Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and ...catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.
Thrombosis is the most frequent cause of mortality worldwide and is closely linked to haemostasis, which is the biological mechanism that stops bleeding after the injury of blood vessels. Indeed, ...both processes share the core pathways of blood coagulation and platelet activation. Here, we summarize recent work suggesting that thrombosis under certain circumstances has a major physiological role in immune defence, and we introduce the term immunothrombosis to describe this process. Immunothrombosis designates an innate immune response induced by the formation of thrombi inside blood vessels, in particular in microvessels. Immunothrombosis is supported by immune cells and by specific thrombosis-related molecules and generates an intravascular scaffold that facilitates the recognition, containment and destruction of pathogens, thereby protecting host integrity without inducing major collateral damage to the host. However, if uncontrolled, immunothrombosis is a major biological process fostering the pathologies associated with thrombosis.
Numerous causes have been provided for the development of Cerebral Sinovenous Thrombosis (CSVT), which can be broadly divided into two categories-infectious, and non-infectious. Formation of thrombi ...in venous channels draining the brain is a consequence of the characteristic risk factors under the heading of Virchow's triad, which includes local trauma to vessel wall, stasis and a hypercoagulable state, the latter being the most important factor in development of CSVT. The diagnosis of CSVT is based on the presence of risk factors for venous thrombosis, to exclude a diagnosis using D-dimer, and brain imaging using MRI / MRV as gold standard. Myxoma in the heart causes the triad complications, which are the blockage associated with the size and location of the tumor, stasis, pulmonary and systemic embolism as well as the constitutional symptoms due to the release of pro-inflammatory cytokines due to hypercoagulability.
Occlusion of blood vessels with pathological thrombi can have disastrous consequences due to obstruction of blood supply to vital organs. Fibrinolytic therapy warrants systemic administration of ...thrombolytics like streptokinase, which is associated with serious bleeding complications. In this study we have provided proof-of-concept of photothermal ablation of thrombus. Thrombi were generated in vitro from purified fibrinogen, or in vivo in murine blood vessels. Gold nanorods were added on fibrin-rich clots in vitro, followed by irradiation with a 808 nm near-infrared laser source at power density 1-05 W/cm.sup.2. Local rise in temperature was monitored with an infrared thermal camera. Extent of thrombolysis under arterial shear was higher than that at venous shear. Superficial femoral veins were exposed in mice and thrombus formation was induced by topical application of FeCl.sub.3. Anti-fibrin antibody-conjugated gold nanorods, which target towards fibrin-rich thrombi, were injected in mice. NIR-laser irradiation of exposed femoral veins containing thrombi led to clot degradation and the re-establishment of vascular patency, which was demonstrated by the restored blood flow recorded in Doppler spectral scans, as well as histopathological investigations. Remarkably, streptokinase has multimodal additive effect in accelerating photothermal lysis of thrombi even at a dose significantly lower than therapeutic concentration, thus minimizing life-threatening side effects and adverse complications. In conclusion, this is the first report on application of photothermal therapy as an anti-thrombotic measure.
The Earth turns on its axis every 24 h; almost all life on the planet has a mechanism - circadian rhythmicity - to anticipate the daily changes caused by this rotation. The molecular clocks that ...control circadian rhythms are being revealed as important regulators of physiology and disease. In humans, circadian rhythms have been studied extensively in the cardiovascular system. Many cardiovascular functions, such as endothelial function, thrombus formation, blood pressure and heart rate, are now known to be regulated by the circadian clock. Additionally, the onset of acute myocardial infarction, stroke, arrhythmias and other adverse cardiovascular events show circadian rhythmicity. In this Review, we summarize the role of the circadian clock in all major cardiovascular cell types and organs. Second, we discuss the role of circadian rhythms in cardiovascular physiology and disease. Finally, we postulate how circadian rhythms can serve as a therapeutic target by exploiting or altering molecular time to improve existing therapies and develop novel ones.
Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus ...characteristics with recanalization over time is important for stroke triage and future trial design.
To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase.
Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA).
Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA.
Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 primary occlusive lesion remains the same to 3 complete revascularization of primary occlusion).
Among 575 patients (median age, 72 years IQR, 63-80; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes IQR, 74-180), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% 95% CI, 10.2%-25.8%). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time 95% CI, 1.18-1.38), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 46.4%) vs internal carotid artery (10/92 10.9%) (OR, 5.61 95% CI, 2.38-13.26), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 66.7%) vs none (91/377 24.1%) (OR, 7.03 95% CI, 3.32-14.87).
In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular ...pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.
Cardiovascular diseases represent the main cause of death. A common feature of cardiovascular disease is thrombosis resulting from intravascular accumulation of fibrin. In the last years, several ...fibrinolytic enzymes have been discovered in many medicinal or edible mushrooms as potential new antithrombotic agents. This study aimed to compare the fibrin(ogen)olytic activity of crude extracts from the fruiting bodies of four cultivated edible mushrooms: Lentinula edodes, Pleurotus ostreatus, Pleurotus eryngii, and Agrocybe aegerita. Fibrin(ogen)olytic activity was assessed by fibrin plate, spectrophotometric assay and electrophoretic analysis (SDS-PAGE and zymography). The highest activity was detected for P. ostreatus followed by P. eryngii, L. edodes and A. aegerita. Results indicated that enzymes exhibited maximum activity at pH 6-7 and 30-40 °C, respectively. Enzyme activity was inhibited by serine and metalloprotease inhibitors. We proposed a new index called the Specific Fibrin(ogen)olytic Index (SFI), which allows specification of the proportion of the total proteolytic capacity due to the fibrin(ogen)olytic activity. These data suggest that the extracts from fruiting bodies or powdered mushrooms can be used as functional ingredients for the development of new functional foods that may act as thrombolytic agents responding, at the same time, to the increasing demand for safe, healthy and sustainable food.
PDF
