Page 121 - JSOM Summer 2023

Impairment of Anticoagulant Systems and diagnosis with viscoelastic testing for SIC and DIC. Of
There exists a normal homeostatic interplay between pro- note, this viscoelastic technology or hemostatic assay (VHA)
and anticoagulant systems where clot and clot formation are allows for the diagnosis of general coagulopathy, not neces-
kept in balance. In SIC, thrombin continues to play a key role, sarily whether it is SIC or another specific etiology. The two
and antithrombin normally acts to inhibit thrombin. 13,14 An- most popular and common methods of viscoelastic testing
tithrombin provides critical inhibition of thrombin and coag- include rotational thromboelastometry (ROTEM) and throm-
ulation factors. However, antithrombin levels are decreased boelastography (TEG). These systems employ whole blood as
15
in sepsis because of consumption and impaired synthesis from samples for testing, and they provide a graphical interface to
23
activated neutrophils. Sepsis causes extensive vascular leak- demonstrate clot start and breakdown. It measures real-time
16
age, and extravasation of fluids into the lung and other ograns. coagulation and can reflect in-vivo conditions. Surgical in-
Antithrombin interacts with the glycocalyx to preserve its an- tensive care units (ICUs) and trauma centers increasingly use
24
ticoagulant effects in sepsis. This is why repletion of anti- these point-of-care devices. Unfortunately, this type of tech-
17
thrombin may have protective effects and beneficial effects in nology is unlikely to be found in forward and austere locations
SIC/DIC. due to availability and durability. Furthermore, we have yet to
test their usefulness in a large cohort of sepsis patients. It has
The thrombomodulin/protein C system is another key part been reported that hypercoagulability viscoelastic findings on
of the anticoagulation system. Protein C pathways main- admission correlate with the early detection of sepsis. 25
tain the homeostasis between hemostasis and host response
to infection. Thrombomodulin activates protein C. In doing Differential Diagnoses of SIC and DIC
so, activated protein C can have antithrombotic and anti- Thrombocytopenia is common in several different kinds of
inflammatory actions. In addition, activated protein C can in- clinical conditions, and in particular critically ill patients.
activate Factors Va and VIIIa. Severe sepsis is known to upset However, thrombocytopenia is common in sepsis and DIC
18
the thrombomodulin/protein C system. In fact, in severe septic and often used to facilitate diagnosis. Conditions such as hep-
patients, protein C level is a known laboratory biomarker. Ad- arin-induced thrombocytopenia (HIT) and thrombotic micro-
ditionally, the levels of both protein C and antithrombin can angiopathy (TMA) also need to be considered as etiologies of
be used to prognosticate mortality. 19 thrombocytopenia in critically ill patients. TMA is a larger
umbrella syndrome, which is comprised of thrombotic throm-
bocytopenic purpura (TTP) in addition to hemolytic uremic
Diagnosis of SIC and DIC
syndrome (HUS). TMA is defined by hemolytic anemia and
How to Diagnose thrombocytopenia due to a wide variety of pathogeneses. In
There is a wide range in practice patterns of how DIC is di- TTP, there is a shortage or inhibition of a metalloproteinase
agnosed and treated. For example, the ISTH criteria for DIC (ADAMTS13), which leads to aggressive platelet clumping
uses a variety of laboratory testing to come up with a compos- and aggregation. Since ADAMTS13 is a protease that cleaves
ite score. There are proposals to include other criteria to help VWF multimers that help platelets adhere to sites of action,
identify patients who are at risk of having potential to develop severe depletion is recognized in TTP. 26
DIC and to confirm the diagnosis of DIC. ISTH’s criteria were
modeled after the classic definition of DIC, and research has HUS is a syndrome that typically features thrombocytopenia,
shown that scoring also correlates with sepsis severity. Given acute renal insufficiency or failure, and hemolytic anemia. It
20
our focus on austere critical care, the authors acknowledge typically stems from an infection by a specific type of 0157:H7
that this scoring system has readily available laboratory tests E. Coli that produces Shiga toxin. 27
at stateside or fixed facility hospitals, including platelet counts,
fibrin/fibrinogen degradation products and D-dimers, and the HIT is also a thrombotic microangiopathy that requires stop-
prothrombin time. This type of testing is not usually available ping heparin and using anticoagulation therapy with an al-
as a point-of-care far-forward or in austere remote locations. ternative non-heparinoid anticoagulant. Of note, HIT occurs
after some form of heparin exposure. Antibodies recognize
How to Diagnose SIC platelet factor 4 bound to heparin, causing HIT. These types of
Coagulopathy is a downstream effect of acute infections and/ patients are also prone to thrombosis. The clinical probability
or shock. Coagulopathy is defined as the body’s inability to of HIT can be evaluated using a clinical scoring system based
clot blood. In DIC, hemostasis is abnormal, but can also be on 4Ts: thrombosis, timing of onset, thrombocytopenia, and
21
associated with concomitant hypercoagulability. Further, as- other causes of thrombocytopenia. In a stateside fixed-facil-
28
ymptomatic patients may also have abnormal lab tests. For ity hospital, one can order a laboratory test to confirm a diag-
most stateside and fixed-facility clinicians, managing abnor- nosis of HIT (usually a positive platelet factor 4 ELISA), but
29
mal coagulation lab values in a critically ill patient is challeng- there is also a positive test for platelet-activating antibodies.
ing. Further, the ability of monitoring coagulation in a remote This can be confusing because HIT can resemble (non-HIT)
or far-forward location would be nearly impossible. However, DIC by clinical signs and laboratory testing. Since each of
any delays in diagnosis and treatment of coagulopathy in sep- these conditions requires specific treatment, prompt discrim-
tic patients could be catastrophic. To define SIC, we need ination of these diseases is important. 30
22
to have evidence of coagulopathy based on laboratory testing
demonstrating specific abnormalities, including thrombocyto- Treatment of SIC and DIC
penia and a prolonged prothrombin time.
Heparin
Viscoelastic Testing for Coagulopathy We treat SIC by treating the underlying etiology—infection.
31
There are potential methods to further evaluate and monitor Heparin and heparinoids are common anticoagulants, but are
coagulopathy, including technology to aid laboratory studies used mostly for venous thromboembolic prophylaxis. Heparin

DIC in Austere Critical Care | 119