Thrombosis Research 133 (2014) 1164–1165
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Letter to the Editors-in-Chief The association between red cell distribution width and venous thromboembolism: A biochemical evaluation
Dear Editors, In a recent issue of Thrombosis Research, we read with great interest the published article by Zölleret al. entitled with “Red cell distribution width and risk for venous thromboembolism:A population-based cohort study” [1]. They have shown that the hazard ratios (HR) for venous thromboembolism (VTE) for the second, third and fourth red cell distribution width (RDW) quartiles were 1.15 (95% confidence interval 0.94–1.41), 1.41 (1.14–1.73), 1.74 (1.38–2.21), respectively. In the multivariate model,they have found that subjectswith the top 5% of RDW values compared with the bottom quartile had also an even higher risk (HR = 2.51,1.78–2.54). However, we think that some points should be discussed. RDW represents the variability in the red blood cell volume distribution and can be considered an index of heterogeneity in size of circulating erythrocytes [2]. This parameter is easily measured by automated hematology analyzers and reported as a component of complete blood count. Authors have excluded patients have a condition known to increase RDW such as pregnancy, inflammatory bowel disease or recent transfusion within the past 3 months. However, the RDW levels may also reflect neurohumoral activation, thyroid disease, nutritional deficiencies of folate, vitamin B12, and iron, bone marrow dysfunction, chronic or acute systemic inflammation [3], and some medications [4]. Patients have these situations are mostly excluded from the studies showing the prognostic and predictor value of the RDW [2]. In conclusion, the authors investigated to whether RDW is an independent predictor of first event of VTE in asymptomatic middleaged subjects in the Malmö Diet and Cancer Study [1]. However, authors only measured hemoglobin, mean corpuscular volume (MCV), leucocyte and platelet counts and RDW levels. They did not measure other factors including iron, vitamin B12, folate, thyroid function tests, and inflammatory markers. In this study, because of all these causes, RDW levels could not be associated with long-term incidence of first event of VTE in the middle-aged subjects. The explanation of these concerns could provide clearer information to the readers of the journal to show the association between RDW and incident VTE in patients with VTE. References [1] Zöller B, Melander O, Svensson P, Engström G. Red cell distribution width and risk for venous thromboembolism: A population-based cohort study. Thromb Res 2014; 133:334–9. [2] Yaman H, Celik T, Akgul EO, Cayci T, Kurt Y. Red cell distribution width and acute coronary syndromes. Int J Cardiol 2010;145:353. [3] Balta S, Demirkol S, Arslan Z, Unlu M, Celik T. Inflammatory status as a major role of risk factor for atrial fibrillation. J Thromb Thrombolysis 2013. http://dx.doi.org/ 10.1007/s11239-013-0973-1, PMID:23884696 [Epub ahead of print].
[4] Fici F, Celik T, Balta S, Iyisoy A, Unlu M, Demitkol S, et al. Comparative effects of nebivolol and metoprolol on red cell distribution width and neutrophil/lymphocyte ratio in patients with newly diagnosed essential hypertension. J Cardiovasc Pharmacol 2013;62:388–93.
Ibrahim Aydin Department of Biochemistry, Sarikamis Military Hospital, Sarikamis, Kars, Turkey Corresponding author. E-mail address: [email protected]. FevziNuri Aydin Department of Biochemistry, Sirnak Military Hospital, Sirnak, Turkey Mehmet Agilli Department of Biochemistry, Agri Military Hospital, Agri, Turkey 24 March 2014
http://dx.doi.org/10.1016/j.thromres.2014.03.049 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
Response to the Authors Dear Editor,
Red cell distribution width (RDW) is a new and easily available risk marker for cardiovascular disease (CVD) including venous thromboembolism (VTE) [1–7]. As pointed out by Aydin et al. [8], the underlying causal links are unclear [1–7]. The causal links could hypothetically involve some of the factors mentioned by Aydin et al., but also properties of the red cells per se. Residual bias is a potential source of error in all studies. Thus, we cannot exclude that variations of iron, vitamin B12, folate, thyroid function tests, and inflammatory markers may contribute to the association between RDW and VTE. However, it is very unlikely that these factors explain all of the association. The majority of patients were healthy at baseline and the results were also adjusted for 18 covariates including cardiovascular comorbidities. Moreover, as the results were adjusted for hemoglobin, mean corpuscular volume, leucocyte count, and platelet count deficiencies of vitamin b12, folate, and iron are unlikely to explain the results. The relationship between RDW and risk of VTE remained unchanged when leucocyte count was taken into account [6]. This suggests that inflammation is not the major mechanism for the increased incidence of VTE. However,
Letter to the Editors-in-Chief
adjustment for leukocyte count is not sufficient to draw firm conclusions on inflammation, but CRP data were not available [6]. In conclusion there is a consistent association between RDW and cardiovascular disease including VTE in a large number of studies. Still, the possible mechanism underlying the association between RDW and incident CVD remains to be elucidated. References [1] Montagnana M, Cervellin G, Meschi T, Lippi G. The role of red blood cell distribution width in cardiovascular and thrombotic disorders. Clin Chem Lab Med 2011;50: 635–41. [2] Zorlu A, Bektasoglu G, Guven FM, Dogan OT, Gucuk E, Ege MR, et al. Usefulness of admission red cell distribution width as a predictor of early mortality in patients with acute pulmonary embolism. Am J Cardiol 2012;109:128–34. [3] Ozsu S, Abul Y, Gunaydin S, Orem A, Ozlu T. Prognostic Value of Red Cell Distribution Width in Patients With Pulmonary Embolism. Clin Appl Thromb Hemost 2012;20:365–70. [4] Cay N, Unal O, Kartal MG, Ozdemir M, Tola M. Increased level of red blood cell distribution width is associated with deep venous thrombosis. Blood Coagul Fibrinolysis 2013;24:727–31. [5] Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter S. Hematological variables and venous thrombosis: red cell distribution width and blood monocytes are associated with an increased risk. Haematologica 2014;99:194–200. [6] Zöller B, Melander O, Svensson P, Engström G. Red cell distribution width and risk for venous thromboembolism: A population-based cohort study. Thromb Res 2014; 133:334–9. [7] Demir R, Saritemur M, Ozel L, Ozdemir G, Emet M, Ulvi H. Red Cell Distribution Width Identifies Cerebral Venous Sinus Thrombosis in Patients With Headache. Clin Appl Thromb Hemost Oct 1 2013 [Epub ahead of print]. [8] Aydin Ibrahim, Aydin Fevzi Nuri, Agilli Mehmet. The association between red cell distribution width and venous thromboembolism: A biochemical evaluation. Thromb Res 2014;133:1164 [in this issue].
Bengt Zöller Center for Primary Care Research, Lund University/Region Skåne, Malmö, Sweden Corresponding author at: Center for Primary Health Care Research, CRC, building 28, floor 11, Jan Waldenströms gata 35, Skåne University Hospital, S-205 02 Malmö, Sweden. Tel.: +46 40 391954; fax: +46 40 391370. E-mail address: [email protected].
1165
Olle Melander Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden Peter Svensson Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden Department of Coagulation Disorders, Skåne University Hospital, Malmö, Sweden Gunnar Engström Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden 26 March 2014 http://dx.doi.org/10.1016/j.thromres.2014.03.048 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
Contents lists available at ScienceDirect
Thrombosis Research journal homepage: www.elsevier.com/locate/thromres
Letter to the Editors-in-Chief The association between red cell distribution width and venous thromboembolism: A biochemical evaluation
Dear Editors, In a recent issue of Thrombosis Research, we read with great interest the published article by Zölleret al. entitled with “Red cell distribution width and risk for venous thromboembolism:A population-based cohort study” [1]. They have shown that the hazard ratios (HR) for venous thromboembolism (VTE) for the second, third and fourth red cell distribution width (RDW) quartiles were 1.15 (95% confidence interval 0.94–1.41), 1.41 (1.14–1.73), 1.74 (1.38–2.21), respectively. In the multivariate model,they have found that subjectswith the top 5% of RDW values compared with the bottom quartile had also an even higher risk (HR = 2.51,1.78–2.54). However, we think that some points should be discussed. RDW represents the variability in the red blood cell volume distribution and can be considered an index of heterogeneity in size of circulating erythrocytes [2]. This parameter is easily measured by automated hematology analyzers and reported as a component of complete blood count. Authors have excluded patients have a condition known to increase RDW such as pregnancy, inflammatory bowel disease or recent transfusion within the past 3 months. However, the RDW levels may also reflect neurohumoral activation, thyroid disease, nutritional deficiencies of folate, vitamin B12, and iron, bone marrow dysfunction, chronic or acute systemic inflammation [3], and some medications [4]. Patients have these situations are mostly excluded from the studies showing the prognostic and predictor value of the RDW [2]. In conclusion, the authors investigated to whether RDW is an independent predictor of first event of VTE in asymptomatic middleaged subjects in the Malmö Diet and Cancer Study [1]. However, authors only measured hemoglobin, mean corpuscular volume (MCV), leucocyte and platelet counts and RDW levels. They did not measure other factors including iron, vitamin B12, folate, thyroid function tests, and inflammatory markers. In this study, because of all these causes, RDW levels could not be associated with long-term incidence of first event of VTE in the middle-aged subjects. The explanation of these concerns could provide clearer information to the readers of the journal to show the association between RDW and incident VTE in patients with VTE. References [1] Zöller B, Melander O, Svensson P, Engström G. Red cell distribution width and risk for venous thromboembolism: A population-based cohort study. Thromb Res 2014; 133:334–9. [2] Yaman H, Celik T, Akgul EO, Cayci T, Kurt Y. Red cell distribution width and acute coronary syndromes. Int J Cardiol 2010;145:353. [3] Balta S, Demirkol S, Arslan Z, Unlu M, Celik T. Inflammatory status as a major role of risk factor for atrial fibrillation. J Thromb Thrombolysis 2013. http://dx.doi.org/ 10.1007/s11239-013-0973-1, PMID:23884696 [Epub ahead of print].
[4] Fici F, Celik T, Balta S, Iyisoy A, Unlu M, Demitkol S, et al. Comparative effects of nebivolol and metoprolol on red cell distribution width and neutrophil/lymphocyte ratio in patients with newly diagnosed essential hypertension. J Cardiovasc Pharmacol 2013;62:388–93.
Ibrahim Aydin Department of Biochemistry, Sarikamis Military Hospital, Sarikamis, Kars, Turkey Corresponding author. E-mail address: [email protected]. FevziNuri Aydin Department of Biochemistry, Sirnak Military Hospital, Sirnak, Turkey Mehmet Agilli Department of Biochemistry, Agri Military Hospital, Agri, Turkey 24 March 2014
http://dx.doi.org/10.1016/j.thromres.2014.03.049 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
Response to the Authors Dear Editor,
Red cell distribution width (RDW) is a new and easily available risk marker for cardiovascular disease (CVD) including venous thromboembolism (VTE) [1–7]. As pointed out by Aydin et al. [8], the underlying causal links are unclear [1–7]. The causal links could hypothetically involve some of the factors mentioned by Aydin et al., but also properties of the red cells per se. Residual bias is a potential source of error in all studies. Thus, we cannot exclude that variations of iron, vitamin B12, folate, thyroid function tests, and inflammatory markers may contribute to the association between RDW and VTE. However, it is very unlikely that these factors explain all of the association. The majority of patients were healthy at baseline and the results were also adjusted for 18 covariates including cardiovascular comorbidities. Moreover, as the results were adjusted for hemoglobin, mean corpuscular volume, leucocyte count, and platelet count deficiencies of vitamin b12, folate, and iron are unlikely to explain the results. The relationship between RDW and risk of VTE remained unchanged when leucocyte count was taken into account [6]. This suggests that inflammation is not the major mechanism for the increased incidence of VTE. However,
Letter to the Editors-in-Chief
adjustment for leukocyte count is not sufficient to draw firm conclusions on inflammation, but CRP data were not available [6]. In conclusion there is a consistent association between RDW and cardiovascular disease including VTE in a large number of studies. Still, the possible mechanism underlying the association between RDW and incident CVD remains to be elucidated. References [1] Montagnana M, Cervellin G, Meschi T, Lippi G. The role of red blood cell distribution width in cardiovascular and thrombotic disorders. Clin Chem Lab Med 2011;50: 635–41. [2] Zorlu A, Bektasoglu G, Guven FM, Dogan OT, Gucuk E, Ege MR, et al. Usefulness of admission red cell distribution width as a predictor of early mortality in patients with acute pulmonary embolism. Am J Cardiol 2012;109:128–34. [3] Ozsu S, Abul Y, Gunaydin S, Orem A, Ozlu T. Prognostic Value of Red Cell Distribution Width in Patients With Pulmonary Embolism. Clin Appl Thromb Hemost 2012;20:365–70. [4] Cay N, Unal O, Kartal MG, Ozdemir M, Tola M. Increased level of red blood cell distribution width is associated with deep venous thrombosis. Blood Coagul Fibrinolysis 2013;24:727–31. [5] Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter S. Hematological variables and venous thrombosis: red cell distribution width and blood monocytes are associated with an increased risk. Haematologica 2014;99:194–200. [6] Zöller B, Melander O, Svensson P, Engström G. Red cell distribution width and risk for venous thromboembolism: A population-based cohort study. Thromb Res 2014; 133:334–9. [7] Demir R, Saritemur M, Ozel L, Ozdemir G, Emet M, Ulvi H. Red Cell Distribution Width Identifies Cerebral Venous Sinus Thrombosis in Patients With Headache. Clin Appl Thromb Hemost Oct 1 2013 [Epub ahead of print]. [8] Aydin Ibrahim, Aydin Fevzi Nuri, Agilli Mehmet. The association between red cell distribution width and venous thromboembolism: A biochemical evaluation. Thromb Res 2014;133:1164 [in this issue].
Bengt Zöller Center for Primary Care Research, Lund University/Region Skåne, Malmö, Sweden Corresponding author at: Center for Primary Health Care Research, CRC, building 28, floor 11, Jan Waldenströms gata 35, Skåne University Hospital, S-205 02 Malmö, Sweden. Tel.: +46 40 391954; fax: +46 40 391370. E-mail address: [email protected].
1165
Olle Melander Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden Peter Svensson Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden Department of Coagulation Disorders, Skåne University Hospital, Malmö, Sweden Gunnar Engström Department of Clinical Sciences, Lund University, Clinical Research Center (CRC), Entrance 72, house 60, level 13, Skåne University Hospital, SE 205 02 Malmö, Sweden 26 March 2014 http://dx.doi.org/10.1016/j.thromres.2014.03.048 0049-3848/© 2014 Elsevier Ltd. All rights reserved.
