Apparent heterozygous type II protein C deficiency caused by the factor V 506 Arg to Gln mutation.
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Biomedical subjects
Publications and source records attributed to G Finazzi.
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To assess the organization and the quality of care of an anticoagulation clinic, the structure, the process of laboratory control and the clinical outcome in our Center are described. 1068 patients under control in 1994 (M/F 572/496; median age 63 range 6-91 ys., 74% in long-term prophylaxis) were evaluated. The clinic was run twice weekly by a physician, two nurses and a technician; management for emergencies was always warranted. Prothrombin time was carried out with a sensitive thromboplastin (ISI < 1.1) and a computer program provided calculation and graphical representation of INR, comparison with therapeutic range, automatic dosage prescription and print out. Laboratory quality of therapy was assessed by three different techniques: 'cumulative INR', 'last check in file' and 'linear change', yielding respectively 69% of laboratory controls, 71% of patients and 80% of days within the therapeutic range. The rate of thrombosis, major and total bleeding were respectively 0.2%, 0.2% and 12.5%. An anticoagulation clinic represents an effective organizational model for the management of patients taking oral anticoagulants.
Essential thrombocytemia (ET) is a clonal myeloproliferative disorder of unknown cause, characterized by an increased number of apparently normal platelets. It has been related to a large number of mild ischemic complications, but rarely to acute stroke associated with documented large vessel thrombosis. We report the cases of 6 patients with acute ischemic stroke associated with ET (4 men and 2 women; mean age 61.7: range 49-78 years). The diagnosis of ET followed the onset of the stroke. The number of platelets was never greatly increased at the time of the stroke, and two patients presented no major risk factors for stroke. The involvement of the posterior circulation was observed in three patients, that of the anterior circulation in two patient and that of the border territory in one. The obstruction of large intracranial or extracranial vessels was detected in all of the patients, and all of them were treated with antiplatelet agents (aspirin or ticlopidine). The outcome was good in 3 patients, fair in one and bad in two. We retain that ET might be a cause of acute ischemic stroke as a result of large vessel obstruction.
Congenital protein S deficiency is an important risk factor for venous and, more rarely, arterial thrombosis. Here, we describe the case of a 35-year old patient with cerebral ischemia, protein S deficiency and carotid stenosis. Other members of the family were found to have the same protein S deficit and a history of venous thrombotic manifestations.
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A prospective, randomized, double-blind clinical trial was carried out in a single center to compare the clinical and laboratory quality of oral anticoagulant therapy monitored with recombinant tissue factor (RTF) or with a sensitive, human-derived, conventional thromboplastin (CT) in the PT test. Seven hundred and fifty-seven consecutive patients receiving oral anticoagulation for various indications were randomized to RTF (n = 379) or CT (n = 368) for 6 months. Total follow-up was 167 and 153 patient-years for RTF and TP groups respectively. Fifty-six bleeding events were observed: 31 in the RTF group and 25 in the TP group. The incidence of bleeding was 18.5 and 16.5% pt-yrs for RTF and TP patients respectively (n.s.). The event-free follow-up curves were not significantly different between the two groups. The laboratory quality of oral anticoagulation was evaluated with the "last check in file" method: therapeutic INR was found in the same proportion of RTF and TP patients (70.2% vs 68.8%). Our study shows that RTF is as effective as a sensitive, conventional thromboplastin for monitoring oral anticoagulation.
The clinical history of 238 patients with inherited thrombophilia (AT III = 94, PC = 103, PS = 41) was analyzed retrospectively at diagnosis and in the follow-up period after diagnosis. At diagnosis 129 patients (54%) had suffered from thrombosis, with a recurrence rate of 48%. The most frequent onset manifestation was deep vein thrombosis of lower limbs (58%). Thrombotic history started before 40 in 80% of the cases. Forty-nine percent of the venous thromboses were preceded by a triggering event, in most cases pregnancy (17%) and surgery (12%). After diagnosis, follow-up lasted a total of 1,113 pt-years. A policy of short-term prophylaxis during risk situations for all patients and long-term prophylaxis in symptomatic patients failed to prevent venous thrombotic episodes (diagnosed by objective methods) in 4 previously asymptomatic subjects and recurrence in 7 previously symptomatic subjects. After knowledge of the patients' diagnosis the incidence of venous thrombosis/100 pt-years was reduced as compared before diagnosis as total episodes (onset+recurrencies) (1.0 vs 1.9), onset episodes (0.7 vs 1.3) and recurrent episodes (1.3 vs 4.8), even though the differences were not statistically significant. However most of the venous thromboses occurred at a more advanced age (67% after 40 years) and without any apparent cause (83%), at significant variance with the period preceding the diagnosis; in particular the incidence of venous thrombotic onset in patients younger than 40 passed from 1.3/100 pt-years to 0.2/100 pt-years. In 6 recurrences after diagnosis a poor compliance for antithrombotic treatment was recognized.(ABSTRACT TRUNCATED AT 250 WORDS)
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A cohort study was undertaken to compare the incidence of thrombosis in patients with inherited deficiency of Antithrombin III (n = 9), Protein C (n = 36) and Protein S (n = 36). The patients were stratified for schedule of antithrombotic prophylaxis and followed for a total period of 160 patient-years. Seven venous thrombosis were observed for a total incidence of 4.3% pts.-ys. The incidence of thrombosis was not significantly different in patients of different age, sex and schedule of prophylaxis, although there was a trend to a lower incidence in young individuals and in those receiving long-term oral anticoagulation. Patients with AT III deficiency had an higher incidence of thrombosis than patients with Protein C or Protein S deficiency (12 vs. 2.8 vs. 3.3% pts.-ys, p < 0.05), despite the fact that they were, on average, younger and more prophylaxed. This study suggests that congenital Antithrombin III deficiency constitutes a greater risk of thrombosis than congenital deficiencies of Protein C and Protein S.
This study evaluated the advantage of an anticoagulation clinic in terms of the improvement of the clinical quality of oral anticoagulation (i.e. prevention of thromboembolism and low rate of hemorrhagic complications). The incidence of thromboembolic events and major hemorrhagic complications was assessed in a series of 271 patients on oral anticoagulation for mechanical heart valve prosthesis before and after their enrollment in our anticoagulation clinic from January 1987 to December 1990. Risk factors for hemostatic events were also analyzed. The incidence of major hemostatic complications was significantly lower when patients attended the clinic: 1.0 vs 4.9%/pt-yr for hemorrhage and 0.6 vs 6.6%/pt-yr for thrombosis. This depended on three main factors: better dose regulation of warfarin, continuous patient education and early identification of clinical conditions potentially at risk for thrombosis and hemorrhage. Only previous hemorrhagic or thromboembolic events were recognized as major risk factors for hemostatic complications. In conclusion, our study shows that an anticoagulation clinic offers a real advantage to patients with mechanical heart valve prosthesis in terms of prevention of thromboembolic events and hemorrhagic complications.
We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5' untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection.
OBJECTIVE: To study the association of a variety of dermatological manifestations related to vascular abnormalities with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome. METHOD: Case-control study. Consecutive patients referred to the coagulation and haemostasis service of a general hospital for the first determination of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and newly diagnosed disorders (for example, thrombocytopenia, thrombotic disorders, and unexplained repeated abortions) were selected. Patients were examined by two dermatologists according to predefined criteria, and information about general characteristics and relevant dermatological and medical histories were collected using an ad hoc questionnaire. The study was limited to patients without evidence of systemic lupus erythematosus. A total of 35 patients was examined; 13 subjects were positive for lupus anticoagulant or anticardiolipin antibodies, or both (cases), and 22 were negative (controls). RESULTS: Moderate to severe livedo reticularis and acrocyanosis were significantly associated with antiphospholipid antibodies, with relative risks of 13.1 (95% confidence interval 1.1 to 149.0) and 8.6 (95% confidence interval 1.1 to 65.1). Capillaritis was also associated with the antibodies. Histories of Raynaud's phenomenon and superficial thrombophlebitis were more common in cases than controls. CONCLUSIONS: This study provides quantitative evidence of the association of antiphospholipid antibodies with several cutaneous diseases in which vascular abnormalities seem to play a major part. The study suggests that these manifestations might appear early in the development of the antiphospholipid syndrome.
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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.
OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). DESIGN: Prospective, nonrandomized comparative study. SETTING: Hematology department in a general hospital. PATIENTS: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/HUS. Three had a severity score at diagnosis less than or equal to 4 and were treated with IVIG and 14 had a severity score of greater than or equal to 5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy. RESULTS: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP-HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17). CONCLUSIONS: Our study does not confirm the utility of IVIG in the management of TTP-HUS, as suggested by earlier single case reports.
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