Page 14 - Journal of Special Operations Medicine - Fall 2015

of 13.2 gm/dL, hematocrit of 40.6%, and a total red Figure 2 Mechanism for the neutralization of ROS.
blood cell (RBC) count of 4.49 million RBCs/μL with
mean corpuscular value (MCV) of 90.4fL. Bilirubin was
not measured and no peripheral smear was obtained.
The patient improved throughout his hospital stay and
was discharged with orthotic fracture shoes, oral anal-
gesics, and a wheelchair. Outpatient treatment included
weeks of povidine-iodine soaks, blister care, and hyper-
baric oxygen treatments. In September 2014, the patient
underwent amputation and surgical debridement of the Note: *G6PD; †NADP, nicotinamide adenine dinucleotide phosphate;
dry gangrenous portions of toes 1 through 3 bilaterally ‡NADPH, reduced nicotinamide adenine dinucleotide phosphate;
and partial amputation of toes 4 and 5 bilaterally, for §GSH, reduced glutathione; ||GSSH, oxidized glutathione; and ¶ROS
–
improved function. The surgical wounds were closed via (H O or O ).
2
2
2
wound vacuum and delayed coverage by plastic surgery.
by the degree of G6PD deficiency and the relative amount
of oxidative stress.
Discussion
AHA in an individual with G6PD deficiency manifests Many substances have been identified as having the
as a normocytic anemia. Anemia was not seen in this ability to cause hemolysis in G6PD-deficient RBCs. A
patient. This does not, however, exclude the possibility multitude of medications, including many analgesics, an-
of a mild G6PD deficiency exacerbation. Given his 2 timalarials, and sulfonamides, have been recognized. 2,4,6
weeks in a high-altitude environment, it is expected that A variety of infectious agents, herbs, and chemical
he have an increase in hematocrit due to dehydration products have been detected. Fava beans have long been
and an increase in total RBC count via increased pro- known as a significant source of oxidative stress. There
7
duction. Thus, these laboratory values may represent a is evidence that high altitude alone is associated with the
3
mild hemolysis and thus a greater degree of pathology generation of ROS. 8
than one would expect seeing with these values in isola-
tion. Unfortunately, other indicators of AHA (e.g., bili- The common presentations of acute hemolysis in G6PD
rubin levels and a peripheral smear) were not obtained at deficiency are a sudden onset of jaundice, dark urine,
Alaska Regional Hospital. The patient did exhibit dark abdominal or back pain, and all symptoms standard for
urine and distinct fatigue, compared with his fellow ex- anemia (i.e., pallor, fatigue, and dyspnea)with onset 2 to

peditioners, which is out of proportion to his previous 4 days after the insult. Frostbite has not previously been
2
performance. Although it cannot be proved in this case, recognized as a possible presentation of AHA.
it is possible that AHA played a role in the development
of frostbite in this patient with G6PD deficiency. Acetazolamide (Diamox Sequel ) is a carbonic anhy-
®
drase inhibitor. It is categorized as a nonbacterial sulfon-
G6PD is an enzyme that functions in the hexose-mo- amide. Although this category of medications includes
nophosphate (HMP) shunt. The primary function of many drugs considered to not be safe in those with
4
HMP is to indirectly protect RBCs against oxidative in- GDPD deficiency, there is some evidence that acetazol-
jury. RBCs have no other means of protection against amide activates the enzyme G6PD and therefore may be
this insult (Figure 2). Reactive oxygen species (ROS) protective against AHA in those with this disease. Be-
4
9
are formed naturally within RBCs via reactions of he- cause one of the effects of acetazolamide is the urinary
moglobin with oxygen. Oxidants are also produced by excretion of bicarbonate, acetazolamide can directly
many exogenous factors such as drugs, foods, herbs, contribute to frostbite due to dehydration. 10
and infections. Individuals with G6PD-deficient eryth-
rocytes, when exposed to oxidative stress, lack the abil- Frostbite is described as the actual freezing of tissue.
11
ity to neutralize ROS in sufficient quantities (Figure 2). Pathological changes occurs via direct cellular injury due
5
to ice formation and indirect cellular injury from micro-
Without ample G6PD, hemoglobin becomes oxidized vascular insults. These indirect processes lead to even
and will accumulate within RBCs, leading to decreased more severe tissue damage than direct injury, occur-
11
function and cell death. The accumulation of oxidized ring via thrombosis and hypoxia. Severity varies with
9
hemoglobin leads to insoluble buildup and crosslinking, rate, duration, and extent of freezing as well as with a
causing RBCs to become rigid and making them increas- multitude of interacting individual and environmental
ingly susceptible to destruction by the macrophages in the factors. These include anemia, increasing altitude, de-
spleen, marrow, and liver. The end product is the devel- hydration, tobacco use, tight clothing, vasoactive medi-
5
opment of normocytic anemia with severity determined cations, Raynaud disease, atherosclerosis, and others,
11

2 Journal of Special Operations Medicine Volume 15, Edition 3/Fall 2015