Management of pregnancy in women with previous left ilio-caval stenting.

BACKGROUND: Ilio-caval stenting now represents the first line treatment for disabling obstructive ilio-caval lesions. Most patients are young women of child-bearing age. We herein report our experience of pregnancy in women who have a history of ilio-caval stenting. MATERIALS AND METHODS: From November 1995 to April 2008, 119 patients had ilio-caval stenting for obstructive venous disease in our department. Of these, 62 women were able to become pregnant. When pregnancy occurred, they received preventive treatment with low molecular weight heparin (LMWH) from the 3rd month of pregnancy to 1 month after delivery and had to wear elastic stockings. Patients also had to sleep on their right side if possible. They were followed during the pregnancy by duplex scanning at 3, 6, and 8 months, and then 1 month after delivery. RESULTS: Eight pregnancies occurred in 6 patients (mean age 26.5 years) who had a patent self-expanding stent (1 patient had 3 pregnancies). They had stenting for May-Thurner disease in 3 patients, for post-deep venous thrombosis (DVT) left common iliac vein occlusion in 1 patient, and during venous thrombectomy in 2 patients. All stents were self-expanding metallic stents located on the left common iliac vein. One patient had unrelated spontaneous abortion after 2 months of pregnancy. No DVT or symptomatic pulmonary embolism occurred during pregnancy, delivery, or during the postpartum period. Four patients needed cesarean delivery and none had hemorrhagic complications. None of the patients had adverse effects from the treatment. Duplex scan showed compression of the stent(s) at 8 months in 4 patients with inflow obstruction in 3 patients. Postpartum duplex-scan showed no remaining stenosis in all patients. No stents had structural damage. CONCLUSION: Ilio-caval stent compression can occur during pregnancy but does not lead to structural damage to the self-expanding stents. Despite this, no cases of DVT occurred with preventive LMWH treatment.

Multicenter evaluation of a bilayer polymer blood collection tube for coagulation testing: effect on routine hemostasis test results and on plasma levels of coagulation activation markers.

We compared the results of different hemostasis tests obtained in an evacuated bilayer polymer tubes (Vacuette, Greiner Bio-One) and in a siliconized glass tubes containing the same citrate concentrations (0.109 M and 0.129 M). For that purpose, blood was collected in five centers from 60 untreated patients and from patients on oral anticoagulant (n = 168), unfractionated heparin (n = 111) or a low molecular weight derivative (n = 108). Test results obtained in polymer tubes were not significantly different from those in glass tubes, except for INR when a high ISI thromboplastin was used (p < 0.0001 for tubes containing 0.129 M sodium citrate) and for APTT (p < 0.05 for both citrate concentrations). However, these differences had no clinical relevance (Bland-Altman analysis). In addition, no effect of aging of the polymer tubes on the test results could be demonstrated. The plasma levels of F1+2 and TAT, measured in a subset of 30 untreated patients, were significantly lower when blood was collected in polymer than in glass tubes, for both citrate concentrations. These results suggest that samples collected into the Vacuette polymer tubes allow accurate routine hemostasis testing both in untreated patients and in patients on traditional anticoagulant treatment during the whole shelf-life indicated by the manufacturer.

Type 1 and type 2 diabetic patients display different patterns of cellular microparticles.

The development of vasculopathies in diabetes involves multifactorial processes including pathological activation of vascular cells. Release of microparticles by activated cells has been reported in diseases associated with thrombotic risk, but few data are available in diabetes. The aim of the present work was to explore the number and the procoagulant activity of cell-derived microparticles in type 1 and 2 diabetic patients. Compared with age-matched control subjects, type 1 diabetic patients presented significantly higher numbers of platelet and endothelial microparticles (PMP and EMP), total annexin V-positive blood cell microparticles (TMP), and increased levels of TMP-associated procoagulant activity. In type 2 diabetic patients, only TMP levels were significantly higher without concomitant increase of their procoagulant activity. Interestingly, in type 1 diabetic patients, TMP procoagulant activity was correlated with HbA(1c), suggesting that procoagulant activity is associated with glucose imbalance. These results showed that a wide vesiculation process, resulting from activation or apoptosis of several cell types, occurs in diabetes. However, diabetic patients differ by the procoagulant activity and the cellular origin of microparticles. In type 1 diabetic patients, TMP-procoagulant activity could be involved in vascular complications. Moreover, its correlation with HbA(1c) reinforces the importance of an optimal glycemic control in type 1 diabetes.

Protein Z in patients with pregnancy complications.

OBJECTIVE: This study was undertaken to evaluate the association between protein Z concentration and pregnancy complications. STUDY DESIGN: A prospective case-control study was conducted over a 2-year period to evaluate the prevalence of protein Z deficiency in pregnancy complications. Protein Z levels were measured at the time of diagnosis of complications such as preeclampsia, intrauterine growth restriction, and intrauterine fetal demise. Protein Z deficiency was defined as a plasma level below 1.2 mg/L. In addition to patients presenting with pregnancy complications, healthy age-matched nonpregnant and pregnant women were invited to participate. RESULTS: A total of 145 women were included in the study: 50 nonpregnant women, 34 healthy pregnant women, 29 women with preeclampsia, 25 women presented with intrauterine growth restriction, and 7 women with intrauterine fetal demise. The median protein Z level was similar in healthy pregnant and nonpregnant women (1.63 [0.47-3.1] mg/L and 1.69 [0.7-3] mg/L, respectively). Three women with normal pregnancies had a low protein Z level (8.8%), compared with 8 patients presenting with intrauterine growth restriction (33.3%) and 8 patients with intrauterine fetal demise (50%). Compared with normal pregnancy, the frequency of decreased protein Z was significantly higher in cases of intrauterine growth restriction and in intrauterine fetal demise (relative risk [RR] 1.96, 95% CI 1.16-3.32; P = .041 and RR 3.36, 95% CI 1.65-6.8; P = .0031, respectively), but not in preeclampsia (RR 1.6, 95% CI 0.9-2.8; P = .23). Placenta histologic examination revealed vascular lesions in 50% of patients with protein Z deficiency and in 33% of patients with normal levels of protein Z (RR 0.84; 95% CI 0.6-1.2). CONCLUSION: Protein Z deficiency is associated with late fetal demise and intrauterine growth restriction. The pathophysiologic role of protein Z deficiency, either congenital or caused by the presence of specific antibodies remains unclear and should be further investigated.

Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) refers to persistent anti-phospholipid antibodies (aPL) associated with thrombotic and/or obstetrical complications. The endothelial cell is a target of aPL which can induce a procoagulant and proinflammatory endothelial phenotype, as reported both in vivo and in vitro. Microparticle production is a hallmark of cell activation. In the present study, the presence of endothelial microparticles (EMP) in the plasma of APS patients was investigated. To determine if there is a correlation with certain biological and clinical features, EMP levels were measured in thrombosis-free patients with systemic lupus erythematosus (SLE) patients, with and without aPL, in patients with non aPL-related thrombosis, as well as in healthy controls. Compared to healthy subjects, elevated plasma levels of EMP were found in patients with APS and in SLE patients with aPL, but not in SLE patients without aPL or in non aPL-related thrombosis. EMP levels were also associated with Lupus Anticoagulant (LA) detected by a positive Dilute Russell's Viper Venom time (DRVVT). In parallel, we analyzed the capacity of these plasma to induce vesiculation of cultured endothelial cells. We demonstrated an increase of EMP generated in response to plasma from patients with auto-immune diseases. Interestingly, only APS plasma induced the release of EMP with procoagulant activity. These ex vivo and in vitro observations indicate that generation of EMP in APS and SLE patients results from an autoimmune process involving aPL. Production of procoagulant microparticles in APS patients may represent a new pathogenic mechanism for the thrombotic complications of this disease.

Increased risk of gestational vascular complications in women with low free tissue factor pathway inhibitor plasma levels out of pregnancy.

Tissue factor pathway inhibitor (TFPI) plays a crucial role in haemostasis by regulating TF-induced initiation of coagulation. Since it is expressed by endothelial and trophoblastic cells, TFPI is of particular importance at the placental level and might be involved in the occurrence of gestational vascular complications (GVC). In the present study, we investigated plasma free TFPI antigen in four groups of women: healthy non-pregnant women without history of pregnancy complications; women at the beginning (<12 weeks) and women during the third trimester of a normal pregnancy; women with late pregnancy complications (pre-eclampsia / HELLP syndrome, intra-uterine fetal death, fetal growth retardation) at the time of obstetrical event and/or at distance from pregnancy. In normal pregnancy, TFPI increased between first trimester and delivery (median 5.0 ng/ml vs. 7.1 ng/ml; p<0.0001) but remained lower than in non-pregnant controls (median 8.2 ng/ml; p<0.0001). In patients, when measured concomitantly to the obstetrical event, TFPI showed no difference with normal late pregnancy levels. In contrast, at distance from pregnancy, in the absence of any hormonal influence, TFPI was significantly lower than in non-pregnant controls (median 5.9 vs. 8.2ng/ml, p < 0.0001). After categorisation into quartiles, an inverse dose-effect relationship was demonstrated between TFPI categories recorded apart from pregnancy and GVC risk, with a crude odds ratio of 43.5 (95% confidence interval 8.2-230) for patients with TFPI values in the lowest quartile (< 5.7 ng/ml). In conclusion, low free TFPI at distance from pregnancy appears to be a strong indicator of GVC risk.