This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lower gastrointestinal hemorrhage is a common reason for hospital admission. Their morbidity is high, as is their economic impact. Certain genetic mutations in clotting factors and platelet aggregation have been identified that may increase the risk of bleeding: they have been observed in the setting of intracranial hemorrhage, subconjunctival hemorrhave, or intrathoracic hemorrhage following coronary artery bypass grafting, but they have not been investigated in gastrointestinal hemorrhage. In addition, other genetic mutations in clotting factors may be protective against hemorrhage. Factor XIII levels decrease both preoperatively and postoperatively in patients with hemorrhage after intracranial surgery. An increased prevalence of factor XIII Val34Leu polymrphism has been shown in patients with both subconjunctival and primary intracerebral hemorrhae, and is associated with decreased levels of factor XIII. Decreased platelet activating factor (PAF) acetylhydrolase activity has been shown in patients with intracranial hemorrhage. The Val279Phe mutation in the PAF acetylhydrolase gene, both heteroxygous and homozygous, is associated with decreased PAF acetylhydrolase activity and susceptibility to intracranial hemorrhage. Factor VII-323 deletion/insertion allele has also been associated with an increased risk of intracranial hemorrhage. Factor V Leiden has been demonstrated to protect against excessive intrathoracic blood loss and transfusion following cardiac surgery, and to be present in decreased frequency in patients with intracranial hemorrhage. A recent study suggests this is related to inhibition of in vivo fibrinolysis. This is a case-control study examinig the influence if these mutation on gastrointestinal hemorrhage. Retrospective cases and controls will be required to give a single venous blood specimen for genetic analysis. The use of the GCRC facilities would be limited to one visit for a single phlebotomy per patient for all retrospective patients. Enrollment is expected to be between 450 and 600 total patients. We expect an increased frequency of factor XIII Val34Leu, factor VII -323 del/ins, asnd PAF acetylhydrolase Val279Phe in patients with gastrointestinal bleeding, while Factor V Leiden is expected to be decreased in frequency in these patients. Through these results, we would hope to identify patietns at increased risk or gastrointestinal hemorrhage, especially when faced with the need for anticoagulation.
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