TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

Coronary artery disease among asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography

OBJECTIVES: The aim of this study was to determine the prevalence and severity of coronary artery disease (CAD) and the plaque composition in asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography (CCTA). BACKGROUND: CAD is the major cause of death among patients with diabetes. The true prevalence of CAD in asymptomatic diabetic patients, however, remains unknown. MATERIALS AND METHODS: A total of 328 consecutive patients (each with at least one risk factor or abnormal stress-test results) were referred for cardiac evaluation, 42 with diabetes and 286 without diabetes, all asymptomatic for cardiac-related symptoms. Groups were matched for age, sex, and CAD risk factors. CAD was defined as coronary atherosclerosis, with obstructive or nonobstructive lesions. CCTA was performed and findings compared between patients with diabetes and those without. RESULTS: CAD was present in 39 (93%) diabetic patients and in 211 (73%) nondiabetic patients (P=0.006). Obstructive CAD was more common in diabetic patients than in nondiabetic patients (29 vs. 6.6%, respectively; P<0.0001). In diabetic patients, more coronary segments with atherosclerosis per patient were detected (5.5 segments/patient vs. 2.8 segments/patient in nondiabetics; P<0.0001). The total Agatston score was significantly higher in diabetic patients vs. nondiabetic patients (370+/-96 and 79.9+/-16, respectively; P<0.0001). CONCLUSION: Our results indicate a high prevalence (93%) of CAD in asymptomatic diabetic patients with either nonobstructive or obstructive lesions. CCTA may be a useful imaging modality for selecting patients at high risk who would benefit most from further evaluation for subclinical ischemia.     

A Toolbox for Herpesvirus miRNA Research: Construction of a Complete Set of KSHV miRNA Deletion Mutants

Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (ΔmiR-K12-1 through -12), and for mutants deleted for 10 of 12 (ΔmiR-cluster) or all 12 miRNAs (ΔmiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community.     

Pearling in cells: A clue to understanding cell shape

Gradual disruption of the actin cytoskeleton induces a series of structural shape changes in cells leading to a transformation of cylindrical cell extensions into a periodic chain of "pearls." Quantitative measurements of the pearling instability give a square-root behavior for the wavelength as a function of drug concentration. We present a theory that explains these observations in terms of the interplay between rigidity of the submembranous actin shell and tension that is induced by boundary conditions set by adhesion points. The theory allows estimation of the rigidity and thickness of this supporting shell. The same theoretical considerations explain the shape of nonadherent edges in the general case of untreated cells.     

When Sentinel Lymph Node is Intramammary

Introduction Sentinel lymph node biopsy is an accepted standard of care for staging the axilla in patients with early-stage breast cancer. Little attention has been placed to the presence of intramammary sentinel lymph nodes (intraMSLNs) on preoperative lymphoscintigraphy. Methods Between December 2001 and September 2006, in 9632 breast cancer patients with clinically uninvolved axillary nodes, lymphoscintigraphy was performed at the European Institute of Oncology (EIO). An axillary SLN (axSLN) was identified in 99.4% of cases. An intraMSLN was identified in association with the axillary sentinel lymph node in 22 patients (0.2%). In 15 cases both the axSLN and the intraMSLN were excised. Results The intraMSLN was positive in six patients (micrometastatic in three cases). The axSLNs were negative in all 15 cases. Two patients with positive intraMSLNs and one patient with a negative intraMSLN underwent axillary dissection; all three cases had negative axillary nodes. At a median follow-up of 24 months, no locoregional or systemic recurrences were observed. Conclusions Positive intraMSLNs can improve disease staging but do not necessarily portend axillary lymph node metastasis. When intraMSLNs and axSLNs are present, we advocate biopsy of both sites and that management of the axilla should rely on axSLN status. In cases with intraMSLNs as the only draining site on lymphoscintigraphy, decisions on axillary management should be made on individualized basis.     

Thalidomide treatment prevents chronic graft rejection after aortic transplantation in rats – an experimental study

Cardiac allograft vasculopathy (CAV) affects approximately 30% of cardiac transplant patients at 5 years post‐transplantation. To date, there are few CAV treatment or prevention options, none of which are highly effective. The aim of the study was to investigate the effect of thalidomide on the development of CAV. The effect of thalidomide treatment on chronic rejection was assessed in rat orthotopic aortic transplants in allogeneic F344 or syngeneic Lew rats (n = 6 per group). Animals were left untreated or received thalidomide for 30 days post‐transplant, and evidence of graft CAV was determined by histology (trichrome and immunohistochemistry) and intragraft cytokine measurements. Animals that received thalidomide treatment post‐transplant showed markedly reduced luminal obliteration, with concomitant rescue of smooth muscle cells (SMCs) in the aortic media of grafts. Thalidomide counteracted neointimal hyperplasia by preventing dedifferentiation of vascular SMCs. Measurement of intragraft cytokine levels after thalidomide treatment revealed downregulation of matrix metalloproteinase 8 and monocyte chemotactic protein 1, cytokines involved in tissue remodelling and inflammation, respectively. Importantly, no negative side effects of thalidomide were observed. Thalidomide treatment prevents CAV development in a rodent model and is therefore potentially useful in clinical applications to prevent post‐transplant heart rejection.