Abstract

Abstract 3140

Poster Board III-77

Introduction

Hypotensive transfusion reactions (HTRs) have been associated with the transfusion of different blood products. They are characterized by the rapid onset and disappearance of hypotension upon starting and finishing the transfusion respectively. The use of ACE inhibitors has been associated with HTRs. However, there are reported HTRs in patients not taking ACE inhibitors. An inability to break down bradykinin (BK) generated during the infusion/transfusion is suggested to be responsible for the hypotensive effect. Angiotensin-converting enzyme (ACE) and aminopeptidase P (APP) are primarily responsible for degradation of BK. We hypothesize that the C-2399A single-nucleotide polymorphism in the membrane-bound APP gene XPNPEP2 (SNP rs3747343) may be linked to HTRs. This polymorphism is present upstream of the coding sequence of the APP gene and has already been associated with severe hypotension in an angioedema patient treated with an ACE inhibitor. This suggests that it may have an important regulatory role.

Patients and Methods

With the approval of our IRB, patients' samples were collected, de-identified, and then used for testing. Specimens from 4 patients who presented with classic HTRs while not taking ACE inhibitors were analyzed through sequencing of DNA acquired from pre-transfusion blood samples. The same primers were used for PCR and sequencing (5'-GAGTATTATGTGGGGACCATCC-3' and 5'-ATGCCTCGCAGAGACAAGAG-3'). Samples were sequenced in both sense and antisense directions.

Results

Among these patients, two (50%) were found to possess the C-2399A mutation. One was found to have changes in both reference and complementary strands while the other had a C/A mutation only in one strand.

Conclusions

These results indicate that the C-2399A polymorphism may be a contributing factor in the development of HTRs and that it may promote HTRs in the absence of ACE inhibitors. The hypotensive effect may be due to a structural or regulatory change caused by C-2399A though it also seems that other factors may be involved since not all patients assayed possessed the mutation. Further screening of additional contributing factors responsible for HTRs is necessary to fully comprehend the pathogenesis of this type of transfusion reaction.

Keywords: XPNPEP2, C-2399A, ACE Inhibitors, Hypotensive Transfusion Reactions, aminopeptidase P.

Figure 1: Table of Results

Patient1 Age/Sex Transfusion Product1 ACE Inhibitors Sequencing Result2 Clinical Setting 
70/M SDP No A,T Post CABG4 
79/F RBC No C,T Post CABG 
70/F RBC No C,G Post CABG 
17/F FFP No C,G Endoscopic procedure 
Patient1 Age/Sex Transfusion Product1 ACE Inhibitors Sequencing Result2 Clinical Setting 
70/M SDP No A,T Post CABG4 
79/F RBC No C,T Post CABG 
70/F RBC No C,G Post CABG 
17/F FFP No C,G Endoscopic procedure 

1Randomly Assigned ID; 2 SDP = Single donor platelets; RBC = Red Blood Cells; FFP = Fresh Frozen Plasma; 3Normal result is C,G;

4CABG = Coronary Artery Bypass Graft Surgery

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.