Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries

Wada, Hideo; Mori, Yoshitaka; Shimura, Minori; Hiyoyama, Katsuyo; Ioka, Mika; Nakasaki, Takahiro; Nishikawa, Masakatsu; Nakano, Masahiko; Kumeda, Kousuke; Kaneko, Toshihiro; Nakamura, Shin; Shiku, Hiroshi

doi:10.1002/(sici)1096-8652(199807)58:3<189::aid-ajh5>3.0.co;2-n

Cited by 57 publications

(18 citation statements)

References 22 publications

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“…SF and D-dimer are considered as markers of hypercoagulable state, as both parameters are reported to be elevated in DVT [3,21], DIC [22,23], and hyperlipidemia [24]. In the present study, plasma concentrations of D-dimer and SF were significantly high in patients with DVT, but those levels were also significantly high in patients without DVT.…”

Section: Discussionsupporting

confidence: 49%

Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer

et al. 2005

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The present study was designed to determine the cutoff values of D-dimer and soluble fibrin (SF) for the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in Japanese patients. Plasma levels of these molecules were measured in 243 patients suspected of having DVT and 100 healthy volunteers (controls). Out of 243 patients, 20 patients were diagnosed with DVT. In the control group, plasma levels of D-dimer and SF did not show normal distribution, and the 95% confidence intervals (CI) of D-dimer and SF were 2.45 mg/mL and 6.92 mg/mL, respectively. Plasma levels of D-dimer and SF of patients with DVT were significantly higher than of those without DVT. In patients with DVT, the minimum values of D-dimer and SF were 1.71 and 1.44 mg/mL, respectively. When the cutoff value was set at the average + 1 SD of those of the control (D-dimer, about 1.8 mg/ mL; SF, about 1.4 mg/mL), 1 and 0 patient with DVT was overlooked, respectively. The sensitivity and specificity of D-dimer and SF for DVT were 95% and 100%, and 61.9% and 53.8%, respectively. When the cutoff value was set at 95% CI of the control (D-dimer, 2.5 mg/ mL; SF, 6.9 mg/mL), 2 and 9 patients with DVT were overlooked, respectively. The sensitivity and specificity of D-dimer and SF were 90% and 50%, and 77.6% and 88.3%, respectively. When the cutoff values set at 2.5 mg/mL of D-dimer or 6.9 mg/mL of SF, 1 DVT patient was overlooked, with sensitivity and specificity of 95% and 69.5%. Our data suggest that both D-dimer and SF are useful markers for the diagnosis of DVT and that measurement of both D-dimer and SF increases the sensitivity and specificity for the diagnosis of DVT/PE.

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Section: Discussionsupporting

confidence: 49%

Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer

et al. 2005

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“…Diseases characterized by vascular abnormalities, such as acute renal failure, hemorrhagic shock, hemolytic uremic syndrome, and thrombotic thrombocytic purpura, are associated with increased hemolysis, [61][62][63][64] and one could speculate that heme causes the inflammatory onset in these diseases. Moreover, it was recently postulated that excessive heme release plays a major role in vaso-occlusive events in sickle cell disease.…”

Section: Discussionmentioning

confidence: 99%

Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase

Wagener

Eggert

Boerman

et al. 2001

Blood

384

324

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Various pathologic conditions, such as hemorrhage, hemolysis and cell injury, are characterized by the release of large amounts of heme. Recently, it was demonstrated that heme oxygenase (HO), the heme-degrading enzyme, and heme are able to modulate adhesion molecule expression in vitro. In the present study, the effects of heme and HO on inflammation in mice were analyzed by monitoring the biodistribution of radiolabeled liposomes and leukocytes in conjunction with immunohistochemistry. Small liposomes accumulate in inflamed tissues by diffusion because of locally enhanced vascular permeability, whereas leukocytes actively migrate into inflammatory areas through specific adhesive interactions with the endothelium and chemotaxis. Exposure to heme resulted in a dramatic increase in liposome accumulation in the pancreas, but also intestines, liver, and spleen exhibited significantly increased vascular permeability. Similarly, intravenously administered heme caused an enhanced influx of radiolabeled leukocytes into these organs. Immunohistochemical analysis showed differential up-regulation of the adhesion molecules ICAM-1, P-selectin, and fibronectin in liver and pancreas in heme-treated animals. Heme-induced adhesive properties were accompanied by a massive influx of granulocytes into these inflamed tissues, suggesting an important contribution to the pathogenesis of inflammatory processes. Moreover, inhibition of HO activity exacerbated hemeinduced granulocyte infiltration. Here it is demonstrated for the first time that heme induces increased vascular permeability, adhesion molecule expression, and leukocyte recruitment in vivo, whereas HO antagonizes heme-induced inflammation possibly through the down-modulation of adhesion molecules. IntroductionThe inflammatory response consists of a complex cascade of orchestrated signals resulting in increased permeability of blood vessels, changes in blood flow, and migration of leukocytes from blood to affected tissues. 1 Vascular permeability results from the partial retraction of endothelial cells of small venules in the vicinity of inflammation, leaving small intercellular gaps (approximately 0.1-0.4 m). This so-called vascular leakage results in slower blood flow by allowing the passage of water, salts, and small proteins from the plasma into the damaged area, whereas blood cells are retained within the vessels. 1 In normal circumstances the endothelial layer is nonadhesive for leukocytes. However, during inflammation, activated endothelial cells increase the surface expression of specific adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), endothelial leukocyte adhesion molecule (E-selectin), and P-selectin. 2 This increased cell surface adhesion enables circulating activated leukocytes to specifically interact with their ligands on the endothelium. 2 Although the inflammatory response of the host is considered essential in the protection against pathogens, activated leukocytes and endothelial cells ma...

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“…Certainly endothelial injury has long been considered by many to be the prime event in TTP, although the exact nature of the endothelial insult remains unclear. Thrombomodulin, 25 P-selectin (GMP-140), 26 27 tissue plasminogen activator (tPA), 28 and plasminogen activator inhibitor 1 (PAI-1) 29 are all raised, whereas tissue factor pathway inhibitor (TFPI) 30 is reduced, consistent with endothelial damage. These observations of endothelial activation, together with histological findings of intimal proliferation, luminal stenosis, and absent inflammatory changes, are consistent with apoptosis.…”

Section: Vwf Proteolysismentioning

confidence: 99%