Akihiro Ihara

Relationship between Platelet Indexes and Coronary Angiographic Findings in Patients with Ischemic Heart Disease

To understand the mechanisms linking platelets to the risk of coronary artery disease, we investigated the relation between coronary angiographic morphology and platelet indexes – platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW) – in patients with ischemic heart disease. Eighty-four patients with ischemic heart disease and 120 aged controls (AC) were enrolled in the study. The patients without any signs of acute myocardial infarction and acute coronary syndromes who underwent coronary angiography were divided into two groups, an ‘angiographically negative group’ (group 0) and an ‘angiographically positive group’ (group 1), with positive coronary obstruction depending on the diagnostic criteria in our hospital. Platelet indexes were measured in peripheral venous blood. The mean platelet counts were significantly lower in groups 1 and 0 than in AC (p = 0.0128 and p = 0.0041, respectively). MPV, P-LCR and the PDW were significantly higher in group 0 than in group 1 and AC (p = 0.0352 and 0.0433, p = 0.0059 and 0.0052, p = 0.00461 and 0.0146, respectively). The indexes of group 1 were almost the same compared with AC with respect to MPV, P-LCR and PDW. In conclusion, these findings suggest that the measurement of platelet indexes may reflect the underlying pathophysiological state and subsequent clinical events in the patients. In particular, lower P-LCR seems to identify patients with positive coronary angiography.

Relationship between Hemostatic Factors and the Platelet Index in Patients with Ischemic Heart Disease

To understand the heterogeneity of platelets, we investigated the correlation between hemostatic factors and the platelet index [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] in patients with ischemic heart disease (IHD). Ninety-seven patients with IHD and 120 aged controls (AC) were enrolled in the study. D-dimer, thrombin-antithrombin III complex (TAT), von Willebrand factor antigen (VWF:Ag) and platelet indexes were measured in the peripheral venous blood. The D-dimer and TAT levels in the patients were significantly elevated compared to the AC. VWF:Ag was also elevated, but not significantly so. However, no differences were observed in the platelet index between the patients and the AC. In the patients, the level of VWF:Ag was significantly inversely correlated with the platelet count, but such correlations were not observed in the D-dimer and TAT. TAT was significantly positively correlated with MPV, P-LCR and PDW. VWF:Ag was also correlated, though not significantly, with MPV, P-LCR and PDW. The D-dimer was not correlated with the platelet index. In the AC, the platelet count was inversely correlated with VWF:Ag, but not significantly so. VWF:Ag showed significant positive correlations with MPV, P-LCR and PDW. However, the D-dimer and TAT were not correlated with the platelet index in AC. These findings suggest that VWF:Ag and TAT seem to be profoundly related to platelet volume.

Relationship between coagulation cascade, cytokine, adhesion molecule and aortic aneurysm.

OBJECTIVES Patients with aortic aneurysm (AA) were in the chronic inflammatory condition and are often combined with disseminated intervascular coagulation. Recent studies demonstrated that atherosclerosis was inflammatory disease. AA and severe atherosclerosis with ulcer formation contain macrophages and T lymphocytes and accelerate the production of interleukin (IL)-2, which activates lymphocytes and lead to further adhesion of leukocytes. This study was designed to clarify the coagulation condition, cytokine, adhesion molecule, and collagen turnover in patients with AA and finally their relationship with the aneurysmal size. METHODS Thrombin-antithrombin III complex (TAT), plasma D-dimer, serum type III procollagen peptide (PIIIP), serum soluble IL-2 receptor (sIL-2R), Free tissue factor pathway inhibitor (TFPI), and soluble intercellular adhesion molecule (ICAM-1) were measured preoperatively around the same period when computed tomography (CT) was taken in 17 patients with AA (mean age: 72.2 years). Age-matched (mean age:70 years) volunteers were served as control. Maximum aneurysmal size was measured by CT and aneurysmal volume was also calculated from CT. RESULTS AA patients showed significantly higher level in preoperative TAT and D-dimer compared to control (TAT: control 2.5+/-1.2 ng/ml, pre 7.2+/-4.5,ng/ml; P=0.0001; D-dimer: control 107+/-46 U/ml, pre 420+/-256 U/ml; P=0.0001). Cytokine also showed higher level preoperatively (sIL-2R: control 398+/-132 U/ml, pre 735+/-260 U/ml; P=0.0001). TFPI showed higher value preoperatively (control 22.9+/-4.9 ng/ml, pre 30.4+/-6.9 ng/ml; P=0.003). PIIIP (collagen turnover) showed no difference between the groups (P=0.0057) and neither did ICAM-1(P=0.0087). TAT (r=0.799, P=0.0001), D-dimer (r=0.56, P=0.0193), sIL-2R (r=0.709, P=0.0021), PIIIP (r=0.561, P=0.00239), and sICAM-1 (r=0.505, P=0.046) level showed positive correlation with aortic aneurysmal size and also TAT D-dimer, and sIL-2R levels were positively correlated with aneurysmal volume (r=0.714 P=0.0013, r=0.556 P=0.00204, r=0.693 P=0.0029, respectively). CONCLUSIONS AA patients were in the hypercoagulation and inflammatory condition. Aneurysmal size was well correlated with TAT, D-dimer, sIL-2R, PIIIP, and sICAM-1, suggesting that these markers could be good diagnostic and monitoring tool for the disease progression.

Relationship between hemostatic markers and platelet indices in patients with aortic aneurysm.

The purpose of this study was to investigate whether platelet indices [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation in patients with aortic aneurysm (AA). Blood samples were obtained from 54 patients with AA (mean age 73 years; 40 males and 14 females), and from 120 age-matched controls (AC; mean age 74 years; 61 males and 59 females). Blood platelet indices were measured using an automated counter for all AC (n = 120) and AA (n = 54). Plasma thrombin-antithrombin III complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), D-dimer, von Willebrand factor antigen (vWF:Ag) and interleukin-6 (IL-6) were also measured in part of AC and AA. In AA patients, TAT, PIC, D-dimer, vWF:Ag and IL-6 levels were significantly (p ≤0.0005) higher than in AC. In the patients, TAT was significantly inversely correlated with platelet count (ρ = –0.302, p = 0.038, n = 48), and significantly positively correlated with MPV (ρ = 0.329, p = 0.0373, n = 48), P-LCR (ρ = 0.361, p = 0.0134, n = 48) and PDW (ρ = 0.315, p = 0.0466, n = 48). PIC was negatively correlated with platelet count and inversely correlated with MPV, P-LCR and PDW. vWF:Ag was not correlated with platelet count, and inversely correlated with MPV, P-LCR and PDW in the patients. IL-6 was positively correlated with platelet count, and significantly inversely correlated with MPV, P-LCR and PDW in the patients. In AC, vWF:Ag was inversely correlated with platelet count and significantly positively correlated with MPV, P-LCR and PDW. However, PIC, TAT and IL-6 were not correlated with platelet indices in AC. D-dimer was not at all correlated with platelet indices both in AA and AC. In conclusion, the correlation between platelet indices and plasma hemostatic factor levels, e.g. TAT, PIC, D-dimer, vWF:Ag and IL-6, will be important factors for the understanding of platelet heterogeneity in patients with AA.

Relationship between Hemostatic Markers and Circulating Biochemical Markers of Collagen Metabolism in Patients with Aortic Aneurysm

Our objective was to determine the relationship between plasma levels of hemostatic molecular markers – D-dimer and thrombin-antithrombin III complex (TAT) – and circulating biochemical markers of collagen metabolism – aminoterminal propeptide of type III procollagen (PIIIP) and carboxyterminal propeptide of type I procollagen (PICP) – in patients with aortic aneurysm. The subjects were 43 patients with aortic aneurysm (AA; mean age 71 years) and 26 age-matched controls (mean age 75 years). The mean D-dimer, TAT and PIIIP levels were higher in the patients than in the controls (p < 0.0001, 0.0001 and 0.012, respectively), while the mean PICP level was similar to that in the controls. Increased D-dimer had a significant correlation with PIIIP (r = 0.412, p = 0.006) and PICP (r = 0.342, p = 0.0246), while TAT correlated with PIIIP (r = 0.3194, p = 0.0374), but not with PICP. There was also a significant correlation (r = 0.306, p = 0.0463) between PIIIP and PICP. As shown by the significant positive correlations among D-dimer, TAT and PIIIP, accelerated fibrinolysis and thrombogenesis induce an increase of collagen degradation and procollagen synthesis in atherosclerotic lesions. These findings show that D-dimer and TAT, especially the former, may be useful markers to monitor the progression and predict the prognosis of AA.

Evaluation of Platelet Indexes in Patients with Aortic Aneurysm

The purpose of this study was to investigate whether platelet indexes [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR), and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation. Blood samples were obtained from 54 patients with aortic aneurysm (AA; mean age 73 years; 40 males, 14 females), from 120 age-matched controls (AC; mean age 74 years; 61 males, 59 females), and from 38 young controls (YC; mean age 30 years; 20 males, 18 females). We measured the blood platelet indexes using an automated counter, as well as plasma D-dimer and thrombin-antithrombin III complex (TAT) using ELISA. The AA patients were divided into two groups, group A (platelet count more than 150 × 109/l, n = 36) and group B (platelet count below 150 × 109/l, n = 18). There was no difference in the platelet count between AC and YC. However, P-LCR was significantly higher (p = 0.0113) in AC. MPV and PDW were also higher, but not significantly so. The platelet count was not different between group A and AC. MPV (p = 0.0024 and <0.0001, respectively), P-LCR (p < 0.0012 and <0.0001, respectively) and PDW (p = 0.0006 and 0.0005, respectively) were significantly lower in group A than in group B and AC. The platelet indexes were significantly lower in the 54 AA patients than in the AC. There were significant inverse relationships between the platelet count and other indexes in the AC and 54 AA patients; however, no relationships were observed in group A, B and YC. The D-dimer and TAT levels were significantly higher in group B than in groups A and YC. In conclusion, these findings suggest that large platelets decrease rather than increase in patients with AA.

Granulocyte Colony-Stimulating Factor Increases the Platelet Volume in Peripheral Stem Cell Apheresis Donors

We investigated the short-term influence of granulocyte colony-stimulating factor (G-CSF) administration on platelet counts and platelet indices in 12 donors (8 males and 4 females; median age 34 years, range 16–49) for peripheral stem cell transplantation using an automated blood cell analyzer. On day 3 (D3) compared with D0, 11 donors with normal laboratory and physical findings showed increases in platelet indices (χ2 = 12.0, p = 0.0025). Furthermore, mean platelet volume (MPV) was significantly increased (p = 0.04). Also, platelet count decreased, and platelet distribution width and platelet-large cell ratio were increased, but these were not significant. On the contrary, 1 donor with abnormal laboratory findings who had large platelets (MPV 11.4 fl) before G-CSF administration showed decreases in platelet indices (MPV 10.3 fl) on D3, although platelet count (18.2 × 104/μl) decreased after G-CSF administration. G-CSF administration induces an inflammatory process with endothelial cell activation. This is probably the reason why platelet volume increases after G-CSF use. This is the first report showing that G-CSF administration immediately induces increases in large platelets in peripheral stem cell transplant donors before harvest.