Biomedical Engineering Reference
In-Depth Information
or Hemassist, from Baxter Healthcare, is a DCLHb tetramer made from outdated
human blood. This product underwent Phase III clinical trials for coronary artery
bypass grafting procedures and was determined to decrease the need for trans-
fused packed red blood cells. The adverse effects include hypertension and gas-
trointestinal distress.
The fi rst recombinant hemoglobin product, rHb 1.1 or Optro, is a genetically-
engineered variant of human hemoglobin and the product could be genetically
altered to produce more favorable characteristics [Sakai (16)]. Its current intra-
vascular half-life is two to nineteen hours and is dose-dependent. It has similar
adverse effects when compared to DCLHb, including vasoconstriction, gastroin-
testinal distress, fevers, chills, and backache.
There are other promising products like Poly-SFH, or PolyHeme, which is
made from pyridoxylated, polymerized, outdated human blood or Polyethylene
glycol (PEG) hemoglobin. This product is currently being evaluated for use in
cancer therapy to increase tumor oxygenation and enhance the effi cacy of radia-
tion and chemotherapy.
There is another interesting product with potentialities known as Hemolink,
which is human hemoglobin polymerized with a ring-opened raffi nose structure
creating intratetrameric and intertetrameric cross-linking. Hemolink, too, is
derived from outdated human red cells, which makes future availability a concern.
This product can be stored at 4 °C for at least one year.
Apart from these, HbOC-201, or Hemopure, is a promising product. This is a
polymerized form of bovine hemoglobin. Bovine hemoglobin has a P-50 of
30 mm Hg, which is closer to human hemoglobin than stroma-free hemoglobin.
The advantages of this product include its availability and its ability to be stored
at room temperature. Its intravascular half-life is 8 to 23 hours and is dose-
dependent. Hemopure has a shelf life of 36 months at room temperature. It has
been used in patients undergoing elective abdominal aortic surgery; this product
also increased mean arterial pressure and systemic vascular resistance.
However, as mentioned, none of these products passed the FDA Phase III
trial, and as such they are unavailable for unrestricted global use [Henkel-Honke
and Oleck (17)].
From 1970 onwards, perfl uorocarbons (PFCs), too, have been investigated as
blood substitutes [Jin (18)]. Replacing the hydrogen atoms of hydrocarbons with
fl uorine atoms creates these products. PFCs have a high affi nity for oxygen,
approximately ten to twenty times higher than plasma or water. The oxygen
content of PFCs is directly proportional to oxygen partial pressure; therefore,
patients require supplemental oxygen. The fi rst product to be marketed was a
mixture of perfl uorodecalin and perfl uorotripropylamine emulsifi ed with Pluronic
F-68 called Fluosol-DA. Ultimately, this product was ineffective at signifi cantly
improving oxygen delivery in case of acute hemorrhage. Other shortfalls of
Fluosol-DA included a short effective intravascular half-life, temperature insta-
bility, low oxygen-carrying capacity, and a poor shelf life. Its major adverse effects
included acute complement activation, uptake by the reticuloendothelial system,
and disruption of normal pulmonary surfactant.
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