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Laboratory Diagnostics in Septic Disseminated Intravascular Coagulation
An overall score of 5 is compatible with overt DIC.
1
A five-year overview and acquired or inherited deficiencies of coagulation factors of the
by the ISTH SSC on DIC has recently confirmed that a score of 5 or intrinsic and common pathway. Prolonged APTT values have been
greater can reliably identify overt DIC with a sensitivity of 91% and a reported in up to 50% of patients with DIC, but in the other 50% they
specificity of 97%.
13
It was also shown that patients with overt DIC can be normal or even shortened (mirroring the acute-phase-induced
diagnosed according to the ISTH DIC score had a significantly higher increase of von Willebrand factor). Accordingly, its clinical usefulness
risk of death and of developing septic shock. However, since more than is limited in the diagnostics of DIC; it certainly cannot be used to rule
95% of sepsis patients have elevated fibrin-related markers, the DIC
score is strongly dependent on prolongation of PT and platelet count.
14
Many of the underlying conditions that
The Japanese Ministry of Health and Welfare (JMHW) established the
are associated with disseminated
diagnostic criteria for DIC in 1987. These criteria are also based on a
scoring system relying on the presence of underlying disease, intravascular coagulation (DIC) may in fact
bleeding, organ failure and the results of global coagulation tests,
cause a low platelet count in the absence
and include:
of DIC, such as severe local infections,
• platelet count: ≤120x10
9
/l = 1, ≤80x10
9
/l = 2, ≤50x10
9
/l = 3;
malignancy or anticancer therapy.
• elevated fibrin degradation products: ≥10µg/ml = 1, ≥20µg/ml = 2,
≥40µg/ml = 3;
•PT:≥1.25 = 1, ≥1.67 = 2; and out the diagnosis, and overall it is even more unreliable than the PT.
22
• fibrinogen levels: ≤150mg/dl = 1, ≤100 mg/dl = 2. Fibrinogen levels often decline in patients with DIC due to massive
consumption of the protein entrapped within the thrombi. However,
An overall score of ≥4 or ≥7 is compatible with DIC in patients with or the overall sensitivity of plasma fibrinogen levels for the diagnosis of
without haematological malignancies, respectively.
15
The rate of DIC is low, since the protein is an additional well-recognised acute-
agreement in the diagnosis of DIC by ISTH and JMHW criteria was 67%; phase reactant and its levels are often within the normal range for a
only 2% of non-DIC patients by JMHW criteria were diagnosed with long period of time, especially in patients with severe infections. Thus,
overt DIC by ISTH criteria, suggesting that the ISTH criteria for overt hypofibrinogenaemia is frequently detected only in very severe cases
DIC may include typical cases of DIC.
16
of DIC, or in the advanced stages of the disease.
2,22
More important is
the longitudinal comparison of fibrinogen values of the patient,
The Japanese Association for Acute Medicine (JAAM) DIC Study Group because a sudden and dramatic drop often underlies massive
recently announced new DIC diagnostic criteria for critically ill consumption, as is commonplace in patients with DIC.
2,22
patients, reaffirming the reliability of using a four-parameter scoring
card that includes: In contrast to fibrinogen, platelet count is considered a very sensitive
test in the diagnosis of DIC. Platelet count is strongly correlated with
• inflammatory response syndrome criteria: ≥3 = 1, 0–2 = 0; markers of thrombin generation, since thrombin-induced platelet
• platelet count: <80x10
9
/l or 50% decrease within 24 hours = 3, aggregation is to a large extent responsible for platelet consumption.
≥80x10
9
/l, <120x10
9
/l or >30% decrease within 24 hours = 1 and Moreover, platelet count is not influenced by the acute-phase
>120x10
9
/l = 0; response, so overall it is more reliable than fibrinogen testing.
•PT:≥1.2 = 1, <1.2 = 0; and However, since the normal platelet count varies between 150 and
• fibrin/fibrinogen degradation products: ≥25 mg/l = 3, ≥10 and 450x10
9
/l, a single determination might be misleading; the
<25mg/dl = 1, <10 = 0. longitudinal comparison of data may provide more valuable
information in this setting. Many of the underlying conditions that are
An overall score of ≥4 is compatible with DIC.
17
Two subsequent associated with DIC may in fact cause a low platelet count in the
prospective surveys demonstrated the natural history of DIC patients absence of DIC, such as severe local infections, malignancy or
diagnosed by the JAAM DIC diagnostic criteria in a critical care anticancer therapy. Accordingly, a continuous drop in the platelet
setting, highlighting progression from the JAAM DIC to the ISTH overt count, mainly determined at intervals between one and four hours,
DIC,
18
especially in patients with sepsis,
19
thus enabling them to underlies thrombin generation and the subsequent intravascular
receive early treatment. More interestingly, a recent study by the platelet aggregation. Conversely, a stable platelet count suggests that
JAAM DIC Study Group also showed that more than 50% of JAAM DIC thrombin formation has stopped.
2,22
patients with sepsis who died within 28 days could not be detected by
ISTH DIC criteria during the initial three days.
20
Consumption of Natural Inhibitors
The natural anticoagulants, especially antithrombin and protein C, are
Global Tests of Haemostasis frequently reduced in patients with DIC, and they also have prognostic
The PT is a simple, rapid and relatively inexpensive haemostatic test significance.
23,24
A decrease in plasma antithrombin levels below 50% of
that explores the extrinsic and common pathways of blood normal is strongly associated with increased mortality in patients with
coagulation.
21
Although its values have been reported to be prolonged DIC.
25
Wilson et al. observed that in surgical patients with sepsis,
in the vast majority of patients with DIC (up to 70%), the use of PT as antithrombin levels below 70 and 65% are associated with 90 and
a diagnostic test is questionable because elevations often occur in a 100% mortality, respectively.
26
Accordingly, baseline antithrombin levels
later stage of the disease when the outcome of the patients may have the best prognostic value for prediction of subsequent death in
already be compromised.
22
The activated partial thromboplastin time patients affected by septic shock.
27
A significant prognostic value of
(APTT) is a global clotting test sensitive to several plasma inhibitors protein C concentrations in neutropenic patients affected by septic
EUROPEAN HAEMATOLOGY 21
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