family of Kunitz-type serine protease inhibitors.

It is one of the most thoroughly studied proteins in terms of structure and folding pathway. BPTI was one of the first proteins to have its structure solved by NMR spectroscopy. Nevertheless, its physiological function remains unknown.

Mechanism of action
Aprotinin inhibits several serine proteases, specifically trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/ml, and kallikrein at 300,000 IU/ml. Its action on kallikrein leads to the inhibition of the formation of factor XIIa. As a result, both the intrinsic pathway of coagulation and fibrinolysis are inhibited. Its action on plasmin independently slows fibrinolysis.

Efficacy
In cardiac surgery with a high risk of significant blood loss, aprotinin significantly reduced bleeding, mortality and hospital stay. Beneficial effects were also reported in high-risk orthopedic surgery. In liver transplantation, initial reports of benefit were overshadowed by concerns about toxicity.

In a meta-analysis performed in 2004, transfusion requirements decreased by 39% in coronary artery bypass graft (CABG) surgery. In orthopedic surgery, a decrease of blood transfusions was likewise confirmed.

What should the patient tells his health care provider before he take this medicine?
They need to know if you have any of these conditions:
► Kidney disease
► Previous treatment with aprotinin; it is very important that your prescriber or health care professional knows this as repeat use increases the possibility of having an allergic reaction
► An unusual or allergic reaction to aprotinin, other medicines, foods, dyes, or preservatives
► Pregnant or trying to get pregnant

How this medicine is used?
Aprotinin is for slow infusion into a vein. It is given by a health-care professional in a hospital or clinic setting.
Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What drug(s) may interact with aprotinin?
► Agents that dissolve blood clots
► Captopril
► Heparin

Safety
There have been concerns about the safety of aprotinin.
► Anaphylaxis (a severe allergic reaction) occurs at a rate of 1:200 in first-time use, but serology (measuring antibodies against aprotinin in the blood) is not carried out in practice to predict anaphylaxis risk because the correct interpretation of these tests is difficult.
► Thrombosis, presumably from overactive inhibition of the fibrinolytic system, may occur at a higher rate, but until 2006 there was limited evidence for this association.
► While biochemical measures of renal function were known to occasionally deteriorate, there was no evidence that this greatly influenced outcomes. A study performed in cardiac surgery patients reported in 2006 showed that there was indeed a risk of acute renal failure, myocardial infarction and heart failure, as well as stroke and encephalopathy The study authors recommend older antifibrinolytics (such as tranexamic acid) in which these risks were not documented. The same group updated their data in 2007 and demonstrated similar findings.
► No cases of bovine spongiform encephalopathy transmission by aprotinin have been reported, although the drug was withdrawn in Italy due to fears of this.

► In vitro use
Small amounts of aprotinin can be added to tubes of drawn blood to enable laboratory measurement of certain rapidly degraded proteins such as glucagon.

What side effects might I notice from receiving aprotinin?
Most side effects are those that are likely to occur as a result of open-heart surgery regardless of treatment with aprotinin.
Side effects that you should report to your prescriber or health care professional as soon as possible:
► Decrease or increase in the amount of urine or difficulty passing urine
► Difficulty breathing or shortness of breath
► Fast heart beat
► Nausea, vomiting
► Skin rash, irritation or inflammation
► Sudden or severe pain in the chest, legs, head, or groin
► Swelling of the face, lips, tongue or neck

What should I watch for while taking aprotinin?
Your condition will be closely monitored while you receive aprotinin.

History
Initially named "kallikrein inactivator", aprotinin was first isolated from cow parotid glands in 1928 and independently as "bovine pancreatic trypsin inhibitor" from cow pancreas in 1936. It was purified from bovine lung in 1964. As it inhibits pancreatic enzymes, it was initially used in the treatment for acute pancreatitis, in which destruction of the gland by its own enzymes is thought to be part of the pathogenesis.Its use in major surgery commenced in the 1960s.

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