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Biomedical subjects

A Tosetto

Publications and source records attributed to A Tosetto.

At least 55 records · Page 3Linked to original sources
PubMed1996

The VITA Project: population-based distributions of protein C, antithrombin III, heparin-cofactor II and plasminogen--relationship with physiological variables and establishment of reference ranges.

A proper laboratory diagnosis of inherited thrombophilia due to defects of the coagulation system may be obtained only by a stringent definition of the diagnostic reference ranges taking into account the influence exerted by major physiological variables. To this purpose, we analyzed the data for Protein C, Antithrombin III, Heparin-Cofactor II and plasminogen coming from the first 4,000 subjects enrolled in the VITA Project. This is the first study that allows the establishment of reference ranges in a non-selected, active population using stringent standardization of clinical and laboratory measurements and multivariable regression techniques for data analysis. Serum triglycerides and total cholesterol, together with plasma fibrinogen were found to influence the functional plasma level of the four considered proteins. Menopause increased AT-III concentration, while pill use increased Heparin-Cofactor II and plasminogen. PT and PTT ratio, gender, age, smoking, body-mass index, HDL cholesterol and blood group had minor effects. The effect of these variables should be taken into account for both clinical and epidemiologic purposes, using appropriate reference ranges or covariance analysis for adjustment.

Adolescent↗
PubMed1995

An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide.

We report a new case of severe bleeding diathesis due to an acquired inhibitor of fibrin crosslinking. The patient, an 80-year-old woman, was admitted to the hospital for a massive subcutaneous hematoma, with severe anemia requiring red cell transfusion; a subsequent retroperitoneal hematoma developed 2 weeks later. Coagulation studies were normal except for a thromboelastographic pattern suggestive of FXIII deficiency. Clot solubility test was abnormal even after 1:1 mix with normal plasma. Immunochemical studies confirmed the presence of a monoclonal IgG lambda inhibitor directed against FXIII activity (type II FXIII inhibitor). The patient IgG fraction selectively inhibited FXIII transamidating activity but did not inhibit the thrombin-mediated activation of FXIII. The patient was treated with high doses of FXIII concentrate to overcome the inhibitor and immunosuppressive therapy with cyclophosphamide and discharged in good conditions. High doses of commercially available FXIII appear to be a safe and effective method of controlling acute episodes of bleeding in patients with acquired FXIII deficiency.

Aged↗
PubMed1995

Platelet von Willebrand factor abnormalities in myeloproliferative syndromes.

Plasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern and subunit composition of plasma vWF were obtained in 29 consecutive patients with chronic myeloproliferative syndromes. In the 8 patients with chronic myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11 patients with essential thrombocythemia (ET) and in the 10 patients with polycythemia vera (PV). The RiCof/vWF:Ag ratio was low in all these groups of patients (mean 0.64 +/- 0.1, 0.66 +/- 0.2, and 0.61 +/- 0.2; normal 0.97 +/- 0.2). Bleeding time was prolonged (> 7.5 min) in 1/8 CML patients, 1/10 with PV, and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in 9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of vWF, expressed by a major increase of the 140-Kd fragment and decrease of the intact 225-Kd subunit in ET patients, whereas the 176-Kd fragment was significantly increased in all the subgroups of patients. Platelet vWF was significantly higher in CML patients in comparison to ET and normal controls. However, minor losses of the larger multimers were evident in all the subsets of patients. In ET patients also the intermediate forms were lacking in platelets, accompanied by a significant decrease of platelet RiCof. This abnormality was significantly correlated with the occurrence of bleeding symptoms in PV and ET patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF abnormalities are common findings in myeloproliferative syndromes and are more severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect the more frequent bleeding symptoms observed in this disorder.

Adult↗
PubMed1992

The bleeding time in normal subjects is mainly determined by platelet von Willebrand factor and is independent from blood group.

Bleeding time (BT) is the most important test "in vivo" evaluating the primary hemostasis. No relationship between plasma von Willebrand factor (vWF) and BT has been found in normal subjects, whereas no data are available on the relationship between platelet vWF and blood group or BT in normal subjects. To clarify the reciprocal relationship between blood group, vWF and BT, we studied 177 normal subjects. The influence of blood group on BT was analyzed in 116 subjects and the distribution of platelet and plasma vWF between different blood groups in 111 subjects. Furthermore, in a subgroup of 50 subjects, a multivariate regression model, including age, platelet count, plasma and platelet vWF:Ag and Ristocetin Cofactor (RiCof), hematocrit, sex and O or non-O blood group was used to assess the joint influence of these variables on BT. BT was similar in O and non-O group (P = 0.310) and, although plasma vWF was significantly lower in O group (P less than 0.0001), platelet vWF content was similarly distributed (P = 0.873 vWF:Ag and P = 0.322 RiCof). Furthermore, platelet vWF was not correlated with plasma vWF (r = 0.06, P = 0.526). In the multivariate regression analysis, only platelet vWF, age and platelet count showed a significant, inverse correlation with BT (P = 0.004), explaining 25% of the total variation of this test. Platelet vWF resulted therefore the main determinant of BT.

Adolescent↗
PubMed1992

Effectiveness of high-dose intravenous immunoglobulin in a case of acquired von Willebrand syndrome with chronic melena not responsive to desmopressin and factor VIII concentrate.

A patient with benign monoclonal IgG lambda paraproteinemia, acquired von Willebrand syndrome (AVWS), and chronic melena successfully responding to high-dose intravenous immunoglobulin (lvlg) is reported. Coagulation parameters at admission were APTT (ratio) 1.68; VIII:C 11 IU/dL; vWF:Ag 7 IU/dL:Ricof less than 3 IU/dl. RIPA was greater than 1.8 mg/ml, and bleeding time (BT) was prolonged (18 min). No evidence for an in vitro inhibitor against the VIII/vWF complex was observed. VIII/vWF measurements showed a short-lived increase after both DDAVP and Hemate P, and BT was transiently normalized. After intravenous Ig (1 g/kg for 2 days), VIII/vWF measurements, hemostatic parameters and multimeric pattern were completely corrected (VIII/C 106 IU/dl, vWF:Ag 168 IU/dl, RiCof 147 IU/dl, APTT ratio 0.89, BT 5'), with a return to pre-infusion values after 15 days. Hemoccult test became negative and packed red cell transfusions, of which 130 units were administered during the last year, were no longer required. After 18 months the patient is on maintenance treatment with repeated courses of Ig, at 3 to 4-week intervals based on VIII/vWF and BT monitoring.

Bleeding Time↗
PubMed1992

Fibrin glue from single-donation autologous plasmapheresis.

A method is described for preparing fibrin glue from fibrinogen obtained by double cryoprecipitation of plasma collected by plasmapheresis. Plasma (average volume, 528.8 +/- 86 mL), collected from 12 plasmapheresis donors was cryoprecipitated twice. When the cryoprecipitated pellet was resuspended in 0.5 to 2 mL of saline (total volume of saline-resuspended fibrinogen: 5 mL), the average yield of fibrinogen was 78.4 +/- 18.3 mg per mL. This is comparable to commercial preparations, is suitable for clinical use, and offers greater safety at a reduced cost.

Electrophoresis, Polyacrylamide Gel↗
PubMed1991

Clinical pharmacokinetics of a placenta-derived factor XIII concentrate in type I and type II factor XIII deficiency.

Limited data are available about the pharmacokinetics of placenta-derived factor XIII (FXIII) concentrate in patients with FXIII deficiency. This concentrate contains only the active subunit A but not the carrier subunit B of the factor, and perplexities have been raised about its clinical use. Moreover, no data are available on its use in the rare patients completely lacking both subunit A and subunit B. Therefore, we evaluated the pharmacokinetics of a commercial placenta concentrate in three patients with FXIII deficiency: two lacking subunit A (type II) and one lacking both subunits (type I). The elimination half-life of the infused placenta subunit A in the three patients was very similar (280, 283, and 272 hr) and was also consistent with the previously reported data for plasma-derived FXIII. No thrombin-independent activity was observed in our concentrate batches. The recovery was significantly lower in the type I patient, in whom infusion of subunit A was not able to elicit a monthly increment of subunit B, as usually observed in type II patients. Monthly infusions of placenta concentrate (at higher dosage in type I patient) have been administered to our patients for two to three years and no evidence of inhibitor against factor XIII activity has been observed. We conclude that placenta concentrates may be as effective as plasma derivatives in replacement therapy of factor XIII deficiency, even in patients who lack subunit B.

Adult↗
PubMed1991

Parallel line bioassay in a coagulation laboratory. A program for personal computer use and an example application to Ristocetin Cofactor assay.

The authors review the statistical principles of parallel line bioassay and describe a computer program written to facilitate a correct approach to most coagulation assays. This program should be especially useful for those assays in which linearization of dose-response curves may prove difficult, or in which careful analysis of assay validity is required. How the knowledge of bioassay theory can be applied to von Willebrand factor Ristocetin Cofactor activity measurement is shown as a general example.

Biological Assay↗
PubMed1990

von Willebrand factor antigen is less sensitive than ristocetin cofactor for the diagnosis of type I von Willebrand disease--results based on an epidemiological investigation.

Recently, in an epidemiological investigation involving 1,218 children aged 11-14, we demonstrated that the prevalence of von Willebrand's disease, based on a low ristocetin cofactor activity (RiCof) in children with a personal and/or family history of hemorrhage, was at least 1% (Blood 1987; 69: 454). All the diagnosed cases had multimeric patterns typical of type I von Willebrand's disease (vWd). Since standardization of RiCof is difficult and the test is not easily performed in a clinical laboratory, we measured von Willebrand factor antigen (vWf:Ag) in all available unthawed plasma samples of previously investigated children by ELISA, to assess the relative sensitivity of this more simple test for diagnosing vWd. Separate normal ranges were calculated by non-parametric methods for 0 and non-0 subjects, and for children and adults, since values were higher in non-0 subjects and in children. Taking into account the 90% confidence interval around the lower limit of the normal range, 7 (50%) of the 14 cases diagnosed by RiCof were detected by vWf:Ag. Furthermore, two new cases would have been diagnosed by vWf:Ag, leading to a relative Ag/RiCof global sensitivity of 64%. A similar figure was obtained when the two tests were compared in the group of relatives of the affected children. In conclusion, measurement of vWf:Ag seems to be definitely less sensitive than the RiCof assay for detecting patients with vWd, even in type I patients, and RiCof remains the test of choice for screening for vWd in hemorrhagic patients.

Adult↗
PubMed1990

Platelet von Willebrand factor assay: results using two methods for platelet lysis.

Two different methods (using Triton X-100 and glycerol) for lysing platelets to measure platelet vWF concentrations were compared directly. The platelet concentration of von Willebrand factor antigen (vWF:Ag) was similar for both methods, whereas ristocetin cofactor activity (Ricof) was higher with Triton than with glycerol. After storing platelet lysates for two months at -80 degrees C vWF:Ag and Ricof concentrations decreased with both methods of lysis. Larger than normal (supranormal) vWF multimeric forms could be visualized in platelet lysates obtained using both methods, with no change of the multimeric pattern during storage. Triton can be recommended as the agent of choice to lyse platelets for measurement of their vWF concentration, but the samples must be assayed within two weeks to avoid decay of Ricof activity.

Blood Platelets↗