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J Fontcuberta

Publications and source records attributed to J Fontcuberta.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lack of association between venous thrombosis and subsequent malignancy in a retrospective cohort study in young patients.

Since the publication of Trousseau in 1865, several studies have documented an increased incidence of cancer in patients with deep venous thrombosis (DVT) especially those with idiopathic or recurrent DVT, but in young patients this association is not clear and is therefore a subject of controversy. We performed a retrospective study in a consecutive cohort of 40 young patients (age <40 years) with a DVT and without a known cancer. All patients were diagnosed in our hospital during the period of 1988-1992. At the time of diagnosis, a routine examination to detect the presence of malignant disease was made. For the follow-up, all patients included in the study were asked to return to our unit and were interviewed for symptoms that could suggest a malignant disease. The mean follow-up was five years (from three to eight years). Twenty-four patients had DVT in the lower limbs and three in the upper extremities, nine had pulmonary embolism (six of them with DVT) and four had DVT in other sites. Sixteen patients (40%) had secondary DVT due to nonbiological causes, abnormalities in hemostasis were found in 14 patients (35%), and biological or environmental triggering factors were not identified in 10 patients (25%). Malignancies were not detected at diagnosis and in the follow-up. In our experience, venous-thrombotic patients under the age of 40 have a low incidence of subsequent cancer. Further studies should be performed to confirm this observation and to ascertain whether extensive screening for cancer is a cost-effective approach.

Adult↗
PubMed1999

Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency.

DNA sequence analysis of the protein S gene (PROS1) in 22 Spanish probands with type I or III PS deficiency, has allowed the identification of 10 different mutations and 2 new sequence variants in 15 probands. Nine of the mutations, 8 of which are novel, cosegregate with type I or quantitative PS deficiency in 12 of the 13 pedigrees analyzed. One of these mutations (Q238X) also cosegregates with both type I and III PS-deficient phenotypes coexisting in a type I/III pedigree. Another mutation identified in a pedigree with these two PS phenotypes is the missense mutation R520G, present in the homozygous form in the type I propositus and in the heterozygous form in his type III relatives. By contrast, no cosegregating PROS1 mutation has been found in any of the six families with only type III phenotypes. Three of these families, as well as the two families with type I and I/III phenotypes where no other PROS1 mutation has been identified, segregate the P allele of the S460P variant, although this allele does not always cosegregate with the deficient phenotype. From these results we conclude that while mutations in PROS1 are the main cause of type I PS deficiency, the molecular basis of the type III phenotype is probably more complex, with many cases not being explained by a PROS1 mutation.

Adolescent↗
PubMed1999

Elevated levels of plasmin-alpha2 antiplasmin complexes in unstable angina.

The evidence of elevated levels of several biochemical markers of prothrombotic state in patients with unstable angina suggests that thrombus formation and lysis play a pivotal role in acute coronary syndromes. The clinical syndrome of unstable angina encompasses a variety of clinical presentations of transient episodes of myocardial ischemia. This study was designed to assess plasmin generation in different settings of unstable angina. Evidence of plasmin generation in patients with unstable angina was measured by circulating plasmin-alpha2 antiplasmin complexes (PAP). A second objective was to identify whether PAP levels had a prognostic value to predict outcome. Eighty-five patients admitted to the coronary care unit for unstable angina were classified into three groups. Group A included 26 patients with postinfarction angina; group B comprised 26 patients with new onset angina; and group C included 33 patients with crescendo angina. Mean PAP levels were higher in the three groups compared to healthy controls. A significant correlation was found between levels of PAP and D-dimer, particularly in postinfarction angina (r = 0.6; p <0.0005). This trial adds new insights into the pathophysiology of unstable angina. It demonstrates that plasmin is generated in the different settings of unstable angina but particularly in postinfarction angina patients where a fibrin-rich thrombus is responsible of the symptoms. However, in this series PAP levels do not predict an uneventful outcome neither in the acute phase nor at long term (6 months).

Aged↗
PubMed1999

Homozygotes for prothrombin gene 20210 A allele in a thrombophilic family without clinical manifestations of venous thromboembolism.

BACKGROUND AND OBJECTIVE: A new genetic risk factor for venous thromboembolism has recently been described which involves a G to A transition at position 20210 in the 3' untranslated region of the prothrombin gene. To date, only a few homozygotes for this mutation have been reported and in most of cases, they suffered from thrombotic disease. Here, we describe a pedigree including both heterozygous and homozygous subjects for prothrombin (PT) 20210 A. DESIGN AND METHODS: This family was recruited in 1996 as part of our GAIT (Genetic Analysis of Idiopathic Thrombophilia) project. To qualify for the GAIT study, a pedigree was required to have at least 10 living individuals in three or more generations (i.e. extended pedigree). The pedigrees were selected through probands with idiopathic thrombophilia. A complete set of plasma and DNA determinations related to hemostasis was performed on this family. RESULTS: The plasma studies yielded normal results in all of the individuals. The family members who had a history of thromboembolism were heterozygous carriers of the PT 20210 A variant. In addition, 4 relatives who were heterozygous, and two who were homozygous for this A allele, failed to show clinical manifestations. These two homozygotes were 51 and 19 years old. INTERPRETATION AND CONCLUSIONS: This case exemplifies the complexity of thrombotic disease since individuals homozygous for a mutant gene do not exhibit symptoms while heterozygous individuals often do exhibit the disease. This case suggests that the new genetic risk factor for thrombosis (i.e. PT 20210 A) may not be as strong as most of the previously described genetic risk factors.

3' Untranslated Regions↗
PubMed1998

Short-course thrombolysis as the first line of therapy for cardiac valve thrombosis.

OBJECTIVE: To retrospectively evaluate the clinical and echocardiographic criteria of thrombolytic therapy for mechanical heart valve thrombosis. METHODS: Nineteen consecutive patients with 22 instances of prosthetic heart valve thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with short-course thrombolytic therapy as first option of treatment in absence of contraindications. The thrombolytic therapy protocol consisted of streptokinase (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4). RESULTS: Overall success was seen in 82%, immediate complete success in 59%, and partial success in 23%. Six patients without total response to thrombolytic therapy underwent surgery, and pannus was observed in 83%. Six patients showed complications: allergy, stroke, transient ischemic attack, coronary embolism, minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial thrombus by transesophageal echocardiography, 3 of whom experienced peripheral embolism during thrombolysis. Four episodes of rethrombosis were observed (16%). The survivorship was 84% with a mean follow-up of 42.6 months. CONCLUSIONS: A short-course of thrombolytic therapy may be considered first-line therapy for prosthetic heart valve thrombosis. The risk of peripheral embolism may be evaluated for the presence of atrial thrombus by transesophageal echocardiography at diagnosis.

Drug Administration Schedule↗
PubMed1998

Coagulation and fibrinolytic parameters in normal pregnancy and in pregnancy complicated by intrauterine growth retardation.

The objective of this article is to evaluate the plasma levels of coagulation and fibrinolysis parameters in the third trimester of gestation and 72 hr postdelivery. Antithrombin III (ATIII), thrombin-antithrombin III complexes (TAT), heparin cofactor II (HCII), protein C (PC), protein S (PS), tissue plasminogen activator (t-PA), D-dimer, and plasminogen activator inhibitors (PAI-1 and PAI-2) levels in uncomplicated pregnancies and in pregnancies complicated by intrauterine growth retardation (IUGR) have been determined. Normal pregnant women (n = 63) and women whose was complicated by IUGR (n = 10) formed the study population. Coagulation and fibrinolysis parameters were estimated using commercial tests. There were no differences in ATIII, HCII, and PS levels between normal and IUGR pregnancies. TAT, t-PA, and D-dimer levels were higher in IUGR pregnancy than in the uncomplicated pregnancy group. PAI-1 and PAI-2 were found depressed in IUGR pregnancy when compared with normal pregnancy. Changes in coagulation and fibrinolytic systems occur in plasma of women with pregnancies complicated by IUGR. The results suggest an activation of the coagulation system in pregnancies complicated by IUGR. Reduced PAI-2 and high TAT levels correlate with birth weight. In IUGR pregnancies a hypercoagulative state with hyperfibrinolytic compensatory mechanisms is suggested.

Adult↗
PubMed1998

Coagulation and fibrinolysis parameters in normal pregnancy and in gestational diabetes.

The changes in coagulation and fibrinolysis parameters during pregnancy, delivery and 3 days after delivery were evaluated in normotensive and gestational diabetes pregnant women. Normal pregnant women (n = 60) and pregnant women with gestational diabetes (n = 15) formed the study population. Coagulation and fibrinolysis parameters were estimated using commercial tests. Antithrombin III, thrombin-antithrombin III complexes, heparin cofactor II, protein C, protein S, tissue plasminogen activator, (t-PA) D-dimer and plasminogen activator inhibitor (PAI-1 and PAI-2) activities in normal and gestational diabetes pregnancies were determined. Thrombin-antithrombin III complexes increased and coagulation inhibitors decreased in gestational diabetes. Plasminogen activator inhibitors remained unchanged and t-PA levels increased in gestational diabetes.

Adult↗
PubMed1998

Increased risk of venous thrombosis in carriers of natural anticoagulant deficiencies. Results of the family studies of the Spanish Multicenter Study on Thrombophilia (EMET study).

Several studies have demonstrated a higher risk of thrombosis in carriers of anticoagulant deficiencies than in non-deficient individuals from families with thrombophilia. The prevalences in Spain were established in a multicenter study (the EMET study) and all the deficient individuals were invited to recruit all available family members to be screened for the same deficiency in order to establish the risk of thrombosis in deficient individuals. Five-hundred-and-eighty-three individuals from 114 families with natural anticoagulant deficiencies were analysed. Propositi and relatives with a history of thrombosis were asked about the localization and the age at the first episode and whether or not it was spontaneous. Three families with antithrombin deficiency, 35 with protein C, 60 with protein S, four with plasminogen, four with heparin cofactor II, seven with combined deficiencies and one family with dysfibrinogenemia were included in the analysis. The risk of thrombosis was increased for individuals deficient in antithrombin (adjusted odds ratio 21.23; 95% confidence interval 5.71-78.94), protein C (adjusted odds ratio 12.62; 95% confidence interval 4.75-33.51), protein S type I (adjusted odds ratio 19.95; 95% confidence interval 7.40-53.82), protein S type III (adjusted odds ratio 8.11; 95% confidence interval 2.66-21.99) or in protein C plus protein S (adjusted odds ratio 8.99; 95% confidence interval 2.79-28.93), but not for those deficient in plasminogen or heparin cofactor II. The thrombosis-free survival was shortened for deficient individuals in antithrombin (median 30 years), protein C (median 46 years), protein S type-I (median 48 years), protein S type III (median 61 years) and combined protein C and S (median 40 years). In conclusion, individuals carrying anticoagulant deficiencies have an increased risk of thrombosis, especially those with antithrombin, protein C or type I protein S deficiencies.

Adult↗
PubMed1998

Tissue factor pathway inhibitor and anti-FXa kinetic profiles of a new low-molecular-mass heparin, Bemiparin, at therapeutic subcutaneous doses.

Low-molecular-mass heparins (LMMHs) exert an anti-FXa effect through antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) displaced from endothelium and lipoproteins. This global anti-FXa potency is specific for different compounds. Whether these effects have a similar kinetic and duration is a matter of interest. We compared the kinetic profile of the TFPI effect (total and free) to the anti-FXa amidolytic activity induced by therapeutic subcutaneous doses of a new LMMH, Bemiparin. The overall kinetics of the anti-FXa amidolytic activity and the TFPI effect were different, TFPI achieving a maximal effect earlier than the anti-FXa activity and completely disappearing before it. The anti-FXa amidolytic activity of Bemiparin followed a linear dose-response pattern. Neither total nor free TFPI was directly proportional to the dose. At therapeutic subcutaneous doses, Bemiparin exerted an anti-FXa effect through TFPI during the first 2 h, through both ATIII and TFPI during the following 8 h (range 2-10 h) and through ATIII during the last 8 h (range 10-18 h).

Adult↗
PubMed1998

Skin necrosis at the injection site induced by low-molecular-weight heparin: case report and review.

Heparin-induced skin necrosis at the injection site is a rare adverse effect, more commonly associated with standard heparins than with low-molecular-weight heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH-induced skin necrosis in a female during prophylactic treatment with LMWH after a surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced antibodies was positive. This case describes the occurrence of LMWH-induced skin necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is more frequent than previously suspected.

Aged↗
PubMed1998

Heparin cofactor II: a new marker for pre-eclampsia.

The plasma levels of heparin cofactor II were determined in pregnant women who were either normotensive, or had essential hypertension, gestational hypertension or pre-eclampsia during the third trimester and 72 h after delivery. Heparin cofactor II levels in the pre-eclampsia group were depressed. The clinical relevance of this finding is the potential utility of heparin cofactor II plasma levels in the differential diagnostic between non-proteinuric hypertension and pre-eclampsia.

Adult↗
PubMed1998

The prothrombin 20210A allele is the most prevalent genetic risk factor for venous thromboembolism in the Spanish population.

We investigated the prevalence of the new recently reported mutation in the prothrombin gene (20210 A) in a sample of 116 unrelated patients with venous thromboembolism. We found 20 heterozygous carriers (17.2%, CI 95% 10.4-21.1). In comparison, we observed 13 carriers among 201 healthy unmatched controls (6.5%, CI 3.5-10.8). The 20210 A mutation seems to increase the risk of venous thrombosis 3-fold (odds ratio 3.1, 95% CI 1.4-6.6). Considering only patients with a first event (n = 62) the OR was 2.0 (p = 0.18, NS) while those with recurrent events (n = 54) showed an OR of 5.9 (95% CI 2.5-14.4). A majority of heterozygous patients (55%) presented a second thrombophilic factor and 60% of affected females had their first event before 30 years of age, while on oral contraceptive treatment. The prevalence found in this study for healthy people is the highest reported to date. The 20210 A variant appears to be the most prevalent genetic risk factor among patients with thrombosis in our geographical area.

Adolescent↗
PubMed1998

Moderate hyperhomocysteinemia is a highly prevalent defect in Spanish patients with venous thromboembolic disease.

Recent studies suggest that mild hyperhomocysteinemia may be a risk factor for venous thromboembolic disease (VTED). In this work we evaluated the prevalence of moderate hyperhomocysteinemia in patients with VTED in our area. We found hyperhomocysteinemia in 23.4% of 64 patients studied compared with 7.35% of 68 healthy controls (p = 0.014). Our results suggest that moderate hyperhomocysteinemia is one of the most prevalent abnormalities associated with VTED.

Aged↗
PubMed1997

Activated protein C resistance assay when applied in the general population.

We estimated the predictive values of activated protein C resistance in the diagnosis of women who are carriers of factor V Leiden. When the prevalence of factor V Leiden is 2%, the positive predictive value is 44% and the cost of preventing one thromboembolic death is $44,180,000. Thus the activated protein C resistance assay is not cost-effective in ruling out factor V Leiden in this population.

Bayes Theorem↗
PubMed1997

Fibrinolysis changes in normal pregnancy.

The aim of this study was to evaluate the changes in fibrinolysis parameters during pregnancy. Normal pregnant women (n = 60) formed the study population. Blood samples were taken in the first, second and third trimester, during delivery and three days after delivery. Fibrinolysis parameters were estimated using commercial tests. Tissue plasminogen activator, D-dimer and plasminogen activator inhibitors (PAI-1 and PAI-2) were determined. Tissue plasminogen activator and D-dimer increased after the first trimester and reached maximum levels during delivery. Plasminogen activator inhibitors type 1 and type 2 were also higher, in particular PAI-2, and reached maximum levels in the third trimester. On the third day after delivery, fibrinolysis activity recovered, but D-dimer and PAI-2 levels remained above the normal non-pregnant range.

Adult↗