Inconsistencies in the planning of the duration of anticoagulation among outpatients with acute deep-vein thrombosis. Results from the OTIS-DVT Registry

Three-month anticoagulation is recommended to treat provoked or first distal deep-vein thrombosis (DVT), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) Registry of 502 patients with acute objectively confirmed lower extremity DVT (59% provoked or first distal DVT; 41% unprovoked proximal, unprovoked recurrent, or cancer-associated DVT) from 53 private practices and 11 hospitals, we investigated the planned duration of anticoagulation at the time of treatment initiation. The decision to administer limited-duration anticoagulation therapy was made in 343 (68%) patients with a median duration of 107 (interquartile range 91-182) days for provoked or first distal DVT, and 182 (interquartile range 111-184) days for unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. Among patients with provoked or first distal DVT, anticoagulation was recommended for < 3 months in 11%, 3 months in 63%, and for an indefinite period in 26%. Among patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT, anticoagulation was recommended for < 6 months in 22%, 6-12 months in 38%, and for an indefinite period in 40%. Overall, there was more frequent planning of indefinite-duration therapy from hospital physicians as compared with private practice physicians (39% vs. 28%; p=0.019). Considerable inconsistency in planning the duration of anticoagulation therapy mandates an improvement in risk stratification of outpatients with acute DVT.

von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models

Deep vein thrombosis (DVT) and its complication, pulmonary embolism, are frequent causes of disability and mortality. Although blood flow disturbance is considered an important triggering factor, the mechanism of DVT initiation remains elusive. Here we show that 48-hour flow restriction in the inferior vena cava (IVC) results in the development of thrombi structurally similar to human deep vein thrombi. von Willebrand factor (VWF)-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the IVC. Mice with half normal VWF levels were also protected in the stenosis model. Besides promoting platelet adhesion, VWF carries Factor VIII. Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF(-/-) mice, indicating that impaired coagulation was not the primary reason for the absence of DVT in VWF(-/-) mice. Infusion of GPG-290, a mutant glycoprotein Ib?-immunoglobulin chimera that specifically inhibits interaction of the VWF A1 domain with platelets, prevented thrombosis in wild-type mice. Intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was dramatically higher in wild-type than in VWF(-/-) IVC. Our results demonstrate a pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis.

Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes

The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A (RPA), an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy.

Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis

The original and modified Wells score are widely used prediction rules for pre-test probability assessment of deep vein thrombosis (DVT). The objective of this study was to compare the predictive performance of both Wells scores in unselected patients with clinical suspicion of DVT.

Outpatient management of acute deep vein thrombosis: Results from the OTIS-DVT registry

We aimed to investigate clinical practice patterns for the outpatient management of acute deep vein thrombosis (DVT).

Accuracy of diagnostic tests for clinically suspected upper extremity deep vein thrombosis: a systematic review

The best available test for the diagnosis of upper extremity deep venous thrombosis (UEDVT) is contrast venography. The aim of this systematic review was to assess whether the diagnostic accuracy of other tests for clinically suspected UEDVT is high enough to justify their use in clinical practise and to evaluate if any test can replace venography.

Deep ocean ventilation, carbon isotopes, marine sedimentation and the deglacial CO2 rise

The link between the atmospheric CO2 level and the ventilation state of the deep ocean is an important building block of the key hypotheses put forth to explain glacial-interglacial CO2 fluctuations. In this study, we systematically examine the sensitivity of atmospheric CO2 and its carbon isotope composition to changes in deep ocean ventilation, the ocean carbon pumps, and sediment formation in a global three-dimensional ocean-sediment carbon cycle model. Our results provide support for the hypothesis that a break up of Southern Ocean stratification and invigorated deep ocean ventilation were the dominant drivers for the early deglacial CO2 rise of ~35 ppm between the Last Glacial Maximum and 14.6 ka BP. Another rise of 10 ppm until the end of the Holocene is attributed to carbonate compensation responding to the early deglacial change in ocean circulation. Our reasoning is based on a multi-proxy analysis which indicates that an acceleration of deep ocean ventilation during the early deglaciation is not only consistent with recorded atmospheric CO2 but also with the reconstructed opal sedimentation peak in the Southern Ocean at around 16 ka BP, the record of atmospheric δ13CCO2, and the reconstructed changes in the Pacific CaCO3 saturation horizon.