Kai Halbritter

Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis.

Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this prospective outcome study, 1646 consecutive patients with clinically suspected DVT were examined once by a standardized protocol of complete compression ultrasound comprising all proximal and distal veins (CCUS) as the only diagnostic test. The examination was equivocal in 15 patients (1% technical failure rate). Another 366 patients (22%) were tested positive for proximal DVT, distal DVT, muscle vein thrombosis, or phlebitis. Of 1265 patients in whom CCUS findings were negative, 242 met exclusion criteria for follow-up (age <18, life expectancy <3 months, other reasons for anticoagulation, postthrombotic lesions of the leg veins, or lack of informed consent). During the 3 months of follow-up, three of 1023 patients with negative CCUS findings experienced a symptomatic venous thromboembolic event (0.3% [95% CI 0.1%-0.8%]). We conclude that the CCUS protocol has a low technical failure rate and is safe with respect to excluding DVT, thereby reducing the diagnostic workup of patients with suspected DVT to a single ultrasound examination.

Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study

Summary.  Background: Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose‐finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non‐invasive alternative to venography. Objectives: A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. Patients/Methods: Patients received study drugs until mandatory, bilateral venography was performed 7 ± 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. Results: A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. Conclusions: Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.

Therapy of isolated calf muscle vein thrombosis: A randomized, controlled study

BACKGROUND Treatment of isolated calf muscle vein thrombosis (ICMVT) is controversial. There are no data from prospective, controlled studies. Objective of this article was to compare the efficacy and safety of a short-term course of anticoagulation with compression therapy alone. METHODS We prospectively randomized patients with symptomatic, sonographically proven ICMVT in the soleal and/or gastrocnemial muscle veins in two treatment arms. The first received low-molecular-weight heparin for 10 days at therapeutic dosage (nadroparin 180 anti-activated factor X units once daily) and compression therapy for three months, and the second received compression therapy alone. Primary efficacy endpoint of the study was sonographically proven progression of ICMVT into the deep veins and clinical pulmonary embolism (PE) as confirmed by objective testing. Secondary efficacy and primary safety endpoints were major bleeding, death not due to PE, and complete sonographically proven recanalization of the muscle vein. We assessed transient and permanent risk factors for venous thromboembolism. RESULTS One-hundred seven patients were finally ruled eligible for evaluation: 89% outpatients, 11% hospitalized patients. In the heparin group (n=54) progression to deep vein thrombosis (DVT) occurred in two patients (3.7%), in the group compression therapy alone (n=53) progression to DVT occurred in two patients (n.s.). No clinical PE and no death occurred. Thrombus recanalization after 3 months was not statistically significant different between the two study groups. No major bleeding occurred. CONCLUSION The data do not show superiority of a short-term regimen of low-molecular-weight heparin and compression therapy in comparison with compression therapy alone in patients with ICMVT in a rather low-risk population.

Bridging anticoagulation for patients on long-term vitamin-K-antagonists. A prospective 1 year registry of 311 episodes.

there are no reports on the use of real-time fluorescence monitoring in LD-PCR. A combination of two real-time PCRs allowed detection and discrimination of inversion-positive individuals, inversion-negative individuals and carrier women (see Fig. 1 for details). For validation purposes a total of 30 samples of known genotype were analyzed with this new longdistance real-time PCR (LD real-time PCR) and full concordance was observed. In addition, LD real-time PCR aliquots subjected to agarose gel electrophoresis again gave results that were in total agreement with the expected genotypes. In summary, we report new LD-PCR parameters for FVIII intron 22 inversion detection, which circumvent the complications that have appeared as the manufacturer introduced modifications in the kit originally used by Liu et al. [2] Moreover, and importantly, we describe an innovative singlestepmethod for convenient intron 22 inversion detectionwithin one working day. LD real-time PCR in combination with SYBR Green I chemistry is a simple, fast automated technique that obviates the lengthy electrophoretic processes with extremely fragile low-percentage agarose gels used in LD-PCR. To our knowledge, this is the fastest method described for amplification and specific detection of very large PCR products and could be adapted to other LD-PCR diagnostic applications [7–9].

Hospitalization for vitamin-K-antagonist-related bleeding: treatment patterns and outcome

Bleeding complications are common side effects of vitamin‐K antagonist (VKA) therapy. Data on the in‐hospital management and outcomes of these bleeding events are scarce and information is mostly derived from trial cohorts.

Central adjudication of venous ultrasound in VTE screening trials: reasons for failure

Summary.  Background: The accuracy of screening ultrasound for venous thrombosis in asymptomatic patients is still a matter of debate. The VENUS study evaluated the accuracy of centrally adjudicated venous ultrasound against venography in patients after major orthopedic surgery and found the sensitivity of ultrasound to be poor for both proximal and distal deep vein thrombus (DVT). Objectives: To evaluate whether thrombus characteristics such as location or size influence the diagnostic performance of centrally adjudicated venous ultrasound. Methods: All false negative sonograms of the VENUS study were re‐evaluated against the corresponding venograms. Discrepancies were categorized into types of diagnostic failures. Within these categories, thrombus characteristics such as location, length or size of thrombus were evaluated. Results: One hundred and twelve pairs of discrepant ultrasound and venography documents were compared with 28 pairs with concordant results. Discrepancies were caused by local documentation failure (37.5%), failure of the ultrasound method (43.7%) and failure of the central adjudication process (18.7%). The overall size of thrombi was small, which caused about 40% of all sonographic failures with a detection threshold of five Marder points, a thrombus length of 9.5 cm and a number of 3.5 pathological compression manoeuvres. Proximal or distal location of DVT did not affect thrombus detection. Conclusion: If centrally adjudicated ultrasound is to be used in future VTE screening trials, training of local sonographers and central adjudicators needs to be intensified, because asymptomatic DVTs seem to be small and ultrasound sensitivity depends on the number of pathological compression manoeuvres documented in the ultrasound document. In contrast, distal or proximal thrombus location itself does not influence sensitivity.

Efficacy and safety of venous thromboembolism prophylaxis with apixaban in major orthopedic surgery

Over the last 15 years, low-molecular-weight heparins (LMWHs) have been accepted as the “gold standard” for pharmaceutical thromboprophylaxis in patients at high risk of venous thromboembolism (VTE) in most countries around the world. Patients undergoing major orthopedic surgery (MOS) represent a population with high risk of VTE, which may remain asymptomatic or become symptomatic as deep vein thrombosis or pulmonary embolism. Numerous trials have investigated LMWH thromboprophylaxis in this population and demonstrated high efficacy and safety of these substances. However, LMWHs have a number of disadvantages, which limit the acceptance of patients and physicians, especially in prolonged prophylaxis up to 35 days after MOS. Consequently, new oral anticoagulants (NOACs) were developed that are of synthetic origin and act as direct and very specific inhibitors of different factors in the coagulation cascade. The most developed NOACs are dabigatran, rivaroxaban, and apixaban, all of which are approved for thromboprophylaxis in MOS in a number of countries around the world. This review is focused on the pharmacological characteristics of apixaban in comparison with other NOACs, on the impact of NOAC on VTE prophylaxis in daily care, and on the management of specific situations such as bleeding complications during NOAC therapy.

Cancer in males and risk of venous thromboembolism

Venous thromboembolism (VTE) is a common complication associated with increased mortality in cancer patients. Adequate treatment of thrombotic complications increases survival in these patients although additional complications such as thrombus progression with pulmonary embolism and bleeding events are common. The incidence of types of cancer as well as malignancy-associated VTE varies between genders. This article focuses on cancers more common in male patients and reviews the risk of VTE with special regard to types of cancer and anticancer therapy.

Heparin-induced thrombocytopenia II-induced critical limb ischaemia treated with urokinase and argatroban

Heparin-induced thrombocytopenia II-induced critical limb ischaemia treated with urokinase and argatroban -

Diagnostic of venous thromboembolism - Is the gold standard 'venogaphy' outdated in the nearer future?

Diagnostic strategies to diagnose deep vein thrombosis (DVT) and pulmonary embolism (PE) have changed significantly over the last 15 years. Whereas venography still is the gold standard for detecting DVT, the introduction of DVT-scores, d-dimer-testing and venous ultrasound made it replaceable in most cases for detecting venous thromboembolisms. The same is true for the diagnostic approach to pulmonary embolism: the combination of d-dimer-testing and venous ultrasound followed by szintigraphic or computertomographic lung scan almost replaced pulmonal angiography. This review focuses on different diagnostic strategies for clinicians in hospitals using practical approaches. Combination of these procedures in a graduated scheme - as postulated in guidelines - enables clinicians to diagnose deep vein thrombosis and pulmonary embolism fast and on a firm basis. Therefore the use of venography is not mandatory in most cases.