A novel association between high red blood cell
alloimmunization rates and hereditary hemorrhagic
Jeanne E. Hendrickson,
Christopher A. Tormey
telangiectasia (HHT) is an autosomal dominant disorder
associated with multiple arteriovenous malformations.
HHT patients may require red blood cell (RBC)
transfusion due to spontaneous hemorrhage or surgical
bleeding. Because HHT-associated hemorrhage often
occurs in submucosa we hypothesized that RBC
alloimmunization rates in HHT patients may be higher
than those observed in other transfused patients and
investigated this in a retrospective study.
STUDY DESIGN AND METHODS:
patients with HHTwho were transfused at our tertiary
care facility were identified. A group of randomly
selected, chronically transfused patients without HHT
were used as controls (n 5 207). RBC transfusion and
alloantibody data were extracted from medical records.
Alloimmunization rates among patients with
HHT were significantly higher than those of controls
(15.29% vs. 2.42%; p < 0.001), while HHT patients
received fewer RBC transfusions at our institution
compared to controls (4.27 units vs. 8.84 units;
p < 0.0001). Anti-E, -K, and -c were the three most
common alloantibodies identified in HHT patients. There
was a trend for HHT patients to make more antibodies
per alloimmunized patient than controls (2.38
alloantibodies vs. 1.60 alloantibodies), although this
difference was not significant (p 5 0.37).
To our knowledge, this is the first study
to evaluate RBC alloimmunization rates in patients with
HHT. It is unclear whether the high alloimmunization
rates observed are due to lifetime transfusion burden,
underlying disease pathophysiology, or other variables.
Additional studies are needed to evaluate the
generalizability of our findings to other HHT populations
and to consider the utility of prophylactic antigen
matching for C/E/K.
lloimmunization to non-ABO red blood cell
(RBC) antigens is one of the most common
complications of repeated RBC transfusions.
Alloimmunization rates are approximately 1%
to 3% in general hospital–based patients and can reach up
to 50% in transfusion-dependent patients such as patients
with sickle cell disease.
Non-ABO RBC alloantibodies
increase the risk of immediate and delayed hemolytic
transfusion reactions, which are one of the leading causes
of transfusion-related mortality reported to the Food and
Patients with alloantibodies are
also more likely to experience delays in transfusions
because the numbers of compatible RBCs for transfusions
are limited; such delays can also lead to complications
resulting in morbidity and mortality.
In addition, mater-
nal alloantibodies in the setting of pregnancy may lead to
severe hemolytic disease of the fetus and newborn.
ABBREVIATIONS: ACVRL1/ALK1 5 activin receptor-like
kinase; APC(s) 5 antigen-presenting cell(s); AVM(s) 5
arteriovenous malformation(s); DC(s) 5 dendritic cell(s);
ENG 5 endoglin; HHT 5 hereditary hemorrhagic
Department of Laboratory Medicine; the
Department of Radiology and Biomedical Imaging; the
Department of Pediatrics, Yale University School of Medicine,
New Haven, Connecticut; and the
Pathology & Laboratory
Medicine Service, VA Connecticut Healthcare System, West
Address reprint requests to: Christopher A. Tormey, MD,
Department of Laboratory Medicine, Yale University School of
Medicine, 333 Cedar Street, PO Box 208035, New Haven, CT
06520; e-mail: firstname.lastname@example.org.
Received for publication June 21, 2017; revision received
October 28, 2017; and accepted November 1, 2017.
Volume 58, March 2018 TRANSFUSION 775