Antihypertensive treatment with beta-blockers in the metabolic syndrome: a review.

Metabolic syndrome, a "cluster" of metabolic disorders including hypertension, increases the cardiovascular risk, and insulin resistance plays a key role in its pathogenesis. In this syndrome antihypertensive treatment with beta-blockers is underused because of their adverse metabolic effects. The aim was to review the evidences supporting the reasons for underusing beta-blockers in hypertensive patients with metabolic syndrome. A review of Literature has been carried out via PubMed from 1998 to 2008: most of beta-blockers have adverse effects on insulin sensitivity, carbohydrate and lipid metabolism, and are not recommended in metabolic syndrome. However, some recent large studies have shown a better metabolic profile with newer third generation vasodilating beta-blockers, such as Carvedilol and Nebivolol. Vasodilating action of Carvedilol and Nebivolol, due respectively to alpha1-blocking effect and release of nitric oxide, explains the lack of adverse metabolic effects of these beta-blockers that could also be used in hypertensive patients with metabolic syndrome.

A case of ischemic stroke in acute promyelocytic leukemia at initial presentation. Relevance of all-trans retinoic acid treatment.

Acute promyelocytic leukemia (APL) is frequently associated, often from the earliest phases, with a life-threatening coagulation/bleeding syndrome; disseminated intravascular coagulation (DIC) is described in majority of patients. We report a case of 49-year-old male, without cardiovascular risk factors, who suddenly developed ischemic stroke and splenic infarction as presenting symptoms of APL and related DIC. The patient was immediately treated with all-trans retinoic acid (ATRA) and the alterations of hemocoagulation parameters promptly returned in normal range. The coagulation/bleeding syndrome of the onset of APL is associated with high mortality; both diagnostic and therapeutic approaches require special and timely consideration of this condition. Treatment with ATRA is essential.

Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia.

We have recently studied a case series of 46 unrelated patients with inherited thrombocytopenias and identified 18 cases that did not fit any known platelet disorder. In two unrelated families, a mild thrombocytopenia with normal platelet size was transmitted in an autosomal dominant fashion. Bleeding time was prolonged in 5 investigated patients. In all of them, flow cytometry and SDS-PAGE of platelet glycoproteins (GP) showed a reduced content of GPIa, a subunit of the GPIa-IIa complex (also known as integrin alpha 2 beta(1)) that is a major collagen receptor on platelets. All other membrane GPs were within the normal range. GPIa deficiency was associated with severely reduced in vitro platelet adhesion to molecules known to interact selectively with GPIa. In vitro platelet aggregation was normal in all subjects, except for a suboptimal platelet response to fibrillar collagen in two patients. A mild defect of alpha-granules was observed in all affected subjects. No mutation was identified in the genes encoding for GPIa or GPIIa. Since no other similar cases have been reported in the literature, we suggest that an autosomal dominant thrombocytopenia associated with GPIa deficiency and alpha-granule defect represents a new form of inherited thrombocytopenia.

Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients.

BACKGROUND AND OBJECTIVES: The Italian Gruppo di Studio delle Piastrine recently developed a diagnostic algorithm to assist clinicians in the diagnosis of inherited thrombocytopenias. This algorithm is based on the simplest possible diagnostic investigations and can also be used in centers that are not highly specialized. The aim of the present study was to validate this diagnostic algorithm by applying it to a case series of genetic thrombocytopenias. DESIGN AND METHODS: The diagnostic algorithm was applied retrospectively to 46 consecutive patients observed during the last five years at a single institution. Twenty-eight were affected by defined illnesses or their variants, while 18 had a disorder that did not fit the criteria for any known genetic thrombocytopenia. The study was based on the evaluation of clinical records and laboratory tests. RESULTS: The diagnostic algorithm recognized: 4 homozygous and 4 heterozygous Bernard-Soulier syndromes, 11 MYH9-related diseases, one von WillebrandOs disease type 2B, one gray platelet syndrome and one X-linked thrombocytopenia with thalassemia. Moreover, it identified 4 patients with the clinical and laboratory features of heterozygous Bernard-Soulier syndrome not caused by mutations in the coding region of the GPIbalpha, GPIbbeta, GPIX or GPV genes, and two patients with the clinical phenotype of MYH9-related disease but without MYH9 mutations. Since the diagnostic flow chart did not allow prompt recognition of two subjects with MYH9-related disease, we introduced a small change to the previously proposed flow chart to obviate this defect. INTERPRETATION AND CONCLUSIONS: The diagnostic algorithm correctly diagnosed 26 of 28 patients with known disorders or phenotypic variants of known disorders. By a simple modification of the investigation sequence, its sensitivity reached 100%. The algorithm also identified 18 patients with new, as yet uncharacterized forms of genetic thrombocytopenia.

Defective expression of GPIb/IX/V complex in platelets from patients with May-Hegglin anomaly and Sebastian syndrome.

BACKGROUND AND OBJECTIVES: May-Hegglin anomaly (MHA) and Sebastian syndrome (SBS) are inherited macrothrombocytopenias with D hle-like bodies in leukocytes. MHA-SBS are due to mutations of the gene (MYH9) for the heavy chain of non-muscle myosin IIA (NMMHC-IIA), the only myosin II expressed in platelets. The bleeding tendency is often more severe than expected on the basis of platelet count, but no abnormality of platelet function has been identified. To characterize platelet abnormalities deriving from MYH9 mutations better, we studied surface glycoproteins (GPs) in platelets from MHA-SBS patients. DESIGN AND METHODS: Eight patients from 4 unrelated families were studied. Platelet surface GPs were studied by flow cytometry in both the whole platelet population and subpopulations of platelets identified according to their size. RESULTS: Flow cytometry identified a defect of the GPIb/IX/V complex in the whole platelet population in 7 of 8 patients. Moreover, in all patients the subpopulation of large platelets had defective expression of this complex. INTERPRETATION AND CONCLUSIONS: These findings indicate that MYH9 mutations may be responsible for reduced surface expression of GPIb/IX/V. This defect could contribute to the bleeding tendency of these patients. The identification of a GPIb/IX/V defect in MHA-SBS platelets raises the question of the differential diagnosis from heterozygous Bernard-Soulier syndrome.