Thrombus Recanalization Research Articles

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Woven coronary artery with acquired etiology: the natural history documented by serial angiography and optical coherence tomography

Woven coronary artery (WCA) is a rare anomaly and its etiology remains speculative. Both congenital and acquired factors are considered to be concerned with the pathogenesis. In a 35-year-old man, the tissue characteristics of WCA were evaluated by optical coherence tomography. Serial coronary angiography indicated that acquired factor is the cause, and thrombus recanalization is the most likely pathological mechanism.

Constructing a Transient Ischemia Attack Model Utilizing Flexible Spatial Targeting Photothrombosis with Real-Time Blood Flow Imaging Feedback.

Transient ischemic attack (TIA) is an early warning sign of stroke and death, necessitating suitable animal models due to the associated clinical diagnostic challenges. In this study, we developed a TIA model using flexible spatially targeted photothrombosis combined with real-time blood flow imaging feedback. By modulating the excitation light using wavefront technology, we precisely created a square light spot (50 × 250 µm), targeted at the distal middle cerebral artery (dMCA). The use of laser speckle contrast imaging (LSCI) provided real-time feedback on the ischemia, while the excitation light was ceased upon reaching complete occlusion. Our results demonstrated that the photothrombus formed in the dMCA and spontaneously recanalized within 10 min (416.8 ± 96.4 s), with no sensorimotor deficits or infarction 24 h post-TIA. During the acute phase, ischemic spreading depression occurred in the ipsilateral dorsal cortex, leading to more severe ischemia and collateral circulation establishment synchronized with the onset of dMCA narrowing. Post-reperfusion, the thrombi were primarily in the sensorimotor and visual cortex, disappearing within 24 h. The blood flow changes in the dMCA were more indicative of cortical ischemic conditions than diameter changes. Our method successfully establishes a photochemical TIA model based on the dMCA, allowing for the dynamic observation and control of thrombus formation and recanalization and enabling real-time monitoring of the impacts on cerebral blood flow during the acute phase of TIA.

Recanalization of port-superior mesenteric vein thrombosis with long-term anticoagulant therapy after failed early anticoagulant therapy

BackgroundAnticoagulant therapy with heparin is the first-line treatment for acute mesenteric vein thrombosis and is effective in improving outcomes. Conversely, patients with failed early anticoagulant therapy occasionally develop bowel infarction requiring surgery. The efficacy of long-term anticoagulant therapy on recanalizing mesenteric vein thrombosis in patients with failed early anticoagulant therapy remains unclear. Herein, we report a patient who achieved recanalization of port-superior mesenteric vein thrombosis treated with anticoagulant therapy for 10 years after failed early anticoagulant therapy, followed by bowel resection.Case presentationA 38-year-old male patient visited an outpatient clinic due to acute exacerbation of abdominal pain that had persisted for a month. He was diagnosed with port-superior mesenteric vein thrombosis on contrast-enhanced computed tomography (CT) scan and was transferred to our institution. Although he presented with abdominal pain, his respiration and circulation were stable upon hospital arrival. Anticoagulant therapy with heparin was started, and the patient was admitted to the intensive care unit. However, the patient’s abdominal pain worsened, and he began to develop signs of peritonitis. Repeat CT scan revealed bowel infarction. Thus, the patient underwent bowel resection 6 h after admission. The initial surgery was completed with open abdomen management. Bowel anastomosis was performed on the second-look surgery on the first postoperative day. Finally, the abdomen was closed on the third postoperative day after confirming the absence of bowel ischemia progression. The patient had prolonged impaired bowel function with paralytic ileus, but was discharged on the 60th postoperative day. He was then diagnosed with protein C and S deficiency based on the tests performed. Anticoagulant therapy with warfarin was initiated. He also received anticoagulant therapy in the outpatient setting. The patient’s port-superior mesenteric vein thrombosis had improved gradually with warfarin during the follow-up period. At 10 years after surgery, total occlusion of the port-superior mesenteric vein was recanalized with improvement of the portal collateral vessels. In addition, no gastric or esophageal varices were observed.ConclusionsLong-term anticoagulation therapy could affect the recanalization of extensive thrombus in multiple segments in patients with mesenteric venous thrombosis.

HOXD9 regulated mitophagy to promote endothelial progenitor cells angiogenesis and deep vein thrombosis recanalization and resolution

BackgroundDeep vein thrombosis (DVT) is a common vascular surgical disease caused by the coagulation of blood in the deep veins, and predominantly occur in the lower limbs. Endothelial progenitor cells (EPCs) are multi-functional stem cells, which are precursors of vascular endothelial cells. EPCs have gradually evolved into a promising treatment strategy for promoting deep vein thrombus dissolution and recanalization through the stimulation of various physical and chemical factors.MethodsIn this study, we utilized a mouse DVT model and performed several experiments including qRT-PCR, Western blot, tube formation, wound healing, Transwell assay, immunofluorescence, flow cytometry analysis, and immunoprecipitation to investigate the role of HOXD9 in the function of EPCs cells. The therapeutic effect of EPCs overexpressing HOXD9 on the DVT model and its mechanism were also explored.ResultsOverexpression of HOXD9 significantly enhanced the angiogenesis and migration abilities of EPCs, while inhibiting cell apoptosis. Additionally, results indicated that HOXD9 specifically targeted the HRD1 promoter region and regulated the downstream PINK1-mediated mitophagy. Interestingly, intravenous injection of EPCs overexpressing HOXD9 into mice promoted thrombus dissolution and recanalization, significantly decreasing venous thrombosis.ConclusionsThe findings of this study reveal that HOXD9 plays a pivotal role in stimulating vascular formation in endothelial progenitor cells, indicating its potential as a therapeutic target for DVT management.Graphical

Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma

Purpose or ObjectiveProspective evaluation of stereotactic body radiotherapy (SBRT) with Robotic Radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and MethodsPatients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function (up to Child Pugh B7) were accrued after ethical and scientific committee approval [CTRI: 2022/01/050234] for treatment on Robotic Radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring and gross tumor volume (GTV) included contrast enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22- 50Gy in 5 fractions) while achieving the constraints of mean liver dose <15Gy, 800 cc liver <8Gy and the duodenum max of <24 Gy). Response assessment done at 2 months follow up for recanalization. Patient and treatment related factors evaluated for influence in survival function. ResultsBetween Jan 2017 till May 2022, 317 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score 5-7 90%, mean age 63 years (38-85yrs), CLIP <3: 84 (40%), 3-6 117 (56%), infective etiology 9.5%, Performance status (PS) 0-37%; 1-56%]. Among 209 consecutive patients after accrual SBRT treatment done (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow up). At mean follow up of 10.2 months (SD 8.43), 88 (63%) patients expired and 51 (36%) were alive. 82 (59%) patients had recanalization of PVT (response), 57 (41%) pts did not recanalize, 28 (17%) had progressive disease had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival in responders and non-responders were 18.4 (SE 2.52) and 9.34 month (SE 0.81) respectively (p<0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (p- 0.019) respectively. Overall survival (OS) in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1, 30.3 months respectively (p-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification (BCLC) stage, gender, age, RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (p-0.019). OS in patients with response to treatment, no response to treatment, fit but not accrued and not suitable patients were 18.4, 9.34, 5.9, 2.6 months respectively (p-<0.001). 36/139 patients (24%) had RILD [10 (7.2%) had Classic Radiation induced liver disease (RILD) & 26 (19%) had non-classic RILD]. Derangement in Child Pugh Score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after Robotic Radiosurgery. 18 (13%) had unplanned admissions, two patients required embolization due to fiducial related bleeding, 20 (14%) had ascites of which 9 (6%) patients required abdominocentesis. ConclusionPVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Agonal Thrombus at Necropsy-A Third Category of Blood Coagulation in Domestic Carnivores.

Agonal thrombus is infrequently discussed in veterinary forensic pathology, being misdiagnosed as postmortem coagulation. The main purpose of the present study is to confirm that agonal thrombosis is an important tool in ruling out sudden death and to characterize it by gross, histological, and immunohistochemical approaches. The investigations have been conducted on 56 domestic carnivores. Fibrin was observed as rosette-like arrangements around platelet aggregates, loose network, wave-like pattern or short fibers and the additional tendency of lines of Zahn being noted inconsistently. All agonal thrombi had positive reactions for anti-CD61 for platelets, disposed in variable-sized clumps or in a linear pattern close to endothelial cells of endocardium. The same positive reaction has been noted to anti-fibrinogen and anti-fibrin antibodies. CD45, CD68 and von Willebrand factor had a very low to absent expression. Cardiac lesions were found in 22 cases (39.29%) suggesting predisposition to agonal thrombosis in animals with cardiovascular diseases. The results prove that agonal thrombus is a third category of blood coagulation that forms strictly during agonal death. The microscopical findings describe the agonal thrombus similar to the morphology of recent thrombus vera. Given the results, the agonal thrombus is a useful tool that confirms the agonal suffering prior to death.

Topographic distribution of inflammation factors in a healing aneurysm

BackgroundHealing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing.MethodsDecellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall.ResultsCoiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing.ConclusionThe presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

Review of the Protective Mechanism of Paeonol on Cardiovascular Disease.

Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.

The atherogenic index of plasma complicates the thrombotic tendency of chronic myeloproliferative disorders: A retrospective cohort study

Objectives: Chronic myeloproliferative diseases (CMPD) are neoplastic disorders leading to hypercoagulability and thrombosis. The critical hemostatic abnormalities include alterations in the blood viscosity and a history of recent thrombus. The aim of this study is to assess the interrelationships among the atherogenic index of plasma (AIP) and thromboembolism of CMPD with JAK2 V617F mutation. &#x0D; Methods: Ninety-two patients diagnosed as CMPD with JAK2 V617F mutation and 73 controls were included into the study. The patients were evaluated for the presence of any venous or arterial thromboembolic events. AIP was calculated by using the formula log (Tg/HDL) from serum triglyceride and high-density lipoprotein values.&#x0D; Results: The study group consisted of 30 patients (33%) with myelofibrosis (MF), 42 patients (46%) with polycythemia vera (PV) and 20 patients (21%) with essential thrombocythemia (ET). Two study groups were similar in terms of sex, age and other comorbidities (p &gt; 0.05). CMPD group had higher levels of right blood cell count (RBC), red blood cell distribution width (RDW), platelets (PLT), hemotocrit (Hct) and AIP. Univariate and multivariate logistic regression analysis revealed that platelet count, RBC and AIP were independent predictors for thrombosis in both groups. The comparison of ROC curve analysis disclosed that AIP was superior to platelet count and RBC in predicting thrombosis.&#x0D; Conclusion: AIP can be used to determinate higher risk of thromboembolism in patients with CMPD. As a reliable and ‘easy-to-assess’ diagnostic tool, AIP could be useful for the determination of thrombotic events in CMPD clinicobiological disease course.

Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6−/− mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6−/− mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6−/− mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6−/− mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6−/− mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6−/− mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6−/− mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

Resistance exercise promotes the resolution and recanalization of deep venous thrombosis in a mouse model via SIRT1 upregulation

BackgroundEarly exercise for acute deep venous thrombosis (DVT) improves the patient’s symptoms and does not increase the risk of pulmonary embolism. However, information about its effect on thrombus resolution is limited. The aim of this study was to investigate the role of resistance exercise (RE) in thrombus resolution and recanalization and determine its underlying mechanisms. MethodsNinety-six C57BL/6 J mice were randomly divided into four groups: Control group (C, n = 24); DVT group (D, n = 24); RE + DVT group (ED, n = 24); and inhibitor + RE + DVT group (IED, n = 24). A DVT model was induced by stenosis of the inferior vena cava (IVC). After undergoing IVC ultrasound within 24 h post-operation to confirm DVT formation, mice without thrombosis were excluded. Other mice were sacrificed and specimens were obtained 14 or 28 days after operation. Thrombus-containing IVC was weighed, and the thrombus area and recanalization rate were calculated using HE staining. Masson’s trichrome staining was used to analyze the collagen content. RT-PCR and ELISA were performed to examine IL-6, TNF-α, IL-10, and VEGF expression levels. SIRT1 expression was assessed using immunohistochemistry staining and RT-PCR. VEGF-A protein expression and CD-31-positive microvascular density (MVD) in the thrombus were observed using immunohistochemistry. ResultsRE did not increase the incidence of pulmonary embolism. It reduced the weight and size of the thrombus and the collagen content. Conversely, it increased the recanalization rate. It also decreased the levels of the pro-inflammatory factors IL-6 and TNF-α and increased the expression levels of the anti-inflammatory factor IL-10. RE enhanced VEGF and SIRT1 expression levels and increased the MVD in the thrombosis area. After EX527 (SIRT1 inhibitor) was applied, the positive effects of exercise were suppressed.ConclusionsRE can inhibit inflammatory responses, reduce collagen deposition, and increase angiogenesis in DVT mice, thereby promoting thrombus resolution and recanalization. Its underlying mechanism may be associated with the upregulation of SIRT1 expression.

Abstract 12777: The Lingering Snag in Era of Mechanical Pumps: A Case of Acute Pump Thrombosis Immediately After Heartmate 3 Implantation

Background: Pump thrombosis (PT) remains a dreaded complication of left ventricle assist device (LVAD) implantation. PT immediately after HeartMate 3 (HM3) implantation is rare but should be kelp in mind if early low flow alarms are noted. Case: A 57-year-old male with ischemic cardiomyopathy, Stage D heart failure (LVEF ~20%), INTERMACS category 3 on 5mcg/kg/min Dobutamine drip underwent advanced heart failure therapy evaluation and was deemed suitable candidate for LVAD implant. His ECHO showed LVIDD 6.04 cm and LV Diastolic Volume Index 122 mL. He underwent HM3 implantation via left anterior thoracotomy and upper-hemi sternotomy on 5/24/2022. Surgery was successful and the patient was taken off bypass. Pre-implant some LV trabeculations and debris were removed. However, less than 1 hour from being off bypass, the low flow alarms began which did not resolve after volume and blood pressure optimization. No RV failure was noted on TEE. Decision was made to re-open the sternum. Upon exploration, no compression of the outflow graft was noted, and inlet cannula was not mispositioned. Inspection of LVAD inlet and outlet cannula showed significant amount of white thrombus (Figure 1) and device was ultimately exchanged. Thrombus was confirmed on histopathological analysis. Post-operatively no low flow alarms were noted after pump exchange. Factor V Leiden screen and protein C activity were normal and Antithrombin 3 was falsely low (due to recent thrombus) on post-op day 1. Discussion: This is the second case of HM 3 device thrombosis within 1 hour of implant in the literature. Most of the earlier reported cases were on post-Op Day 3. The etiology of PT is unknown and further investigation is required to elucidate the same. This case will create awareness among physicians to keep PT in differentials when low flow alarms are encountered immediately post-op despite volume and BP optimization.

Effect of Solitaire FR Stent Thrombectomy Combined with the Suction Thrombus on the Clinical Effect and Prognosis of Acute Middle Cerebral Artery Occlusion.

To determine the curative effect and prognosis of Solitaire FR stent thrombectomy integrated with the suction thrombus on the treatment of acute middle cerebral artery occlusion (AMCAO). Based on the treatment, patients suffering from AMCAO were separated into the Solitaire FR group (Solitaire FR stent + suction thrombus) and suction group (suction thrombus). Modified thrombolysis in cerebral infarction grading, National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score, and safety performance were compared between the two groups. The operation time in the suction group was obviously shorter than the Solitaire FR group (P < 0.05). Significant differences were observed in the NIHSS scores 1 week and 4 weeks after the operation between the Solitaire FR group and the suction group (P < 0.05). The NIHSS scores 1 week and 4 weeks after operation were significantly lower than those before operation (P < 0.05). NIHSS scores 1 week after operation did not show obvious difference (P > 0.05). The Solitaire FR group showed obvious lower NIHSS scores than the suction group 4 weeks after surgery (P < 0.05). Statistically obvious difference in cerebral infarction grading of modified thrombolysis between the Solitaire FR group and the suction group were observed (P < 0.05). The recanalization rate of the Solitaire FR group was obviously higher than the suction group (P < 0.05). The difference in the monthly modified Rankin Scale score was obvious (P < 0.05). The good prognosis rate of the Solitaire FR group was obviously higher than the suction group (P < 0.05). No obvious differences in the incidence of internal bleeding, reocclusion, and 3-month postoperative mortality were observed (P > 0.05). These results showed that the treatment of the Solitaire FR stent + suction thrombus in AMCAO patients has a good thrombus recanalization rate and is helpful in improving the prognosis and safety performance.

Direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension and the presence of recent thrombus during pulmonary endarterectomy.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulant therapy. The safety and efficacy of direct oral anticoagulant (DOAC) in the chronic and transitional management of CTEPH has not been investigated. We performed a retrospective analysis of 405 consecutive pulmonary endarterectomy (PEA) cases at the University of California, San Diego, from July 2015 through July 2017. PEA specimen was reviewed for the presence of acute or subacute thrombotic material distinct from the expected chronic disease removed at the time of PEA by two investigators blinded to the patient information. Of 405 PEA cases, 166 patients (41.0%) were anticoagulated with one of three available DOACs; 239 (59.0%) presented on either oral vitamin‐K antagonist or chronic injectable therapy. There were no significant differences in baseline characteristics between DOAC and non‐DOAC groups. Evidence of recent thrombus was observed in 22 (13.3%) in the DOAC group versus 16 (6.7%) within the non‐DOAC group. The odds ratio of DOACs usage and evidence of recent thrombus was 2.34 (95% confidence interval: 1.1–5.0, p = 0.03) after adjusting for age, gender, race, body mass index, and history of antiphospholipid antibody syndrome. CTEPH patients referred for PEA while on DOAC therapy were twice as likely to have associated acute or subacute thrombi present at the time of surgery compared with those on more traditional, non‐DOAC anticoagulant therapies. This raises questions of the safety and efficacy of DOACs in the chronic management of CTEPH.

Portal vein thrombosis and pylephlebitis following laparoscopic appendectomy in a patient with esophageal varices

Pylephlebitis is defined as infectious suppurative thrombosis of the portal vein. The etiologies of pylephlebitis are variable, however, nearly all cases represent a rare albeit serious complication of an intraabdominal infectious process due to the regional portal venous system drainage. Appendicitis is a well-documented cause of pylephlebitis. A 1995 review of 19 cases of reported pylephlebitis demonstrated appendicitis as the second most common pre-disposing etiology in the development of pylephlebitis, with Bacteroides and E. coli being the most commonly cultured organisms. The utility of therapeutic anticoagulation following diagnosis is presently undetermined. We describe a case of pylephlebitis presenting 5 days status post laparoscopic appendectomy for uncomplicated acute appendicitis in a 62-year-old adult male with a history of cirrhosis and esophageal varices. Considering the patient’s history of cirrhosis and resultant esophageal varices, this uncertainty regarding the use of anticoagulation was particularly problematic. Given the lack evidence-based guidelines, a multidisciplinary approach weighing the risks and benefits of systemic anticoagulation was employed. Ultimately, the decision was made to proceed with therapeutic anticoagulation under close supervision with serial imaging to identify thrombus propagation and/or recanalization. While the patient did not demonstrate evidence of recanalization after 58 days of therapy, the throm-bus did indeed fail to propagate further. Clarification regarding the utility of anticoagulation in the setting of pylephlebitis in conjunction with risk stratification based on individual patient factors is certainly warranted to optimize future clinical outcomes.

New surgical model to induce irreversible liver fibrosis by surgical closure of major duodenal orifice in dogs

This study was conducted to induce and evaluate irreversible hepatic fibrosis in dogs by surgical closure of the major duodenal orifice. The study was performed on six healthy local adult dogs. Irreversible hepatic fibrosis was surgically induced in all animals by surgical closure of major duodenal papilla using non-absorbable suture material for 60 days. Induced hepatic fibrosis was evaluated by clinical, ultrasonographical examination, laboratory and histopathological methods. The clinical manifestation of the jaundiced dogs showed reduced food intake, pale-yellowish mucus membrane, inflammatory signs of wound site and severe post-operative pain. Biochemically, there was significant increased values of the aspartate aminotransferase , alkaline phosphatase , alanine aminotransferase , indirect bilirubin, direct bilirubin and total bilirubin especially during first two days after surgery followed by a gradual decrease of these values until the end of the but still higher than normal values. Ultrasonographic examinations showed abnormal change in the liver tissue such as increase in both size and wall thickness of the gall bladder and mottled heterogeneous appearance of the liver during the first two weeks following the surgical induction of the hepatic fibrosis and lasted until the end of the study. Histopathological evaluation of liver samples revealed necrosis of hepatocytes and deposition of eosinophilic material, infiltration of inflammatory cells, recent thrombus in the hepatic vein, fatty change. In conclusion, surgical induction of irreversible hepatic fibrosis in dogs was feasible technique by surgical closure of major duodenal papilla and the results were confirmed by the clinical, ultrasonographical, laboratory and histopathological examination.

Comparative Therapeutic Effectiveness of Anticoagulation and Conservative Management in Traumatic Cerebral Venous Sinus Thrombosis.

Consensus is currently lacking in the optimal treatment for blunt traumatic cerebral venous sinus thrombosis (tCVST). Anticoagulation (AC) is used for treating spontaneous CVST, but its role in tCVST remains unclear. To investigate the characteristics and outcomes of patients treated with AC compared with patients managed conservatively. We retrospectively reviewed patients who presented to a Level 1 trauma center with acute skull fracture after blunt head trauma who underwent dedicated venous imaging. There were 137 of 424 patients (32.3%) presenting with skull fractures with tCVST on venous imaging. Among them, 82 (60%) were treated with AC while 55 (40%) were managed conservatively. Analysis of baseline characteristics demonstrated no significant difference in age, sex, admission Glasgow Coma Scale, admission Injury Severity Score, rates of associated intracranial hemorrhage, or neurosurgical interventions. New or worsening intracranial hemorrhage was seen in 7 patients treated with AC. Patients on AC had significantly lower mortality than non-AC (1% vs 15%; P = .003). There was no difference in the Glasgow Coma Scale or Glasgow Outcome Scale at last clinical follow-up. On follow-up venous imaging, patients treated with AC were more likely to experience full thrombus recanalization than non-AC (54% vs 32%; P = .012), and subsequent multiple regression analysis revealed that treatment with AC was a significant predictor of full thrombus recanalization (odds ratio, 5.18; CI, 1.60-16.81; P = .006). Treatment with AC for tCVST due to blunt head trauma may promote higher rates of complete thrombus recanalization when compared with conservative management.

Circulating Endothelial Cell Levels Correlate with Treatment Outcomes of Splanchnic Vein Thrombosis in Patients with Chronic Myeloproliferative Neoplasms.

Circulating endothelial cells (CECs) are viable, apoptotic or necrotic cells, identified by CD 146 surface antigen expression, considered a biomarker of thrombotic risk, given their active role in inflammatory, procoagulant and immune processes of the vascular compartment. Growing evidence establishes that CECs are also involved in the pathogenesis of several hematological and solid malignancies. The primary aim of this study was to verify if CEC levels could predict both the course and treatment responses of splanchnic vein thrombosis (SVT), either in patients affected by myeloproliferative neoplasms (MPNs) or liver disease. Thus, a retrospective multicenter study was performed; fifteen patients receiving anticoagulant oral treatment with vitamin k antagonists (VKA) for SVT were evaluated. Nine patients were affected by MPN, and all of them received cytoreduction in addition to anticoagulant therapy; four of these patients had primary myelofibrosis (PMF) and were treated with ruxolitinib (RUX), and one patient with primary myelofibrosis, two patients with essential thrombocythemia (ET), and two patients with polycythemia vera (PV) were treated with hydroxyurea (HU). Six patients affected by liver diseases (three with liver cirrhosis and three with hepatocellular carcinoma) were included as the control group. CECs were assayed by flow cytometry on peripheral blood at specific time points, for up to six months after enrollment. The CEC levels were related to C-reactive protein (CRP) levels, splenic volume reduction, and thrombus recanalization, mainly in MPN patients. In patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), for which the mechanism of SVT development is quite different, the relationship between CEC and SV reduction was absent. In conclusion, the CEC levels showed a significant correlation with the extent of venous thrombosis and endothelial cell damage in myeloproliferative neoplasm patients with splanchnic vein thrombosis. Although preliminary, these results show how monitoring CEC levels during cytoreductive and anticoagulant treatments may be useful to improve SVT outcome in MPN patients.