Three-month cumulative incidence of thromboembolism and bleeding after periprocedural anticoagulation management of arterial vascular bypass patients

The objective of this study was to determine 3-month cumulative incidence of peri-procedural thromboembolism (TE) including graft occlusion, and peri-procedural bleeding for chronically anticoagulated vascular bypass graft (BG) patients requiring temporary warfarin interruption for an invasive procedure. Appropriate peri-procedural management of patients receiving chronic warfarin therapy to preserve lower extremity arterial BG patency is unknown. In a protocol driven, cohort study design, all BG patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation (1997–2007) were followed forward in time to estimate the 3-month cumulative incidence of TE and bleeding. Decisions to provide “bridging” low molecular weight heparin (LMWH) were individualized based on estimated risk of TE and bleeding. There were 78 BG patients (69 ± 10 years; 38 % women), of whom 73 % had a distal autogenous and 53 % had prosthetic BG; 45 % received antiplatelet therapy. Peri-procedural LMWH was prescribed for 77 % of patients and did not vary by BG distal anastomosis location or type. The 3-month cumulative incidence of TE was 5.1 % (95 % CI 1.4–12.6), including two BG occlusions, one DVT, and one myocardial infarction. Major bleeding occurred in 1 patient (1.28 %, 95 % CI 0.0–6.94). One patient died due to heart failure. TE and bleeding did not differ by bridging status. The 3-month cumulative incidence of TE among BG patients in whom warfarin is temporarily interrupted for an invasive procedure may be higher than in other “bridging” populations (atrial fibrillation, prosthetic heart valve, venous thromboembolism). This finding underscores the often tenuous nature of distal bypass grafts necessitating an aggressive approach to peri-procedural anticoagulation management.     

Platelet recruitment to venous stent thrombi

Thrombosis following venous stent placement is a morbid clinical outcome. Whether to target platelets or coagulation factors for venous stent thromboprophylaxis remains unclear. We sought to determine whether integrin α_IIbβ₃ antagonism with lamifiban would inhibit platelet recruitment to venous stent thrombosis. Anti-thrombotic efficacy was compared between venous and arterial circulations. Pigs received either lamifiban (0.2 mg/kg bolus plus 0.2 mg/kg/h infusion; n = 6) or saline (n = 12). Carotid arteries were crush injured and then harvested 30 min later to provide an assessment of antithrombotic efficacy in the arterial circulation. Iliac venous stents were then deployed and thrombi allowed to propagate for 2 h before harvesting. Platelet deposition was measured by scintillation detection of autologous ¹¹¹In-platelets. Venous thrombi were quantified by weight and compared to platelet, Von Willebrand factor (VWF) and fibrinogen content. Arterial platelet deposition (×10⁶/cm²) was reduced >80 % by lamifiban (398 ± 437) compared to controls (1,540 ± 883; p < 0.005). Lamifiban also reduced venous thrombus platelet deposition (139 ± 88 vs. 281 ± 167) however did not prevent thrombosis. In control animals, venous stent platelet deposition correlated with plasma fibrinogen content (R² = 0.29; p = 0.03). Fibrinogen content correlated directly with venous stent platelet deposition (p = 0.03) but not thrombus weight. Neither venous platelet deposition nor thrombus weights varied by VWF content. Platelet recruitment to venous stent thrombi occurs in part through the integrin α_IIbβ₃ receptor. Unlike arterial thrombosis, inhibition of this receptor is insufficient to prevent venous stent thrombosis.     

Thrombophilia differences in splanchnic vein thrombosis and lower extremity deep venous thrombosis in North America

Background

The utility of thrombophilia testing in patients with splanchnic vein thrombosis (SpVT) has not previously been rigorously evaluated. The purpose of this study was to characterize differences in the prevalence of thrombophilia in patients with SpVT involving portal (PVT), mesenteric (MVT), splenic (SVT), or hepatic (HVT) veins in isolation or with multisegmental (M-SpVT) involvement compared to patients with lower extremity deep vein thrombosis (DVT).

Methods

An inception cohort of patients with incident SpVT was identified for whom comprehensive thrombophilia testing was performed between 1995 and 2005 and compared to DVT controls.

Results

341 patients with SpVT (mean age 50 ± 16 years, 53 % women) including isolated PVT (n = 112), MVT (n = 67), HVT (n = 22), SVT (n = 11), and M-SpVT (n = 129) involvement and 3621 DVT controls (mean age 55 ± 16 years, 56 % women) had comprehensive thrombophilia testing. The prevalence of abnormal results was similar for SpVT (24.6 %) and DVT (25.9 %) patients. “Strong” thrombophilias were more prevalent among SpVT patients (12.3 vs. 8.5 %, p = 0.0168). Patients with splenic (45.5 %) and mesenteric (41.8 %) thrombosis had the highest thrombophilia prevalence. Protein S deficiency was more common in SpVT patients (3.5 vs. 0.9 %, p < 0.001). In contrast, FV Leiden was more prevalent among DVT patients (15.8 vs. 10.9 %, p = 0.0497).

Conclusion

The prevalence of selected thrombophilia factors differ comparing SpVT and DVT patients. The prevalence is particularly high for patients with splenic and mesenteric vein thrombosis. Whereby the finding of strong thrombophilia impacts duration of anticoagulant therapy, such testing is warranted in the evaluation of patients with unprovoked SpVT.     

Three-dimensional histological specimen preparation for accurate imaging and spatial reconstruction of the middle and inner ear

Purpose

   This paper presents a highly accurate cross-sectional preparation technique. The research aim was to develop an adequate imaging modality for both soft and bony tissue structures featuring high contrast and high resolution. Therefore, the advancement of an already existing microgrinding procedure was pursued. The central objectives were to preserve spatial relations and to ensure the accurate three-dimensional reconstruction of histological sections.

Methods

   Twelve human temporal bone specimens including middle and inner ear structures were utilized. They were embedded in epoxy resin, then dissected by serial grinding and finally digitalized. The actual abrasion of each grinding slice was measured using a tactile length gauge with an accuracy of one micrometre. The cross-sectional images were aligned with the aid of artificial markers and by applying a feature-based, custom-made auto-registration algorithm. To determine the accuracy of the overall reconstruction procedure, a well-known reference object was used for comparison. To ensure the compatibility of the histological data with conventional clinical image data, the image stacks were finally converted into the DICOM standard.

Results

   The image fusion of data from temporal bone specimens’ and from non-destructive flat-panel-based volume computed tomography confirmed the spatial accuracy achieved by the procedure, as did the evaluation using the reference object.

Conclusion

   This systematic and easy-to-follow preparation technique enables the three-dimensional (3D) histological reconstruction of complex soft and bony tissue structures. It facilitates the creation of detailed and spatially correct 3D anatomical models. Such models are of great benefit for image-based segmentation and planning in the field of computer-assisted surgery as well as in finite element analysis. In the context of human inner ear surgery, three-dimensional histology will improve the experimental evaluation and determination of intra-cochlear trauma after the insertion of an electrode array of a cochlear implant system.     

Clinical Predictors and Hemodynamic Consequences of Elevated Peripheral Chemosensitivity in Optimally Treated Men With Chronic Systolic Heart Failure

AimsAugmented peripheral chemoreflex response is an important mechanism in the pathophysiology of chronic heart failure (CHF). This study characterizes prevalence and clinical predictors of this phenomenon in optimally managed male CHF patients, and seeks to describe the hemodynamic consequences of chemoreceptor hypersensitivity.Methods and ResultsThirty-four optimally managed CHF patients and 16 control subjects were prospectively studied. Hypoxic ventilatory response (HVR)—a measure of peripheral chemosensitivity—was calculated with the use of short nitrogen gas administrations. Systolic blood pressure (SBP) and heart rate (HR) following transient hypoxic challenges were recorded with a Nexfin monitor. Hemodynamic responses to hypoxia were expressed by the linear slopes between oxygen saturation (%) and SBP (mm Hg) or HR (beats/min). Elevated HVR was present in 15 (44%) of the CHF patients. Patients with elevated HVR exhibited higher levels of N-terminal pro–B-type natriuretic peptide, lower left ventricular ejection fraction, and higher prevalence of atrial fibrillation. CHF patients with elevated HVR had significantly greater SBP and HR responses to hypoxia than CHF patients with normal HVR.ConclusionsDespite comprehensive pharmacotherapy, elevated HVR is prevalent in CHF patients, related to severity of the disease and associated with augmented hemodynamic responses to hypoxia. CHF patients with elevated HVR may be prone to unfavorable hemodynamic changes.     

D‐chiro‐inositol as a treatment in plaque psoriasis: A randomized placebo‐controlled clinical trial

Cyclitols are widely available natural sugars which do not exert toxic effects. Their anti‐inflammatory and antioxidant properties may be used in the treatment of psoriasis. The aim of this placebo‐controlled, double‐blind study was to evaluate the clinical effects of D‐chiro‐inositol (DCI) in mild plaque psoriasis (46 psoriatic patients and 10 healthy volunteers). Three stable psoriatic plaques were selected for evaluation in every patient. Different samples were applied on each lesion twice a day: vehiculum without an active agent, containing 1% DCI and 0.25% DCI. The lesions were assessed using the PSI, VAS scale, and the objective measurement of hydration, transepidermal water loss (TEWL), elasticity, and thickness (DermaLab Combo) at 0, 3, and 6 weeks. PSI and VAS were improved in all groups without significant statistical differences. 1% DCI sample presented the highest statistically significant increase in the hydration of 50%, but it was still significantly lower than in healthy controls. TEWL increased for 1% DCI, which was a statistically significant difference compared to 0.25% DCI and still higher than in controls. An improvement in elasticity was observed in all lesions—it was statistically significant for 1% DCI. The thickness of the lesion decreased for 1% DCI, but the change was not statistically significant. Subepidermal low‐echogenic band showed a decreasing tendency in all groups, but it was not statistically significant. Favorable 1% DCI sample results indicate that it may be used as an adjuvant to the local treatment of psoriasis.