Do Microemulsion-based Nanoparticles Affect Blood Coagulation?
Yan Li, M.D., David G. Bjoraker, M.D., Timothy E. Morey, M.D.,
Donn M. Dennis, M.D.
Department of Anesthesiology, University of Florida,
Gainesville, FL
Original Science
Introduction: Each year there are >300,000 emergency room visits
due to poisoning. The cost of treatment exceeded $10
billion/year in 2000, not including $80 billion/year attributed
to alcohol related treatment. There are few specific antidotes
(e.g., naloxone) available to treat patients. Therefore, the
mainstay of therapy remains supportive and symptomatic
treatment. Microemulsion-based nanoparticles are nanometer-sized
droplets formed of biologically compatible oils and surfactants
that offer the ability to absorb large quantities of lipophilic
drugs and poisons. One synthetic microemulsion, ME-6, absorbs
97% of bupivacaine in an in vitro assay of whole human blood. As
part of toxicity evaluation for this microemulsion, global
coagulation function was assessed using the thromboelastograph (TEG).
Methods: After IRB approval, informed consent was obtained from
6 healthy volunteers for venipuncture. Two ml of blood was drawn
with a butterfly catheter and discarded. Subsequently, another 2
ml of blood was collected for TEG analysis. No anticoagulant was
used. Within 6 min from venipuncture, 330 ?l of blood was
transferred into TEG cuvettes prepared with either 30 ?l of
normal saline (NS) or ME-6 (0.1 ?g/ml final concentration). No
activator other than the plastic cuvette and pin surfaces were
used. Assays were performed using a thromboelastograph
coagulation analyzer (2000 D, Haemoscope, Skokie, IL). The r
time, k time, a angle, and maximum amplitude (MA) of both test
and control groups were compared and analyzed. In addition, a
CBC was performed. A paired Student t test was used for
statistical analysis. P<0.05 was considered to be a
statistically significant.
Results: In vitro thromboelastograph and blood count values with
and without ME-6 treatment (mean±SD).
|
|
R (min) |
K (min) |
a (º) |
MA (mm) |
Platelet (106/ml) |
Hg (g/dl) |
WBC (103/ml) |
|
Control |
22.4± 3.5 |
9.9± 1.4 |
29.1± 3.9 |
51.0± 3.2 |
175± 28 |
13.3± 1.2 |
5.6± 1.7 |
|
Microemulsion |
19.1± 2.4 |
19.4± 4.3 |
13.8± 3.8 |
16.3± 5.3 |
182± 23 |
13.7± 1.8 |
5.2± 1.3 |
|
P value |
0.145 |
0.0013 |
0.00007 |
0.00003 |
0.1225 |
0.1772 |
0.206 |
Discussion: From other studies (data unpublished), ME-6 absorbed
97% of bupivacaine in vitro and, therefore, may be a potential
antidote for bupivacaine toxicity. In this study, ME-6 in vitro
affected the coagulation profile significantly. The lack of
effect on the onset time of clot formation suggests that
impairment of coagulation factor biochemistry did not occur.
However, the marked loss of maximum amplitude with ME-6 suggests
either severe platelet dysfunction or fibrin polymerization
interference. Further studies are needed to define its
mechanism.
References:
1. Statistical Abstract of the United States, 120th Edition,
2000.
2. Dennis D. et al. Unpublished data from this group.
