Abnormal biphasic waveform (BPW) patterns were previously reported when the activated partial thromboplastin time (aPTT) was performed in plasma from patients with disseminated intravascular coagulation (DIC). In this study, the prevalence of the BPW was examined in a cohort of 508 hospitalized patients with elevated fibrinogen degradation products (FDP) levels (>10 microg/mL). The presence of a BPW was automatically flagged by the MDA analyzer when the slope of the precoagulation phase in the waveform exceeded a threshold value of -0.25%T/sec. In our cohort, 76 patients (15%) were diagnosed with overt DIC according to the criteria recently proposed by the International Society of Thrombosis and Haemostasis (ISTH), whereas 96 patients (18.9%) were diagnosed with DIC following the criteria of the Japanese Ministry of Health and Welfare (JMHW). The JMHW and ISTH criteria agreed in 93% of cases (kappa coefficient 0.76). The concordance between both scoring systems was high in patients with infection but low in solid cancer. The BPW appeared in 65 patients (12.8%), with the highest prevalence (23.6%) in patients with infection. The BPW was more prevalent in the subgroup of patients with DIC: 59.2% and 47.9% for DIC diagnosed by ISTH and JMWH scores, respectively. The prevalence of the BPW was particularly high in patients with DIC and infection: 86.4% and 75.0% for DIC diagnosed by ISTH and JMWH scores, respectively. For the total cohort, the presence of the BPW was significantly associated with DIC. Odds ratios were 29.9 and 19.0 for ISTH and JMWH scores, respectively (p<0.0001). The BPW showed a moderate sensitivity (59.2% for the ISTH score; 47.9% for the JMWH score), but a high specificity (95.4% for both scores). Waveform analysis of the aPTT potentially provides a practical tool in risk assessment of critical care patients, in whom development of DIC is known to worsen the prognosis.

Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.

We examined haemostatic abnormalities and thrombotic disorders in 217 patients with malignant lymphoma. Plasma levels of fibrinogen and D-dimer were significantly higher in patients with malignant lymphoma than in healthy subjects. The incidence of severe complications, such as disseminated intravascular coagulation (DIC) and interstitial pneumonia (IP), differed with each clinical stage or histological type, but they occurred frequently in stage IV or natural killer (NK) cell lymphoma. Plasma levels of fibrinogen degradation products (FDP) and D-dimer, leukocyte tissue factor (TF) mRNA and plasma TF antigen were significantly higher in stage IV than in stage I, II or III. Plasma levels of FDP, D-dimer, and leukocyte TF mRNA in NK cell lymphoma were markedly higher than in other types of lymphoma. Immunohistochemical staining of NK cell lymphoma revealed that granulocyte macrophage colony-stimulating factor was positive in tumour cells, whereas von Willebrand factor and TF were positive in vascular endothelial cells of surrounding tissue. Our results suggested that patients with stage IV disease and NK cell lymphoma were in abnormal thrombotic and haemostatic state, and may frequently develop DIC and IP. One of the mechanisms of DIC and IP may involve elevated cytokine production by lymphoma cells, which can stimulate the expression of TF in blood cells or surrounding tissue.

Background/Aims: There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). Methods: We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. Results: Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the noncholangiocarcinoma patients (57.1% vs 57.1%, respectively). Conclusions: TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma. (Gut Liver 2014;8:669-673)

SummaryIn a preliminary study, we have demonstrated that tissue factor (TF) is immunohistochemically stained in monocytes from patients with disseminated intravascular coagulation (DIC) but not from healthy volunteers, and that leukocytes from DIC patients induce enhanced activated factor X (FXa) generation in the presence of a mixture of FVIIa, FX and Ca2+. Then, TF mRNA levels in leukocytes were measured to evaluate the role of TF in the pathophysiology of various diseases. TF mRNA levels in leukocytes were low in healthy volunteers but they were significantly increased in various diseases, especially in patients with infectious diseases, solid cancer, anemd hematopoietic tumors. TF mRNA levels in leukocytes were significantly higher in patients with high levels of C reactive protein (CRP) than in those with low CRP. TF mRNA levels were significantly higher in patients with DIC than in those without DIC. TF mRNA levels were well correlated with TF antigens in plasma and leukocytes. These findings suggest that the expression of TF mRNA in leukocytes is increased in various diseases and that this may play an important role in hypercoagulability or DIC.