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Prethrombotic state of Chinese diabetic patients
Clinica Chimica Acta 316 (2002) 187 – 189 www.elsevier.com/locate/clinchim
Letter to the Editor
Prethrombotic state of Chinese diabetic patients Keywords: Diabetes; Viscosity; Thrombotic; Rheologic
The prognosis is not good when diabetic patients suffer from cardiovascular or cerebrovascular thrombotic diseases [1]. Epidemiological studies have shown that diabetes mellitus is a strong risk factor for development of stroke, atherosclerotic vascular disease and coronary heart disease [2– 4]. For many years, investigators have sought to use sensitive laboratory tests to predict thrombotic events among high-risk patients [5,6]. Early detection of the prethrombotic state is critical for the administration of preventive therapy. Previous studies have failed to identify hypercoagulation parameters in diabetic patients [7]. We examined 50 diabetic out-patients (25 males and 25 females, age range 34– 70 years) which were recruited from the First Teaching Hospital of Peking University. The diagnosis of diabetes was made on the basis of the blood glucose concentration, the glucose and insulin tolerance tests, and clinical symptoms. Of these cases, four were type I diabetes and the remaining 46 cases were type II diabetes; 13 had microangiopathy (including microcirculation disturbance and retinopathy) and 29 were hyperlipidemic. None showed any thrombotic complications.
Abbreviations: PT, prothrombin time; PTA, activity of prothrombin; INR, international normalized ratio; FIB, fibrinogen; APTT, activated partial thromboplastin time; HSV, high shear viscosity; MSV, middle shear viscosity; LSV, low shear viscosity; RI, rigidity index; AI, aggregation index; HRV, high shear reduced viscosity; LRV, low shear relative viscosity; LT, length of thrombus; WHT, weight of humid thrombus; WDT, weight of dry thrombus; ARP, aggregation ratio of platelets; AT-III, antithrombin III.
The reagent used for PT, FIB, APTT, AT-III were purchased from Instrumentation Laboratory (Lexington, MA). The assay for D-dimer was from Nycomin (Norway). These analytes were tested on the ACL Futura (IL), N6A blood viscosity meter, platelet aggregometer from Chrono-Log (PA, USA). Blood Viscosity meter and thrombus meter are products of Pulisheng group (China). Twenty routine tests related to thrombus and blood viscosity were selected, including hematocrit (Hct), prothrombin time (PT), activity of prothrombin (PTA), international normalized ratio (INR), fibrinogen (FIB), activated partial thrombplastin time (APTT), D-dimer, plasma viscosity, high shear viscosity (HSV), middle shear viscosity (MSV), low shear viscosity (LSV), rigidity index (RI), aggregation index (AI), high shear reduced viscosity (HRV), low shear relative viscosity (LRV), length of thrombus (LT), weight of humid thrombus (WHT), weight of dry thrombus (WDT), aggregate ratio of platelets (ARP) and antithrombin III (AT-III). All tests were performed following the instruction provided by the manufacturer. Morning fasting venous blood was collected in tubes (Greiner Labortechnik, Kremsmunster, Austria) sodium citrate (3.2%) and heparin as anticoagulants, for the thrombus and rheology tests, respectively. The in vitro thrombus test was performed immediately after the blood collection. Patients under anticoagulant and antiplatelet drugs were withdrawn from therapy at least one week before the study. All laboratory tests were performed within 4 h after blood collection. The accuracy of laboratory tests were checked with commercial available quality control plasma. Between-run precision of the tests performed are listed as follow: FIB, PT, HRV, HSV, INR, PTA were < 2%; Hct, D-dimer, APTT, MSV, RI, AT-III were < 3%; AI, LR, LSV were < 5%, LT, ARP were < 10% and WHT was < 20%. The proto-
0009-8981/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 8 9 8 1 ( 0 1 ) 0 0 7 4 3 - 4
188
Letter to the Editor
col was approved by the Human Subject Ethics Committee of the First Teaching Hospital of Peking University. Among the 20 selected tests, > 30% diabetic patients exhibited abnormal value in RI and HRV. In addition, > 50% diabetic cases reviewed abnormal results in HSV, MSV, LSV and LRV (Fig. 1). Results were compared to the reference ranges established from the local Chinese population by our laboratory. Results were divided into two groups based on patient’s blood lipid level. Statistical analysis was made on normal lipid level group and hyperlipidemic
group. The result showed that the aggregation index (AI) of erythrocyte was obviously higher in the hyperlipidemic group (3.01 ± 0.43) than that of the normal blood lipid group (2.76 ± 0.36) ( p < 0.05, Mann – Whitney U-test). No statistical difference was observed in the remaining tests between the two groups. Comparison was also made between patients with and without microangiopathy (including retina disease and microcirculation disturbance). No statistical significant difference (Mann –Whitney U-test) was observed between the two groups in any of the 20 tests.
Fig. 1. Comparison of results from diabetic patients (25 males, 25 females) to reference ranges of selected blood viscosity parameters.
Letter to the Editor
Higher blood viscosity in diabetes was reported in Western population [8]. In this study, about half of the Chinese diabetic subjects showed high plasma viscosity. The blood viscosity examination as screening test provide a means for detection of the prethrombotic state of the diabetes patients. None of the 50 patients had thrombus. The tests which were mainly used for thrombus detection were PT, PTA, INR, FIB, Ddimer, aggregation rate of platelet and AT-III. The percentage of cases with abnormal results of these tests was found to be < 30%. With regard to the blood viscosity parameters, i.e., HSV, MSV, LSV, AI, HRV, LRV, demonstrated a much higher percentage of abnormal results (52%, 66%, 50%, 34%, 36%, 50%, respectively). In another words, those blood viscosity parameters were likely to be more sensitive markers for the detection of thrombus formation, before abnormalities were observed from traditional coagulation tests. We, therefore, suggest the use of blood viscosity test a better and more specific investigation of the prethrombotic state. The in vitro indices PT, PTA, INR, APTT, FIB and platelet aggregation test can be offered as secondary markers for screening evaluation. Hyperlipidemic patients showed higher aggregation index which may contribute the pathophysiology of cardiovascular complications.
References [1] Chen KT, Chen CJ, Fuh MM, Narayan KM. Causes of death and associated factors among patients with non-insulin-dependent diabetes mellitus in Taipei, Taiwan. Diabetes Res Clin Pract 1999;43:101 – 9. [2] Laakso M, Lehto S. Epidemiology of risk factors for cardio-
[3]
[4]
[5] [6]
[7]
[8]
189
vascular disease in diabetes and impaired glucose tolerance. Atherosclerosis 1998;137:S65 – 73. Suppl. Tschoepe D, Roesen P. Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. Exp Clin Endocrinol Diabetes 1998;106:16 – 24. Lukovits TG, Mazzone TM, Gorelick TM. Diabetes mellitus and cerebrovascular disease. Neuroepidemiology 1999;18:1 – 14. Plebani M, Zaninotto M. Cardiac markers: present and future. Int J Clin Lab Res 1999;29:56 – 63. Lopez Y, Paloma MJ, Rifon J, Cuesta B, Paramo JA. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res 1999;93:71 – 8. Ho CH, Jap TS. Do smoking and diabetes change the hemostatic parameters? A study in the Chinese people. Thromb Res 1994;6:569 – 76. Skovborg K, Nielsen AV, Schlichtkrull J, Ditzel J. Blood viscosity in diabetic patients. Lancet 1966;1:129 – 31.
Christine M.N. Yow * S. Szeto Department of Nursing and Health Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China E-mail address: [email protected].
J.Z.H. Wang J.Y. Yuan L.H. Zhu Department of Clinical Laboratory Medicine, The First Teaching Hospital of Peking University, Beijing, China 3 May 2001 * Corresponding author. Tel.: +852-2766-4954; fax: +8522364-9663.
Letter to the Editor
Prethrombotic state of Chinese diabetic patients Keywords: Diabetes; Viscosity; Thrombotic; Rheologic
The prognosis is not good when diabetic patients suffer from cardiovascular or cerebrovascular thrombotic diseases [1]. Epidemiological studies have shown that diabetes mellitus is a strong risk factor for development of stroke, atherosclerotic vascular disease and coronary heart disease [2– 4]. For many years, investigators have sought to use sensitive laboratory tests to predict thrombotic events among high-risk patients [5,6]. Early detection of the prethrombotic state is critical for the administration of preventive therapy. Previous studies have failed to identify hypercoagulation parameters in diabetic patients [7]. We examined 50 diabetic out-patients (25 males and 25 females, age range 34– 70 years) which were recruited from the First Teaching Hospital of Peking University. The diagnosis of diabetes was made on the basis of the blood glucose concentration, the glucose and insulin tolerance tests, and clinical symptoms. Of these cases, four were type I diabetes and the remaining 46 cases were type II diabetes; 13 had microangiopathy (including microcirculation disturbance and retinopathy) and 29 were hyperlipidemic. None showed any thrombotic complications.
Abbreviations: PT, prothrombin time; PTA, activity of prothrombin; INR, international normalized ratio; FIB, fibrinogen; APTT, activated partial thromboplastin time; HSV, high shear viscosity; MSV, middle shear viscosity; LSV, low shear viscosity; RI, rigidity index; AI, aggregation index; HRV, high shear reduced viscosity; LRV, low shear relative viscosity; LT, length of thrombus; WHT, weight of humid thrombus; WDT, weight of dry thrombus; ARP, aggregation ratio of platelets; AT-III, antithrombin III.
The reagent used for PT, FIB, APTT, AT-III were purchased from Instrumentation Laboratory (Lexington, MA). The assay for D-dimer was from Nycomin (Norway). These analytes were tested on the ACL Futura (IL), N6A blood viscosity meter, platelet aggregometer from Chrono-Log (PA, USA). Blood Viscosity meter and thrombus meter are products of Pulisheng group (China). Twenty routine tests related to thrombus and blood viscosity were selected, including hematocrit (Hct), prothrombin time (PT), activity of prothrombin (PTA), international normalized ratio (INR), fibrinogen (FIB), activated partial thrombplastin time (APTT), D-dimer, plasma viscosity, high shear viscosity (HSV), middle shear viscosity (MSV), low shear viscosity (LSV), rigidity index (RI), aggregation index (AI), high shear reduced viscosity (HRV), low shear relative viscosity (LRV), length of thrombus (LT), weight of humid thrombus (WHT), weight of dry thrombus (WDT), aggregate ratio of platelets (ARP) and antithrombin III (AT-III). All tests were performed following the instruction provided by the manufacturer. Morning fasting venous blood was collected in tubes (Greiner Labortechnik, Kremsmunster, Austria) sodium citrate (3.2%) and heparin as anticoagulants, for the thrombus and rheology tests, respectively. The in vitro thrombus test was performed immediately after the blood collection. Patients under anticoagulant and antiplatelet drugs were withdrawn from therapy at least one week before the study. All laboratory tests were performed within 4 h after blood collection. The accuracy of laboratory tests were checked with commercial available quality control plasma. Between-run precision of the tests performed are listed as follow: FIB, PT, HRV, HSV, INR, PTA were < 2%; Hct, D-dimer, APTT, MSV, RI, AT-III were < 3%; AI, LR, LSV were < 5%, LT, ARP were < 10% and WHT was < 20%. The proto-
0009-8981/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 9 - 8 9 8 1 ( 0 1 ) 0 0 7 4 3 - 4
188
Letter to the Editor
col was approved by the Human Subject Ethics Committee of the First Teaching Hospital of Peking University. Among the 20 selected tests, > 30% diabetic patients exhibited abnormal value in RI and HRV. In addition, > 50% diabetic cases reviewed abnormal results in HSV, MSV, LSV and LRV (Fig. 1). Results were compared to the reference ranges established from the local Chinese population by our laboratory. Results were divided into two groups based on patient’s blood lipid level. Statistical analysis was made on normal lipid level group and hyperlipidemic
group. The result showed that the aggregation index (AI) of erythrocyte was obviously higher in the hyperlipidemic group (3.01 ± 0.43) than that of the normal blood lipid group (2.76 ± 0.36) ( p < 0.05, Mann – Whitney U-test). No statistical difference was observed in the remaining tests between the two groups. Comparison was also made between patients with and without microangiopathy (including retina disease and microcirculation disturbance). No statistical significant difference (Mann –Whitney U-test) was observed between the two groups in any of the 20 tests.
Fig. 1. Comparison of results from diabetic patients (25 males, 25 females) to reference ranges of selected blood viscosity parameters.
Letter to the Editor
Higher blood viscosity in diabetes was reported in Western population [8]. In this study, about half of the Chinese diabetic subjects showed high plasma viscosity. The blood viscosity examination as screening test provide a means for detection of the prethrombotic state of the diabetes patients. None of the 50 patients had thrombus. The tests which were mainly used for thrombus detection were PT, PTA, INR, FIB, Ddimer, aggregation rate of platelet and AT-III. The percentage of cases with abnormal results of these tests was found to be < 30%. With regard to the blood viscosity parameters, i.e., HSV, MSV, LSV, AI, HRV, LRV, demonstrated a much higher percentage of abnormal results (52%, 66%, 50%, 34%, 36%, 50%, respectively). In another words, those blood viscosity parameters were likely to be more sensitive markers for the detection of thrombus formation, before abnormalities were observed from traditional coagulation tests. We, therefore, suggest the use of blood viscosity test a better and more specific investigation of the prethrombotic state. The in vitro indices PT, PTA, INR, APTT, FIB and platelet aggregation test can be offered as secondary markers for screening evaluation. Hyperlipidemic patients showed higher aggregation index which may contribute the pathophysiology of cardiovascular complications.
References [1] Chen KT, Chen CJ, Fuh MM, Narayan KM. Causes of death and associated factors among patients with non-insulin-dependent diabetes mellitus in Taipei, Taiwan. Diabetes Res Clin Pract 1999;43:101 – 9. [2] Laakso M, Lehto S. Epidemiology of risk factors for cardio-
[3]
[4]
[5] [6]
[7]
[8]
189
vascular disease in diabetes and impaired glucose tolerance. Atherosclerosis 1998;137:S65 – 73. Suppl. Tschoepe D, Roesen P. Heart disease in diabetes mellitus: a challenge for early diagnosis and intervention. Exp Clin Endocrinol Diabetes 1998;106:16 – 24. Lukovits TG, Mazzone TM, Gorelick TM. Diabetes mellitus and cerebrovascular disease. Neuroepidemiology 1999;18:1 – 14. Plebani M, Zaninotto M. Cardiac markers: present and future. Int J Clin Lab Res 1999;29:56 – 63. Lopez Y, Paloma MJ, Rifon J, Cuesta B, Paramo JA. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res 1999;93:71 – 8. Ho CH, Jap TS. Do smoking and diabetes change the hemostatic parameters? A study in the Chinese people. Thromb Res 1994;6:569 – 76. Skovborg K, Nielsen AV, Schlichtkrull J, Ditzel J. Blood viscosity in diabetic patients. Lancet 1966;1:129 – 31.
Christine M.N. Yow * S. Szeto Department of Nursing and Health Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China E-mail address: [email protected].
J.Z.H. Wang J.Y. Yuan L.H. Zhu Department of Clinical Laboratory Medicine, The First Teaching Hospital of Peking University, Beijing, China 3 May 2001 * Corresponding author. Tel.: +852-2766-4954; fax: +8522364-9663.