Pharmacological approaches to reducing allogeneic blood exposure

Abstract

This article discusses evidence for the role of pharmacological interventions such as the protease inhibitor aprotinin (Trasylol), lysine analogue anti-fibrinolytics [tranexamic acid (Cyclokapron) and epsilon aminocaproic acid (Amicar)], DDAVP (Desmopressin) and recombinant Factor VIIa (NovoSeven), in preventing the need for blood and blood-component therapies after major (cardiac, hepatic and orthopaedic/trauma) surgery. The data show that aprotinin is consistently effective in reducing globally the transfusion burden in cardiac and hepatic surgical procedures. However, there are little data to support its use in routine elective orthopaedic surgery. Multiple studies have failed to show an increased risk for myocardial ischaemia or infarction with aprotinin, and there may even be a reduced incidence of perioperative stroke in patients undergoing cardiac surgery. An increased probability of a hypersensitivity reaction when the drug is readministered within a 6-month period remains a significant issue. The data for the lysine analogue anti-fibrinolytics show no evidence of efficacy in reducing the transfusion burden for epsilon aminocaproic acid and inconsistent results with tranexamic acid in cardiac and hepatic surgery. As with aprotinin therapy, there is a paucity of data to support their use in routine elective orthopaedic surgery. There are no data to support the routine use of DDAVP to reduce the transfusion burden. Limited data suggest that this drug may be effective when a defect in platelet function is demonstrated. This aspect deserves further investigation. Recombinant activated Factor VII (rFVIIa) has proven benefit for its licensed indication to reduce bleeding in haemophiliacs with inhibitors to Factors VIII and IX. Reports of benefit in other instances are largely anecdotal. Hence, at this time it is therefore speculative and premature to suggest whether there is a place for this agent in routine clinical practice. No adequately powered, placebo-controlled prospective studies are available to investigate the safety of the lysine analogues, DDAVP or rFVIIa in cardiac, hepatic or orthopaedic surgery.

Postoperative Complications in Patients Undergoing Scoliosis: Review

“…Most cases with Cobb angle greater than 100 degrees develop chronic respiratory disease, pulmonary hypertension and right ventricular hypertrophy, and these situations contribute to increase in morbidity and mortality. [1][2][3][4][5][6][7] Risk for development of chronic respiratory disease and pulmonary hypertension is increased in patients with Cobb angle greater than 100 degrees. 1 Factors determining postoperative mechanical ventilation need after scoliosis surgery are; presence of neuromuscular disease, restrictive pulmonary dysfunction with vital capacity lower than 35%, congenital heart disease, right ventricular dysfunction, obesity, surgery with anterior thoracic approach and blood loss greater than 30 ml/kg during surgery.…”

What is the evidence for using hemostatic agents in surgery?

“…Adverseeffect concerns with the use of systemic hemostatic medications must be balanced with possible transfusion-related reactions and infectious diseases that are avoided by reductions in blood requirements. A very large RCT would be required to address comparative medication, and transfusion-related adverse events considering safety concerns have not been resolved by previous investigations [17]. Hopefully, the Canadian trial that is in progress will address some of the adverse effects as well as efficacy concerns [29].…”

Efficacy of FDA-approved hemostatic drugs to improve survival and reduce bleeding in rat models of uncontrolled hemorrhage

“…Indeed, drugs have been used in the treatment of bleeding complications for over 30 years [1]. For example, the drugs aprotinin, desmopressin (DDAVP), epsilon-amino caproic acid (EACA), and tranexamic acid (TXA) have been used to reduce bleeding complications and blood loss in a variety of clinical situations including cardiac surgery, hepatic surgery, orthopedic surgery, and in patients with bleeding disorders [1][2][3]. Three of these drugs (aprotinin, EACA and TXA) are FDAapproved for use in perioperative hemostasis, while the fourth (desmopressin) has an approved indication for use in bleeding in patients with hemophilia or von Willebrand's Disease.…”