- Email: [email protected]
Changing the guard
Thrombosis Research 141 (2016) 196–197
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Editorial
Changing the guard Dear Friends, We are very excited to begin our journey as Co-Editors in Chief for Thrombosis Research. We are also very grateful to Per Morten Sandset who has managed the Journal successfully for more than 14 years. Our goal is to further transform the Thrombosis Research into an indispensable tool for clinical and basic science experts in Thrombosis and Hemostasis. In upcoming issues you will see high quality narrative reviews and important practice relevant and science relevant manuscripts. But allow us to introduce ourselves; Marc Rodger is a Hematologist and Clinician Scientist whose clinical practice is focused on venous thrombosis. His clinical research career has been focused on diagnostic and therapeutic management of venous thrombosis with a special interest in pregnancy. He has led case control studies, cohort studies, decision analyses and randomized trials. He currently co-leads a panCanadian venous thrombosis clinical research network (CanVECTOR — www.canvector.ca) and is spearheading the development of an international network of clinical research networks (INVENT — www.inventVTE.com). In his clinical practice, on a weekly basis, Marc sees pregnant women who struggle with the decision about using anti-partum thromboprophylaxis or foregoing thromboprophylaxis. Guidelines provide us with recommendations, but of course in pregnancy there are very few randomized controlled trials that are conducted so most of this evidence is weak and as clinicians we struggle. As a consequence of weak evidence guideline developers implore us to have values and preferences based discussion with women. However, there is very little research that has been conducted exploring values and preferences for thromboprophylaxis in pregnancy let alone for thromboprophylaxis in the anti-natal period. Interestingly, in the March issue of the journal, we published an important paper exploring women's values and preferences for thromboprophylaxis during the ante-natal period in pregnancy. This paper is a valuable contribution that will help us anchor our discussions with our patients [1]. Also in the March issue, we saw a description of a randomized controlled trial, in the important area of preventing preeclampsia, comparing high dose antithrombin supplementation to no supplementation however, the trial could not be completed due to poor recruitment [2]. It is important for feasibility studies to be published in the peer reviewed literature. If feasibility studies are not published, investigators, sponsors and governments may waste years of important time and resources replicating the inability to complete the trials. Trial feasibility publications permit us to design future feasible trials that hopefully will answer the questions that clinicians and patients, guideline makers and governments demand we answer. Only a fraction of the clinical questions that we ask on a daily basis actually have level 1A evidence to guide us. We rely on industry, but more heavily on the academic community, to ensure that these
http://dx.doi.org/10.1016/j.thromres.2016.04.009 0049-3848/© 2016 Published by Elsevier Ltd.
questions are answered in well-designed and feasible trials. So we encourage future authors and investigators to tell us what are the questions that need to be answered, tell us how you will answer them, tell us about your efforts to answer these questions (whether they were successful or not!) and finally, tell us about the questions that you have answered so that we can help clinicians, patients, policy makers and government to bring evidence into clinical practice. Henri Versteeg is a PhD and full professor in Thrombosis and Haemostasis and his research focuses on the interplay between the blood coagulation system and cancer, including venous thrombosis as a consequence of cancer. Cancer-associated thrombosis (CAT) was first described by Jean Baptiste Bouillaud and Armand Trousseau, some 150 years ago. Despite the fact that the causes and risk factors for venous thrombosis have been largely identified, the causes underlying CAT remain largely unidentified. In addition, emerging data suggest that cancer may also increase the risk of arterial thrombosis, but this link has not been extensively investigated. Nevertheless, in previous issues of Thrombosis Research a number of papers have extensively dealt with thrombosis in cancer patients. In our January issue Edwin and colleagues concluded that recurrent VTE is highly prevalent among glioblastoma patients with a second primary malignancy [3]. Long term anticoagulation appears to reduce this risk, although long term anticoagulation is often not utilized. In our March issue, Thalin and coworkers described a higher prevalence of cancer in ischemic stroke patients with elevated high sensitive Troponin levels [4]. The enhanced levels of markers for NETosis — the release of chromatin from neutrophils — in the plasma of these patients led the investigators to the conclusion that NETosis is an important contributor to arterial thrombosis in cancer patients. Tissue factor-positive microvesicles (TF-MVs) in the blood of cancer patients have also been suggested to play a role in CAT (elegantly reviewed in our March issue [5]), but some studies have not been able to confirm this [6]. This may be attributed to the fact that various methods, including TF antigen measurements, TF activity assays and flow cytometry approaches have been used to detect TF-MVs, all with their distinct limitations. Nevertheless, it is now clear that TF-MV activity strongly associates with mortality in pancreatic cancer [7]. In the coagulation and fibrinolysis section of the current issue, Claussen and colleagues [8] present data showing that combined analysis of plasma D-dimer levels and TF-MV activity provides additional information in the preoperative diagnosis of ovarian cancer. In fact, based on their findings they propose a two-step diagnosis, in which women with an abnormal plasma D-dimer levels are further tested for serum levels of the ovarium cancer-specific marker Ca-125 and TF-MV activity to identify those women that are likely to have ovarian cancer. Another interesting aspect of this study is that TF antigen detection and activity measurements on TF-MVs do not yield similar results. The authors elegantly show that many commercially available TF ELISAs do not detect
Editorial
TF on the surface of microvesicles. Thus, caution is suggested when detecting TF antigen on the surface of microvesicles, in valuable patient plasma. Finally, the authors did not find associations between TF-MV activity and perioperative VTE, and consequently the relationship between TFMV activity and CAT remains unclear. We therefore invite future authors to contribute as many papers as possible on this interesting yet unsolved matter. In closing, we hope that we can achieve our goal of making Thrombosis Research a must read for you and your colleagues. Onwards and upwards! References [1] S.M. Bates, P. Alonso-Coelloc, K.A.O. Tikkinen, S. Ebrahimc, L. Cruz Lopes, S.D. McDonald, et al., Women's values and preferences and health state valuations for thromboprophylaxis during pregnancy: a cross-sectional interview study, Thromb. Res. 140 (2016) 22–29. [2] A. D'Angelo, L. Valsecchi, High dose antithrombin supplementation in early preeclampsia: a randomized, double blind, placebo-controlled study, Thromb. Res. 140 (2016) 7–13. [3] N.C. Edwin, M.N. Khoury, D. Sohal, K.R. McCrae, M.S. Ahluwalia, A.A. Khorana, Recurrent venous thromboembolism in glioblastoma, Thromb. Res. 137 (2016) 184–188. [4] C. Thålin, M. Demers, B. Blomgren, S.L. Wong, M. von Arbin, A. von Heijne, et al., NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation, Thromb. Res. 139 (2016) 56–64.
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[5] Y. Hisada, W. Alexander, R. Kasthuri, P. Voorhees, F. Mobarrez, A. Taylor, et al., Measurement of microparticle tissue factor activity in clinical samples: a summary of two tissue factor-dependent FXa generation assays, Thromb. Res. 139 (2016) 90–97. [6] L.G. van den Hengel, A.Q. van Steijn-van Tol, R.M. Bertina, H.H. Versteeg, S. Osanto, Microparticle-associated tissue factor activity in plasma is unaffected by cytolytic chemotherapy treatment in metastatic testicular cancer patients, Thromb. Res. 131 (2) (2013) 187–189. [7] J. Thaler, C. Ay, N. Mackman, R.M. Bertina, A. Kaider, C. Marosi, N.S. Key, D.A. Barcel, W. Scheithauer, G. Kornek, C. Zielinski, I. Pabinger, Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients, J. Thromb. Haemost. 10 (7) (2012) 1363–1370. [8] C. Claussen, A.-V. Rausch, S. Lezius, A. Amirkhosravi, M. Davila, J.L. Francis, et al., Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer, Thromb. Res. 141 (2016) 39–48 (in this issue).
Marc Rodger The Ottawa Hospital, Canada E-mail address: [email protected] Henri H. Versteeg Leiden University Medical Center, Netherlands E-mail address: [email protected]
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Editorial
Changing the guard Dear Friends, We are very excited to begin our journey as Co-Editors in Chief for Thrombosis Research. We are also very grateful to Per Morten Sandset who has managed the Journal successfully for more than 14 years. Our goal is to further transform the Thrombosis Research into an indispensable tool for clinical and basic science experts in Thrombosis and Hemostasis. In upcoming issues you will see high quality narrative reviews and important practice relevant and science relevant manuscripts. But allow us to introduce ourselves; Marc Rodger is a Hematologist and Clinician Scientist whose clinical practice is focused on venous thrombosis. His clinical research career has been focused on diagnostic and therapeutic management of venous thrombosis with a special interest in pregnancy. He has led case control studies, cohort studies, decision analyses and randomized trials. He currently co-leads a panCanadian venous thrombosis clinical research network (CanVECTOR — www.canvector.ca) and is spearheading the development of an international network of clinical research networks (INVENT — www.inventVTE.com). In his clinical practice, on a weekly basis, Marc sees pregnant women who struggle with the decision about using anti-partum thromboprophylaxis or foregoing thromboprophylaxis. Guidelines provide us with recommendations, but of course in pregnancy there are very few randomized controlled trials that are conducted so most of this evidence is weak and as clinicians we struggle. As a consequence of weak evidence guideline developers implore us to have values and preferences based discussion with women. However, there is very little research that has been conducted exploring values and preferences for thromboprophylaxis in pregnancy let alone for thromboprophylaxis in the anti-natal period. Interestingly, in the March issue of the journal, we published an important paper exploring women's values and preferences for thromboprophylaxis during the ante-natal period in pregnancy. This paper is a valuable contribution that will help us anchor our discussions with our patients [1]. Also in the March issue, we saw a description of a randomized controlled trial, in the important area of preventing preeclampsia, comparing high dose antithrombin supplementation to no supplementation however, the trial could not be completed due to poor recruitment [2]. It is important for feasibility studies to be published in the peer reviewed literature. If feasibility studies are not published, investigators, sponsors and governments may waste years of important time and resources replicating the inability to complete the trials. Trial feasibility publications permit us to design future feasible trials that hopefully will answer the questions that clinicians and patients, guideline makers and governments demand we answer. Only a fraction of the clinical questions that we ask on a daily basis actually have level 1A evidence to guide us. We rely on industry, but more heavily on the academic community, to ensure that these
http://dx.doi.org/10.1016/j.thromres.2016.04.009 0049-3848/© 2016 Published by Elsevier Ltd.
questions are answered in well-designed and feasible trials. So we encourage future authors and investigators to tell us what are the questions that need to be answered, tell us how you will answer them, tell us about your efforts to answer these questions (whether they were successful or not!) and finally, tell us about the questions that you have answered so that we can help clinicians, patients, policy makers and government to bring evidence into clinical practice. Henri Versteeg is a PhD and full professor in Thrombosis and Haemostasis and his research focuses on the interplay between the blood coagulation system and cancer, including venous thrombosis as a consequence of cancer. Cancer-associated thrombosis (CAT) was first described by Jean Baptiste Bouillaud and Armand Trousseau, some 150 years ago. Despite the fact that the causes and risk factors for venous thrombosis have been largely identified, the causes underlying CAT remain largely unidentified. In addition, emerging data suggest that cancer may also increase the risk of arterial thrombosis, but this link has not been extensively investigated. Nevertheless, in previous issues of Thrombosis Research a number of papers have extensively dealt with thrombosis in cancer patients. In our January issue Edwin and colleagues concluded that recurrent VTE is highly prevalent among glioblastoma patients with a second primary malignancy [3]. Long term anticoagulation appears to reduce this risk, although long term anticoagulation is often not utilized. In our March issue, Thalin and coworkers described a higher prevalence of cancer in ischemic stroke patients with elevated high sensitive Troponin levels [4]. The enhanced levels of markers for NETosis — the release of chromatin from neutrophils — in the plasma of these patients led the investigators to the conclusion that NETosis is an important contributor to arterial thrombosis in cancer patients. Tissue factor-positive microvesicles (TF-MVs) in the blood of cancer patients have also been suggested to play a role in CAT (elegantly reviewed in our March issue [5]), but some studies have not been able to confirm this [6]. This may be attributed to the fact that various methods, including TF antigen measurements, TF activity assays and flow cytometry approaches have been used to detect TF-MVs, all with their distinct limitations. Nevertheless, it is now clear that TF-MV activity strongly associates with mortality in pancreatic cancer [7]. In the coagulation and fibrinolysis section of the current issue, Claussen and colleagues [8] present data showing that combined analysis of plasma D-dimer levels and TF-MV activity provides additional information in the preoperative diagnosis of ovarian cancer. In fact, based on their findings they propose a two-step diagnosis, in which women with an abnormal plasma D-dimer levels are further tested for serum levels of the ovarium cancer-specific marker Ca-125 and TF-MV activity to identify those women that are likely to have ovarian cancer. Another interesting aspect of this study is that TF antigen detection and activity measurements on TF-MVs do not yield similar results. The authors elegantly show that many commercially available TF ELISAs do not detect
Editorial
TF on the surface of microvesicles. Thus, caution is suggested when detecting TF antigen on the surface of microvesicles, in valuable patient plasma. Finally, the authors did not find associations between TF-MV activity and perioperative VTE, and consequently the relationship between TFMV activity and CAT remains unclear. We therefore invite future authors to contribute as many papers as possible on this interesting yet unsolved matter. In closing, we hope that we can achieve our goal of making Thrombosis Research a must read for you and your colleagues. Onwards and upwards! References [1] S.M. Bates, P. Alonso-Coelloc, K.A.O. Tikkinen, S. Ebrahimc, L. Cruz Lopes, S.D. McDonald, et al., Women's values and preferences and health state valuations for thromboprophylaxis during pregnancy: a cross-sectional interview study, Thromb. Res. 140 (2016) 22–29. [2] A. D'Angelo, L. Valsecchi, High dose antithrombin supplementation in early preeclampsia: a randomized, double blind, placebo-controlled study, Thromb. Res. 140 (2016) 7–13. [3] N.C. Edwin, M.N. Khoury, D. Sohal, K.R. McCrae, M.S. Ahluwalia, A.A. Khorana, Recurrent venous thromboembolism in glioblastoma, Thromb. Res. 137 (2016) 184–188. [4] C. Thålin, M. Demers, B. Blomgren, S.L. Wong, M. von Arbin, A. von Heijne, et al., NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation, Thromb. Res. 139 (2016) 56–64.
197
[5] Y. Hisada, W. Alexander, R. Kasthuri, P. Voorhees, F. Mobarrez, A. Taylor, et al., Measurement of microparticle tissue factor activity in clinical samples: a summary of two tissue factor-dependent FXa generation assays, Thromb. Res. 139 (2016) 90–97. [6] L.G. van den Hengel, A.Q. van Steijn-van Tol, R.M. Bertina, H.H. Versteeg, S. Osanto, Microparticle-associated tissue factor activity in plasma is unaffected by cytolytic chemotherapy treatment in metastatic testicular cancer patients, Thromb. Res. 131 (2) (2013) 187–189. [7] J. Thaler, C. Ay, N. Mackman, R.M. Bertina, A. Kaider, C. Marosi, N.S. Key, D.A. Barcel, W. Scheithauer, G. Kornek, C. Zielinski, I. Pabinger, Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients, J. Thromb. Haemost. 10 (7) (2012) 1363–1370. [8] C. Claussen, A.-V. Rausch, S. Lezius, A. Amirkhosravi, M. Davila, J.L. Francis, et al., Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer, Thromb. Res. 141 (2016) 39–48 (in this issue).
Marc Rodger The Ottawa Hospital, Canada E-mail address: [email protected] Henri H. Versteeg Leiden University Medical Center, Netherlands E-mail address: [email protected]