Fatal Anaphylactic Shock After Aprotinin Reexposure in Cardiac Surgery

Diefenbach, C.; Abel, Manfred; Limpers, Barbara; Lynch, John; Ruskowski, H.; Jugert, Frank K.; Buzello, W.

doi:10.1213/00000539-199504000-00031

Cited by 5 publications

(6 citation statements)

References 13 publications

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“…Aprotinin is widely used as a therapeutic drug and there are reports of side‐effects such as vein graft occlusion, arterial thrombosis and fatal anaphylactic shock during cardiac surgery (Cosgrove et al , 1992; Westaby, 1993; Samama et al , 1994; Diefenbach et al , 1995; Van der Meer et al , 1996; Alderman et al , 1998). Aprotinin has widespread effects on the components of haemostasis, binding to other proteases such as kallikrein, and it may prevent blood loss by a more complex series of events (Willmott et al , 1995).…”

Section: Discussionmentioning

confidence: 99%

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A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

et al. 2002

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Summary. Two peptides, textilinins 1 and 2, isolated from the venom of the Australian common brown snake, Pseudonaja textilis textilis, are effective in preventing blood loss. To further investigate the potential of textilinins as antihaemorrhagic agents, we cloned cDNAs encoding these proteins. The isolated full-length cDNA (430 bp in size) was shown to code for a 59 amino acid protein, corresponding in size to the native peptide, plus an additional 24 amino acid propeptide. Six such cDNAs were identified, differing in nucleotide sequence in the coding region but with an identical propeptide. All six sequences predicted peptides containing six conserved cysteines common to Kunitz-type serine protease inhibitors. When expressed as glutathione S-transferase (GST) fusion proteins and released by cleavage with thrombin, only those peptides corresponding to textilinin 1 and 2 were active in inhibiting plasmin with K i values similar to those of their native counterparts and in binding to plasmin less tightly than aprotinin by two orders of magnitude. Similarly, in the mouse tail vein blood loss model only recombinant textilinin 1 and 2 were effective in reducing blood loss. These recombinant textilinins have potential as therapeutic agents for reducing blood loss in humans, obviating the need for reliance on aprotinin, a bovine product with possible risk of transmissible disease, and compromising the fibrinolytic system in a less irreversible manner.

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Section: Discussionmentioning

confidence: 99%

“…As repeated use of aprotinin is contraindicated in humans for immunogeneic reasons (Wüthrich et al , 1992; Diefenbach et al , 1995), active Txln may be of value as an alternative in reducing blood loss. To prove the efficacy and safety of recombinant Txln, a large‐animal model would need to be established, requiring milligram quantities of Txln.…”

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confidence: 99%

A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

et al. 2002

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“…In the literature, the reported risk of anaphylaxis ranges between 0.3% and 9.1%. 93,94 There are many case reports describing fatal reactions with aprotinin therapy. 93 The risk of a reaction is approximately 4.5% in patients previously exposed to aprotinin, making a strong case to reserve its first use for patients who return for a second or third cardiac operation with CPB.…”

Section: Renal Effects Aprotinin Is Freely Filtered By the Kidneymentioning

confidence: 99%

“…93,94 There are many case reports describing fatal reactions with aprotinin therapy. 93 The risk of a reaction is approximately 4.5% in patients previously exposed to aprotinin, making a strong case to reserve its first use for patients who return for a second or third cardiac operation with CPB. In determining who should receive aprotinin, one must weigh the complications of blood product transfusions against the risk of anaphylaxis.…”

Section: Renal Effects Aprotinin Is Freely Filtered By the Kidneymentioning

confidence: 99%

Pharmacotherapeutic Considerations in Anesthesia

Amar

2003

Heart Disease

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This article focuses on new findings leading to improved understanding of the pathophysiology and mechanisms of potential drug interactions between anesthetic drugs or techniques and cardiovascular medications in patients scheduled for surgery. Only the most frequently used drugs are reviewed. Elective surgery provides the luxury to consider these risks and alter therapy accordingly. Under urgent circumstances, however, the increased risks associated with these agents should be anticipated with the goal to minimize adverse effects while maintaining optimal cardiovascular function in the perioperative period.

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“…Prospective randomized trials failed to detect significant adverse effects of aprotinin on postoperative renal function in patients undergoing cardiac surgery [43,50]; however, further investigations are needed to clarify the role of antifibrinolytic therapy in the setting of deep hypothermic circulatory arrest. Diefenbach et al [53] recently reported a fatal episode of anaphylactic shock following reexposure to aprotinin. As a naturally occurring protein, aprotinin induces an immunologic response following administration.…”

Section: Complications Associated With Antifibrinolytic Therapymentioning

confidence: 99%

Antifibrinolytic drugs and perioperative hemostasis

Slaughter¹,

Greenberg²

1997

Am. J. Hematol.

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Although excessive bleeding is widely recognized as a common complication of cardiac surgery, the recent success of antifibrinolytic drugs as prophylactic hemostatic agents has received little attention outside the surgical literature. The etiology of the coagulopathy following cardiac surgery is clearly multifactorial; however, the success of antifibrinolytic drugs as hemostatic agents suggests that fibrinolysis contributes to bleeding in this setting. Increasingly widespread administration of these drugs necessitates increased awareness of the risks and benefits posed by perioperative antifibrinolytic therapy. The objectives of this review are to understand the mechanisms of action of antifibrinolytic drugs in the context of the normal hemostatic response and to review evidence pertaining to the efficacy and safety of antifibrinolytic drugs as hemostatic agents during cardiac surgery. Am.

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Fatal Anaphylactic Shock After Aprotinin Reexposure in Cardiac Surgery

Cited by 5 publications

References 13 publications

A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

Pharmacotherapeutic Considerations in Anesthesia

Antifibrinolytic drugs and perioperative hemostasis

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