CiteULike: A_Hoogendam's venous

Anticardiolipin Antibodies Predict Early Recurrence of Thromboembolism and Death Among Patients with Venous Thromboembolism Following Anticoagulant Therapy

Sam Schulman — 2008-05-20T14:19:19-00:00

The American Journal of Medicine, Vol. 104, No. 4. (April 1998), pp. 332-338.

Purpose: To compare the risk of recurrent venous thromboembolism in patients with and without antiphospholipid antibodies. Patients and Methods: Anticardiolipin antibodies were tested 6 months after a first or second episode of venous thromboembolism. Of the patients with a first episode of venous thromboembolism only the 412 who received 6 months of anticoagulation were studied. Two hundred and eleven patients with a second episode received oral anticoagulation for 6 months or indefinitely. The therapy was targeted at an international normalized ratio (INR) of 2.0 to 2.85. All patients were followed up for 4 years after enrollment. Results: Among the 412 patients with a first episode of venous thromboembolism the risk of recurrence was 29% in patients with anticardiolipin antibodies and 14% in those without antibodies (P = 0.0013). In those with antibodies, there was an increased risk during the first 6 months after cessation of anticoagulation. The risk of recurrence increased with the titer of the antibodies. Four-year mortality rate was 15% in those with antibodies and 6% in those without (P = 0.01). Among 34 patients with a second event of venous thromboembolism and anticardiolipin antibodies, there were no recurrences during anticoagulant therapy versus 20% in those who received only 6 months of treatment (P = 0.08). Conclusions: The presence of elevated titers of anticardiolipin antibodies 6 months after an episode of venous thromboembolism is a predictor for an increased risk of recurrence and of death. Patients with anticardiolipin antibodies and venous thromboembolism seem to benefit from prolonged oral anticoagulation.

A Comparison of Three Months of Anticoagulation with Extended Anticoagulation for a First Episode of Idiopathic Venous Thromboembolism

Clive Kearon — 2008-05-20T14:19:10-00:00

N Engl J Med, Vol. 340, No. 12. (25 March 1999), pp. 901-907.

Background Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. Methods In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. Results A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 percent vs. 0 percent per patient-year, P=0.09). Conclusions Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months. 10.1056/NEJM199903253401201

Antibodies to oxidized LDL/[beta]2-glycoprotein I in antiphospholipid syndrome patients with venous and arterial thromboembolism

V Pengo — 2008-05-20T11:28:16-00:00

Thrombosis Research, Vol. In Press, Corrected Proof

It has been reported that IgG to oxidized LDL/[beta]2-glycoprotein I (oxLDL/[beta]2GPI) complexes are associated with arterial thromboembolism (TE) in patients with antiphospholipid syndrome (APS). How these antibodies behave in arterial as compared to venous TE in APS is unknown. The aim of the present study was to evaluate the association of IgG anti-oxLDL/[beta]2GPI with clinical manifestations in category I APS patients. Fifty-seven APS patients with triple positivity (Lupus Anticoagulant (LAC), anti cardiolipin (aCL) and anti-[beta]2-glycoprotein I (a[beta]2GPI) antibodies), 28 with arterial and 29 with venous thromboembolism, were included in the study. There were no differences in the dRVVT ratio, IgG/IgM aCL and IgG/IgM a[beta]2GPI titers in the two patient groups. There were no differences in the IgG (78.5 U ± 59.8 vs. 112.2 U ± 92.3) and IgM (16.3 U ± 15.9 vs. 21.1 U ± 14.3) anti-oxLDL/[beta]2GPI mean values. A significant correlation was found between IgG anti-oxLDL/[beta]2GPI and IgG anti-[beta]2GPI titers in the whole group of APS patients. Patients in the arterial group were older and had more risk factors for atherosclerosis. Data from this study do not support the hypothesis that IgG anti-oxLDL/[beta]2GPI are specifically associated to arterial TE in Category I APS patients.

Anticardiolipin IgG subclasses association of IgG2 with arterial and/or venous thrombosis

Lisa Sammaritano — 2007-12-31T09:42:15-00:00

Arthritis & Rheumatism, Vol. 40, No. 11. (1997), pp. 1998-2006.

Objective. To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (Fc?R) with differential binding preferences contribute to an increased risk of thrombotic complications.Methods. In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzymelinked immunosorbent assay (ELISA) with murine antihuman IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fc? receptor IIA (Fc?RIIA) genotypes of aCL patients with thrombosis and of non-systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele-specific probes.Results. IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgG1, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial and/or venous thrombosis (P < 0.04). The presence of Fc?RIIA-H131, a receptor expressed on platelets, monocytes, and endothelial cells and the only human Fc?R which efficiently recognizes IgG2, was associated with thrombosis in aCL patients. Among 45 high-titer (>40 GPL [IgG phospholipid] units) aCL patients with thrombosis, 40% were homozygous for Fc?RIIA-H131, compared with 25% of disease-free controls (P = 0.042).Conclusion. While all 4 IgG subclasses are found in autoimmune aCL, only the presence of IgG2 is significantly associated with thrombotic complications. Reactivity in aCL ELISA is largely due to the presence of IgG2 in high-titer patients. The presence of IgG2 aCL, particularly in association with Fc?RIIA-H131, may be a useful clinical predictor of increased thrombotic risk in patients with autoimmune IgG aCL. Allelic variants of Fc?RIIA with distinct capacities to interact with IgG subclasses provide a mechanism for genetic susceptibility to an autoantibody-induced prothrombotic state.

Stenting of the venous outflow in chronic venous disease: Long-term stent-related outcome, clinical, and hemodynamic result

Peter Neglen — 2007-11-19T07:44:47-00:00

Journal of Vascular Surgery, Vol. 46, No. 5. (November 2007), pp. 979-990.e1.

Background Stenting of chronic nonmalignant obstruction in the venous outflow tract started in earnest in 1997. Data sets are now available to perform long-term analysis of stent-related outcome and clinical and hemodynamic results of this intervention.Materials From 1997 to 2005, 982 chronic nonmalignant obstructive lesions of the femoroiliocaval vein were stented under intravascular ultrasound guidance. Median patient age was 54 years (range, 14 to 90 years), the female/male was 2.6:1, and left/right limb symptoms, 2.4:1. Clinical score of CEAP was 2 in 7%, 3 in 47%, 4 in 24%, 5 in 5%, and 6 in 17%; primary/secondary etiology was 518:464. Stent-related outcome (morbidity, thrombotic events, patency, in-stent recurrent stenosis), clinical outcome, quality of life (QOL) as assessed by the Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), and hemodynamics were evaluated before and after intervention.Result Monitoring for 94% of patients lasted a mean 22 months (range, 1 to 107 months). Stenting was performed with no mortality (<30 days) and low morbidity. Thrombotic events were rare (1.5%) during the postoperative period (<30 days) and during later follow-up (3%). At 72 months, primary, assisted-primary, and secondary cumulative patency rates were 79%, 100%, and 100% in nonthrombotic disease and 57%, 80%, and 86% in thrombotic disease, respectively. Cumulative rate of severe in-stent restenosis (>50%) occurred in 5% of limbs at 72 months (10% in thrombotic limbs, 1% in nonthrombotic limbs). The main risk factors associated with stent occlusion were the presence and severity of thrombotic disease; thrombophilia by itself was not a risk factor. The median pain score and degree of swelling decreased significantly poststent. Severe leg pain (visual analogue scale >5) and leg swelling (grade 3) decreased from 54% and 44% prestent to 11% and 18% poststent, respectively. At 5 years, cumulative rates of complete relief of pain and swelling were 62% and 32%, respectively, and ulcer healing was 58%. The mean CIVIQ scores of QOL improved significantly in all categories. Mean hand-foot pressure differential decreased and mean ambulatory venous pressure improved in stented limbs with no concomitant reflux. The hemodynamic response was modified, depending on the presence of deep and superficial reflux in subsets of patients with adjunct saphenous procedures. No increase in venous reflux was observed.Conclusions Venous stenting can be performed with low morbidity and mortality, long-term high patency rate, and a low rate of in-stent restenosis. It resulted in major symptom relief in patients with chronic venous disease, which was not consistently reflected in any substantial hemodynamic improvement by conventional measurements. The beneficial clinical outcome occurred regardless of presence of remaining reflux, adjunct saphenous procedures, or etiology of obstruction.

Successful iliac vein and inferior vena cava stenting ameliorates venous claudication and improves venous outflow, calf muscle pump function, and clinical status in post-thrombotic syndrome.

KT Delis — 2007-11-19T07:43:04-00:00

Ann Surg, Vol. 245, No. 1. (January 2007), pp. 130-139.

OBJECTIVES: Stent therapy has been proposed as an effective treatment of chronic iliofemoral (I-F) and inferior vena cava (IVC) thrombosis. The purpose of this study was to determine the effects of technically successful stenting in consecutive patients with advanced CVD (CEAP3-6 +/- venous claudication) for chronic obliteration of the I-F (+/-IVC) trunks, on the venous hemodynamics of the limb, the walking capacity, and the clinical status of CVD. These patients had previously failed to improve with conservative treatment entailing compression and/or wound care for at least 12 months. METHODS: The presence of venous claudication was assessed by > or =3 independent examiners. The CEAP clinical classification was used to determine the severity of CVD. Outflow obstruction [Outflow Fraction at 1- and 4-second (OF1 and OF4) in %], venous reflux [Venous Filling Index (VFI) in mL/100 mL/s], calf muscle pump function [Ejection Fraction (EF) in %] and hypertension [Residual Venous Fraction (RVF) in %], were examined before and after successful venous stenting in 16 patients (23 limbs), 6 females, 10 males, median age 42 years; range, 31-77 yearas, left/right limbs 14/9, using strain gauge plethysmography; 7/16 of these had thrombosis extending to the IVC. Contralateral limbs to those stented without prior I-F +/- IVC thrombosis, nor infrainguinal clots on duplex, were used as control limbs (n = 9). Excluded were patients with stent occlusion or stenoses, peripheral arterial disease (ABI <1.0), symptomatic cardiac disease, unrelated causes of walking impairment, and malignancy. Preinterventional data (< or =30 days) were compared with those after endovascular therapy (8.4 months; interquartile range [IQR], 3-11.8 months). Nonparametric analysis was applied. RESULTS: Compared with the control group, limbs with I-F +/- IVC thrombosis before stenting had reduced venous outflow (OF4) and calf muscle pump function (EF), worse CEAP clinical class, and increased RVF (all, P < 0.05). At 8.4 months (IQR, 3-11.8 months) after successful I-F (+/-IVC) stenting, venous outflow (OF1, OF4) and calf muscle pump function (EF) had both improved (P < 0.001) and the RVF had decreased (P < 0.001), at the expense of venous reflux, which had increased further (increase of median VFI by 24%; P = 0.002); the CEAP status had also improved (P < 0.05) from a median class C3 (range, C3-C6; IQR, C3-C5) [distribution, C6: 6; C4: 4; C3: 13] before intervention to C2 (range, C2-C6; IQR, C2-C4.5) [distribution, C6: 1; C5: 5; C4: 4; C2: 13] after intervention. At this follow up (8.4 months median), venous outflow (OF1, OF4), calf muscle pump function (EF), and RVF of the stented limbs did not differ significantly from those of the control; significantly worse (P < 0.025) were the amount of venous reflux (VFI), and the CEAP clinical class, despite the improvement with stenting. Incapacitating venous claudication noted in 62.5% (10 of 16, 95% CI, 35.8%-89.1%) of patients (15 of 23 limbs; 65.2%, 95% CI, 44.2%-86.3%) before stenting was eliminated in all after stenting (P < 0.001). CONCLUSIONS: Successful I-F (+/-IVC) stenting in limbs with venous outflow obstruction and complicated CVD (C3-C6) ameliorates venous claudication, normalizes outflow, and enhances calf muscle pump function, compounded by a significant clinical improvement of CVD. The significant increase in the amount of venous reflux of the stented limbs indicates that elastic or inelastic compression support of the successfully stented limbs would be pivotal in preventing disease progression.