MYH9-related platelet disorders are inherited macrothrombocytopenias with additional clinical manifestations including renal failure, hearing loss, pre senile cataract and inclusion bodies in leucocytes that are present in different combinations. The MYH9 gene codes for the cytoplasmic contractile protein non-muscular myosin heavy chain IIA, present in several tissues. The bleeding tendency is usually mild to moderate but rarely, thrombotic complications are also seen. We report on the thrombin generation potential (ETP) in patients with MYH9-related disease with and without arterial thrombosis.In family A, four affected members (c.5521G>A mutation causing p.(Glu1841Lys)) were evaluated. Three of them had a moderate bleeding tendency and in two renal insufficiency and hearing loss were already present. These two patients had an arterial thrombosis (myocardial infarction and pons infarction, respectively) before 50 years of age. In family B two members were affected (c.4679T>G, resulting in p.(Val1560Gly)). Their bleeding tendency was mild (bleeding scores 4 and 3, respectively). Thrombelastography (ROTEM) was normal in all six individuals. ETP was below the normal range in family B. However, in family A, the two members affected by thrombosis had a normal ETP, indicating that other factors compensated for the low platelet count and might have contributed to the arterial thrombosis.

Development of atherosclerotic lesions in animals, preferrably induced by a high-cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2-3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1-year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of atherosclerotic lesions in animals, preferrably induced by a high-cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2-3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1-year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS)

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