Indian Journal of Anaesthesia  
About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions
Home | Login  | Users Online: 2279  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size    




 
EDITORIAL
Year : 2009  |  Volume : 53  |  Issue : 3  |  Page : 268-269 Table of Contents     

AntifibrinolyticAgents: Aprotinin, and Desmopressin


Editor, IJA, India

Date of Web Publication3-Mar-2010

Correspondence Address:
Pramila Bajaj

India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


PMID: 20640133

Rights and PermissionsRights and Permissions

How to cite this article:
Bajaj P. AntifibrinolyticAgents: Aprotinin, and Desmopressin. Indian J Anaesth 2009;53:268-9

How to cite this URL:
Bajaj P. AntifibrinolyticAgents: Aprotinin, and Desmopressin. Indian J Anaesth [serial online] 2009 [cited 2020 Mar 30];53:268-9. Available from: http://www.ijaweb.org/text.asp?2009/53/3/268/60289

Antifibrinolytic agents are synthetic lysine analogs that include ξ-aminocaproic acid (EACA, Amicar) and tranexanlic acid. These molecules inhibit fibrinolysis by attaching to the lysine binding site ol'the plasminogen molecule, displacing plasminogen from fibrin. Because librinolysis exhibits a major cause of bleeding, these agents have been reported to be effective in multiple surgical procedures [1] .

Desmopressin acetate (DDAVP) is a synthetic analog of vasopressin that increases plasma levels oifactor VIII and stimulates vascular endothelium to release the larger multinlers of von Willebrand factor(vWF) [2] . vWF mediates platelet adherence to vascular subendotheliurn by functioning as a protein bridge between glycoprotein Ib receptors on platelets and subendothelial vascular basement membrane proteins. DDAVP shortens the bleeding time of'patients with mild forms oihenlophiliaA or von Willebrand disease (vWD) [2],[3] . Which patients might benefit from use of DDAVP. Patients with mild to moderate forms of hemophilia or vWD undergoing surgery are likely to benefit from its use. In addition, patients with uremic platelet dysfunction and patients with chronic liver disease undergoing major surgery may benefit. Mongan and Hosking reported thatpatients with a thromboelastogram (TEG) taken afterprotamine administration and with maximal amplitude<50mm benefit from the effects of DDAVP [4] . DDAVP administered IV at a dose of 0.3 mg/kg achieves maximal increases in levels of factor VIII and vWF in 30-60 min with no further increases achieved by higher doses. It should be diluted and given over 15-30 min to avoid hypotension. Side effects include hyponatremia with repeated dosing. Unfortunately, most studies do not demonstrate consistent efficacy of DDAVP [5] .

Aprotinin is a broad-spectrum serine protease inhibitor that inhibits factor XII, kallikrein, plasmin, and PAR 1 receptors [6] . In cardiac surgery when used prophylactically, Multiple randomized placebo-controlled trials on aprotinin safety and efficacy have demonstrated that aprotinin therapy reduces bleeding (i.e., mediastinal and chest tube drainage) and decrease [3] the need for allogeneic transfusion, and the proportion olpatients needing transfusion of allogeneic blood [7],[8] .

Sedrakyan reported data from 35 CABG trials (n=3879) confirming that aprotinin reduces transfusion requirements (relative risk 0.61) relative to placebo, with a 39% risk reduction, and was not associated with increased or decreased mortality (relative risk 0.96), myocardial infarction (relative risk 0.85), or renal failure (relative risk 1.01) risk, but it was associated with a reduced risk of stroke (relative risk 0.53). Aprotinin's mecha­nism ofaction is complex and may also involve reduction ofthe inflammatory response [9] . Multiple mechanisms are responsible for aprotinin's ability to reduce bleeding after CPB and in other surgical procedures.

Aprotinin has also been studied in clinical trials in vascular, liver transplantation [10] , and orthopedic surgery [1] . Aprotinin decreased intra- and postoperative bleeding and blood transfusion in these settings. In orthopedic Sur­gety, aprotinin moderately decreases blood loss and transfusion requirements during total hip replacement. One or two packed red cell units per patient may be saved when aprotinin is used. In a double-blind study in high-risk septic and cancer patients undergoing pelvic and hip surgery, aprotinin proved to be effective in significantly reduc­ing the need for blood transfusion as compared with a placebo group. Samama et al evaluated two doses of aprotinin with placebo after major orthopedic surgery and reported blood loss decreased in the Large-Dose Aprotinin group (calculated bleeding, whole blood, hematocrit 30%, median [range], 2023 ml, (633-4113) as compared with placebo, 3577 mL [1670-21,758 rnL]. The total number ofhomologous and autologous units was also significantly decreased in the Large-Dose Aprotinin group (2 U [0-5 U] as compared with placebo, 4 U [0-­42U]) [11]



 
   References Top

1.Zuferey P. Merquiol F, Laporte S, et al. Do antifibrinolytics reduce alloeeneic blood transfusion in orthopedic surgery. Anesthesiology 2006:105:1034-46.  Back to cited text no. 1      
2.Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med 2004:351:683-94.  Back to cited text no. 2      
3.Mannucci PM. Hemostatic drugs. N Engl J Med 1998;339:245-53.  Back to cited text no. 3      
4.Mongan PD, Hosking MR The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification. Anesthesiology 1992;77:38-46.  Back to cited text no. 4      
5.de Prost D. Barbier-Boehm G, Hazebroucq J, et al. Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass. Thromb Haemost 1992;68:106-10.  Back to cited text no. 5      
6.Landis RC, Asimakopoulos G. Poullis M, et al. The antithrombotic and ant i inflammatory mechanisms of action of aprotinin. Ann Thorac Surg 2001;72:2169-75.  Back to cited text no. 6      
7.Royston D. Levy JH, Fitch J, et al. Full-dose aprotinin use in coronary artery bypass graft surgery: an analysis of perioperative pharmacotherapy and patient outcomes. Anesth Analg 2006;103:1082-8.  Back to cited text no. 7      
8.Sedrakyan A, Wu A, Sedrakyan G, et al. Aprotinin use in thoracic aortic surgery: safety and outcomes. J Thorac Cardiovasc Surg 2006;132:909-17.  Back to cited text no. 8      
9.Mojcik CF. Levy JH. Aprotinin and the systemic inflammatory response after cardiopulmonary bypass. Ann Thorac Surg 2001; 71:745-54.  Back to cited text no. 9      
10.Porte RJ, Molenaar IQ, Begliomini B, et al. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group. Lancet 2000;355:1303-9.  Back to cited text no. 10      
11.Samama CM, Langeron 0, Rosencher N, et al. Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded. dose-ranging study. Anesth Analg 2002;95:287-93.  Back to cited text no. 11      




 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    References

 Article Access Statistics
    Viewed989    
    Printed65    
    Emailed0    
    PDF Downloaded342    
    Comments [Add]    

Recommend this journal