Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant‐associated thrombotic microangiopathy (BMT‐TM)

Zeigler, Z.R.; Rosenfeld, C.S.; Andrews, D.F.; Nemunaitis, J.; Raymond, J.M.; Shadduck, R.K.; Kramer, R.E.; Gryn, J.F.; Rintels, P.B.; Besa, E.C.; George, J.N.

doi:10.1002/(sici)1096-8652(199612)53:4<213::aid-ajh1>3.3.co;2-n

Cited by 6 publications

(10 citation statements)

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“…ANG2 is upregulated in a variety of inflammatory conditions [32,33]. TM is a high-affinity receptor for thrombin on the surface of vascular endothelial cells and a cofactor for the activation of protein C. Therefore, the dysregulation of TM induces endothelial cell injury in SOS, TAM, and GVHD [34,35]. D-dimer is one of the markers for activated coagulation and fibrinolysis, and its increase has been implicated in the development of SOS [36].…”

Section: Discussionmentioning

confidence: 99%

A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage–Related Complications in Allogeneic Transplantation

Tatekawa

Kohno

Ozeki

et al. 2016

Biology of Blood and Marrow Transplantation

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Noninfectious transplantation-related complications (TRCs), such as graft-versus-host disease or TRC with endothelial cell damage (TRC-EC), remain as the major obstacle for successful allogeneic hematopoietic cell transplantation (allo-HCT). However, the diagnosis and prognosis for the emergence of these complications are difficult to define during the early post allo-HCT period. Here, we tried to generate a novel diagnostic system for TRC-EC by analyzing 188 adult patients who received allo-HCT. Our study found that the peripheral blood levels of angiopoietin 2 (ANG2), C-reactive protein (CRP), D-dimer, and thrombomodulin (TM) at the onset of TRCs were significantly associated with the development of TRC-EC. We next developed a composite biomarker panel incorporating the risk values of ANG2, CRP, D-dimer, and TM at the onset of TRCs, which classified these patients into 3 risk groups: low, intermediate, and high risk. As a result, the panel was useful not only for the diagnosis of TRC-EC with high specificity and sensitivity, but also for the prediction of the patients' long-term outcome. The 5-year overall survival (OS) rates of patients in the low-, intermediate-, and high-risk groups since the occurrence from TRCs were 76.2%, 54.9%, and 26.9%, respectively, and the high-risk score was significantly associated with both poor OS (hazard ratio [HR], 5.60; 95% confidence interval [CI], 2.81 to 11.20; P < .01) and frequent nonrelapse mortality (HR, 19.75; 95% CI, 5.59 to 69.77; P < .01). Thus, the composite panel proposed in this study provides a powerful tool for the diagnosis of TRC-EC and for the prediction of survival for patients with TRC-EC after allo-HCT.

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Section: Discussionmentioning

confidence: 99%

A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage–Related Complications in Allogeneic Transplantation

Tatekawa

Kohno

Ozeki

et al. 2016

Biology of Blood and Marrow Transplantation

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“…In contrast to classic TMA, metalloproteinase activity is normal in the BMT‐associated TMA (23). However, indicators of endothelial injury such as vWF concentration and thrombomodulin/creatinine ratio have shown to be increased (24, 25). In contrast to BMT–TMA, our patient (and other reports of CMV‐associated TMA) responded well to plasmapheresis.…”

Section: Discussionmentioning

confidence: 99%

Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case‐based review

Ramasubbu

Mullick

Koo

et al. 2003

Transplant Infectious Dis

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“…[66][67][68] Endothelial activation is attested by the increased levels of E-selectin, sVCAM-1, VWF, PAI-1, and TM in the plasma of TAM patients. 53,69,70 VWF and TM levels correlate with the severity of the syndrome and their altered levels are not solely explained by disturbed renal excretion (►Table 1). 69 High-dose chemotherapy with or without body irradiation is likely the offending event in the pathogenesis of this disease, although the risk is not reduced with nonmyeloablative conditioning regimen.…”

Section: Transplant-associated Microangiopathymentioning

confidence: 99%

“…53,69,70 VWF and TM levels correlate with the severity of the syndrome and their altered levels are not solely explained by disturbed renal excretion (►Table 1). 69 High-dose chemotherapy with or without body irradiation is likely the offending event in the pathogenesis of this disease, although the risk is not reduced with nonmyeloablative conditioning regimen. 63 According to epidemiological data, 71 GVHD may contribute to the development of TAM.…”

Section: Transplant-associated Microangiopathymentioning

confidence: 99%

Interplay of Inflammation and Endothelial Dysfunction in Bone Marrow Transplantation: Focus on Hepatic Veno-Occlusive Disease

Vion

Rautou

Durand

et al. 2015

Semin Thromb Hemost

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Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT.

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Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant‐associated thrombotic microangiopathy (BMT‐TM)

Cited by 6 publications

References 0 publications

A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage–Related Complications in Allogeneic Transplantation

A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage–Related Complications in Allogeneic Transplantation

Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case‐based review

Interplay of Inflammation and Endothelial Dysfunction in Bone Marrow Transplantation: Focus on Hepatic Veno-Occlusive Disease

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