Summary To study the effects of cigarette smoking and atherosclerosis on platelet size, we measured the mean platelet volume (MPV) and other platelet parameters in 142 elderly smokers and nonsmokers with or without atherosclerotic risk factors. The MPV and the platelet count were highest and their inverse correlation was strongest in the atherosclerotic smokers (r= 0.54, P < 0.05) when compared with the nonsmoking and non‐atherosclerotic groups. A 10% decrease of MPV was found in 8 smoking subjects in the atherosclerotic group, who successfully discontinued smoking (P < 0.05). These results suggest that smoking may increase platelet consumption in atherosclerotic vessels and that subsequently megakaryocytes are activated to produce larger platelets, which are more active. Thus, an increase in MPV due to smoking may also contribute to the acceleration of atherosclerosis and should be considered as a risk factor for atherosclerotic disease.

To investigate the etiology of the age-related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum ferritin levels in 247 elderly subjects aged 60-99 years. EPO levels were determined by radioimmunoassay. An age-related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = -0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with pre-anemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron.

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We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 ± 15.2 mU/ml), was significantly higher than that in younger controls (15.8 ± 5.0 mU/ml, p < 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = ––0.559, p < 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.

Nafamostat mesilate (FUT) is a synthetic serine protease inhibitor with a short half-life that is used during hemodialysis (HD) in patients with a high risk of bleeding because it does not prolong the systemic coagulation time. To evaluate whether or not FUT is able to effectively prevent clot formation in the extra-corporeal circuit without increasing systemic bleeding, HD using FUT was carried out for 33 sessions in 12 patients with a high risk of bleeding. FUT was continuously infused during HD at 20-40 mg/h to maintain a 2-fold prolongation of activated partial thromboplastin time (APTT) at the dialyzer outlet on the venous side of the circuit. No APTT prolongation was observed on the arterial side of the circuit before FUT infusion, and none of the patients showed increased bleeding during or after HD. However, clots formed in the arterial chamber (30.3%), the dialyzer (36.6%), and the venous chamber (15.1 %). In 2 of the 12 patients, HD was discontinued due to clot formation despite sufficient prolongation of APTT. The mean levels of the thrombin-antithrombin III complex and prothrombin activation fragment 1+2 in the circuit gradually increased on both the arterial and venous sides during HD using FUT, and protein C activity decreased. No significant changes in these parameters occurred during heparin HD in the same patients after the bleeding episode had resolved. Despite sufficient prolongation of APTT in the circuit, FUT was less effective in suppressing thrombin generation when compared to heparin. Therefore, FUT cannot be recommended as an alternative drug to heparin for hemodialysis patients with a bleeding risk.