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Chapter 139 Disseminated Intravascular Coagulation 2071

α 2-antiplasmin is a helpful test for assessing the dynamics of fibrino- Diagnostic Algorithm for the Diagnosis of Overt
lysis. Markers of plasmin generation include plasmin–α 2-antiplasmin BOX 139.2 Disseminated Intravascular Coagulation a
(PAP) complexes, which are moderately elevated in patients with
DIC. However, because the normal plasma concentration of α 2- 1. Presence of an underlying disorder known to be associated with
antiplasmin is about half that of plasminogen, α 2-antiplasmin is sus- disseminated intravascular coagulation (DIC) (Table 139.2)
ceptible to consumption when there is excessive plasmin generation. (no = 0, yes = 2)
Therefore PAP levels may underestimate total fibrinolytic activity. 2. Score global coagulation test results
With α 2-antiplasmin consumption, other protease inhibitors, such • Platelet count (>100 = 0; <100 = 1; <50 = 2)
as antithrombin, α 2-macroglobulin, α 1-antitrypsin, and C1-inhibitor • Level of fibrin markers (e.g., D-dimer, fibrin degradation
may act as plasmin inhibitors as well. Fibrinolytic activity may be products) b
insufficient to degrade intravascular fibrin in patients with DIC. (no increase: 0; moderate increase: 2; strong increase: 3)
• Prolonged prothrombin time
Fibrinolysis is suppressed by high levels of PAI-1, the major inhibitor (<3 s = 0; >3 s but <6 s = 1; >6 s = 2)
of tPA and uPA, PAI-1 levels are often elevated in patients with DIC, • Fibrinogen level
and correlate with an unfavorable outcome. A functional mutation in (>1.0 g/L = 0; <1.0 g/L = 1)
the PAI-1 gene, the 4G/5G polymorphism, is associated with high 3. Calculate score
levels of PAI-1, DIC and an increased risk of death in patients with 4. If ≥5: compatible with overt DIC; repeat scoring daily
meningococcal septicemia. If < 5: suggestive (not affirmative) for nonovert DIC; repeat next
1–2 days
a According to the Scientific Standardization Committee of the International
Point of Care Tests Society of Thrombosis and Haemostasis. 5
b Strong increase, greater than 5× upper limit of normal; moderate increase,
Although thrombelastography (TEG) was developed decades ago, greater than upper limit of normal but less than 5× upper limit of normal.
modern techniques, such as rotational thrombelastography (ROTEM),
enable bedside assessment of coagulation and fibrinolysis, which can
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be helpful in acute care settings. A theoretical advantage of TEG
over conventional coagulation assays is that because TEG uses whole assess prognosis in critically ill patients. Similar scoring systems have
blood, it provides a global assessment of platelet function, coagula- been developed and extensively evaluated in Japan. The major differ-
tion, and fibrinolysis. Increased and decreased coagulation as dem- ence between the international and Japanese scoring systems is a
onstrated with TEG was shown to correlate with clinically relevant slightly higher sensitivity of the Japanese algorithm, which may reflect
morbidity and mortality in several studies, although the superiority differences in the patient populations because the Japanese series
of TEG over conventional tests has not been unequivocally proven. include relatively large numbers of patients with hematologic
TEG may be overly sensitive to some interventions, such as fibrinogen malignancies.
administration, which is of questionable therapeutic value. Although
there are no systematic studies on the diagnostic accuracy of TEG for
the diagnosis of DIC, the test may be useful for assessing the global DIFFERENTIAL DIAGNOSIS
status of the coagulation and fibrinolytic systems in critically ill
patients. There are several other causes of coagulation abnormalities in patients
The aPTT biphasic waveform analysis is a sensitive and specific with underlying disorders known to be associated with DIC. A
test for hypercoagulability in critically ill patients. This test, which complicating factor is that patients may have multiple explanations
requires specific instrumentation, detects the presence of precipitates for their coagulopathy. For example, a patient with sepsis with DIC
of complexes of very low density lipoprotein and C-reactive protein may also have liver failure and vitamin K deficiency.
that form early in DIC. The appearance of such complexes in the The differential diagnosis of thrombocytopenia in patients with
plasma of individuals with diseases known to predispose to hyperco- suspected DIC is shown in Table 139.1. Sepsis itself is a risk factor
agulability confer a greater than 90% sensitivity and specificity for for thrombocytopenia in critically ill patients and the severity of
subsequent development of DIC and fatal outcome. sepsis correlates with the extent of thrombocytopenia. The princi-
pal factors that contribute to thrombocytopenia in patients with
Diagnostic Algorithm for Disseminated sepsis are decreased platelet production, increased consumption
or destruction, or sequestration platelets in the spleen or on the
Intravascular Coagulation endothelial surface. The decreased production of platelets in the
bone marrow in patients with sepsis occurs despite high levels of
A simple scoring system for the diagnosis of overt DIC was developed proinflammatory cytokines, such as TNF-α and IL-6, and increased
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by the subcommittee on DIC of ISTH (Box 139.2). The score can levels of thrombopoietin. Platelet production is impaired because of
be calculated using routinely available laboratory tests including the hemophagocytosis, a pathologic process characterized by phagocyto-
platelet count, the PT, a fibrin-related marker (usually D-dimer), and sis of megakaryocytes and other hematopoietic cells by monocytes
the fibrinogen concentration. Tentatively, a score of 5 or higher is and macrophages. Hemophagocytosis may be driven by the high
compatible with DIC, whereas a score below 5 may be indicative but levels of macrophage colony-stimulating factor (M-CSF) in patients
is not affirmative for nonovert DIC. More refined scoring systems with sepsis.
have been developed for the diagnosis of nonovert DIC. A recent Heparin-induced thrombocytopenia (HIT) is caused by a heparin-
study showed that the international normalized ratio (INR) can be induced antibody that binds to the heparin-platelet factor 4 (PF4)
used in place of the PT, further facilitating international exchange complex on the platelet surface (see Chapter 133). This may result
and standardization. Using receiver-operating characteristic curves, in platelet activation and consumption and arterial and venous
an optimal D-dimer cut-off was identified, thereby optimizing the thrombosis. A consecutive series of critically ill patients who received
sensitivity and the negative predictive value of the test. Prospective heparin revealed an incidence of HIT of 1%. The risk of HIT is
studies show that the sensitivity and specificity of the DIC score are higher with unfractionated heparin than with low-molecular-weight
93% and 98%, respectively. Studies in series of patients with specific heparin (LMWH). Thrombosis may occur in 25% to 50% of patients
underlying disorders causing DIC (e.g., cancer or obstetrical compli- with HIT (with fatal thrombosis in 4%–5%). The diagnosis of HIT
cations) show similar results. The severity of DIC according to this is based on detection of HIT antibodies in combination with the
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scoring system is related to the mortality in patients with sepsis. occurrence of thrombocytopenia in a patient receiving heparin, with
Linking prognostic determinants from critical care measurement or without concomitant arterial or venous thrombosis. The immu-
scores such as APACHE-II to DIC scores is an important means to noassay for heparin-PF4 antibodies has a high negative predictive