Hemanext Anaerobic Storage Platform
The Hemanext Anaerobic Storage Platform (HASP) is a novel technology used to deliver
red blood cells (RBCs) of higher efficacy for transfusion therapy, and at the same
time, extend the shelf life of refrigerated RBCs.
With HASP, RBCs are stored in a modified additive solution under oxygen-depleted
(anaerobic) conditions. Anaerobically stored RBCs are characterized by higher efficacy
as well as extended shelf life (9 weeks or more) as compared to same-aged blood
stored by conventional methods.
Stored RBCs, even if transfused within the current 6-week storage limit, deteriorate
in a variety of significant ways – including hemolysis (red cell destruction), low
survival rate of transfused red cells in recipients, reduced deformability (inability
to reach capillary beds), inability to release oxygen at tissue, and inability to
dilate arterioles to increase perfusion. Numerous Phase I studies, including a recent
clinical trial funded by a SBIR Phase I grant, have shown repeatedly that RBCs stored
using HASP have higher ATP and 2,3-DPG levels, lower hemolysis, and higher post-transfusion
recovery compared to conventionally stored cells, as well as a 50-100% extension
in shelf life. These results have been presented in professional meetings as well
as published in prominent peer reviewed journals, including Transfusion and Vox
Sanguinis. This improved efficacy, while beneficial
in all circumstances, will particularly benefit subjects who require chronic transfusion
therapy (e.g., sickle cell disease or beta-thalassemia) by reducing transfusion
frequency, time-averaged blood transfusion volume, and total iron burden. Additionally,
an extended shelf-life will improve the logistics of general blood banking, help
alleviate periodic blood shortages, and enhance the utility of pre-operative autologous
blood collection.
Research into HASP started in the early 1990s at Los Alamos National Laboratory
by two scientists, Mark W. Bitensky M.D. and Tatsuro Yoshida Ph.D. The project was
transferred to Boston University with both scientists in 1996, and continued until
2006. During that time numerous small-scale clinical trials using experimental storage
protocols were conducted under FDA guidance.
RBC Storage
There are currently three main issues involved in the storage of refrigerated blood:
- 1. Red cells stored for extended periods become less effective
and potentially toxic.
- a. Up to 25% of red cells are destroyed by the body soon after
transfusion.
- b. Destroyed cells cause iron overload in chronically transfused
patients.
- c. Transfusion does not achieve intended outcome of increased
delivery of oxygen to organs.
- d. Transfusing red cells stored for longer periods result in
higher morbidity and longer hospital stays compared to fresher red cells.
- 2. Refrigerated red cells can be stored for only 6 weeks.
- a. 3.3% of stored blood is discarded as out-of-date.
- b. Periodic blood shortages occur around summer and holidays
(also results in idled surgical suites).
- c. Requires high costs in maintaining just-in-time infrastructure.
- d. Causes logistical problems at remote locations and small hospital
blood banks.
- e. Places limits on quantity and usefulness of pre-operative
autologous blood collection.
- 3. There are no practical alternatives for refrigerated blood.
- a. Frozen blood has a shelf life that exceeds 10 years. However,
the procedure is too cumbersome and expensive for routine use.
- b. Artificial blood substitutes (chemical or cross-linked hemoglobins)
have long shelf lives, but they cannot be used for general transfusion therapies.
“The [HASP] anaerobic storage approach has the potential to enhance the quality of RBC storage
and transfusion therapy and will help us to improve and optimise the care of patients in the near future.”
Blood Transfusion 2010;8: DOI 10.2450/2010.0060-10 by:
James AuBuchon, M.D., President & CEO, Puget Sound Blood Center Professor of Medicine & Laboratory Medicine, University of Washington, and
Giancarlo Maria Liumbruno M.D., Research and Clinical Immunohaematology, Transfusion Medicine and Clinical Pathology at the Hospital Fatebenfratelli, Isola, Tiberina.
HASP Technology
The HASP system uses the following components:
- 1. An additive solution;
- 2. An oxygen / carbon dioxide sorbant;
- 3. A membrane with high oxygen permeability in
contact with a red cell suspension enclosing oxygen sorbant;
- 4. An carbon dioxide /oxygen depletion
device (OCDD) to remove oxygen from RBCs before they are placed
in storage; and
- 5. A RBC storage bag that can maintain
an anaerobic state throughout the extended storage duration.
HASP: A single use plastic disposable set comprised of an O2/CO2 depletion device
(OCDD), a custom blood storage outer bag, interconnection tubing, labels and packaging.
SBIR Funding Overview
In June 2008, the Company clearly established proof of concept in humans following
completion of a Phase I clinical trial funded by a $134,000 SBIR Phase I grant from
the National Heart, Lung, and Blood Institute (NHLBI). Following this success, the
NHSi applied for and NHLBI awarded a $1.9 million a Phase II SBIR grant The primary
objective of the Phase II grant is to design and fabricate an anaerobic RBC storage
system that can be readily accommodated by current blood banking practices without
incurring major alteration in procedures or equipment.
Phase 1 Accomplishments
In the SBIR-funded Phase I trial, a dual arm study conducted at Dartmouth-Hitchcock
Medical Center, eight subjects were transfused with RBCs stored under HASP and conventional
methods. Anaerobic storage demonstrated a superior 24-hour recovery compared to
conventionally stored RBCs after 6 weeks of storage, and equivalent 24-hour recovery
after 9 weeks.
Additional Phase 1 trials have shown:
- Extended shelf life of refrigerated RBCs to 9 weeks using additive solution currently
in wide use.
- Extended shelf life of refrigerated RBCs to 12 weeks using advanced additive solution
coupled with metabolic supplementation during storage.
- Extended shelf life of refrigerated RBCs to 9 weeks using advanced additive solution.
These promising results, reported in Transfusion and Vox
Sanguinis induced the NIH
to award a Phase II SBIR grant.
Phase II SBIR Project
The anaerobic storage of RBCs has repeatedly been shown to improve metabolic status
as well as to extend the shelf life. However, in all preliminary trials, a gas exchange
process was used as a means to deplete oxygen prior to storage, and RBCs were kept
in an anaerobic chamber during storage. To introduce this technology to the market
and test its benefits in large-scale trials, a simple, self-contained blood collection/storage
bag set is needed that does not require materially higher costs or major alterations
in manufacturing infrastructure or operating procedures of blood banks. Primary
design specifications include:
- 1. functional capabilities that replicate or exceed blood quality
and shelf life results achieved in the Phase I trial;
- 2. maximum design and production engineering compatibility with
existing blood collection technology; and
- 3. minimal incremental RBC unit costs.
NHSi has utilized the SBIR Phase II grant funds to:
- 1. Successfully complete development of a prototype of the disposable HASP device;
- 2. Launch in vitro testing of the prototype device at Dartmouth-Hitchcock Medical Center
- 3. Complete and submit an Investigational New Device (IND) filing with the US Food and Drug Administration.
Upon receipt of FDA’s approval of the IND application (anticipated by November 2010), NHSi will commence in
vivo trials of the prototype device, again at Dartmouth-Hitchcock Medical Center.
The in vivo trial is designed to demonstrate that, after 3 and 6 weeks of storage, a significantly higher
24 hour post-transfusion recovery can be achieved compared to conventionally stored blood; and that such RBCs
can achieve a 9-week shelf life.
In April 2011, NHSi plans to use preliminary results from the in vivo trial to support a NIH SBIR Phase IIb
application. The Phase IIb funds, if awarded, will be used to fund the pivotal trial required to support an FDA
application for approval to market HASP in the United States.
In addition to demonstrating the improved quality characteristics of anaerobically stored blood, small samples
of the red cells collected and stored anaerobically during the in vivo trial will be shared with four other
institutions – University of Tuscia (Italy), Puget Sound Blood Center, Mayo Clinic and Tulane University –
who are studying the effects of storage (with and without HASP) on the therapeutic quality of red cells. The data
generated by wide range of biochemical and biophysical measurements will be correlated with the 24-hour
post-transfusion recovery measured in the in vivo trial.