Page 122 - JSOM Summer 2023

has a mechanism of action in which it binds to several pro- insidious pathologies such as invasive fungal infections, renal
teins in the aforementioned coagulation cascade. It finds anti- failure, sepsis, coagulopathies, respiratory failure, and acute
thrombin and binds to it. In doing so, it causes a surface change respiratory distress syndrome will manifest. In the Global War
and inactivates antithrombin. It then blocks two factors of the on Terror (GWOT) or 9/11 conflicts, these “ICU problems”
clotting cascade, thrombin (Factor IIa) and Factor Xa. When usually manifested most often when the patient arrived at a
thrombin is inactivated, fibrinogen is unable to convert to fibrin. U.S. military hospital. Now, in future conflict post-9/11 PCC,
7
Without fibrin, new clots cannot form. In the United States, medics and intensivists may have to be diagnosing and treating
forward damage control resuscitation and surgery teams have “ICU problems” very near the fighting and for extended times.
commonly deployed with heparin in recent conflicts. Previous
studies have researched how effective heparin/heparinoids are The review above describes how challenging it is to even dia-
as a treatment modality and as a potential therapeutic approach gose DIC and SIC with differing criteria and guidelines. One
for DIC. However, their effectiveness and safety remain under way to help address this is to employ the aforementioned
question. Unfortunately, a meta- analysis showed that septic, VHAs. In fact, there are no current studies describing the use
critically ill patients bleed more after heparin therapy and did of VHAs in austere and far-forward locations. Bates et al.
not have a reduction in organ dysfunction or mortality. 32 proposed using VHAs as point-of-care testing on aeromedical
transport to help guide initial resuscitation. A recent paper
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Antithrombin discussed using VHA in far-forward combat environments or
Internationally, there are different approaches of how to treat austere locations as a way to improve survival and guide re-
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SIC. Japan is on the cutting edge of DIC research, and based suscitation. However, the logistical challenges of doing VHA
on their guidelines, antithrombin concentrate and/or recom- in remote areas remains, and the use of VHAs near battlefields
binant thrombomodulin are commonly used. This is contrary may only be feasible in the near future.
to the rest of the world in which international sepsis guide-
lines routinely recommend against the use of antithrombin due More importantly, LSCO simulations have suggested over-
33
to the reported increased risk of bleeding. KyberSept was a whelming casualty rates in a magnitude and scale not seen
large-scale phase III clinical trial conducted to examine the in GWOT. Such a staggering number of casualties would
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high-dose effects of antithrombin, whose results led to the rec- quickly overhelm combat field hospitals and deplete medical
ommendation against antithrombin in DIC care. Although supplies. This is essentially true in remote and austere loca-
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the recommendation of not using antithrombin is based on tions, especially if there is no ability to resupply or evacuate
this trial, sub-analysis of the patients with DIC who did not casualties due to lack of air superiority. In such situations,
receive heparin but received antithrombin had improved knowledge of DIC and SIC may be helpful because it remains
survival. However, conclusions must be carefully drawn in a diagnostic challenge and a treatment nightmare. There are
34
assessing antithrombin and other potential therapies for anti- few treatment options, and the treatment may not be effica-
coagulation strategies in sepsis, as the patient population with cious. With this knowledge, medical providers can triage their
sepsis may not necessarily have DIC. 34 casualties to those that would most benefit from medical evac-
uation, critical care transport, and even employment of extra-
Heparin is often paired with antithrombin because heparin corporal life support. And when resources like blood products
binding to antithrombin increases anticoagulation activity. and heparin become short in supply, this knowledge may also
However, when this strategy is employed, there is a significant equip medical providers to make difficult decisions on patients
increase in bleeding and with some reports of reduced mortal- with a universally poor prognosis.
ity benefit when used along with heparin. 35
Prolonged Casualty Care Implications Lastly, as Special Operations Forces (SOF) have pushed the
boundaries of prolonged field care in remote and austere lo-
The prognosis for DIC is poor and often fatal. What compli- cations, these practices have evolved into PCC. LSCO will in-
cates this scenario is that it often occurs in septic patients with volve both conventional forces and SOF assets. Both Forces
multi-system organ failure. Foremost, like any infection, sepsis have unique medical capabilities, niches, skills, and assets.
must be first treated with source control and appropriate an- GWOT may have highlighted differences in these approaches.
ti-microbial coverage. With respect to coagulopathy, 70% of Future conflicts may see a merging or interesting interplay be-
DIC cases are complicated by multiple organ dysfunction syn- tween conventional and SOF PCC as LSCO may require an
dromes, and 31.3% of DIC patients do not survive. DIC is not “all-hands” solution to resources, capabilities, and approach.
rare; it is estimated that there is a point prevalence of roughly
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4.45% in septic patients. Furthermore, as described above, Summary
the diagnosis and treatment of DIC and SIC are challenging.
DIC is an ominous and likely harbinger of certain death. The
The fighting in Nagorno-Karabakh and the current Russian therapy to treat this is to treat the underlying disease, and early
invasion of Ukraine demonstrate that future U.S. military con- intervention with antibiotics and source control is critical due
flicts may be large-scale combat operations (LSCO) with peer to the increased mortality. Coagulopathy is a possible conse-
and pacing threats. These operations are usually comprised of quence of shock and severe organ dysfunction. As septic pa-
multi-domain operations and are of totality in scale and de- tients may also bleed abnormally, it becomes imperative we
struction. In such conflicts, we will lack air superiority and the appropriately diagnose and manage SIC and DIC. In an aus-
ability to quickly evacuate patients to Germany or the U.S. due tere and far-forward combat environment, erudite recognition
to enemy anti-access/area denial operations and our own lack of a lurking possible coagulopathy and early initiation of tar-
of air superiority. We will be dealing with contested air, land, geted therapy may alter outcomes of SIC. PCC providers are
and sea. Instead of point-of-injury and initial resuscitation, we more likely to see coagulopathies like this in LSCO, and the
will be forced to do PCC over longer time domains, in which difficulty in both diagnosis and treatment of DIC and SIC may

120 | JSOM Volume 23, Edition 2 / Summer 2023