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Laboratory Diagnostics in Septic Disseminated Intravascular Coagulation
intact procalcitonin occurs, which is followed by secretion within the The routine use of other traditional laboratory tests (e.g. leukocyte
bloodstream.
43
Basically, procalcitonin levels can help distinguish count, blood differential counting and CRP) is prompted by low cost,
between bacteraemia and non-infectious inflammatory states easy availability and historical practice rather than strong evidence.
accurately and quickly in critically ill patients, and its current use However, their reliability is hampered by a protracted response with
encompasses diagnosis and monitoring of therapy in patients with late peak levels, low specificity compared with procalcitonin,
infections and systemic inflammation (values >0.5ng/ml generally especially in patients with MOF,
49,53,54
and a reduced increase in
indicate an acute infection accompanied by a systemic inflammatory patients undergoing steroid or other immunosuppressive therapies.
reaction, whereas particularly high values are reported in severe Moreover, unlike procalcitonin, the dynamics of CRP and blood
bacterial infections and septic inflammation, severe sepsis or septic differential counting have limited prognostic implication.
49,54
shock), differential diagnosis of inflammatory diseases and fever
of unknown origin (e.g. acute pancreatitis), differential diagnosis of Conclusions
infectious microbial-induced fever versus non-bacterial fever (e.g. Although the contribution of laboratory diagnostics to the diagnosis
in immunosuppressed patients), differential diagnosis of acute organ of DIC is unquestionable, no single test result alone can definitely
rejection versus post-transplantation infection and prognostic establish or rule out the disease. When approaching patients
information and clinical management in sepsis, septic shock and MOF. with suspected DIC it is therefore essential to consider a
Additional diagnostic procedures can be implemented, or a treatment constellation of parameters, including clinical signs and symptoms,
regimen changed or confirmed in septic patients, based on increasing the identification of a potential underlying disease and, last but not
or declining procalcitonin values.
44
In a critically ill patient with clinical least, the results of laboratory testing. When choosing among the
sepsis, Gram-negative bacteraemia could be associated with higher armamentarium of tests that can be used to assist in the diagnosis,
procalcitonin values than those found in Gram-positive bacteraemia, one should first consider that these may ultimately mirror changes
regardless of the severity of the disease.
45
However, procalcitonin in haemostatic function and keep pace with the critical nature of
is of little use in diagnosing fungal (e.g. invasive aspergillosis, this condition.
24
Global tests of haemostasis such as PT, APTT,
candidaemia), viral (e.g. cytomegalovirus) and severe intracellular fibrinogen and platelet count provide important evidence of
infections (e.g. mycoplasma). activation of blood coagulation and, ultimately, consumption of
coagulation factors, but their diagnostic efficiency is as yet
It should be noted that two recent meta-analyses of pooled data both questionable. Fibrinolytic markers (namely D-dimer) reliably reflect
concluded that procalcitonin cannot reliably differentiate sepsis from the extent of activation of both coagulation and fibrinolysis, so
other non-infectious causes of systemic inflammatory response evidence of normal values can be reliably used to rule out the
syndrome in critically ill adult patients, thus arguing against the disease. The contribution of other tests of haemostasis, such as
widespread use of the procalcitonin test in critical care settings.
46,47
antithrombin and protein C, is as yet questionable. Decreased levels
Giamarellos-Bourboulis et al. earlier reported that procalcitonin can of these natural inhibitors are a marker of consumption
be regarded as an early prognostic marker of the advent of DIC and coagulopathy and are frequently observed in patients with septic
MOF, so its daily monitoring may be helpful in the follow-up of DIC, but they are not currently incorporated in any of the three
critically ill patients.
48
Boussekey et al. also observed that widely used diagnostic algorithms. Among the inflammatory
procalcitonin levels were increased in patients with community- biomarkers, procalcitonin is currently regarded as the ideal
acquired pneumonia who developed infection-related DIC during their candidate to differentiate the type of the infection and guide
intensive care unit stay.
49
Interestingly, Ucar et al. did not find any antibiotic therapy due to several advantages over other
significant increase in the levels of TNF-α and serum amyloid A (SAA) inflammatory markers, including earlier increase that is preserved
in newborns with neonatal late-onset sepsis who developed DIC, but in the presence of immunosuppressive medication, a better
procalcitonin was markedly increased in all of these patients on days negative predictive value and a better correlation with outcome
zero, four and eight.
50
(e.g. mortality).
52
However, its clinical usefulness in identifying and
predicting the outcome of patients with DIC is circumstantial;
LBP is an acute-phase protein involved in the endotoxin-mediated therefore, larger studies in which this marker is evaluated against
immune response. Although the overall diagnostic performance of clinical outcome are needed. ■
this test is comparable to that of procalcitonin, LBP has slow kinetics
of induction and elimination, and the severity of the inflammatory
Giuseppe Lippi is an Associate Professor of Clinical
response is not well diagnosed.
51
Biochemistry and Clinical Molecular Biology at the
University of Verona. He is also Senior Assistant in the
ILs, especially IL-1 and IL-6, are biomarkers indicating the severity of the
Laboratory of Clinical Biochemistry, Haematology and
Clinical Molecular Biology at the University Hospital of
inflammatory response, but they are not specific for bacterial infection
Verona. Dr Lippi serves as Chairman of the Scientific
since they can be induced after surgery, autoimmune disorders, Division of the Italian Society of Clinical Chemistry and
transplant rejection and viral infection. Immunosuppression also
Laboratory Medicine (SIBiOC).
decreases the IL response. The kinetics of most ILs is also very fast;
Gian Cesare Guidi is a Professor of Clinical Biochemistry
concentrations increase only briefly or intermittently and decline very
and Clinical Molecular Biology at the University of
quickly in sepsis, so their measurement is not superior to that Verona and Director of the Laboratory of Clinical
of procalcitonin for the diagnosis of sepsis and may be unsuitable to
Biochemistry, Haematology and Clinical Molecular
Biology at the University Hospital of Verona. Dr Guidi is
monitor the clinical course of the disease.
51,52
Finally, the measurements
also Vice Dean of the Faculty of Medicine and Surgery
of most ILs is still challenging for a variety of pre-analytical/analytical at the University of Verona.
reasons, and several instruments in the statistics laboratory are not
equipped to deal with these tests.
EUROPEAN HAEMATOLOGY 23
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