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Biomedical subjects

A Girolami

Publications and source records attributed to A Girolami.

At least 91 records · Page 5Linked to original sources
PubMed2000

Combined heterozygous plasminogen deficiency and factor V Leiden defect in the same kindred.

Combined plasminogen deficiency and resistance to activated protein C defect (factor V Leiden) have been described in a few families and associated with a variable occurrence of thrombotic events. Here we describe a new family with thrombophilia and the presence of hypoplasminogenemia and factor V Leiden mutation. In addition, a brief review of the literature is presented. Nine patients belonging to this kindred underwent coagulation study for hereditary thrombophilia, which included plasminogen antigen and activity assays, an activated protein C resistance test, and genetic analysis for factor V Leiden mutation and for prothrombin variant 20210A. The proposita, a 40-year-old asymptomatic female with a family history of thrombotic diathesis, was affected by heterozygous plasminogen deficiency. Hypoplasminogenemia was found also in her two sisters, in one instance associated with factor V Leiden mutation. The mother was the putative carrier of hypoplasminogenemia, but she refused to be studied. The symptomatic father was heterozygous for factor V Leiden mutation, but presented with normal plasminogen levels. Among the available siblings investigated from the paternal side, resistance to activated protein C due to factor V Leiden mutation was found in three patients, one of whom experienced venous thromboembolism. Another uncle with a history of thrombotic disease showed no coagulation abnormalities. These findings together with the data from literature confirm the role of factor V Leiden as an independent risk factor for venous thromboembolism, whereas isolated hypoplasminogenemia does not seem to increase the risk for thrombosis. There is no clear evidence that the coinheritance of these two defects may be associated with an additional risk for thrombosis compared with the presence of factor V Leiden mutation alone.

Activated Protein C Resistance↗
PubMed2000

Leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

Aged↗
PubMed2000

Heparin-induced thrombocytopenia.

BACKGROUND AND OBJECTIVE: There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight and asymptomatic reduction in platelet count, occurring in the first 1-2 days of therapy, that resolves spontaneously; in contrast, HIT II, which has an immunologic origin, is characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withdrawal. HIT II is the most frequent and dangerous side-effect of heparin therapy; in fact, in spite of thrombocytopenia, it can be complicated by venous and arterial thrombosis. Therefore, the recognition of HIT II may be difficult due to the underlying thrombotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical guidelines for the clinical diagnosis and treatment of HIT II. STATE OF THE ART: The prevalence of HIT II, as confirmed by laboratory tests, seems to be about 2% in patients receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The immunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-heparin/ PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-heparin/PF4 immunocomplex activates platelets mainly through binding with the FcgRIIa (CD32) receptor. The onset of thrombocytopenia is independent of the dosage, schedule and route of administration of heparin. Orthopedic and cardiovascular surgery patients receiving post-surgical prophylaxis or treatment for deep venous thrombosis are at higher risk of HIT II. Besides thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses which carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-dependent antibodies. Functional tests, such as platelet aggregation and (14)C-serotonin release assay and immunologic tests, such as the search for anti-PF4/heparin complex antibodies by an ELISA method are available. If HITT II is probable, heparin must be immediately suspended and an alternative anticoagulant therapy should be initiated before resolution of thrombocytopenia and the following treatment with a vitamin K antagonist. The general opinion is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direct thrombin inhibitors such as hirudin. PERSPECTIVES: Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors that induce the occurrence of thrombotic complications. The best therapeutic strategy remains to be confirmed in larger clinical trials.

Heparin↗
PubMed2000

Nomograms for the administration of unfractionated heparin in the initial treatment of acute thromboembolism--an overview.

Despite the availability of low-molecular-weight heparins, unfractionated heparin (UFH) still remains the drug of choice for the initial treatment of acute venous thromboembolism in many countries. When appropriately employed, UFH treatment results in a degree of efficacy and safety that is fully comparable with that obtained with the use of heparin derivatives. The use of nomograms for the intravenous or subcutaneous administration of UFH assures that virtually all patients will promptly achieve adequate levels of anticoagulation, thus decreasing the likelihood of recurrent venous thromboembolism without extra bleeding-risk. In this article we reviewed clinical studies on the implementation and validation of UFH dosing nomograms, and attempted a quantitative analysis of their performance. According to the results of our analysis, a statistically significantly higher proportion of patients treated on the basis of a nomogram reached a therapeutic anticoagulant level within 24 h of treatment, as compared to patients treated following the standard practice (odds ratio, 3.6; 95% CI, 2.6 to 4.9). The rate of recurrent thromboembolic events was significantly lower for patients treated according to a nomogram (odds ratio, 0.3; 95% CI, 0.1 to 0.8), while no significant differences in terms of either major or minor bleedings were detected between nomogram patients and controls.

Algorithms↗
PubMed1999

The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study.

Deficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.

Adult↗
PubMed1999

Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism.

To establish the prevalence of antibodies against beta2-glycoprotein I (beta2GPI) in unselected patients with venous thromboembolism, as well as the association with antiphospholipid antibodies (aPL) and a history of previous thromboembolism, we investigated the presence of these antibodies in 227 consecutive patients with acute deep vein thrombosis or pulmonary embolism, of whom 63 were carriers of aPL with or without lupus anticoagulant (LA), and seven were carriers of LA alone. The presence of antibodies against beta2GPI was demonstrated in 19 patients [8.4%; 95% confidence interval (CI), 4.5-11.3%]. All of them belonged to the group of 63 patients with aPL (30.2%). A history of a previous thromboembolism was identified in 11 of the 19 patients with anti-beta2GPI antibodies (57.9%) and in 45 of the 208 patients without these antibodies [21.6%; odds ratio (OR)=4.98; 95% CI, 1.89-13.1; p<0.0005]. In the subgroup of patients with aPL and/or LA, the rate of recurrent thromboembolism among patients with anti-beta2GPI antibodies (11 of 19, 57.9%) was significantly higher than that observed in patients without these antibodies (15 of 51, 29.4%; OR=3.3; 95% CI, 1.1-9.83; p=0.28). We conclude that in patients with acute venous thromboembolism the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies seems to identify a subgroup of patients with antiphospholipid antibodies who have a peculiarly high risk of thrombotic recurrences. Further prospective studies are indicated to better define the role of anti-beta2GPI antibodies in the development of recurrent thromboembolism.

Acute Disease↗
PubMed1999

Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis.

BACKGROUND: There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease. METHODS: A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures. RESULTS: In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain-free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]). CONCLUSIONS: Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.

Clinical Trials as Topic↗
PubMed1999

Psychological aspects and coping of parents with a haemophilic child: a quantitative approach.

Although haemophilia is a relatively rare hereditary disease, and is curable by blood products, the psychological and social problems of haemophilic patients and of their families are always serious. Anxiety for the risks of bleedings and the fear for infections transmitted by blood products cause stress and difficulty in coping with the situation. The aim of this paper is to assess resources, stress, and coping in parents with a haemophilic child. In order to measure the dimensions related to family stress and resources, social desirability, tendency to depression, and anxiety, the subjects were administered the short-form of the Questionnaire on Resources and Stress by Friedrich et al. revised by Saviolo & Cristante, along with the Social Desirability Scale, the Beck Depression Inventory, and the Ipat Anxiety Scale. The subjects of this study were 20 couples who were the parents of haemophilic sons. We analysed how the parents perceived the behavioural characteristics of their child, the differences between mothers and fathers in the questionnaire scores, and the correlation among the considered dimensions. The results show that the parents paid great attention to the problems of their sons, but mothers were more depressed and anxious about the disease of their child.

Adaptation, Psychological↗
PubMed1999

Prothrombin and the prothrombin 20210 G to A polymorphism: their relationship with hypercoagulability and thrombosis.

Polymorphisms of several clotting factors have been associated during the past few years with an increased risk of both venous or arterial thrombosis. However, final proof for the existence of a pathogenetic relationship between a given polymorphism and an increased risk for thrombosis is still lacking. Particular emphasis has been placed recently on a 20210 G to A prothrombin polymorphism. A critical review of available data indicates that such an abnormality may be associated with an increased risk of venous thrombosis but not arterial thrombosis (with a possible exception for myocardial infarction). However, this conclusion is based only on retrospective cohort studies which compared the prevalence of the abnormality in a group of patients with past venous or arterial thrombosis with a normal group (with no thrombosis). No prospective study has yet to show that patients with the abnormality, given similar additional acquired risk factors, have a higher incidence of thrombotic complications as compared with controls. The mechanism whereby the abnormality might cause thrombosis has been assumed to be an increase in prothrombin levels. Since an association between two phenomena does not necessarily mean that a causal relationship exists between the same events, it is important to be cautious before claiming that such abnormality is responsible for thrombosis. Therefore, although included commonly in the investigation profile, the search for the 20210 G to A prothrombin abnormality should not be considered yet to be an essential component in the routine study of hypercoagulable and/or thrombotic conditions.

3' Untranslated Regions↗