Safety of therapeutic doses of tinzaparin during pregnancy.

BACKGROUND/AIMS: Low molecular weight heparin is recommended for the treatment of venous thromboembolism (VTE) during pregnancy. However, there are few reliable data regarding the safety of therapeutic doses of tinzaparin in this setting. The objective of this study was to assess the safety of once-daily therapeutic doses of tinzaparin for the treatment of VTE during pregnancy. METHODS: A retrospective study was carried out in 3 tertiary care centres in France, from 1998 to 2009, including consecutive pregnant women who received once-daily therapeutic doses of tinzaparin (175 IU/kg/day). RESULTS: We analyzed 87 pregnancies in 83 women, representing a total of 13,320 patient-days of treatment. Live-birth rate was 97.8%, with one case of miscarriage (<20 weeks of gestation) and one case of intrauterine foetal death (≥20 weeks). There was no antenatal major bleeding. Major bleeding occurred in 4 women during an emergency caesarean section. No case of heparin-induced thrombocytopenia and no maternal death were reported. There was no neonatal haemorrhage and no case of congenital abnormality. VTE recurred on treatment in one patient and after treatment interruption for several days in 2 other patients. CONCLUSIONS: These results support the safety of once-daily tinzaparin at therapeutic dose for the treatment of VTE during pregnancy.

Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.

High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms.

BACKGROUND: The occurrence and mechanisms of nocturnal hypoxemia in precapillary pulmonary hypertension (PH) are not clearly defined. METHODS: In an observational, prospective, and transversal design, we studied 46 clinically stable patients with PH and a BMI < 35 kg/m(2), an FEV(1) > 60% predicted, and idiopathic pulmonary arterial hypertension (n = 29) or chronic thromboembolic pulmonary hypertension (n = 17). They underwent nocturnal polysomnography with transcutaneous capnography. RESULTS: Most patients (69.6%) had New York Heart Association functional class II disease. Mean pulmonary artery pressure was 44 ± 13 mm Hg, and the cardiac index was 3.2 ± 0.6 L/min/m(2). Duration of sleep time spent with oxygen saturation as measured by pulse oximetry <90% was 48.9% ± 35.9%, and 38 of 46 patients (82.6%) had nocturnal hypoxemia. Mean apnea-hypopnea index was 24.9 ± 22.1/h, and 41 patients (89%) had sleep apnea. The major mechanism of nocturnal hypoxemia was a ventilation/perfusion mismatch alone or associated with obstructive apneic events. Multivariate logistic regression identified both FEV(25%-75%) (OR, 0.9519; 95% CI, 0.9089-0.9968; P = .036) and mean pulmonary artery pressure (OR, 1.1068; 95% CI, 1.0062-1.2175; P = .037) as significant predictors of nocturnal hypoxemia. Clinical symptoms were not predictive of nocturnal hypoxemia. CONCLUSIONS: The occurrence of nocturnal hypoxemia is high in PH and should be screened for systematically. Further studies are needed to determine the impact of nocturnal hypoxemia on the outcome of patients with PH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01371669; URL: www.clinicaltrials.gov