Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism (FondaPPP).

We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.

Prevalence of low-risk and high-risk types of human papillomavirus and other risk factors for HPV infection in Germany within different age groups in women up to 30 years of age: an epidemiological observational study.

Human papillomavirus (HPV) infection is frequent in young women and persistent infection may lead to cervical cancer. Therefore, vaccination against HPV is recommended for young women in the age group from 12-17 years in Germany. However, epidemiological data on the prevalence of HPV types and risk factors for infection for younger women in Germany is scarce. To address this, an observational study was performed in Germany including 1,692 women aged 10-30 years. After a routine Pap smear, cervical swabs were tested for high-risk and low-risk HPV, respectively, using the Hybrid Capture 2 (HC2) test, and genotyped using the PCR-based tests SPF(10)/LiPA(25) and PapilloCheck®. In addition, the women were interviewed regarding their medical history and lifestyle factors. Three hundred seventy-seven (22.28%) women had positive HC2 results. The proportion of HPV positive women was highest in the 20-22 age group with 28.3%. Predominant HPV types were HPV 16, 42, 51 and HPV 16, 51, 31 as defined by PapilloCheck® and SPF(10)/LiPA(25), respectively. 95.8% of women did not show signs of any cervical lesion. Adjusted analysis identified number of sexual partners (OR:1.105; 95% CI:[1.069-1.142]), smoking (OR:1.508; [1.155-1.968]), and vaccination against HPV (OR:0.589; [0.398-0.872]) rather than increasing age as risk associated with HPV infection. Comparison of the genotyping assays showed that they correspond well regarding the high-risk HPV types but less well for low-risk HPV types. This epidemiological study shows that high-risk HPV infection is common in young women in Germany. According to our data, vaccination of young women could have a potential impact on the prevention of HPV infection and cervical disease.

Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of Heparin-Induced Thrombocytopenia.

BACKGROUND: Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label. OBJECTIVES: The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT. METHODS: In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings. RESULTS: Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux. CONCLUSIONS: Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).

Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with coronary artery disease: meta-analysis of randomized trials.

CONTEXT: Placement of sirolimus-eluting stents or paclitaxel-eluting stents has emerged as the predominant percutaneous treatment strategy in patients with coronary artery disease (CAD). Whether there are any differences in efficacy and safety between these 2 drug-eluting stents is unclear. OBJECTIVE: To compare outcomes of sirolimus-eluting and paclitaxel-eluting coronary stents on the basis of data generated by randomized head-to-head clinical trials. DATA SOURCES: PubMed and the Cochrane Central Register of Controlled Trials, conference proceedings from major cardiology meetings, and Internet-based sources of information on clinical trials in cardiology from January 2003 to April 2005. STUDY SELECTION: Randomized trials comparing the sirolimus-eluting stent with the paclitaxel-eluting stent in patients with CAD reporting the outcomes of interest (target lesion revascularization, angiographic restenosis, stent thrombosis, myocardial infarction [MI], death, and the composite of death or MI) during a follow-up of at least 6 months. DATA EXTRACTION: Two reviewers independently identified studies and abstracted data on sample size, baseline characteristics, and outcomes of interest. DATA SYNTHESIS: Six trials, including 3669 patients, met the selection criteria. No significant heterogeneity was found across trials. Target lesion revascularization, the primary outcome of interest, was less frequently performed in patients who were treated with the sirolimus-eluting stent (5.1%) vs the paclitaxel-eluting stent (7.8%) (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.49-0.84; P = .001). Similarly, angiographic restenosis was less frequently observed among patients assigned to the sirolimus-eluting stent (9.3%) vs the paclitaxel-eluting stent (13.1%) (OR, 0.68; 95% CI, 0.55-0.86; P = .001). Event rates for sirolimus-eluting vs paclitaxel-eluting stents were 0.9% and 1.1%, respectively, for stent thrombosis (P = .62); 1.4% and 1.6%, respectively, for death (P = .56); and 4.9% and 5.8%, respectively, for the composite of death or MI (P = .23). CONCLUSIONS: Patients receiving sirolimus-eluting stents had a significantly lower risk of restenosis and target vessel revascularization compared with those receiving paclitaxel-eluting stents. Rates of death, death or MI, and stent thrombosis were similar.

Frequent off-label use of fondaparinux in patients with suspected acute heparin-induced thrombocytopenia (HIT)--findings from the GerHIT multi-centre registry study.

INTRODUCTION: In life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on "real-life" management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies. PATIENTS AND METHODS: In a national multi-centre registry study, patients with a 4T's HIT-probability score of ≥ 4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated. RESULTS: Of 195 patients, the 4T's scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%). CONCLUSIONS: The current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.

Post-thrombotic syndrome 3 years after deep venous thrombosis in the Thrombosis and Pulmonary Embolism in Out-Patients (TULIPA) PLUS Registry.

BACKGROUND: Reported post-thrombotic syndrome (PTS) rates may be confounded by including patients with a history of deep venous thrombosis (DVT) before the index event, varicose veins, or chronic venous insufficiency independent of PTS. We were interested in assessing PTS incidence rates of patients without these pre-existing disease conditions. METHODS: A prospective registry with a 3-year follow-up after an initial DVT was assessed. Available for analysis were 135 ambulatory patients without a history of DVT (before the index DVT), signs of varicose veins, or chronic venous insufficiency affecting the ipsilateral or contralateral leg, and Villalta score. RESULTS: PTS was detected in 24.5% of patients, with 17.0% having mild (Villalta score, 5-9), 6.0% moderate (score, 10-14), and 1.5% severe PTS (score ≥15) after a first DVT. Of these, 52.6% had proximal and 47.4% distal DVT; 63.7% were provoked and 35.6% unprovoked (one patient missing). Patients with proximal DVT (32.4%) significantly more often developed any PTS compared with patients with distal DVT (15.6%; P = .024); however, groups were similar with regard to severity of PTS by the four-level Villalta score (P = .109). In univariate analysis, PTS was more frequent (odds ratio, 95% confidence interval) with higher age (1.06 per year; 1.02-1.09), a body mass index of 25 to 30 kg/m(2) (2.38; 0.71-7.97) and ≥30 kg/m(2) (6.08; 1.75-21.14), proximal vs distal DVT (2.59; 1.12-5.98), and calf swelling ≥3 cm larger than the asymptomatic leg (3.77; 1.66-8.55). In a multivariate analysis, age (1.05; 1.01-1.09) and calf swelling ≥3 cm larger than the asymptomatic leg (2.94; 1.20-7.20) remained predictive for PTS. Compression therapy was used by 78.5% of patients at the 1-year follow-up and by 46.7% at the 3-year follow-up. Both rates were higher in patients with PTS (93.9%) vs no PTS (66.7%). CONCLUSIONS: This prospective survey demonstrates a low rate of PTS in patients with a first DVT and no pre-existing DVT, varicose veins, or chronic venous insufficiency, and a high adherence rate to compression therapy, within the first 3 years of follow-up. Age and marked calf swelling were independent predictors of PTS.

Advances in ITP--therapy and quality of life--a patient survey.

BACKGROUND: Current guidelines recommend glucocorticoids and splenectomy as standard 1(st) and 2(nd) line treatments for chronic immune thrombocytopenia (ITP). We sought to find out how German ITP-patients are treated with respect to these guidelines. METHODS: Members of a patient support association ≥18 years with a self-reported history of chronic ITP>12 months were surveyed with a web-based questionnaire. RESULTS: 122 questionnaires were evaluated. 70% of patients had chronic ITP for more than 5 years and 20% an average platelet count of ≤30·10(9)/L. 41% of the patients reported haematomas or petechiae more than once or twice and up to 12 times or more per year and 17% oropharyngeal and nasal bleeds. 11% had been admitted to hospital during the last 12 months. 88% had received or currently receive glucocorticoids, 27% were splenectomised. IVIG had been given to 55%, rituximab to 22%, anti-D to 12%, ciclosporin to 7%, while complementary and alternative medical treatments had been used by 36%. 50 women responded to questions concerning pregnancy. 14 (28%) had been advised not to become pregnant. 23 reported pregnancies and 10 (44%) required treatment for their ITP during pregnancy. CONCLUSION: Glucocorticoids are the most common therapy for chronic ITP but complementary and alternative treatments already come second and less than ⅓ of patients are splenectomised. This and the frequent use of complementary medicines suggests patients' dissatisfaction with conventional approaches. Many patients receive off-label therapies. There is a major need for adequate counselling and care for pregnant ITP-patients.

Impact of gender on the clinical presentation and diagnosis of deep-vein thrombosis.

It is uncertain whether gender influences the clinical presentation of deep-vein thrombosis (DVT) and the discriminative value of the Wells diagnostic pretest probability score. The aim of the study was to determine whether gender impacts the clinical presentation and diagnosis of DVT. The study analysed a cohort of 4,976 outpatients with clinically suspected DVT of the leg prospectively recruited by 326 vascular medicine physicians in the German ambulatory care sector between October and December 2005. The diagnosis of DVT was based on compression ultrasonography in 96% of patients. Among 4,777 patients who had a diagnostic work-up for DVT there were more women (n=2,998) than men (n=1,779). However, the prevalence of confirmed DVT was 37.0% (658/1779) in men vs. 24.3% (730/2,998) in women (p<0.001). Among patients with confirmed DVT, proximal DVT was more common in men (59.6% vs. 44.5% in women, p<0.001). Swelling of the leg, pitting oedema and dilated superficial veins were more frequently reported by men (p<0.001). The percentage of patients with a high probability Wells clinical pretest score was higher in men than in women (67.0% vs. 57.0%, p<0.001). However, overall, the score equally discriminated risk groups for DVT in both sexes. In conclusion, women were more frequently referred for a diagnostic work-up for DVT than men, but the prevalence of DVT was higher in men and their thrombotic events were more severe. Nevertheless, the Wells clinical pretest probability score correctly identified low- and high-risk groups in both genders.

Diagnosis of deep-vein thrombosis: adherence to guidelines and outcomes in real-world health care.

Current guidelines recommend optimised algorithms for diagnosis of suspected deep-vein thrombosis (DVT). There is little data to determine to what extent real-world health care adheres to guidelines, and which outcome in terms of diagnostic efficiency and safety is achieved. This registry involved patients with clinically suspected DVT of the leg recruited in German ambulatory care between October and December 2005. Registry items were: diagnostic methods applied, diagnostic categories at day 1, and venous thromboembolic events up to 90 days in patients without firmly established DVT. A total of 4,976 patients were recruited in 326 centres. Venous ultrasonography was performed in 4,770 patients (96%), D-dimer assay in 1,773 patients (36%) and venography in 288 patients (6%). At day 1, DVT was confirmed in 1,388 patients (28%), and ruled out in 3,389 patients (68%), and work-up was inconclusive in 199 patients (4%). The rate of venous thromboembolism at 90 days was 0.34% (95% confidence interval [CI]: 0.09 to 0.88) in patients in whom the diagnosis of DVT had been ruled out, and 2.50% (95% CI: 0.69 to 6.28) in patients with inconclusive diagnostic workup. This nationwide evaluation in German ambulatory care revealed that the diagnostic work-up for suspected DVT did not adhere to current guidelines. However, the overall diagnostic safety was excellent, although there is potential for improvement in a well defined minority of patients.