Page 120 - JSOM Summer 2023

Sepsis-Induced Coagulopathy and
Disseminated Intravascular Coagulation

What We Need to Know and
How to Manage for Prolonged Casualty Care

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Jason Nam, MD *; An-Kwok Ian Wong, MD, PhD ; David Cantong, NRP ;
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John Alexander Cook, MD ; Zachary Andrews, NRP ; Jerrold H. Levy, MD, FCCM 6
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ABSTRACT
Coagulopathy can occur in trauma, and it can affect septic pa- and shock. Multiple mediators trigger coagulation. These
tients as a host tries to respond to infection. Sometimes, it can tissue-released mediators cause intense coagulopathy and a
lead to disseminated intravascular coagulopathy (DIC) with a hyperinflammatory response. Tissue factor is a key part of
high potential for mortality. New research has delineated risk the extrinsic coagulation pathway; it plays a pivotal role in
factors that include neutrophil extracellular traps and endo- coagulopathy and DIC in sepsis. In addition, these inflam-
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thelial glycocalyx shedding. Managing DIC in septic patients matory mediators activate thrombin as part of a host immuno-
focuses on first treating the underlying cause of sepsis. Further, thrombotic response that can exacerbate multiorgan failure in
the International Society on Thrombolysis and Haemostasis sepsis. 4
(ISTH) has DIC diagnostic criteria. “Sepsis-induced coagu-
lopathy” (SIC) is a new category. Therapy of SIC focuses on Fibrinolysis Shut Down
treating the underlying infection and the ensuing coagulopa- The ISTH defines DIC as a global activation of intravascu-
thy. Most therapeutic approaches to SIC have focused on an- lar coagulation due to a wide range of causes. Especially in
ticoagulant therapy. This review will discuss SIC and DIC and sepsis, fibrinolysis is abnormal and deranged. Plasmin modu-
how they are relevant to prolonged casualty care (PCC). lates fibrinolysis. The plasminogen activator system converts
plasminogen to plasmin. DIC causes endothelial cell injury
Keywords: sepsis; disseminated intravascular coagulation; and dysfunction. Microcirculatory clots form, and deranged
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coagulopathy; antithrombin; prolonged casualty care; PCC; fibrinolysis prevents removal of fibrin and leads to thrombosis
austere critical care throughout the microvascular circulatory system that contrib-
ute to multiorgan dysfunction. 6
Endothelial Dysfunction
Introduction
Sepsis targets the vascular endothelium, and endothelial injury
Sepsis activates a coagulation cascade as the host attempts to leads to a reduced release of prostacyclin and nitric oxide and
fight off infection. The problem with this response is that it increased expression of tissue factor and von Willebrand fac-
can be overwhelming and result in a coagulopathy. DIC is tor (vWF). There is also destruction to the glycocalyx, a thin
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coagulation gone awry, and not a clinical diagnosis but rather layer over the vascular endothelium; the glycocalyx also serves
a response to an underlying condition. Historically, DIC arose as an important locus of infection and inflammation. Anti-
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initially from hemorrhagic syndromes of disordered coagula- thrombin’s antithrombotic activity increases when it binds to
tion. The release of several proinflammatory and procoagu- the glycocalyx. 9,10 During sepsis, components of the glycocalyx
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lant substances following tissue injury in critically-ill septic are lost, resulting in changes that contribute to microcircula-
patients or trauma victims causes a type of consumptive coag- tory dysfunction.
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ulopathy. We will review sepsis-associated DIC and the newly
proposed ISTH term—SIC—and how it pertains to providers Platelet Activation
doing austere critical care and PCC. DIC in sepsis often presents with thrombocytopenia (low
platelet count). Sepsis affects platelet count in a variety of ways
including increased activation. Despite the increased levels of
Pathophysiology of SIC and DIC
thrombopoietin, inflammatory mediators and toxins also sup-
Coagulation Cascade Turns On press the bone marrow’s production of platelets. Thrombin
In sepsis, the body responds to an infection inappropriately also activates platelets as well as the complement cascade. All
and exuberantly, resulting in severe multiorgan dysfunction these processes work in concert in the pathogenesis of SIC. 12
*Correspondence to jason.nam@duke.edu
1 MAJ(P) Jason Nam is a physician affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Hospital,
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Durham, NC. Dr An-Kwok Ian Wong is a physician-scientist affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine,
Duke University Hospital, Durham, NC and the Division of Translational Biomedical Informatics, Department of Biostatistics and Bioinfor-
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matics, Duke University School of Medicine, Durham, NC. SFC David Cantong is an 18D and paramedic affiliated with the 1st Special Forces
Command (A), Fort Bragg, NC. CPT John Alexander Cook is a physician and 18D affiliated with the Department of Emergency Medicine,
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Duke University Hospital, Durham, NC. SFC Zachary Andrews is a SOCM and paramedic affiliated with the Defense POW/MIA Accounting
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Agency, Joint Base Pearl Harbor-Hickam, HI. Dr Jerrold H. Levy is a physician affiliated with the Department of Anesthesiology, Critical Care,
and Surgery, Duke University School of Medicine, Durham, NC.
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