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Biomedical subjects

A Ruffatti

Publications and source records attributed to A Ruffatti.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy and safety of nadroparin in the treatment of pregnant women with antiphospholipid syndrome: a prospective cohort study.

The optimal therapeutic management of patients with antiphospholipid syndrome (APS) during pregnancy is debatable. In the present prospective cohort study the use of a low molecular weight heparin (LMWH) (nadroparin), administered alone twice daily in 30 pregnant women who were diagnosed with APS on the basis of the current classification criteria, is evaluated. Dosage was adjusted according to anti-Xa levels in the patients as the pregnancies progressed. Three women, in whom an important gradual fall in platelet count in the first trimester did not respond to increased nadroparin doses, were shifted to a second-line treatment protocol. Fetal loss occurred in two of the 27 remaining women (7.40%), while 25 (92.59%) delivered 25 live infants, between the 32nd and 40th weeks of gestation. No fetal problems were registered during pregnancies, while maternal complications occurred in two of the 25 patients (8%). Moreover, there were no thrombotic events in any of the women during the study. Patient compliance was good and only minor side-effects were reported. The results of this study indicate that nadroparin alone is useful and safe in the management of pregnant patients with APS. However, in consideration of the good pregnancy outcome obtained in patients with only pregnancy morbidity when heparin and aspirin were used together, other studies comparing nadroparin twice daily with once daily plus Aspirin would be useful to ascertain which is more effective in these patients.

Adult↗
PubMed2005

[Sensibility and specificity for pregnancy morbidity of anti-β2-glycoprotein I antibodies in antiphospholipid syndrome].

OBJECTIVE: This study aimed to evaluate the sensitivity and specificity of the anti-β2-glycoprotein I (GPI) antibodies for pregnancy morbidity in the antiphosoplipid syndrome (APS). METHODS: 335 women were recruited and on the basis of their clinical features were subdivided into 2 groups homogenous for number and age. The first (study) group contained the women whose pregnancy complications satisfied the classification criteria for APS. The second (control) group was made up of women with pregnancy complications not included in the classification criteria for APS. Anti-β2-GPI, anticardiolipin antibodies (aCL) and lupus anticoagulants (LA) were determined in all of these women. RESULTS: The only antiphospholipid antibodies occurring with a significant frequency (p=0,00) in the women with pregnancy criteria for APS were the IgG anti-β2-GPI and the IgG aCL present respectively in 23,92% and in 27,60% of the women. Its association was found to be significant (p=0,000). The distribution of the different levels of positivity of the IgG and IgM anti-β2-GPI in the patients of the study and control groups was not significantly different. The highest sensitivity for pregnancy complications was that of the IgG aCL and of the IgG anti-β2-GPI whose difference was not statistically significant. The comparison of the specificity of the IgG and IgM anti-β2-GPI with that of the IgG and IGM aCL was not statistically significant. CONCLUSIONS: The importance of determining the IgG anti-β2-GPI as part of routine laboratory testing of women with pregnancy complications typical of APS was confirmed. Together with IgG aCL these antibodies have proved to be the most sensitive and specific markers of pregnancy complications in APS.

Adult↗
PubMed2003

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗
PubMed2001

Some patients with antiphospholipid syndrome express hitherto undescribed antibodies to cardiolipin-binding proteins.

Contrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor beta2-Glycoprotein I (beta2GPI). While there is a well-documented link between the risk of thrombosis and the presence of beta2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-beta2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-beta2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients.

Adolescent↗
PubMed2000

Correction for age of anticardiolipin antibodies cut-off points.

Immunoglobulin (Ig) isotypes G, M, and A of anticardiolipin antibodies (aCL) are considered markers of antiphospholipid syndrome (APS). They were determined by ELISA in sera of 100 healthy children aged between 6 months and 16 yrs (mean 5.4 yrs +/-3.4 SD) and 100 healthy elderly subjects aged between 65 and 103 yrs (mean 84.2 yrs +/-8.1 SD). The frequency with which they were detected was compared to that in sera of 100 healthy adults aged between 21 and 47 yrs (mean 25.8 yrs +/-5.2 SD) in order to evaluate if adult aCL cut-off levels were fit for pediatric and elderly populations. The cut-off points were calculated adding 2.5 SD to the mean values and, in the adult group, the results were 11.6 GPL, 7.5 MPL, and 23.9 APL for IgG, IgM, and IgA, respectively. In the children, IgG aCL were positive in 26 cases (26%), IgM and IgA aCL in 1 case (1%) respectively. Statistical comparison of these results to those of adults showed a higher significant frequency for children IgG aCL (P = 0.0001) with the major contribution by children aged between 6 months and 5 yrs, and a lower significant frequency for children IgA aCL (P = 0.041). In elderly subjects IgG aCL were positive in 12 cases (12%), IgM aCL in 4 (4%), and IgA aCL in 37 (37%). In a comparison of these values to those of adults, only elderly IgA aCL frequency was significantly higher (P = 0.0001) with the major contribution by the oldest subgroup. In order to avoid false positive results for IgG aCL in children and for IgA aCL in elderly, as well as false negative results for IgA aCL in children, we introduced three new cut-off points: (1) 27.7 GPL for IgG aCL in children; (2) 13.8 APL for IgA aCL in children; and (3) 51.1 APL for IgA aCL in elderly subjects. These data suggest that a correction for age of aCL cut-off levels should be considered to raise specificity and sensitivity for APS in pediatric as well as in elderly populations.

Adolescent↗
PubMed1997

[Relationship between late ventricular potentials and ventricular arrhythmias in patients in chronic dialysis treatment].

BACKGROUND: Arrhythmias are frequent pathology in patients with chronic hemodialysis. We evaluated whether a relatively new technique, signal averaging, could be useful in predicting the development of complex arrhythmias in these patients. METHODS: Thirty-three patients, 18 male and 15 female, subjected to thrice weekly chronic hemodialytic treatment with various dialysis techniques, were studied. Exclusion criteria were the presence of antiarrhythmic and inotropic treatment. The following examinations were carried out in all patients: a Holter dynamic electrocardiography for a duration of 24 hours, begun on the day of dialysis, high resolution ECG pre- and post-dialysis to find out if there were any ventricular late potential (VLP). Four hundred beats were examined in order to obtain a background noise of less than 0.7 microV and a better definition of the signal. The following parameters were considered significant for the presence of VLP: a) filtered QRS duration > 120 msec; b) the root mean square of the signal expressed in the terminal portion of QRS (RMS) < 25 microV) high frequency low amplitude signals duration (HFLA) > 40 msec. A positive value in two of these parameters was considered indicative of the presence of VLP. In addition various pre and post-dialysis indices of dialytic efficiency and a mono and two-dimensional echocardiogram with pulsed and color Doppler were carried out. Of the 33 patients studied, ten were excluded because they presented too high a background noise at the high resolution ECG. Of the remaining 23 patients, 13 (56%) presented VLP and nine of these (69%) presented complex arrhythmias. Of the ten patients without VLP, 5 (50%) presented complex arrhythmias. The incidence of arrhythmias was highest during the last two hours of dialysis and in the two hours following it. The patients were then divided into two groups (A and B) according to the ejection fraction (EF) found at the echocardiogram. Group A was composed of 17 patients of whom 8 (47%) presented complex arrhythmias; group B (EF < 45%) was composed of the remaining six patients, who all presented complex arrhythmias. In group A nine patients (53%) out of 17 had LVP, in group B four out of six (66%) had it. All the patients except one presented an increase in the thickness of the ventricular wall and alterations of Doppler transmitral filling rate. Left ventricular hypertrophy was diagnosed in 22 out of the 23 patients. Four patients also had chronic ischaemic heart disease; of these three had LVP. There was no correlation between the presence of LVP and the hemodialytic indices and between the latter and complex arrhythmias. CONCLUSIONS: Our study showed that arrhythmias are more frequent in patients with LVP before dialysis than in those without. The difference was statistically significant (p < 0.006); the incidence of arrhythmias was higher in patients with FE < 45% (p < 0.001). The majority of patients (95%) had left ventricular hypertrophy; only four (17%) had ischaemic heart disease too. It is highly probable that the presence of LVP in our patients can be attributed to hypertension and subsequent left ventricular hypertrophy. As patients with LVP at the end of dialysis had a greater incidence of arrhythmias than those without LVP, we suggest that this method could be useful as a first screening in dialysed patients.

Adult↗
PubMed1996

Trends in immunoglobulin G anticardiolipin antibodies in ten successful heparin-treated pregnancies.

The pregnancies of ten women, all with histories of at least two spontaneous abortions of unknown cause, were followed. All patients were positive for immunoglobulin (Ig) G anticardiolipin antibodies (aCL) and one also for IgM aCL, while none had lupus anticoagulant activity. During pregnancy, the patients were treated with calcium heparin in doses varying between 15,000 and 30,000 IU daily. IgG aCL were assayed on average at the 9th, 17th, 24th and 29th weeks of pregnancy and at the moment of delivery. Mean values of IgG aCL levels during the 10 pregnancies steadily fell as the pregnancies progressed, and this decrease was significant (r = 0.985, P = 0.002). All pregnancies terminated favourably, although delivery was brought forward in eight patients and six of the nine placentas examined showed signs of thrombotic events. We assume that a steady fall in IgG aCL levels during pregnancy may be considered as indicative of a favourable outcome.

Adult↗
PubMed1996

Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.

Anti-phospholipid (aPL) antibodies are defined as antibodies detected in systems employing phospholipids (PL). This general definition is misleading as it comprises a large group of autoimmune phospholipid-reactive antibodies that are directed against specific phospholipid-binding plasma proteins, such as beta 2-glycoprotein I (beta 2GPI) and prothrombin. Definition of phospholipid-reacting antibodies according to the plasma protein against which they are directed appears more appropriate and could be useful in understanding clinical events and pathogenic mechanisms. Using ELISA systems we have studied the presence of antibodies directed against specific phospholipid-binding proteins in a series of 22 patients with thrombosis and phospholipid-reactive antibodies of the IgG isotype. High levels of anti-beta 2 GPI IgG were detected in all 22 patients. Normal values were calculated on the basis of OD values at 405 nm (OD405) obtained for 22 age- and sex-matched healthy subjects (cut off value = 0.401). Levels of anti-beta 2 GPI antibodies were linearly correlated with those of cardiolipin-reactive (aCL) antibodies. Eleven out of 22 patients (50%) had values of anti-prothrombin antibodies exceeding the cut-off value of 0.250. No relationship was found between the levels of anti-beta 2GPI and anti-prothrombin antibodies. Tests for antibodies against two natural inhibitors of blood coagulation, protein C and protein S, revealed elevated levels of anti-protein C IgG and anti-protein S IgG in 4 and 12 patients, respectively. A highly significant correlation between anti-protein C IgG and anti-protein S IgG values as well as between antibody titers against the two studied natural coagulation inhibitors and anti-prothrombin IgG was found. When comparing patients positive for aCL and presence or absence of a previous thrombotic episode (aCL+/T+ vs aCL+/T-), the positivity of anti-beta 2GPI IgG was found to be statistically associated with thrombosis. Conversely, among patients with previous thromboembolism with or without aCL (aCL+/T+ vs aCL-/T+ vs aCL-/T+) the positivity of anti-beta 2GPI IgG was strictly associated with the positivity of aCL, thus identifying the aPL antibody syndrome. These data demonstrate that anti-beta 2GPI antibodies are a marker of "autoimmune" thrombosis. Anti-prothrombin antibodies are not a marker of thrombosis and are closely associated with antibodies to protein C and protein S.

Antibodies, Antiphospholipid↗
PubMed1995

Anticardiolipin antibodies and antiphospholipid syndrome in chronic discoid lupus erythematosus.

Anticardiolipin antibodies (aCL) of immunoglobulin (Ig) G and M classes were determined in 28 patients affected with chronic discoid lupus erythematosus (CDLE), comparing their prevalence and levels to those in 60 healthy subjects matched for age and sex. A high and significant frequency of IgG (67.8%) and IgM (50.0%) aCL together with prevalence of high antibody levels was found in CDLE patients, while healthy controls had IgG and IgM aCL in 1.6% and 3.3% of cases respectively. Clinical features in keeping with the diagnosis of antiphospholipid syndrome were found in one patient (3.5%), which, as the first manifestation of the syndrome, showed a pulmonary thromboembolism which appeared some days after prolonged exposure to the sun. These results provide additional data on autoimmune phenomena in CDLE and suggest that aCL test should be considered as useful aids in immunological diagnosis of CDLE.

Adult↗
PubMed1995

Anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome.

Autoimmune antiphospholipid antibodies are a hallmark of patients with antiphospholipid syndrome, and require a protein cofactor, beta 2-glycoprotein I, to bind anionic phospholipids. In these same patients, moreover, IgG directly binding beta 2-glycoprotein I are described. We found high plasma titres of both IgM and IgG anti beta 2-glycoprotein I antibodies in a patient with catastrophic antiphospholipid syndrome. After passing plasma through a Sephacryl S-300 column, an identical distribution pattern between anti beta 2- glycoprotein I and anticardiolipin antibodies was observed. Moreover, when IgG immunocomplexes were isolated from a high molecular fraction, IgM anti- beta 2-glycoprotein I and anticardiolipin antibodies were detected. Thus IgG, IgM ad IgG-IgM complexes of anti-beta 2-glycoprotein I antibodies are present at the same time in a patient with antiphospholipid syndrome.

Acute Disease↗
PubMed1994

Fibrinolytic pattern in recurrent spontaneous abortions: no relationship between hypofibrinolysis and anti-phospholipid antibodies.

Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI-1 levels; only in a few instances a defective fibrinolytic response was due to reduced t-PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia. Our results indicate that patients with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI-1 levels, should be included in the study of females suffering from repeated fetal losses.

Abortion, Habitual↗
PubMed1994

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

Adolescent↗
PubMed1994

A catastrophic antiphospholipid syndrome: the importance of high levels of warfarin anticoagulation.

We report the clinical observation of a 23-year-old woman affected by the so-called 'catastrophic antiphospholipid syndrome'. Within a 3-month period she suffered a number of thrombotic events and haemolytic anaemia with thrombocytopenia and had high levels of immunoglobulins G and M and anticardiolipin antibodies associated with lupus anticoagulant activity. The severity of the clinical and laboratory changes is described and diagnostic and therapeutic difficulties are discussed. The apparent control of thrombotic events only with high levels of warfarin anticoagulation is stressed.

Adult↗
PubMed1994

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?

OBJECTIVE: Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS: A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS: LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS: LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.

Adolescent↗
PubMed1994

Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome?

We describe a 41-year-old woman, in whom antiphospholipid antibody syndrome (APS) occurred at presentation, before the detection of an ovarian endometrial adenocarcinoma. This syndrome was characterized by widespread and worsening thromboembolism and it did not respond to conventional anticoagulant treatment. The paraneoplastic nature of this APS was strongly suggested by the disappearance of both thromboembolism and antiphospholipid antibodies only after surgical removal of the cancer.

Adenocarcinoma↗