Impact of genetic variation on perioperative bleeding

Abstract

Variation in bleeding in the perioperative period is a complex and multifactorial event associated with immediate and delayed consequences for the patient and health care resources. Little is known about the complex genetic influences on perioperative bleeding. With the discovery of multiple variations in the human genome and ever-growing databases of well-phenotyped surgical patients, better identification of patients at risk of bleeding is becoming a reality. In this review, polymorphisms in the platelet receptor genes, plasminogen activator inhibitor, and angiotensin genes among others will be discussed. We will explore the nature, effects, and implications of the genetics that influence perioperative bleeding above and beyond surgical bleeding, particularly in cardiac surgery.

Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report

“…The clinical phenotype of most bleeding disorders is rarely the result of a monogenic defect, but it is often influenced by the interaction between different genes/polymorphisms and/or between genetic and acquired factors. This complex genetic interplay may aggravate or alleviate the severity of the bleeding phenotype in general population 22 . Interesting examples in bleeding disorders may be found in variations in genes that affect VWF levels including CLEC4 M or STXBP5 23,24 or in the presence of prothrombotic mutations, such as factor V Leiden that may attenuate the phenotype of bleeding disorders such as in hemophilia 25 .…”

“…This complex genetic interplay may aggravate or alleviate the severity of the bleeding phenotype in general population. 22 Interesting examples in bleeding disorders may be found in variations in genes that affect VWF levels including CLEC4 M or STXBP5 23,24 or in the presence of prothrombotic mutations, such as factor V Leiden that may attenuate the phenotype of bleeding disorders such as in hemophilia. 25 Furthermore, the impact of a single mutation may be even less predictable, as in the case of multi-subunit molecules such as fibrinogen or multimeric proteins such as von Willebrand factor (VWF).…”

Molecular classification of blood and bleeding disorder genes

“…In some highly inbred populations, consanguineous marriages may increase the burden of mutations in genes associated with AR diseases 23 . Bleeding may be considered as a risk factor for patients undergoing major surgeries, dialysis, and specific treatments where a hidden underlying genetic susceptibility should be investigated and considered 24,25 . Putting all this information in the context of improvement of healthcare plans, minimizing unexpected events that might contribute to mortality or additional burden of health complications highlights the importance of identification and assessment of variants in genes related to bleeding and coagulation.…”

Polymorphism in the protease‐activated receptor‐4 gene region associates with platelet activation and perioperative myocardial injury

“…Functional variation in the human platelet genome affects cell adhesion, cell activation, and cell‐to‐cell contact interactions and has been implicated in cardiovascular disease, arterial thrombosis, and myocardial infarction [ 11–17]. Furthermore, platelet reactivity is a significant predictor of cardiac outcomes after myocardial infarction [18, 19].…”