Diagnostic test accuracy of D-dimer with or without a clinical decision rule in peripartum patients with suspected venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Pregnancy and the peripartum period is a hypercoagulable state increasing the risk of venous thromboembolism (VTE). There may be a role in utilising D-dimer in the peripartum setting. AIMS: The purpose of this review was to summarise the latest evidence regarding the diagnostic accuracy of D-dimer in the peripartum setting with or without the addition of clinical decision rules. METHODS: We searched PubMed and CENTRAL databases to identify articles that included studies of women who had suspected VTE, underwent a D-dimer index test to rule out VTE and where radiological imaging or clinical follow-up, to a minimum of 30 days, was used as the reference standard. RESULTS: We included 11 studies in the systematic review and meta-analysis. The log diagnostic odds ratio (DOR) for identifying VTE using D-dimer was 1.56 (95% confidence interval (CI) 0.59-2.52). The pooled sensitivity was 87% (95% CI 76.8-93%), specificity was 63.2% (95% CI 47.1-76.7%), and the area under receiver operator characteristic (ROC) curves was 0.76. We included four studies evaluating D-dimer combined with YEARS to detect VTE. The log DOR for identifying VTE using D-dimer combined with YEARS was 1.13 (95% CI 0.005-2.25). The pooled sensitivity was 89.8% (95% CI 60.2-98.1%), specificity was 65.7% (95% CI 54.7-75.2%) and the area under ROC for studies included with the YEARS clinical decision rule was 0.49. CONCLUSION: This review highlighted that D-dimer use in the peripartum period for detection of VTE had a high sensitivity and high DOR but a poor area under ROC, which may limit its use in clinical practice.

Regulation of the neuron-specific Ras GTPase-activating protein, synGAP, by Ca2+/calmodulin-dependent protein kinase II.

synGAP is a neuron-specific Ras GTPase-activating protein found in high concentration in the postsynaptic density fraction from mammalian forebrain. Proteins in the postsynaptic density, including synGAP, are part of a signaling complex attached to the cytoplasmic tail of the N-methyl-d-aspartate-type glutamate receptor. synGAP can be phosphorylated by a second prominent component of the complex, Ca(2+)/calmodulin-dependent protein kinase II. Here we show that phosphorylation of synGAP by Ca(2+)/calmodulin-dependent protein kinase II increases its Ras GTPase-activating activity by 70-95%. We identify four major sites of phosphorylation, serines 1123, 1058, 750/751/756, and 764/765. These sites together with other minor phosphorylation sites in the carboxyl tail of synGAP control stimulation of GTPase-activating activity. When three of these sites and four other serines in the carboxyl tail are mutated, stimulation of GAP activity after phosphorylation is reduced to 21 +/- 5% compared with 70-95% for the wild type protein. We used phosphosite-specific antibodies to show that, as predicted, phosphorylation of serines 765 and 1123 is increased in cultured cortical neurons after exposure of the neurons to the agonist N-methyl-d-aspartate.