Subsequent Thrombosis Research Articles

Treatment and Outcomes in Heparin-Induced Thrombocytopenia (HIT) in Patients with Neoplasm: A Single Centre Experience

Background: Heparin-induced thrombocytopenia (HIT) is an immune mediated, pro-thrombotic disorder associated with exposure to heparin and a substantial number of patients develop thrombosis (HITT) in the venous, arterial, or microvascular system. Treatment includes cessation of heparin and starting a non-heparin anticoagulant. Patients with cancer are already at high risk of venous thromboembolism (VTE) as well as recurrent VTE despite anticoagulant therapy and are also at higher risk of bleeding compared with patients without cancer. Consequently, cancer patients may not share similar outcomes as patients without cancer in the setting of HIT. We conducted a single-centre, retrospective study to evaluate baseline characteristics, treatments and outcomes in HIT patients with and without cancer. Methods: Medical records of all patients seen at our tertiary centre between November 1, 2006 and December 31, 2016 who tested positive for HIT antibodies and had a 4T score of 4 or higher were reviewed. Patients with cancer were defined as those who had any evidence of cancer, including myeloproliferative neoplasm (MPN), and/or receiving cancer treatment within 6 months prior to HIT diagnosis. Details of treatments and outcomes were captured up to 6 months after start of HIT treatment. Comparative statistics was performed between the cancer and non-cancer cohorts. Results: We identified 95 patients with confirmed HIT, of whom 39 (41%) had cancer and 41 (43%) had HITT as the index event. The mean age was 65 years (standard deviation 16) and 59% were female. Thirty (77%) cancer patients had at least 3 months of available records and 26 (67%) had at least 6 months, while 37 (66%) non-cancer patients had at least 3 months of available records and 27 (48%) had at least 6 months. Baseline demographics including cancer types are summarized in Table 1. The most common malignancy was polycythemia vera (PV), with those with MPN (7 PV, 2 essential thrombocythemia) representing 23% of the patients with cancer. Cancer patients were more likely to have a history of thromboembolic events prior to index heparin exposure and HIT diagnosis (79.5% vs. 53.6%, p=0.02) than those without cancer. Among patients with HITT, the two groups had similar incidences of pulmonary embolism and/or deep vein thrombosis, although a higher proportion of the non-cancer group had clots in other non-classic locations (32.1% vs. 10.3%, p=0.01) such as splanchnic thrombosis. A variety of non-heparin agents were used, including direct oral anticoagulants (Table 2), with most patients receiving either fondaparinux or argatroban followed by warfarin. The cancer group received fondaparinux more often than the non-cancer group (87.2% vs. 64.3%, p=0.02). In those alive with at least 6 months of follow-up, the median duration of non-heparin anticoagulation was 180 days for both cancer patients and non-cancer patients. During follow-up, 16 (17%) patients had a thrombotic event, 15 (16%) had major bleeding and 11 (12%) died among the 95 patients with HIT. The rates of subsequent thrombosis, bleeding events, and death were similar between the two cohorts over the 6-month follow-up period (Table 3). None of the deaths were from thrombotic or bleeding events but the cause of death for one patient with cancer was unknown. Conclusion: Patient outcomes following a diagnosis of HIT appear similar between patients with and without cancer, with high rates of subsequent thrombosis and major bleeding. Patients with MPN might have a higher risk of HIT. Further studies are warranted to confirm these findings and determine if direct oral anticoagulants might be efficacious and safe in patients with HIT. Disclosures Lee: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. OffLabel Disclosure: Direct oral anticoagulants and fondaparinux were used as non-heparin anticoagulants for the treatment of heparin induced thrombocytopenia.

Dual energy CT in the management of antiplatelet therapy in patients with acute ischemic stroke for carotid obstruction.

Acute tandem occlusions often require carotid stenting. Combination of mechanical and pharmacologic therapies in addition to antiplatelet drugs administered to prevent acute stent thrombosis might increase the risk of intracerebral hemorrhage. We present a protocol of antiplatelet regimen based on early post-procedural dual-energy CT (DE-CT). Fifty consecutive stroke patients with tandem occlusions treated with acute carotid stenting after intracranial thrombectomy and TICI 2b/3 were reviewed. All patients received intravenous lysine acetylsalicylate during the procedure. Dual (aspirin+clopidogrel with or without clopidogrel load, groups A and B, respectively) or mono (aspirin) antiplatelet regimen (group C) was administered 12-24 h later according to brain DE-CT findings. Carotid ultrasonography was performed at 24 h and before discharge. We evaluated the rate of subsequent symptomatic intracranial hemorrhage (SICH) and acute stent thrombosis in each group. Between June 2014 and December 2016, 50 patients were included (mean age 66 years, 76% men, baseline NIHSS 16, median time from symptom onset to recanalization 266 min). According to DE-CT, 24 patients were assigned to group A, 19 to group B and 7 to group C (4 of them had SICH at that time). One patient suffered a subsequent SICH (belonging to group B). There was only one stent thrombosis without clinical repercussions in group B. DE-CT may contribute to select antiplatelet regimen after acute carotid stenting in tandem occlusions.

1970 Spontaneous Page Kidney as a Cause of Gastric Variceal Bleed

INTRODUCTION: Gastric variceal bleeding occurs in 15–50% of patients with non-cirrhotic portal venous thrombosis but can also occur in cases of splenic vein thrombosis (SVT) due to the formation of isolated gastric varices (IGV). We present the first reported case of a page kidney causing splenic vein compression, thrombosis, and subsequent gastric variceal bleeding. CASE DESCRIPTION/METHODS: A 31-year-old stuntman presented with epigastric pain and worsening exertional dyspnea over 3 weeks. History was notable for melena and anemia with no reported ulcers on endoscopy. On admission, he had hemoglobin of 4.1 g/dl with severe iron deficiency and elevated reticulocyte count. There was no serologic evidence of hepatic or renal disease. A computed tomography (CT scan) of the abdomen revealed a large left-sided perirenal collection consistent with page kidney, splenomegaly and decreased caliber of the mid and distal splenic vein suggestive of nonocclusive SVT. His liver was normal. Initial endoscopy revealed an IGV type 1 and mild portal hypertensive gastropathy (Figure 1). CT angiography did not reveal a splenorenal shunt to pursue a balloon retrograde transvenous obliteration (BRTO). While admitted, he developed hematemesis and worsening anemia. Ultimately, underwent IR splenic vein stenting with a bare-metal stent and subsequent decompression of the gastric varices with brisk flow of the portal vasculature (Figure 2). DISCUSSION: Gastric varices are classified primarily by location with most involving the gastroesophageal junction due to portal hypertension. The incidence of bleeding is highest in IGV, typically associated with SVT. Common etiologies of SVT include pancreatitis, malignancy or trauma. Our case described an extrinsic splenic vein compression and subsequent thrombosis due to a sub-capsular renal hematoma possibly of unclear etiology. Treatment for GV often depends on local expertise, but commonly consists of cyanoacrylate injection, banding (especially in type 1 gastro-esophageal varices), transjugular intrahepatic portosystemic shunt (TIPS) placement, BRTO, and even splenectomy. More recently, in cases of IGV due to isolated SVT, splenic vein stenting has been increasingly utilized. In our case, TIPS would not address the pre-hepatic portal hypertension and cyanoacrylate was not available. Splenic vein stenting was thus chosen to decompress the IGV with excellent response seen on subsequent follow-up (Figure 1).

Ostre zapadnięcie się całkowicie rozprężonego stentu III generacji w trakcie przezskórnej interwencji wieńcowej w obrębie rozwidlenia tętnic

Acute stent recoil or radial collapse of a stent is a rare phenomenon leading to subsequent acute stent thrombosis or in-stent restenosis as delayed sequelae. Reduced strut thickness, a larger stent/vessel ratio, and a larger balloon/stent ratio are factors leading to stent recoil. Here, we report a case of acute recoil or radial collapse of Promus Element Plus, a third-generation everolimus-eluting stent with thin stent struts in a 66 year-old male who underwent bifurcation percutaneous coronary intervention of left anterior descending artery (LAD) and diagonal branch (D1). Following kissing balloon inflation at 16 atm pressure after deployment of stents in LAD and D1, acute radial collapse of stent in proximal LAD was noted. It was successfully bailed out by further multiple, short sequential inflations using same size noncompliant balloon. Acute radial collapse probably occurred due to inflation at higher pressure with an oversized balloon, and relatively thin struts of the stent.

Anticoagulant effect of wogonin against tissue factor expression

Tissue factor (TF) is the primary cause of atherothrombosis, the rupture of atherosclerotic plaques with subsequent thrombosis, leading to acute cardiovascular events, such as myocardial infarction and stroke. Wogonin (Wog) is an active component of Scutellaria baicalensis, used for inflammatory diseases, atherosclerosis, and hyperlipidemia. The anticoagulant effect of Wog on TF expression remains unexplored. In this study, we have investigated the effects of Wog on TF gene expression and its underlying molecular mechanism in human vascular endothelial cells (ECs). We found that Wog dose-dependently inhibited PMA-enhanced TF mRNA, protein, and activity in ECs. This inhibition was attributed to its decreasing nuclear accumulations of transcription factors, phospho-c-Jun and early growth response-1(Egr-1), not nuclear factor-κB (NF-κB), through blocking extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. Reduction by Wog of Egr-1 nuclear level and Egr-1/DNA binding activity was associated with its inhibition of Egr-1 de novo synthesis. Wog as well as inhibitors to ERK and JNK suppressed TF promoter activity and protein expression in reporter gene and Western blot analyses. Furthermore, it also exhibited anticoagulant function by inhibiting TF expression and activity in tumor necrosis factor-alpha (TNF-α)- and lipopolysaccharide (LPS)-treated ECs and THP-1 cells. These results suggest that Wog inhibits ERK/Egr-1- and JNK/AP-1-mediated transactivation of TF promoter activity, leading to downregulation of TF expression and activity induced by inflammatory mediators. Wog targeting pathological TF expression without affecting its basal level may be a safer templet in the development of anticoagulant agent for cardiovascular thrombotic diseases related to atherothrombosis.

Catheter-Related Venous Thrombosis in Pulmonary Arterial Hypertension Patients on Intravenous Prostacyclin Therapy

Rationale: Intravenous prostacyclin (PG) therapies are used for managing severe pulmonary arterial hypertension (PAH). Most PAH patients respond to PG therapies, but some experience complications associated with presence of indwelling catheters. We observed development of venous thromboses in patients and present our experience. Methods: A retrospective chart review of PAH patients on long-term intravenous PG therapy was conducted between 2008 and 2017.Demographic, hemodynamic, six-minute walk distance (6MWD), WHO/NYHA functional class (FC) and outcome data were collected. Results: Six of 63 patients on intravenous PG therapy were identified with venous thromboses. Mean age was 44±15 years (mean ±SD, range 31 to 70 years). All patients were female. Duration of PAH diagnosis 15±7 years; duration of IV PG therapy7.4±3.8 years. One patient had antiphospholipid antibody syndrome; hypercoagulable workup was negative for other five patients. Diagnostic right heart catheterization showed mean pulmonary artery pressure of 53.6±5.4 mmHg and thermodilution cardiac output was 4.94±1.4 l/min. Echocardiogram showed RAP of 8.3±6 mmHg. Development of thrombosis occurred 4±2 years after initiation of therapy. most common site of thrombosis was subclavian vein followed by femoral vein. All patients were on anticoagulation therapy with warfarin or a novel oral anticoagulation agent prior to development of thrombosis. Because of repeated catheter infections and poor vascular access, two of three patients were successfully transitioned to oral therapies without significant change in FC. Conclusion: A small percentage of patients on intravenous PG therapy for PAH develop thrombosis in areas of venous access. There does not appear to be a difference in occurrence of thrombosis in patients who have idiopathic PAH or associated PAH. Anticoagulation did not prevent initial or subsequent thrombosis. Development of recurrent thrombosis limits vascular access available for infusion of intravenous PG, thereby necessitating transition to alternative therapy. Transitioning off intravenous PG could affect patient's symptoms and FC. Funding Statement: authors state that no funding was received for this research. Declaration of Interests: authors state: The authors have no conflicts to disclose. Ethics Approval Statement: A waiver of consent was granted by the Institutional Review Board.

Anti-thrombotic therapy strategies with long-term anticoagulation after percutaneous coronary intervention – a systematic review and meta-analysis

ABSTRACTBackground: Long-term oral anticoagulants (OAC) increases bleeding risk after the percutaneous coronary intervention (PCI) with dual antiplatelet therapy (DAPT) with Aspirin and P2Y12 inhibitors. We hypothesize that dual anti-thrombotic therapy (DATT) reduces bleeding without increased cardiovascular events.Objectives: DATT does not increase adverse cardiovascular events compared to triple anti-thrombotic therapy (TATT).Method: We searched MEDLINE, PUBMED, Google Scholar, Cochrane and EMBASE from inception to 6 April 2019 for randomized control trials (RCTs) comparing DATT to TATT after PCI.Results: We identified 641 citations (411 after excluding duplicates). Four RCTs with 5,317 patients (3,039 on DATT vs 2,278 on TATT) were included. DATT arm showed significantly reduced [total bleeding, 731 vs. 784, odds ratio [OR] = 0.51, Confidence Interval [CI] = 0.39–0.67, p < 0.00001, I2 = 71% (I2 = 0% without WOEST study)], [TIIMI major bleeding 60 vs. 80, OR = 0.56, CI = 0.4–0.79, p = 0.0009, I2 = 0%], and [TIIMI minor bleeding, 70 vs 126, OR = 0.43, CI = 0.32–0.59, p < 0.00001, I2 = 0%]. There was no difference in subsequent strokes, myocardial infarction, stent thrombosis, and mortality. A trend towards decreased non-cardiac deaths with DATT was observed, 14 vs 26, OR = 0.55, CI = 0.27–1.10, p = 0.09, I2 = 6%.Conclusions: DATT is associated with significantly reduced bleeding and a trend towards reduced non-cardiac death with no difference in adverse cardiovascular outcomes.

Concentrated Factor Administration and Subsequent Pump Thrombosis on HeartMate II LVAD Support

Purpose Limited data exists regarding concentrated factor administration during continuous flow left ventricular assist device (CF-LVAD) implantation and subsequent rates of pump thrombosis. While the hemocompatability profile of CF pumps are presently changing, this is the largest concentrated factor experience reported in CF-LVAD patients to date. Methods Patients with first time HeartMate II implantation (n=328) were identified from a single center continuous-flow (CF-LVAD) database (n=400). Patients were coded as receiving concentrated factor if prothrombin 4 factor complex or recombinant factor VIIa was charted intra-operatively or within 48 hours of device implantation. Laboratory and hospitalization data were reviewed to determine time to first suspected or confirmed pump thrombosis. Suspected pump thrombosis was defined as a sustained rise in lactate dehydrogenase (LDH) > 2.5 the upper limit of normal. Confirmed pump thrombosis was defined as a pump exchange, cardiac transplant, or death associated with a hemolysis event. Multivariable cox regression was utilized to determine the association between concentrated factor administration and the time to suspected or confirmed pump thrombosis. Results Eighteen percent of patients (59/328) received concentrated factor intra-operatively or within 48 hours of device implantation. On multivariate analysis, concentrated factor administration was not significantly associated with time to first suspected pump thrombosis (HR 1.17, 95 % CI 0.62-2.20, p = 0.62) or confirmed pump thrombosis (HR 1.19, 95 % CI 0.43-3.3, p = 0.73). All models were adjusted for discharge pump speed, age, bridge to transplant status, diabetes, and INTERMACS profile. Conclusion While no statistical association was observed between concentrated factor administration and subsequent pump thrombosis in this large single center analysis, further data will be needed to answer this question in the contemporary continuous flow era.

Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for β2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome.

Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as β2-Glycoprotein I. We investigated the cytokine production induced by β2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of β2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize β2-Glycoprotein I in atherosclerotic lesions. β2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. β2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived β2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that β2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Multicenter Investigation of Channel-Based Subcortical Trans-Sulcal Exoscopic Resection of Metastatic Brain Tumors: A Retrospective Case Series.

Recent advancements have aimed to optimize visualization and minimize insult to healthy cortical and subcortical tissue through the use of tubular-based retractors. To investigate outcomes following resection of cerebral metastases using an integrated tubular retraction system with an exoscope and neuronavigation. A multicenter retrospective analysis of surgical outcomes in consecutive patients who underwent resection of a brain metastasis using a tubular retraction system and exoscope was performed. Twenty-five patients were included, with a mean age of 61 yr (24-81 yr). Primary sources included lung (n=13), breast (n=3), renal cell (n=3), and other (n=6). Locations were frontal (n=5), parietal (n=8), cerebellar (n=8), occipital (n=3), and splenium (n=1). Most lesions had a maximum diameter>3.0 cm (n=20) and a tumor depth>4 cm (n=14). Conversion to open (microscopic) craniotomy was not required in any case. Gross total resection was achieved in 20 cases (80.0%) and subtotal resection in 5 cases (20.0%). Median hospital stay was 2 d (1-12 d). All patients underwent postoperative radiation therapy. Perioperative complications developed in 1 patient (4.0%; hemiparesis and subsequent deep vein thrombosis). At 3-mo follow-up, no mortalities were observed, 19 patients (76.0%) demonstrated neurological improvements, 5 patients (20.0%) had a stable neurological exam, and 1 patient (4.0%) had a neurological decline. Utilization of a channel-based, navigable retractor and exoscope is a feasible option for surgical resection of metastatic brain lesions.

Risk of Subsequent Thrombosis in Patients with Isolated Heparin-Induced Thrombocytopenia

Background: Heparin-Induced Thrombocytopenia (HIT) is one of the most important and commonly encountered immune-mediated drug reactions which can lead to significant morbidity and mortality. In up to 25% of patients, thrombosis can be the presenting finding of HIT. Isolated HIT occurs in patients without clinically evident thrombosis at the time of diagnosis. The management of HIT focuses on reducing the risk of thrombotic complications. In addition to prompt discontinuation of heparin products, anticoagulation is recommended. The risk of thrombosis is thought to remain high for up to 4 weeks due to persistent circulating PF4-heparin antibodies. Prior studies have shown that in patients with isolated HIT, the subsequent 30-day risk of thrombosis is up to 53%.Guidelines recommend 3 months of anticoagulation for patients with HIT-associated thrombosis. The optimal duration of anticoagulation in isolated HIT is unknown. Many experts recommend prophylactic anticoagulation for up to 4 weeks after diagnosis. However in the era of direct thrombin inhibitors, the need for prophylactic anticoagulation and risk of thrombosis beyond normalization of platelet count remains to be determined. The aim of this study was to determine the incidence of subsequent thrombosis in patients with isolated HIT.Methods: In this retrospective review, we identified patients with a documented positive HIT (heparin-PF4 antibody) enzyme immunoassay (ELISA) at our affiliated hospitals between January 2006 and December 2016. Laboratory data from these patients were reviewed. Patients who met criteria for HIT, defined as HIT ELISA optical density ≥ 2 or positive serotonin release assay were included in the analysis. From this cohort of patients with confirmed HIT, clinical data was extracted from the electronic medical record, including anticoagulation management and documented thrombotic events within 3 months of HIT diagnosis. Patients with evidence of thrombosis at the time of diagnosis were excluded in the final analysis as our focus was on patients with isolated HIT. The incidence of subsequent thrombosis was compared in patients who received anticoagulation versus those who did not receive anticoagulation.Results: A total of 403 charts were reviewed from patients with a documented positive HIT ELISA, defined as an optical density of > 0.4. Of the 403 patients, 49.5% (n = 107) met criteria for HIT, with an optical density > 2 or positive serotonin release assay. In patients with HIT, 48.6% (n = 52) did not have evidence of thrombosis at the time of diagnosis. Of these patients with isolated HIT, 14 patients (26.9%) received no prophylactic anticoagulation, 8 patients (15.4%) received prophylactic anticoagulation for at least 4 weeks but less than 3 months, and 30 patients (57.7%) were anticoagulated for 3 months or longer. The total incidence of subsequent thrombosis in isolated HIT was 7.7%. In the cohort of patients that did not receive prophylactic anticoagulation, two patients (14.3%) developed a thrombotic event in the 3 months following the HIT diagnosis. No documented thrombotic complications occurred in the eight patients that received prophylactic anticoagulation for at least 4 weeks but less than 3 months. Three patients (10%) who received long-term anticoagulation (≥3 months) developed a subsequent thrombotic event. There was no significant difference in the incidence of subsequent thrombosis in patients who did not receive prophylactic anticoagulation versus patients who received short-term prophylactic anticoagulation (p=0.141). In addition, there was no significant difference in the incidence of subsequent thrombosis in patients who did not receive prophylactic anticoagulation versus those who received long-term anticoagulation (p=0.701).Conclusions: The optimal duration of anticoagulation in patients with isolated HIT is unknown. Our incidence of thrombosis following the diagnosis of HIT was lower than previously described. Patients who did not receive prophylactic anticoagulation did not have a significantly higher incidence of thrombosis compared to patients who received short-term prophylactic or long-term anticoagulation. The study was limited by the retrospective nature and small sample size. Further studies are needed to better understand the ideal length of anticoagulation to prevent thrombotic complications without leading to unnecessary increased risk of bleeding. DisclosuresNo relevant conflicts of interest to declare.

Optical coherence tomography substudy of a prospective multicentre randomised post-market trial to assess the safety and effectiveness of the Firehawk cobalt-chromium coronary stent (rapamycin target-eluting) system for the treatment of atherosclerotic lesions: TARGET All Comers.

Durable polymer drug-eluting stents (DP-DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this optical coherence tomography (OCT) substudy was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (Firehawk®) (BP-DES) versus the DP-DES (XIENCE) at 90 days in an all-comers patient population. The TARGET All Comers study is a prospective multicentre randomised post-market trial of 1,656 patients randomised 1:1 to Firehawk or XIENCE at 21 centres in 10 European countries. The TARGET OCT substudy enrolled 36 consecutive patients with 52 lesions at six centres proficient in OCT. Follow-up OCT was performed at three months or prior to revascularisation when occurring before the three-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions: Firehawk, n=24; XIENCE, n=28), was not significantly different between groups (Firehawk 75.5 μm vs. XIENCE V 82.3 μm) meeting the primary endpoint of non-inferiority (pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9±0.3% vs. 100±0.1%, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups. Based on OCT, the Firehawk BP-DES has a similar healing response three months after implantation compared to the DP-DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

Intravascular Imaging for Chronic Total Occlusion Intervention

We sought to summarize the current evidence on use of intravascular imaging (with intravascular ultrasound [IVUS] or optical coherence tomography [OCT]) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Utilization of intravascular imaging in CTO PCI is increasing over time, both to facilitate CTO crossing and for optimization of the final result. OCT is used less often than IVUS due to its lower depth of penetration and need for contrast injection. Intravascular imaging has multiple uses in CTO PCI: (a) it can facilitate CTO crossing by resolving proximal cap ambiguity and facilitating and confirming true lumen wire re-entry in case of initial subintimal wire crossing in both the antegrade and retrograde direction (for example by selecting the appropriate balloon size during the reverse controlled antegrade and retrograde tracking (reverse CART) technique; (b) it can be used to optimize the PCI result by ensuring good stent expansion and stent strut apposition, which may in turn result in lower rates of subsequent in-stent restenosis and stent thrombosis; (c) can facilitate evaluation and treatment of complications.

Waterpipe Smoking Is Associated with Changes in Fibrinogen, FVII, and FVIII Levels

Cigarette smoking has been shown to be associated with changes in coagulation factors in the circulation and the subsequent thrombosis development. In this study, the impact of waterpipe smoking on the levels of fibrinogen, factor VII (FVII), and factor VIII (FVIII) was investigated. In addition, the effects of waterpipe smoking were compared to those of cigarette smoking and never smokers. A total of 80 male smokers (40 cigarette smokers and 40 waterpipe smokers) and 40 apparently healthy never smokers were recruited in the study. Both waterpipe smoking and cigarette smoking induced significant increases in the plasma levels of fibrinogen, factor VII, and factor VIII (p < 0.01). The magnitude of the increase in fibrinogen levels induced by waterpipe smoking was higher than that induced by cigarette smoking (p < 0.01), while similar increases were observed in other factors (p > 0.05). In addition, in the waterpipe group, the magnitude of the increase in fibrinogen and factor VIII was higher in the smokers with more than 3 years of use (p < 0.05). In conclusion, similar to cigarette smoking, waterpipe smoking modulates the levels of coagulation factors, suggesting its thrombotic potential.

A retrospective analysis of treatment of wounds caused by calciphylaxis: Hyperbaric oxygen therapy with and without sodium thiosulfate

Calciphylaxis, or calcific uremic arteriolopathy, is a rare, but devastating condition with a mortality approaching 80% in the United States, often seen in patients with chronic kidney disease. It is characterized by calcification and intimal fibrosis with arteriolar stenosis and subsequent thrombosis. Skin changes such as livedo reticularis, tender papules, and violaceous plaques result and progress to necrotic ulceration. Management of calciphylaxis includes maintenance of normal levels of calcium, phosphorus and parathyroid hormone, and optimization of hemodialysis and nutritional status. In our cohort, aggressive wound management coupled with sodium thiosulfate and hyperbaric oxygen therapy (HBOT) has achieved improvement in rates of healing for recalcitrant wounds associated with calciphylaxis but limited evidence for the efficacy of either treatment exists. We conducted a retrospective analysis of 94 patients treated for calciphylaxis at a Wound and Hyperbaric Center at an academic institution between 2000 and 2017 who were considered for HBOT. We assessed whether response to therapy as measured by wound healing varied among patients who received sodium thiosulfate, hyperbaric oxygen treatment, both therapies, or neither therapy. We found HBOT to be beneficial in healing compared to no therapy - 81.7% or 36 of 44 patients with complete or substantial resolution of their wounds vs. neither therapy - 11.4% or 3 of 26 patients. We found sodium thiosulfate to be beneficial in healing compared to neither therapy - 66.6% or 2 of 3 patients with complete or substantial resolution of their wounds vs. no therapy. We found combined HBOT & sodium thiosulfate to be more beneficial in healing compared to either therapy alone and to neither therapy - 86.3% or 19 of 22 patients with complete or substantial resolution of wounds. Given the dramatic clinical improvement, HBOT in combination with sodium thiosulfate has an important adjunctive role in the treatment of calciphylaxis.

LncRBA GSA5, up-regulated by ox-LDL, aggravates inflammatory response and MMP expression in THP-1 macrophages by acting like a sponge for miR-221

Atherosclerosis is a chronic inflammatory process, plaque rupture and subsequent thrombosis underline the major causes of acute cardio-cerebral vascular diseases. Long non-coding RNAs (lncRNAs) participate in diverse pathologic processes, including inflammation and myocardial infarction. Recent study confirmed the elevation of lncRNA growth arrest-specific 5 (GAS5) in atherosclerotic rats. In this study, we aimed to explore the role and mechanism of GAS5 in the progression of atherosclerotic plaque. Here, expression of GAS5 was enriched in atherosclerotic plaques and THP-1 macrophage exposed to oxidized low-density lipoprotein (ox-LDL). Furthermore, overexpression of GAS5 aggravated ox-LDL-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and chemokine MCP-1 secretion in macrophages, which were reversed after GAS5 cessation. Additionally, high expression and secretion of MMP-2 and MMP-9 were increased in ox-LDL-stimulated macrophages following GAS5 elevation, but these increases were inhibited in GAS5-silenced group. Mechanism analysis identified GAS5 as a endogenous sponge to directly bind and suppress miR-221 expression. Notably, miR-221 elevation antagonized GAS5-enhanced inflammatory response and MMPs in macrophages upon ox-LDL. These results suggest that GAS5 can trigger inflammatory response and MMP expression by acting as a sponge of miR-221, which may facilitate fibrous cap degradation and aggravate atherosclerotic plaque destabilization, supporting a promising therapeutic agent against atherosclerosis.

Особенности влияния гепариноида из пиона совместно с аргинином на растворение венозных тромбов у крыс

Цель исследования. Изучить влияние сочетанного применения гепариноида из пиона молочноцветкового, обладающего антикоагулянтным и фибринолитическим действием, и аргинина, улучшающего реологические свойства крови, на процессы фибрино- и тромбообразования, вызванные введением тромбопластина. Методика. Эксперименты выполнены на крысах-самцах Вистар (n = 36) массой 200-220 г. Процессы фибринообразования с последующим тромбообразованием вызывали внутривенным введением 0,4 мл 1% бычьего тромбопластина (модель тромбообразования - МТ). Для изучения эффективности сочетанного подкожного применения препаратов определяли антикоагулянтную и фибриндеполимеризационную активность каждого препарата в отдельности. За 30 мин до введения смеси гепариноида с аргинином (в соотношении 1:4 по весу) внутривенно вводили тромбопластин. Контролем служили животные, которым вводили физиологический раствор в том же объеме и в аналогичных условиях опыта. Результаты. Установлено в условиях in vitro, что препарат, включающий гепариноид из корней пиона молочноцветкового и аргинин при весовом соотношении 1:4, обладал антикоагулянтной и собственной фибриндеполимеризационной активностью. При подкожном введении этого препарата в минимальных дозах (0,05 мг на 200 г массы тела) в крови крыс повышались антикоагулянтная, суммарная, неферментативная и ферментативная фибринолитическая активность и снижалась до нормальных значений концентрация фибриногена. На модели крыс с тромбообразованием, вызываемым введением тканевого тромбопластина, показан антитромботический и тромболитический эффекты исследуемого препарата. Впервые показано, что применение этого препарата через 30 мин после начала тромбообразования у крыс препятствовало развитию процессов тромбообразования или даже способствовало растворению свежих образующихся фибриновых сгустков. Заключение. Сочетанное применение гепариноида из пиона с аргинином в минимально действующих дозах усиливает деполимеризацию фибрина и препятствует процессам тромбообразования. Исследование может служить экспериментальным обоснованием применения препаратов при тромботических осложнениях с целью благоприятного воздействия на растворение свежих только что образующихся тромбов.

Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative

Unlabelled Box BackgroundOral menopausal hormone therapy causes venous thrombosis but whether biomarkers of thrombosis risk can identify women at risk is unknown. MethodsWe completed a nested case control study in the two Women's Health Initiative hormone trials; 27 347 women aged 50‐79 were randomized to hormone therapy (conjugated equine estrogen with or without medroxyprogesterone acetate) or placebo. With 4 years follow‐up, biomarkers were measured using stored baseline samples prior to starting treatment, and one‐year later, in 215 women who developed thrombosis and 867 controls. ResultsOverall, lower protein C and free protein S, and higher D‐dimer, prothrombin fragment 1.2 and plasmin‐antiplasmin complex were associated with risk of future thrombosis with odds ratios ranging from 1.9 to 3.2. Compared to women with normal biomarkers assigned to placebo, the risk of thrombosis with hormone therapy was increased among women with abnormal biomarkers, especially elevated D‐dimer, elevated plasmin‐antiplasmin, and low free protein S; the largest association was for D‐dimer: odds ratio 6.0 (95% CI 3.6‐9.8). Differences in associations by hormone use were not significant on the multiplicative scale. Considering a multi‐marker score of eight biomarkers, women with three or more abnormal biomarkers had 15.5‐fold increased odds of VT (95% CI 6.8‐35.1). One‐year changes in biomarkers were not robustly associated with subsequent thrombosis risk. ConclusionAbnormal levels of biomarkers of thrombosis risk identified women at increased risk of future venous thrombosis with oral menopausal hormone therapy. Findings support the potential for clinical use of D‐dimer testing in advance of hormone therapy prescription.

Abstract No. 624 Technical and patient-related factors predicting TIPS thrombosis with stent grafts

To identify technical and patient related risk factors predicting subsequent TIPS thrombosis with stent grafts. Patients undergoing TIPS creation using stent grafts between 2003 and 2016 were retrospectively reviewed (n = 328). 236 cases with available follow-up were included. Patient demographics, clinical status, liver function, procedural details, and follow-up data were analyzed. Early thrombosis was defined as shunt occlusion within 2 months after TIPS creation. Competing risk Cox regression models were used to evaluate predictors of shunt occlusion, with post-TIPS liver transplant as the competing factor. A separate model including interactions between time and exposure variables was assessed. Risk factors of early thrombosis were evaluated using logistic regression models. P < 0.05 was considered statistically significant. Primary and secondary patency rates were 88.6% and 98.3%, respectively. Median follow-up was 13.1 months. TIPS thrombosis occurred in 27 cases (11.4%) at a median of 6.7 months (1 day–74.1 mo). Early thrombosis occurred in 11 cases (4.7%). 25 patients (10.6%) had a liver transplant a median of 11.5 months after TIPS. In multivariate analysis, technical factors predicting TIPS thrombosis included extension of stents into the portal vein (SHR: 3.03, P = 0.021) and poor flow on completion angiography (SHR: 5.81, P = 0.034). Patient-related factors predicting TIPS thrombosis included older age (SHR: 1.07, P = 0.023). Greater odds of early TIPS thrombosis were seen with portal thrombus on completion angiography (OR: 21.10, P = 0.005), chronic kidney disease (OR: 8.33, P = 0.030) and presence of hematologic disorders (OR: 13.49, P = 0.018). Baseline clinical factors and technical factors predict both early and long-term TIPS malfunction with stent grafts. Better understanding of associated risk factors may enable potential prophylactic measures to optimize shunt patency.

An interesting case of disseminated angioinvasive fungal infection

Angioinvasive fungal infection is a rare but devastating disease especiallyspecially in an immunocompromised patient. Here we aimed to present a case of disseminated mucormycosis in a dialysis recipient. The clinical hallmark of invasive mucormycosis is tissue necrosis resulting from angioinvasion and subsequent thrombosis.