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J Fontcuberta

Publications and source records attributed to J Fontcuberta.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pharmacokinetics and tolerability of a new low molecular mass heparin (RO-11) in healthy volunteers--a dose-finding study within the therapeutical range.

This paper reports on the results of a Phase I, dose-finding study with a new low molecular mass heparin (LMMH) called RO-11. The study focused on pharmacokinetics, dose-effect relationship and on tolerability of three single subcutaneous (s.c.) doses within the therapeutical range. After the injection of 7,500, 9,000 and 12,500 anti-FXa i.u., the anti-FXa effect peaked between 3-6 h and showed a dose-dependent response. The absorption and elimination were first-order processes and the long half-life (> 5 h) kept constant after increasing doses. The compound was tolerated very well and no clinically relevant prolongation of APTT, prothrombin and thrombin clotting tests was observed. At the dose of 7,500 i.u., which corresponded to 110 anti-FXa i.u./Kg, RO-11 exerted anti-FXa effect for at least 18-20 h. We recommend using this dose in a single s.c. injection, to evaluate the efficacy and safety of RO-11 in the initial treatment of DVT or PE.

Adult↗
PubMed1997

Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish Multicentric Study on Thrombophilia (EMET-Study).

Previous studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2.132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinogenemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfibrinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% CI 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% CI 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% CI 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78, 95% CI 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.

Adolescent↗
PubMed1996

[Isolated thrombocytopenia in pregnancy. Etiopathogenic study and therapeutic approach in 60 patients].

BACKGROUND: We analyze the etiopathogenesis and clinical and immunohematological characteristics of 60 pregnant women with isolated thrombocytopenia (TP) (platelet count < 150 x 10(9)/l); and the frequency of TP and hemorrhagic complications in their newborn. We suggest the therapeutic approach for each maternal TP type. PATIENTS AND METHODS: We performed: clinical history, platelet count (EDTA K3, sodium citrate, microscopic exam) and investigation of antiplatelet antibodies (immunofluorescence) in all pregnant women. A familial history and ultrastructure of platelets were studied when hereditary macrothrombocytopenia (HM) was suspected. A Levine's test of homogenicity of variances was applied to compare the mean platelet count in each diagnostic group. A linear regression between maternal and newborn platelet counts was performed. RESULTS: In 37 thrombocytopenic women (62%) no antiplatelet antibodies were found, and the clinical history was negative for previous TP or abnormal bleeding. Four patients (7%) were diagnosed as pseudothrombocytopenia EDTA-mediated, and eight (13%) of HM. Finally, an autoimmune etiology was suspected in 11 women (18%) and antiplatelet antibodies were detected in 9. Mean platelet counts of mother with immune TP did not show statistically significant differences with other diagnostic groups. Abnormal bleeding was not observed in any patient or newborn. There was no correlation between platelet counts of mothers and newborns. Platelet count obtained by skull bone punction led to unnecessary caesarians in four cases. CONCLUSIONS: The frequency of immune thrombocytopenia in pregnant women is low (18%). There is a high prevalence of benign TP (62%). The pseudothrombocytopenias and HM are frequent findings (20%), and special care is advisable in these cases to avoid unnecessary therapeutic procedures.

Female↗
PubMed1996

Increased fetal loss in women with heritable thrombophilia.

BACKGROUND: A successful outcome of pregnancy requires an efficient uteroplacental vascular system. Since this system may be compromised by disorders of haemostasis associated with a prothrombotic state, we postulated that maternal thrombophilia might be a risk factor for fetal loss. We studied the relation between heritable thrombophilic defects and fetal loss in a cohort of women with factor V Leiden or deficiency of antithrombin, protein C, or protein S. METHODS: We studied 1384 women enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). Of 843 women with thrombophilia 571 had 1524 pregnancies; of 541 control women 395 had 1019 pregnancies. The controls were partners of male members of the EPCOT cohort or acquaintances of cases. We analysed the frequencies of miscarriage (fetal loss at or before 28 weeks of gestation) and stillbirth (fetal loss after 28 weeks of gestation) jointly and separately. FINDINGS: The risk of fetal loss was increased in women with thrombophilia (168/571 vs 93/395; odds ratio 1.35 [95% Cl 1.01-1.82]). The odds ratio was higher for stillbirth than for miscarriage (3.6 [1.4-9.4] vs 1.27 [0.94-1.71]). The highest odds ratio for stillbirth was in women with combined defects (14.3 [2.4-86.0]) compared with 5.2 (1.5-18.1) in antithrombin deficiency, 2.3 (0.6-8.3) in protein-C deficiency, 3.3 (1.0-11.3) in protein-S deficiency, and 2.0 (0.5-7.7) with factor V Leiden. The corresponding odds ratios for miscarriage in these subgroups were 0.8 (0.2-3.6), 1.7 (1.0-2.8), 1.4 (0.9-2.2), 1.2 (0.7-1.9), and 0.9 (0.5-1.5). Significantly more pregnancy terminations had been done in women with thrombophilia than in controls (odds ratio 2.9 [1.8-4.8]); this discrepancy was apparent in nine of 11 participating centres and for all thrombophilia subgroups. INTERPRETATION: Women with familial thrombophilia, especially those with combined defects or antithrombin deficiency, have an increased risk of fetal loss, particularly stillbirth. Our findings have important implications for therapy and provide a rationale for clinical trials of thromboprophylaxis for affected women with recurrent fetal loss.

Abortion, Spontaneous↗
PubMed1996

Pentosan polysulfate-induced thrombocytopenia: a case diagnosed with an ELISA test used for heparin-induced thrombocytopenia.

We report a patient who developed severe thrombocytopenia and ischemic stroke following pentosan polysulfate treatment. An ELISA test employed in type-II heparin-induced thrombocytopenia was highly positive. To our knowledge, this is the first case in which this test has been performed in a pentosan polysulfate-induced thrombocytopenia (PIT). Our data suggest that the antibody against pentosan polysulfate-platelet complex also cross-reacts with heparin-platelet factor 4 complex. Due to its greater sensitivity and wider availability, this ELISA test should be used in cases where PIT is suspected.

Cross Reactions↗
PubMed1996

Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study.

PURPOSE: This study assessed the risk associated with several schedules of perioperative treatment with coumadin in anticoagulated patients who underwent oral surgery. PATIENTS AND METHODS: A prospective, randomized study compared bleeding complications with six perioperative schedules in 92 patients chronically treated with acenocoumarol. In three of the perioperative schedules, the dose was reduced before surgery and calcium heparin was added. In the other three, oral anticoagulation was not modified and heparin was not used. The groups also differed regarding the antifibrinolytic agents used and the postoperative measures applied. RESULTS: Those schedules in which the oral anticoagulation was not modified preoperatively and an antifibrinolytic agent was applied locally both during and after surgery were not associated with a significantly higher odds ratio of bleeding complications than those in whom oral anticoagulation was reduced and calcium heparin was added preoperatively. CONCLUSIONS: In orally anticoagulated patients who undergo oral surgery, schedules that maintain the oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic agent postoperatively for 2 days are safe, simple, and less troublesome.

Acenocoumarol↗
PubMed1996

Hereditary macrothrombocytopenia and pregnancy.

INTRODUCTION: Hereditary macrothrombocytopenias (HM) are a group of infrequent disorders characterized by hereditary giant platelets. Little has been published about the course of these diseases during pregnancy and delivery. SUBJECTS AND METHODS: Forty consecutive thrombocytopenic pregnant women were studied. Platelet count, mean platelet volume and blood smear examination were performed. Platelet antibodies were studied by immunofluorescence. Familial study, bleeding time, ultrastructural platelet examination, a von Willebrand disease screening and aggregation tests were carried out when HM was suspected. RESULTS: Four cases of HM were diagnosed. Giant platelets were observed in all cases, with the typical ultrastructural pattern. Döhle-like cytoplasmic inclusions in granulocytes were observed in one case. Platelet antibodies were detected in only one case. No prophylactic measures to prevent haemorrhage were adopted, and all patients underwent vaginal deliveries. Haemorrhagic events were absent in both mothers and children. CONCLUSIONS: The prevalence of HM in pregnant trombocytopenic women is higher than assumed. Prophylactic treatment should be avoided in the absence of a history of haemorrhagic complications and obstetrical risk factors.

Adult↗
PubMed1996

Ectopic transcript analysis indicates that allelic exclusion is an important cause of type I protein C deficiency in patients with nonsense and frameshift mutations in the PROC gene.

Nonsense mutations, deletions and splice site mutations are a common cause of type I protein C deficiency. Either directly or indirectly by altering the reading frame, these lesions generate or may generate premature stop codons and could therefore be expected to result in premature termination of translation. In this study, the possibility that such mutations could instead exert their pathological effects at an earlier stage in the expression pathway, through "allelic exclusion" at the RNA level, was investigated. Protein C (PROC) mRNA was analysed in seven Spanish type I protein C deficient patients heterozygous for two nonsense mutations, a 7bp deletion, a 2bp insertion and three splice site mutations. Ectopic RNA transcripts from patient and control lymphocytes were analysed by RT-PCR and direct sequencing of amplified PROC cDNA fragments. The nonsense mutations and the deletion were absent from the cDNAs indicating that only mRNA derived from the normal allele had been expressed. Similarly for the splice site mutations, only normal PROC cDNAs were obtained. In one case, exclusion of the mutated allele could be confirmed by polymorphism analysis. In contrast to these six mutations, the 2 bp insertion was not associated with loss of mRNA from the mutated allele. In this case, cDNA analysis revealed the absence of 19 bases from the PROC mRNA consistent with the generation and utilization of a cryptic splice site 3' to the site of mutation, which would result in a frameshift and a premature stop codon. It is concluded that allelic exclusion is a common causative mechanism in those cases of type I protein C deficiency which result from mutations that introduce premature stop codons.

Alleles↗
PubMed1995

Low levels of tissue factor pathway inhibitor (TFPI) in two out of three members of a family with thrombophilia.

We describe a family with severe thrombosis of early onset in two siblings and in their father. Low levels of TFPI were detected in the two siblings (50% and 45% respectively) but their parents have normal TFPI levels. All other hemostatic proteins associated with thrombophilia, as well as blood lipids were within the normal range. The release of TFPI, after heparin administration, was proportionally reduced in the two siblings as compared with controls. The study of this family does not permit to conclude that low levels of TFPI are responsible for their thrombophilia. In the future the study of more families with similar characteristics may allow to know the inheritance of TFPI and whether there is a causal relationship between low levels of TFPI and thrombosis.

Aged↗