Lippi.qxp 11/8/09 10:21 am Page 19
Coagulation Disorders
Laboratory Diagnostics in Septic Disseminated Intravascular Coagulation
Giuseppe Lippi
1
and Gian Cesare Guidi
2
1. Associate Professor; 2. Professor, Clinical Biochemistry and Clinical Molecular Biology, University of Verona
Abstract
The diagnosis of septic disseminated intravascular coagulation (DIC) relies on clinical signs and symptoms, identification of the underlying
disease and results of laboratory testing. Since no single test result alone can definitely establish or rule out the diagnosis, the laboratory
diagnostics of septic DIC encompass a combination of tests for which simple diagnostic algorithms are now available. Global tests of
haemostasis provide evidence of activation of blood coagulation and, ultimately, consumption of coagulation factors, but their diagnostic
efficiency is as yet questionable. Fibrinolytic markers, namely D-dimer, reflect the extent of activation of both coagulation and fibrinolysis,
so a normal value can be used in a ruling-out strategy. Decreased levels of the natural inhibitors are frequently observed in patients with
septic DIC, but antithrombin and protein C measurements are not incorporated in any of the widely used diagnostic algorithms. Among the
inflammatory biomarkers, procalcitonin is currently regarded as the gold standard to differentiate the type of infection and guide antibiotic
therapy, but its clinical usefulness in identifying and predicting the outcome of patients with septic DIC is still circumstantial.
Keywords
Disseminated intravascular coagulation (DIC), diagnosis, haemostasis, infection, sepsis
Disclosure: The authors have no conflicts of interest to declare.
Received: 2 April 2009 Accepted: 23 June 2009
Correspondence: Giuseppe Lippi, Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi di Verona, Ospedale Policlinico GB Rossi,
Piazzale Scuro, 10, 37134 Verona, Italy. E: ulippi@tin.it
Disseminated intravascular coagulation (DIC) is a systemic, Although the clinical spectrum of DIC is often heterogeneous and the
life-threatening disease characterised by excess thrombin balance between thrombosis (micro- or macrothrombosis) and
generation and simultaneous activation of the fibrinolytic system. bleeding (petechiae, ecchymoses, mucosal, skin and catheter
The clinical condition that follows is characterised by the presence haemorrhages) varies widely on an individual basis and according to
of various degrees of both intravascular coagulation and the underlying cause, all bodily organs can be affected, such that
haemorrhage resulting from consumption of coagulation factors. multiorgan failure (MOF) is often a catastrophic end-point. In its most
According to the Subcommittee (SSC) on DIC of the International severe form, the combination of thrombosis and haemorrhage may
Society on Thrombosis and Haemostasis (ISTH), the pathology can trigger Waterhouse-Friderichsen syndrome (septicaemia and acute
be defined as an acquired syndrome characterised by the adrenal insufficiency), which is frequently observed in patients with
intravascular activation of coagulation with loss of localisation fulminant meningococcal septicaemia.
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arising from different causes that can originate from and cause
damage to the microvasculature and that, if sufficiently severe, can The magnitude of the mutual clinical relationship between sepsis
lead to organ dysfunction.
1
and DIC is reflected by epidemiological data attesting that DIC is a
rather frequent complication in patients with sepsis (DIC is observed
Contrary to widespread belief, DIC should not be considered as a in up to 50% of patients with sepsis and is a strong predictor of
primary disease, but rather as one of the worst complications of mortality) and, on the other side of the coin, sepsis is by far the most
several underlying illnesses. As such, DIC can arise from a variety of frequent underlying condition identified in patients with DIC.
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systemic or localised pathologies, involving most (if not all) organs and Although lipopolysaccharide (LPS), conventionally referred to as
tissues. Systemic and persistent activation of blood coagulation may endotoxin, is recognised as the most potent microbial mediator
occur in patients with sepsis, severe infections, malignancies (solid implicated in the pathogenesis of sepsis and septic shock,
7
it
tumours and myeloproliferative/lymphoproliferative malignancies), is not alone as a cause of the worst overall complications (MOF
obstetric complications (amniotic fluid embolism, abruptio placentae, and DIC).
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Cell membrane components of several micro-organisms
placenta previa, retained dead foetus syndrome), vascular disorders (LPS or endotoxin) or bacterial exotoxins, such as staphylococcal
(vascular aneurysms, Kasabach-Merritt syndrome), severe organ injury α-haemolysin, can in fact induce a generalised inflammatory
(acute pancreatitis, hepatic failure), massive trauma, extensive burns, response through the activation of pro-inflammatory cytokines and
surgery and severe toxic (snake bites, drugs) or immunological thrombin generation by activation of the tissue factor/factor VIIa
reactions (haemolytic transfusion reaction, transplant rejection).
2–4
pathway (see Figure 1).
© TOUCH BRIEFINGS 2009 19
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