Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study.

OBJECTIVE: Apart from its role in bone metabolism, vitamin D may also influence cardiovascular disease. The objective of this study was: (1) to determine the effect of a single, oral, high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease (PAD) and (2) to investigate the impact of this supplementation on coagulation and inflammation parameters. METHODS: In this double-blind, placebo-controlled, interventional pilot study, we screened 76 Caucasian patients with PAD for vitamin D deficiency. Sixty-two were randomised to receive a single, oral supplementation of 100,000 IU vitamin D3 or placebo. At baseline and after 1 month, we measured serum vitamin D and parathormone levels, and surrogate parameters for cardiovascular disease. RESULTS: Sixty-five of 76 patients (86%) had low 25-hydroxyvitamin D levels (<30 ng ml(-1)); of those, 62 agreed to participate in the study. At baseline, only parathormone was related to vitamin D. In supplemented patients, vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1) (P < 0.001), with wide variations between single patients; in the placebo group vitamin levels did not change. Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1) between summer and winter. After 1 month, none of the measured parameters was influenced by vitamin substitution. CONCLUSION: In this pilot study, most patients with PAD were vitamin D deficient. Vitamin D supplementation increased serum 25-hydroxyvitamin D without influencing endothelial function, arterial stiffness, coagulation and inflammation parameters, although the study was underpowered for definite conclusions.

Stent-Assisted Angioplasty (SAA) at the Level of the Common Femoral Artery Bifurcation: Long-Term Outcomes.

BACKGROUND: The objective of this retrospective single-center study was to report the initial and the long-term outcome after stent-assisted angioplasty of occlusive disease at the common femoral artery. MATERIALS AND METHODS: Between 1995 and 2015, 94 limbs in 79 consecutive patients (54 men; mean age 70 ± 8.6 years) underwent angioplasty with self-expanding stent implantation in 94 common femoral arteries. Critical limb ischemia was present in 15 limbs (16%); the other patients had claudication. RESULTS: Technical success was 99%. Complications occurred in 5/94 interventions (5.3%): puncture site hematomas (2), arteriovenous fistula (1), cholesterol embolism (1), and dissection of the access site artery (1). The intervention was outpatient-based in 98%. Median follow-up was 53 months. Ankle-brachial index (ABI) rose from 0.71 ± 0.17 to 1.0 ± 0.2 (p < .001) immediately after the intervention and was 1.03 ± 0.2 after 1 year and 0.96 ± 0.21 at the last follow-up visit (p < .001 compared to pre-interventional ABI). During follow-up, restenosis was found in 23/94 limbs (25%); 15 limbs were treated by angioplasty, 3 by surgery, and 5 conservatively. One limb was amputated below the knee 6 months after stent-assisted angioplasty (SAA). Death rate during follow-up was 35/79 patients (44%). CONCLUSIONS: SAA of the CFA resulted in high immediate success and a low complication rate. Restenosis rate was moderate, and target lesions could easily be retreated by angioplasty. The main hazard was not restenosis, but death during follow-up.

Accuracy and consistency of anti-Xa activity measurement for determination of rivaroxaban plasma levels.

Essentials Accurate determination of anticoagulant plasma concentration is important in clinical practice. We studied the accuracy and consistency of anti-Xa assays for rivaroxaban in a multicentre study. In a range between 50 and 200 µg L-1 , anti-Xa activity correlated well with plasma concentrations. The clinical value might be limited by overestimation and intra- and inter-individual variation. SUMMARY: Background Determining the plasma level of direct oral anticoagulants reliably is important in the work-up of complex clinical situations. Objectives To study the accuracy and consistency of anti-Xa assays for rivaroxaban plasma concentration in a prospective, multicenter evaluation study employing different reagents and analytical platforms. Methods Rivaroxaban 20 mg was administered once daily to 20 healthy volunteers and blood samples were taken at peak and trough levels (clinicaltrials.gov NCT01710267). Anti-Xa activity was determined in 10 major laboratories using different reagents and analyzers; corresponding rivaroxaban plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Findings Overall Pearson's correlation coefficient of anti-Xa levels and HPLC-MS results was 0.99 for Biophen® Heparin (95% CI, 0.99, 0.99), Biophen® DiXaI (95% CI, 0.99, 0.99) and STA® anti-Xa liquid (95% CI, 0.99, 1.00). Correlation was lower in rivaroxaban concentrations below 50 µg L-1 and above 200 µg L-1 . The overall bias of the Bland-Altman difference plot was 14.7 µg L-1 for Biophen Heparin, 17.9 µg L-1 for Biophen DiXal and 19.0 µg L-1 for STA anti-Xa liquid. Agreement between laboratories was high at peak level but limited at trough level. Conclusions Anti-Xa activity correlated well with rivaroxaban plasma concentrations, especially in a range between 50 and 200 µg L-1 . However, anti-Xa assays systematically overestimated rivaroxaban concentration as compared with HPLC-MS, particularly at higher concentrations. This overestimation, coupled with an apparent interindividual variation, might affect the interpretation of results in some situations.

Multiple, large aneurysms of pulmonary arteries in Behçet's disease. Clinical remission and radiologic resolution after corticosteroid therapy.

We describe the case of a young European woman with Behçet's disease, hemoptysis, and multiple, large aneurysms of pulmonary arteries as confirmed by computed tomographic scan and angiography. Complete resolution of hemoptysis and radiologic signs of pulmonary artery aneurysms was observed three months after prednisone treatment, and a persisting remission was noted after ten months. We reviewed the literature on this rare complication and described the therapeutic approaches.

Interstitial chemotherapy of experimental gliomas.

Two new approaches of interstitial (intratumoral) chemotherapy of gliomas are presented. Using s.c.-transplanted rat gliomas (G616) the therapeutic activity of biologically degradable polylactide rods as carriers for methotrexate was investigated. Carrier-mediated intratumoral chemotherapy was superior both to a systemic treatment and an intratumoral treatment with the free drug. The activity of the alkyllysophospholipids Et-18-OCH3 and BM 41.440 and of the alkylphosphocholine He-PC was investigated in a human glioma xenograft (T 406). All three compounds were highly active following intratumoral administration.

Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases.

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.

Hemostatic activation under anticoagulant treatment: a comparison of unfractionated heparin vs. nadroparin in the treatment of proximal deep vein thrombosis.

BACKGROUND: Multiple clinical trials have been performed to compare standard heparin with low molecular weight heparin in the therapy of deep vein thrombosis, but little is known about the time course of the markers of hemostatic system during the treatment with these two heparin regimens. METHODS: Twenty patients with proximal deep vein thrombosis confirmed by duplex ultrasound and phlebography were randomly assigned to either unfractionated heparin (UH) given as an intravenous bolus of 80 U/kg followed by a constant infusion of 18 U/kg/h, or nadroparin 185 AXa IU/kg once daily subcutaneously. Oral anticoagulants were started at day 4. Markers of hemostatic activation (F1+2, FPA, TAT, D-dimer) were measured daily for 4 days. Primary endpoints were the time course of these markers; secondary endpoints consisted in the evaluation of thromboembolic and hemorrhagic complications by clinical outcome and Marder score. RESULTS: Treatment with UH resulted in a rapid achievement of therapeutic heparin levels. UH reduced markers of fibrin formation and fibrinolysis more rapidly than nadroparin (p < 0.05). Within the nadroparin group activation of prothrombotic markers four hours after the subcutaneous injection (peak level) was significantly lower when compared with the time prior to injection (trough level). Secondary endpoints showed no significant difference between the two groups. CONCLUSION: Continuous intravenous perfusion of UH administered on a basis of a weight-adjusted nomogram controlled markers of the hemostatic system more rapidly than once-daily subcutaneously administered weight-adjusted nadroparin.

Functional characterization of a variant factor XII (F XII Locarno) in a cross reacting material positive F XII deficient plasma.

The plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (less than 0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita's plasma. FXII Locarno is a single chain molecule with the same size (Mr = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita's plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita's plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein. These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (alpha-FXIIa).

Determining prognosis of clinically localized prostate cancer by immunohistochemical detection of mutant p53.

OBJECTIVES: Mutations of the p53 tumor suppressor gene can result in unregulated cellular growth and have been implicated in numerous malignancies. The objective of this study was to determine whether the detection of mutant p53 by immunohistochemical staining is predictive of progression in clinically localized adenocarcinoma of the prostate. METHODS: Immunohistochemical staining for mutant p53 was performed on 40 formalin-fixed radical prostatectomy specimens. Benign glands in the sections served as controls. Immunoreactivity (IR) was categorized semi-quantitatively from 0 to 4+ (0 = no IR, 1+ = 1 % to 10%, 2+ = 11% to 40%, 3+ = 41 % to 70%, 4+ = 71 % to 100%). Results were then compared to Gleason score, Stage (T2 versus T3), surgical margins, lymph node and seminal vesicle involvement, age, race, preoperative prostate-specific antigen (PSA), and biochemical progression. Biochemical progression was defined as a persistently elevated postoperative PSA of 0.2 ng/mL or greater. RESULTS: Thirty-two of the 40 tumors (80%) stained for mutant p53. None of the tumors that did not stain progressed, whereas 20 of 32 (62.5%) of the tumors that did stain progressed, with an overall mean followup of 50.8 months. Immunoreactivity did not correlate with any of the known prognostic variables but did have statistically significant correlation with progression by all three statistical methods used (Fisher's exact test, logistic regression, and log-rank test). CONCLUSIONS: Strict quality control and newer antigen retrieval techniques reveal p53 abnormalities in many prostate cancers. Immunohistochemical detection of mutant p53 appears to be an independent predictor of progression. These data suggest potential utility of p53 as a preoperative prognostic indicator in localized prostate cancer.

Inhibition of posterior capsule opacification by an intraocular-lens-bound sustained drug delivery system: an experimental animal study and literature review.

PURPOSE: To find a way to prevent or significantly reduce posterior capsule opacification (PCO) with modern phacoemulsification and in-the-bag intraocular lens (IOL) implantation. SETTING: Department of Ophthalmology and Institute for Pharmaceutical Technology and Biopharmacy, Ruprecht-Karls-University of Heidelberg, Germany. METHODS: We evaluated the effects of an IOL-bound sustained drug delivery system (SDDS) consisting of the carrier substance poly-DL-lactid and the drug daunorubicin or indomethacin. The system was applied to the IOL surface and implanted in rabbit eyes. At 8 weeks postoperatively, PCO wet mass was determined. Toxic and inflammatory effects were documented by histopathology. RESULTS: The average PCO wet mass was 54.6 mg in the control group, 28.6 mg with daunorubicin, and 64.1 mg with indomethacin. Statistical analysis showed a significant reduction of PCO with daunorubicin (Mann-Whitney U-test, P = .025) and no PCO-reducing effect with indomethacin. Light microscopy of the specimens revealed mild inflammation, especially at the limbus, and some endothelial cell loss in the daunorubicin group and iris and ciliary body inflammation in the indomethacin group. CONCLUSION: In the rabbit eye, slow release of daunorubicin reduced PCO formation by approximately 50%. It must be determined whether the endothelial side effects are specific to the rabbit species or whether the human cornea is as sensitive. The principle of the IOL-bound SDDS and the evaluation procedure can be standardized and used for systematic tests in the future.

Homocysteine, vitamins and gene mutations in peripheral arterial disease.

A case-control study was undertaken involving 51 consecutive patients with peripheral artery obstructive disease (PAOD) scheduled for angioplasty. Blood samples of these patients were analysed for plasma homocysteine (tHcy) and levels of vitamin B12 and folate, and the MTHFR gene was assessed for mutation. Patients were compared with age- and sex-matched controls who did not present with cardiovascular risk factors. Mean tHcy did not differ between cases and controls (13.3 +/- 5.7 and 12.6 +/- 4.9 micromol/l, P = 0.49). More patients were above the 95th percentile as determined from the data in the control group with an odds ratio (OR) that almost reached statistical significance [OR, 2.8; 95% confidence interval (CI), 0.9-8.7], but on separate analyses only female patients showed higher tHcy than female controls (15.6 versus 12.0 micromol/l, P = 0.05), with an odds ratio for tHcy above the 95th percentile of 10.5 (95% CI, 1.1-96.6). The TT genotype of the MTHFR gene was found in 24% of the patients and in 12% of the controls (OR, 2.3; 95% CI, 0.8-6.7). Our findings point to a modest association between tHcy and PAOD, with a difference between cases and controls restricted to the highest percentile in female patients. A weak but not significant association was also found for the TT genotype of the MTHFR gene.

The clinical utility of serologic markers in the evaluation of the acute scrotum.

OBJECTIVE: To examine the presence of interleukin-1 (IL-1), interleukin-6 (IL-6), and creatine phosphokinase-MM (CPK-MM) in patients with acute scrotal pain and assess their clinical utility in the diagnosis of testicular torsion (TT) and epididymitis. METHODS: Twenty-five patients with acute scrotal pain were prospectively enrolled over a two-year period. History, physical examination, complete blood count, urinalysis, and scrotal ultrasound were performed. Testicular torsion was confirmed by surgical exploration. Epididymitis was diagnosed using physical examination, scrotal ultrasound, and positive urinalysis. Venous blood was assayed for IL-1, IL-6, and CPK-MM in triplicate during the routine drawing of blood in the emergency department. The data are reported as medians +/- interquartile ranges (IQRs). RESULTS: Twenty-five patients with acute scrotal pain were evaluated; 11 with TT, three with torsion of the appendix testis (TAT), ten with epididymitis, and one with varicocele. One patient had both TT and epididymitis. Interleukin-1 was not detectable in either group. The CPK-MM values between TT and epididymitis were virtually identical at 99.8 and 100 IU/L, respectively. The median value for IL-6 was 1. 03 (IQR = 0.19 to 2.86) vs 20.86 (IQR = 2.14 to 65.50) pg/mL in the torsion and epididymitis groups, respectively. The 97.5% CI for the difference of medians of 19.9 was 0.4 to 65.1, p = 0.02. Using receiver operating characteristic (ROC) curve analysis for IL-6, the area under the curve was 0.82 for torsion and 0.67 for epididymitis. Using a cutoff value of IL-6 >/= 1.41 pg/mL, the positive predictive value of IL-6 in diagnosing epididymitis was 78.6%, with a negative predictive value of 100% for TT. There were no cases of missed TT on follow-up. CONCLUSIONS: This preliminary investigation of serologic markers demonstrates that IL-6 is significantly elevated in epididymitis as compared with TT. Creatine phosphokinase-MM and IL-1 were not found to be of diagnostic utility. The small sample size of this study precludes a definitive conclusion as to the utility of these markers in the emergency department. However, IL-6 may be clinically useful as an additional element in differentiating the causes of acute scrotal pain, and further study is warranted.

Severe pulmonary hypertension: data from the Swiss Registry.

BACKGROUND: Severe pulmonary hypertension (PH) is a rare disease with a dismal prognosis if untreated. Progress in diagnosis and in the development of effective therapeutic options has created new interest in this pathology. There are, however, only limited data on the prevalence of severe PH unrelated to chronic left ventricular failure or COPD, on the associated conditions and on the parameters with a prognostic impact. With the aid of a retrospective registry we have collected data from 5 centres in Switzerland and attempted to answer the above questions. METHODS: Data on patients with PH from 4 university facilities (Zurich, Basle, Geneva and Lausanne) and one well-defined geographical area (Ticino) were retrospectively collected and analysed up to December 1999. Clinical and haemodynamic parameters and associated diseases were noted. We were also interested in the age distribution of the patients and the year of diagnosis of PH. RESULTS: We found 106 patients with severe PH (43 men, 63 women, median age 43 years); 79% were in NYHA class III or IV. There was a steep rise in diagnosis of PH after 1995. In 74% PH was either primary or associated with collagen vascular disease or thromboembolic disease. By the end of the observation period 30% of the patients had died. The best distinguishing parameters between surviving patients and those who eventually died were the 6-minute walking test (363 vs. 235 metres, p = 0.002), the NYHA class (II vs III/IV, p = 0.015), and mixed venous saturation (66.5 vs. 57.9%, p = 0.006). Therapy consisted of calcium antagonists in 18% and of (inhaled) prostanoids, chiefly iloprost, in 33%. Seven patients underwent lung transplantation. CONCLUSIONS: We conclude that PH is diagnosed more often as diagnostic and therapeutic options improve; that primary forms, and those associated with collagen vascular disease and with chronic venous thromboembolism, make up three-quarters of the aetiologies; and that the 6-minute walking test, the functional class and mixed venous saturation are the best prognostic parameters.

[Concrete approaches to the promotion of prevention. Health education in schools]. / Konkrete Ansatzpunkte zur Förderung der Prävention. Gesundheitserziehung in der Schule.

Society nowadays entrusts the school with formative tasks which earlier were exclusively the role of the family unit. Numerous such tasks are in relation with the integration of the individual in society. As they usually concern attitudes and behaviors which the youth must actively adopt for themselves (get impregnated with), the school cannot limit its action to transmitting knowledge. This is true in particular for health education. Good mental health of the students is the precondition of a positive attitude vis-à-vis physical wellbeing. It is important therefore to give adequate emphasis to mental health requirements in teacher training.

[Improving the effectiveness of health education]. / Rendre l'éducation pour la santé plus efficace.

Discussions concentrated on ways of influencing the behavior of healthy individuals. The following was concluded; 1. Health education is an interdisciplinary activity. It should not merely be aimed at the behavior of individuals but also respect and influence values and institutions of society as well as legislation. 2. Family and school are the most important fields of activity. 3. Health education should be based on experiences from communication sciences. 4. In school, health education should be integrated in as many subjects as possible. Of special importance are the example of the teachers and adequate preparation and training. 5. Health education cannot limit itself to giving information, it also must motivate to a healthy way of life. 6. Exchange of experiences and information in health education should be improved. In Switzerland this can be done by a working party of the Swiss Society for Social and Preventive Medicine. 7. The intervention trials of the Swiss National Research Program can provide important stimuli for innovative approaches to health education is Switzerland.

[Skin necroses, thrombocytopenia and deep venous thrombosis in subcutaneous thromboembolism prophylaxis with heparin: heparin-induced thrombocytopenia (HIT) type II]. / Hautnekrosen, Thrombozytopenie und tiefe Beinvenenthrombose unter subkutaner Thromboembolieprophylaxe mit Heparin: Heparininduzierte Thrombozytopenie (HIT) Typ II.

We present a 52-year-old woman who developed a heparin-induced thrombocytopenia type II (HIT II) with deep vein thrombosis, thrombocytopenia and skin necrosis 7 days after initiating subcutaneous prophylaxis with 2 x 5000 U of unfractionated heparin. The platelet count fell from an initial value of 233 x 10(9)/L to 57 x 10(9)/L and normalized within 3 days after stopping heparin. Oral phenprocoumon was started, and her further course was uneventful. The pathogenesis and diagnosis of HIT II is illustrated, and the possible therapeutic options are discussed. To prevent this potentially lethal complication, it is important to begin oral anticoagulation on the first or second day of heparinization, and to stop heparin if the INR-value has been within a therapeutic range for 2 consecutive days. Platelet counts must be checked after 5 to 7 days of heparin therapy. In the case of suspected HIT II, a diagnostic test has to be performed, the heparin must be stopped, and an anticoagulation with either danaparoid or lepirudin is recommended.

[Diagnosis of deep venous thrombosis]. / Diagnostik der tiefen Venenthrombose.

The clinical diagnosis of deep venous thrombosis (DVT) is unreliable. Phlebography, an invasive method, has gained wide diffusion and is considered as gold standard, but it has several draw-backs such as elevated costs and x-ray exposure. For these reasons, other, non-invasive techniques for diagnosing DVT have been looked for. Among them, CW-Doppler, occlusion plethysmography and, more recently, colour-Duplex-sonography have gained most acceptance. While the first two methods are able to diagnose with sufficient sensitivity and specificity proximal DVT, they are unreliable for isolated calf vein thrombosis. The colour-Duplex-sonography, on the other hand, produces results similar to phlebography for proximal thrombosis and succeeds in detecting isolated calf vein thrombosis with sufficient accuracy. We propose therefore the following non-invasive proceeding when confronted with the question of DVT: The first investigation to be done is a (colour)-Duplex examination. If one lacks such an infrastructure, an investigation with CW-Doppler or occlusion plethysmography has to be performed. If the results are positive, the patient will be treated. Otherwise, the exam will be repeated after five to seven days for CW-Doppler and plethysmography. If now the result is positive, the patient will be treated, otherwise, as with a negative Duplex study, the suspicion of DVT will be dismissed.

Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.

INTRODUCTION: Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests. METHODS: The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories. RESULTS: RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43µg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected. CONCLUSIONS: RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.