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Biomedical subjects

G Palareti

Publications and source records attributed to G Palareti.

At least 19 recordsLinked to original sources

Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes.

In 107 asymptomatic and untreated patients with inherited syndromes associated with thrombophilia (antithrombin III, protein C and protein S deficiencies), we compared in parallel two plasma peptides which reflect activation of the common coagulation pathway: the prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA). Both F1 + 2 and FPA were measured with simple, commercially available ELISA methods. High levels of F1 + 2 or FPA were found in about one fourth of the patients as a whole. When patients were divided according to the type of inherited thrombophilic syndrome, it appeared that F1 + 2 was more frequently elevated in protein C and protein S deficiencies than in antithrombin deficiency; and that, in general, it was no more frequently elevated than FPA. Although our data confirm the existence of a procoagulant imbalance in inherited thrombophilic syndromes due to defects of natural anticoagulant proteins, they do not confirm that such imbalance can be more frequently diagnosed by measuring F1 + 2 levels, particularly in patients with antithrombin deficiency.

Adolescent

An evaluation of several laboratory tests and test combinations in the detection of lupus anticoagulant.

The laboratory assessment of the lupus anticoagulant, a factor frequently associated with venous and arterial thrombosis, recurrent miscarriages and abortions, is not straightforward, as indicated by the variety of tests proposed and the different results obtained. On account of the marked variability and heterogeneity of lupus anticoagulant among patients, no single test or reagent will identify all patients with lupus anticoagulant, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to assess the minimum number of tests necessary for the satisfactory identification of the patient with lupus anticoagulant. Our study confirms that lupus anticoagulant may be present in a significant number of patients with normal routine activated partial thromboplastin time, a test which therefore cannot be used as the sole criterion for identifying patients suspected of having lupus anticoagulant. In contrast all patients who had positive results in at least one test could be detected (100% sensitivity) with two combinations of tests: (1) dilute activated partial thromboplastin time and Kaolin clotting time and (2) dilute activated partial thromboplastin time and tissue thromboplastin inhibition test. Since the latter inhibition test has been reported to give a high number of false-positive or negative results, we suggest the combination of dilute activated partial thromboplastin time and Kaolin clotting time as the standard pair of tests for the screening of suspected lupus anticoagulant patients.

Antiphospholipid Syndrome

Protein S activity in patients with heredofamilial protein S deficiency and in patients with juvenile venous thrombosis. Results of a functional method.

Using an ACL 300R coagulometer (Instrumentation Laboratory) we assessed the clinical usefulness of a new method to measure PS activity (PS:Act), based on the prolongation of prothrombin time of a mixture of diluted plasma sample, PS depleted plasma previously incubated with Protac for protein C activation, bovine thromboplastin and calcium ions. The results were compared with those from immunological assays. PS:Act was measured in 42 apparently healthy subjects, in 12 patients with hereditary PS deficiency (HPSD group) diagnosed on the basis of immunologic tests and in 48 patients with episodes of juvenile venous thromboembolism at least three months prior to testing (JVTE group). All the HPSD patients had PS:Act below the normal range (less than 62%). In JVTE group 9 patients (18.7%) showed abnormal results for PS:Act, 4 (8.3%) had low levels of free PS:Ag; all patients had normal total PS:Ag levels. Levels of antiphospholipid antibodies (immunologic test) were normal in the 9 JVTE patients with low PS:Act. When all the results were considered together (n = 102), the correlation coefficient between PS:Act and free PS:Ag was 0.78 (p less than 0.01).

Adolescent

Ticlopidine.

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Arterial Occlusive Diseases

Ticlopidine lowers plasma fibrinogen in patients with polycythaemia rubra vera and additional thrombotic risk factors. A double-blind controlled study.

Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit, plasma hyperviscosity, hyperfibrinogenemia) were enrolled in a double-blind randomized placebo-controlled study, and 18 were given ticlopidine 250 mg, b.i.d., for 60 days. All the patients had previously been submitted to cytoreduction, and PRV was under control in all cases at the start of the study. During the study, the haematological parameters were controlled every 15 days, and venesection was performed if haematocrit was greater than 46%. Whole blood viscosity, at low and high shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In the ticlopidine group, we recorded a significant 13.14% reduction of the mean fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p less than 0.01). All the other haemorheological parameters were not significantly modified by ticlopidine treatment, nor were there significant modifications recorded in the placebo group. Our study shows that ticlopidine may reduce a probable thrombotic risk factor (hyperfibrinogenemia) in PRV patients.

Aged

Coagulation and fibrinolysis in orthotopic liver transplantation: role of the recipient's disease and use of antithrombin III concentrates. S. Orsola Working Group on Liver Transplantation.

In this study we report the data obtained from extensive haemostatic testing of 25 patients undergoing orthotopic liver transplantation and the results of an open randomized pilot trial of antithrombin III concentrate administration during surgery. Marked differences in transfusional needs and in pre- and intraoperative blood coagulation and fibrinolytic changes were observed between recipients with liver cirrhosis and those with primary biliary cirrhosis. In the former, the increases in tissue-type plasminogen activator activity, total euglobulin fibrinolytic activity, and fibrin-derived degradation products occurred earlier and were more marked, as were the signs of increased thrombin formation. Supplementation of antithrombin III concentrate during surgery failed to induce significant changes in the main parameters studied and in the transfusional needs.

Adult

Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio.

This collaborative study, organized by the Hemostasis Subcommittee of C.I.S.M.E.L., evaluated the accuracy, precision, and comparability of the following six widely used fibrinogen assays: total clottable fibrinogen (Blombäck and Blombäck), clotting time (Von Clauss), turbidimetry (Ellis and Stransky), Chromotime System, prothrombin time (PT)-derived, and radial immunodiffusion (RID). The same frozen samples, with normal and high contents of fibrinogen, were examined in four laboratories. The methods were calibrated with an internal standard whose fibrinogen content was determined gravimetrically. Both the Von Clauss and the RID methods were reliable, accurate, and precise, if adequate calibration was used. The PT-derived method was highly reproducible, but had some problems with accuracy. We demonstrate that an adequate calibration procedure is indispensable for reliable fibrinogen measurements whatever method is used. Because neither the calibration procedures proposed by the manufacturers nor the use of lyophilized commercial plasmas is adequate for this purpose, we urge that an international standard for fibrinogen measurement be promptly established.

Calibration

Association of reduced factor VIII with impaired platelet reactivity to adrenalin and collagen after total thyroidectomy.

Twenty-one thyroprival patients, previously submitted to total thyroidectomy for tumours, were investigated during stabilized L-thyroxine supplementation and at the end of a 20-25 day "no-therapy" period, necessary for a 131I total body scintigraphy. During supplementation therapy a lower than normal mean beta-thromboglobulin (beta-TG) release level was found, the other blood clotting and platelet function tests being normal. After substitution therapy withdrawal, platelet function tests showed reduced adrenalin aggregation, increased collagen threshold aggregating concentrations, decreased beta-TG release values and reduced aggregation to ristocetin, whereas blood clotting tests showed prolonged aPTT values and reduced levels of factor VIII:C and vWf:Ag. We conclude that in acquired hypothyroidism the lowering of factor VIII:C and vWf:Ag (acquired von Willebrand disease) is associated with impaired platelet reactivity not only to ristocetin but also to collagen and especially adrenalin. In the patients investigated these changes were almost completely corrected by substitutive therapy with L-thyroxine at clinically effective doses.

Adult

Lowered antithrombin III activity and other clotting changes in homocystinuria: effects of a pyridoxine-folate regimen.

Few studies have dealt with blood-clotting changes in patients affected by homocystinuria. The aim of this contribution is to briefly review studies published so far on the topic and report the results of our investigation performed in 3 patients. At baseline we found reduced antithrombin III and factor VII levels in all the patients, in line with the results of other authors, and other slight and less constant changes such as lowered factor X activity and protein C antigen, and increased beta-thromboglobulin levels. During pyridoxine and folate treatment, antithrombin III activity rapidly returned to normal; factor VII increased and beta-thromboglobulin decreased. These blood-clotting abnormalities may play a role in the thrombotic tendency associated with homocystinuria. Their nature is still uncertain, but the improvement observed during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some clotting factors.

Adolescent

Long-term effects of ticlopidine on fibrinogen and haemorheology in patients with peripheral arterial disease.

The effects of ticlopidine treatment (250 mg b.i.d. for 21 months) on fibrinogen and other rheological variables, as compared to placebo, were studied in 44 patients with intermittent claudication due to peripheral arterial occlusive disease. Blood samples were collected every 3 months during this double-blind, randomised placebo-controlled trial which lasted 21 months. Consistently lower values of fibrinogen, haematocrit and whole blood viscosity at high and low shear rate levels were found in the ticlopidine group; the intergroup differences were statistically significant at most but not all follow-up examinations. A significant time-related variance was observed in the ticlopidine group for the measured variables, also after correction for the variability found in the placebo group. Thus, the observed changes in the ticlopidine group are mainly treatment related. These effects on fibrinogen and haemorheology may contribute, besides the known antiplatelet activity of the drug, to the clinical improvement reported in a larger group of claudicants to which the present subset of patients belong.

Blood Viscosity

Haemorheologic and fibrinolytic evaluation in obese children and adolescents.

The haemorheologic condition was evaluated in 43 obese children and 35 controls. In 18 of the obese children and in 21 controls the euglobulin lysis time (ELT) was also studied. Blood viscosity at 94.5 and at 0.204 s-1 shear rates, plasma viscosity, fibrinogen and erythrocyte filtration time were significantly higher in obese than in control children. No significant differences were observed in haematocrit levels. Triglycerides, non-esterified fatty acids (NEFA), pre-beta-lipoprotein and insulin rates were all significantly higher in obese than in control children. There were no significant differences in glycaemia and in haemoglobin A1 values. ELT, both basal and after stimulation with 1-deamino-8-D-arginine-vasopressin (DDAVP), was significantly higher in the obese than in control children. The haemorheologic disturbances together with alterations of the haemostatic balance and fibrinolysis may be an important risk factor for the development of vascular changes at paediatric age.

Adolescent

Intravascular coagulation phenomena associated with prevalent fall in fibrinogen and plasminogen during L-asparaginase treatment in leukemic children.

12 children affected by acute lymphoblastic leukemia had higher baseline levels of Normotest, Antithrombin III activity (AT III:A) and antigen (AT III:Ag) than those found in the control group, due to increased liver protein synthesis, as shown by the higher values of 305llbumin. Treatment with L-asparaginase (L-Asp) induced a marked decrease in fibrinogen and plasminogen and only a slight but significant reduction in AT III:A, AT III:Ag, protein C and alpha 2 antiplasmin levels. Platelet counts progressively increased. Each single L-Asp administration acutely induced (as recorded in the 2-hour postadministration samples) a significant increase in fibrinopeptide A values and reduction in several factors and inhibitors, due to activation of coagulation and consumption phenomena. It is suggested that these acute changes, but not the marked and selective reduction in fibrinogen and plasminogen, were partly compensated during L-Asp treatment by an overall increase in clotting and nonclotting protein synthesis in the liver.

Asparaginase

Effect of slimming on metabolic and haemorheologic patterns in a group of obese subjects.

In order to evaluate slimming effects on certain metabolic (cholesterol, triglycerides, basal insulinaemia) and haemorheologic (haematocrit, fibrinogen, whole blood viscosity and plasma viscosity) rates, we studied 24 obese subjects (15 female and nine male) aged 25-58, with BMI ranging from 35.5 to 67, before and after a hypocaloric diet period involving a 20-kg weight loss. All subjects underwent blood sampling to assess: OGTT, plasma proteins, serum total cholesterol, HDL-cholesterol, serum triglycerides, haematocrit, whole blood viscosity at high and low shear rate with and without correction of 45 per cent haematocrit, plasmatic capillary viscosity and fibrinogen level. Our study showed no significant changes in plasma proteins, serum HDL-cholesterol, haematocrit, fibrinogen and whole blood viscosity at high and low shear rate, while basal insulinaemia, total cholesterol, triglycerides, low shear rate corrected at 45 per cent haematocrit blood viscosity and capillary plasmatic viscosity are significantly reduced. However the analysis of possible relation between the differences of assessed rates before and after slimming has shown no significant correlations. In conclusion, we can say that the slimming of very obese subjects improves blood and plasma viscosity, but the mechanism by which this improvement occurs is not the one which usually affects the determination of these rates.

Adult

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Administration, Oral