Systemic Thrombosis Research Articles

Vascular Endothelial Growth Factor (VEGF) Inhibitor Cardiotoxicity: What Should We Know?

Cancer therapy-induced cardiovascular toxicity is a growing clinical problem with many unanswered questions about the optimal screening, prevention, and management, especially in patients treated with new targeted drugs. Among them, the use of vascular endothelial growth factor inhibitors (VEGFi) has become one of the most promising strategies to successfully approach a wide range of tumors. However, they have been associated with important cardiovascular complications such as systemic hypertension, heart failure, QTc prolongation, and venous and arterial thrombosis. This review addresses a multidisciplinary management of VEGFi-induced cardiotoxicity. Optimal management of antiangiogenic drugs side effects is challenging due to limited evidence-based recommendations. The detection and aggressive treatment of hypertension and other cardiovascular risk factors is essential to minimize treatment interruptions, heart failure, and cardiac arrhythmias. Additionally a close monitoring of signs and symptoms that may raise the suspicion of venous or arterial thromboembolic events is recommended. For that purpose, cardio-oncology approach aims to facilitate cancer therapy and to promote cardio-oncology research. VEFGi use is generally limited by uncontrolled hypertension that may trigger heart failure and cardiac arrhythmias. Therefore, a comprehensive cardio-oncology approach is needed to establish effective preventive and monitoring protocols.

Acute coronary syndrome with large thrombus successfully managed with no-stenting revascularization based on intravascular imaging in a patient with hyperhomocysteinemia: a case report

BackgroundHyperhomocysteinemia is caused by genetic and environmental factors, which can result in systemic arteriosclerosis and arteriovenous thrombosis including acute coronary syndrome. Thrombus burden in patients with acute coronary syndrome and hyperhomocysteinemia might involve the culprit lesion as compared with those without any coagulopathy. The primary percutaneous coronary intervention with stent implantation had been established as the treatment strategy for patients with acute coronary syndrome. However, in patients with acute coronary syndrome with high thrombus burden or uncontrolled coagulopathy, stent implantation might lead to slow-flow phenomenon or stent thrombosis. Therefore, the treatment strategy in these patients was not established.Case presentationA 49-year-old Japanese man with history of splenic infarction of unknown cause had continued anticoagulant therapy since its diagnosis, but stopped taking the medication several months ago. He presented with sudden-onset chest dorsalgia. Contrast computed tomography showed a small pulmonary embolism and his troponin I level was elevated on initial laboratory test. Coronary angiography revealed a contrast defect caused by a large thrombus from the proximal to mid portion of the left anterior descending artery. Near-infrared spectroscopy–intravascular ultrasonography showed a large amount of thrombus without lipid plaque. Therefore, revascularization was performed using a thrombus-aspiration catheter and intracoronary thrombolysis. In addition, , hyperhomocysteinemia and a deep vein thrombosis occurred. He was diagnosed with acute coronary syndrome complicated with pulmonary embolism and deep vein thrombosis simultaneously induced by hyperhomocysteinemia. After 1 week of antithrombotic therapy, near-infrared spectroscopy–intravascular ultrasonography and optical coherence tomography revealed a decreased thrombus and no significant residual organic stenosis in the left anterior descending artery. He continued conservative therapy with antithrombotic medications including aspirin and warfarin and had no cardiovascular events after discharge. Follow-up coronary angiography and optical coherence tomography at 9 months revealed complete disappearance of the thrombus and no severe stenosis.ConclusionsHyperhomocysteinemia should be considered as a cause of arterial vein thrombosis of unknown cause. The antithrombotic therapy and percutaneous revascularization without stenting based on intravascular imaging might be a safe and effective treatment option in patients with acute coronary syndrome complicated with hyperhomocysteinemia.

Rare Inherited Defects of the Complement System in Purpura Fulminans

Background: Purpura fulminans (PF) is a rare but devastating complication of sepsis in which patients experience overwhelming systemic thrombosis leading to end organ damage, distal limb ischemia, and death. Survivors are often left with lifelong disfigurement and/or disability due to severe acral tissue injury and the need for amputation of necrotic extremities. Given that most patients who develop PF have no known underlying medical conditions and are much younger than those typically afflicted with sepsis, we sought to investigate whether genetic determinants predispose individuals to developing PF. Methods: We performed whole exome sequencing on the Boston PF Cohort (N=40). We used pathway-based collapsing analysis (PBCA) combined with mutational burden testing to evaluate for enrichment of rare coding variants in the complement system using as a comparator unselected patients with sepsis from the NHLBI ARDSnet iSPAAR cohort (N=87). Several novel variants in integrin complement receptors were identified and subsequently cloned and functionally characterized. Results: Patients in the Boston PF Cohort were relatively young at the time of presentation, with a median (IQR) age of 37.5 (20.3-58.8) years. Patients were afflicted with gram negative organisms 45% of the time, while 27.5% were infected with gram positive organisms. In another 27.5%, no pathogen was identified. PF patients had strikingly abnormal markers of severe sepsis and coagulopathy, including the following median (IQR) values: lactate 7.1 (5.3-11.8) mmol/L, platelet count 28,000 (15,000-48,500) per μl, aPTT 68.0 (48.3-142.5) seconds, INR 2.8 (1.9-4.0), and protein C activity 26.0% (13.5-38.5). No patient had a known congenital immune defect. Whole exome sequencing (mean read depth 80X) identified 30 unique heterozygous complement system variants in 26/40 (65%) patients with PF (Figure 1A-B). Variants in this pathway were highly enriched in PF patients compared to the control cohort (P<0.001, Figure 1C), and the signal remained significant (P=0.02) in a sensitivity analysis comparing only Caucasian patients. By contrast, no enrichment of variants was found in the coagulation system (P=0.51, Figure 1D), and no difference in complement system variants was detected between the two cohorts when only synonymous variants were considered. The number of complement system variants per patient correlated positively with their Sequential Organ Failure Assessment (SOFA) score at the time of presentation (P=0.03) and independently predicted presenting SOFA score in a multivariate regression model (P=0.04). Eleven unique variants were identified in ITGAM, ITGAX, and ITGB2, genes encoding the integrin complement receptors 3 and 4 (CR3 and CR4), which have anti- and pro-inflammatory properties, respectively. Because little is known about the function of these receptors in sepsis, we performed additional in vitro studies and found that 6/8 (75%) CR3 variants resulted in partial or complete loss-of-function, while 3/7 (42.9%) CR4 variants unexpectedly resulted in gain-of-function. Taken together, these results suggest that the immune response to microbial infection in PF patients results in enhanced pro-inflammatory signaling by CR3 and CR4. Conclusions: Our data suggest that rare inherited defects in the complement system predispose individuals to the maladaptive thrombo-inflammatory response to infection that characterizes PF. By advancing our understanding of the molecular pathogenesis of PF, this work could provide important insights into the broader problem of coagulopathy in sepsis. Furthermore, targeted gene discovery approaches based on PBCA may serve as a model for future genomic studies of rare hemostatic diseases. Disclosures No relevant conflicts of interest to declare.

Visit-to-visit systolic blood pressure variability associates with vascular thrombosis in hemodialysis patients

Abstract Background Blood pressure variability (BPV) is an independent risk factor for cardiovascular events and death in general population. Hemodialysis patients have higher BPV and higher vascular events than general population. However, the impact of BPV on vascular events of hemodialysis patients is not clear. Purpose To determine the association of BPV with vascular outcomes in patients on maintenance hemodialysis. Method In this prospective multi-center study, we enrolled 927 maintenance hemodialysis patients from Jan, 2017 to Dec, 2017. We used the coefficient of variation (CV) and the variance independent of mean (VIM) of predialysis systolic blood pressure (SBP) derived from the first 3 months (36 dialysis sessions) after enrollment as the metrics of BPV. Patients were prospectively followed at 3-month interval. Outcomes included death, systemic vascular thrombosis (nonfatal myocardial infarction, ischemic stroke, and acute limb ischemia), and dialysis vascular access thrombosis. Results In all, 707 subjects with at least 20 measurements were included in the analysis. Patients' mean age was 66 years and 50% of patients were male. Baseline factors associated higher BPV included diabetes, high co-morbidity scores, low albumin, high systolic and diastolic blood pressure. The mean pre-dialysis SBP CV was 10.9% and VIM was 28.9%. The median follow-up duration was 2.5 years, during which 103 deaths, 81 systemic vascular thrombosis, and 155 dialysis access thrombosis occurred. In unadjusted model, we found that the highest BPV tertile had a 52% increased risk of vascular thrombosis than the lowest BPV tertile (HR=1.52, 95% CI 1.23–1.86, P<0.001). After multivariable adjustment (including age, diabetes, co-morbidity score, albumin, baseline systolic and diastolic BP), this association remained statistically significant (HR=1.47, 95% CI=1.18–1.84, P=0.001). Systolic BPV was associated with either systemic vascular thrombosis (HR=1.44, 95% CI=1.08–1.93, P=0.01) or dialysis vascular access thrombosis (HR=1.55, 95% CI=1.16–1.82, P=0.001). Conclusion In the cohort of patients on maintenance hemodialysis, high pre-dialysis systolic BPV was associated a higher risk of vascular thrombosis events, both for systemic vascular thrombosis and dialysis vascular access thrombosis. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): National Taiwan University Hsinchu Branch

Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

Controversies over hydroxychloroquine in the prevention of SARS-CoV-2 infection put rheumatologists on the frontline

The outburst of the novel COVID-19 has caused unprecedented stress in the healthcare systems and global economy since its outbreak in December 2019. Effective treatment for severely ill patients still...

S0986 Outcomes of Balloon-Occluded Retrograde Transvenous Obliteration and Its Variants for Treatment of Gastric Varices at a High-Volume North American Center

INTRODUCTION: BRTO is a common alternative to TIPS or endoscopy for controlling gastric variceal bleeding. Its universal adoption has however been limited due to lack of expertise and fears regarding complications. This study evaluates outcomes of BRTO and its variants, Coil-Assisted Retrograde Transvenous Obliteration (CARTO) and Balloon-Occluded Antegrade Transvenous Obliteration (BATO) at a single center. METHODS: A retrospective review of patients undergoing BRTO or a variant procedure from 6/2013-6/2019 at our institution was performed. Data was collected on demographics, indication, MELD score at time of, 1 month and 1-year post procedure, technical success, complications, rebleed events, mortality, worsening of ascites, encephalopathy, esophageal varices, systemic thrombosis and hepatocellular carcinoma (HCC) incidence up to 1 year post procedure. Statistics were calculated using univariate two-group t-tests or Wilcoxon rank-sum test for continuous variables and non-parametric tests. RESULTS: A total of 65 patients, 11 (16.9%) BATO, 6 (9.2%) BRTO, 45 (69.2%) BRTO/CARTO and 3 (4.6%) BATO/BRTO were evaluated. A 93.8% technical success rate was noted with 2 failures in BATO and 2 in BRTO due to intraprocedural vessel rupture and anatomic issues. High risk gastric varices or bleeding was the most common indication occurring in 53 (81.5%) cases. 1 BATO/BRTO case was complicated by post-procedural sepsis. There were a total of 3 (5%) rebleeding events. 1 BATO patient died from rebleeding on day of procedure and 1 BRTO/CARTO patient died the following day. 4 patients developed new esophageal varices of which 2 bled within one year that was controllable endoscopically. 4 (6.5%) patients developed worsening ascites, 2 (3%) had new or worsened encephalopathy and 9 (13%) developed systemic thrombosis. No patients developed HCC post-procedurally. Mean change in MELD was −0.88 1 month post-procedure with no significant difference in MELD scores from procedure time to 1 month (P = 0.769) or 1 month to 1 year (P = 0.132) when comparing BRTO to its variants. CONCLUSION: Our data demonstrates that BRTO and its variants are effective alternatives to TIPS for treatment of gastric varices without significant adverse effect on MELD scores and minimal to no worsening of portal hypertension related complications. Physicians however must remain vigilant for risk of systemic thromboses and esophageal variceal formation. Of note, previous fears of worsening ascites or increased risk for HCC are not supported by our study.

S2803 Bizarre Bariatric Complication With Small Bowel Obstruction in a COVID-19 Patient With Acute Abdomen

INTRODUCTION: Gastrointestinal emergencies in the novel coronavirus pandemic present as acute abdomen in 4-5% of patients as gathered from emerging studies. Nausea, abdominal pain, diarrhea, rectal bleeding, dysgeusia, anorexia and jaundice have been recorded in these patients. Additionally there are cases with hemorrhagic gastritis, ischemia of bowel, and hepatitis often due to systemic immune complex phenomenon and thrombosis. We report a rare case of small bowel obstruction in a Covid-19 patient with a dislodged and migrated EG junction stent, initially placed to circumvent a leak at a prior gastrojejunal (GJ) bypass surgical revision, and then presenting to the emergency room with acute abdomen. CASE DESCRIPTION/METHODS: A 54 year old woman underwent a routine laparoscopic GJ revision in 2/2020 after which she developed a GJ leak 2 weeks later warranting an esophageal stent placement . She was then discharged home, at the height of the Covid-19 outbreak in a pandemic hotspot. She developed a small intra abdominal abscess post op 2 weeks warranting hospitalization for drainage and discharged on antibiotics. 2 months later, she presented with nausea, malaise, vomiting and diarrhea followed by worsening RLQ pain. An Abdominal CT w/ contrast revealed an impacted stent in the distal ileum with localized perforation and obstruction. After reporting generalized body aches and malaise at presentation, PCR testing revealed a positive Covid19 status. She underwent a successful emergency laparoscopic stent retrieval and repair, with no post op complications. DISCUSSION: Covid19 gastrointestinal emergencies are common, and varied with a favorable prognosis in respect to initial presentation. Our patient had subtle nausea, emesis and enteritis, as noted in 10–20% of patients with similar Covid presentation, which likely led to stent dislodgement and distal migration with subsequent bowel obstruction. Fortunately, her clinical course was mild so she was managed with optimal laparoscopic retrieval and supportive medical therapy after which she was successfully discharged from the hospital. Our case is unique in that an acute Covid19 case presenting concomitantly with post bariatric stent migration and bowel obstruction was successfully managed in a standard fashion during the height of a pandemic in a hotspot with stifling restrictions in place for routine emergencies. Though the exposure risk is high for medical staff, all such patients should be optimally managed like any Covid negative patients for optimal outcomes.Figure 1.: Migrated esophageal stent in the right lower quadrant.

Thromboprophylaxis and treatment practices for thromboembolic complications after Total cavopulmonary connection/Fontan operation in children - a survey of pediatric cardiology and cardiothoracic network centers

IntroductionTotal cavopulmonary connection/Fontan circulation patients are at a higher risk of developing systemic and non-systemic thrombosis. A variety of prophylactic agents and treatment options such as drugs and interventional procedures are available for the prevention and treatment of thrombus. We hypothesized a huge variation in these practices due to a lack of robust pediatric evidence. We investigated the current thromboprophylaxis, thrombosis surveillance and treatment practices in these children across the pediatric cardiology and cardiothoracic network centers in the United Kingdom (UK). Materials and methodAn online questionnaire was sent to a cardiologist routinely involved in the management of children on single ventricular pathways from each of the 16 peditaric network centers in the UK. ResultsA total of 12 out of 16 centers (75%) responded to the survey. There was a widespread variation in practice regarding the choice of thromboprophylaxis agent, drug monitoring range(s), and treatment options for symptomatic thromboembolic complications. Warfarin was more commonly prescribed (58%) as the first line agent for thromboprophylaxis. Systemic tissue plasminogen activator (tPA) was the most preferred treatment option (42%) for symptomatic thromboembolism. None of the centers performed routine surveillance for coagulation abnormalities following the Fontan operation. ConclusionThere was a wide variation in practice regarding prophylaxis and treatment of thromboembolism. This is probably based upon institutional preference or experience due to the paucity of robust scientific evidence. Larger prospective multi-center studies with standardized surveillance and prophylaxis pathways are required to truly investigate the preferred agent for thromboprophylaxis and treatment.

Perspectives on Platelet Heterogeneity and Host Immune Response in Coronavirus Disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) represent a global pandemic with largely uncharacterized but dire public health consequences. COVID-19 is now increasingly recognized as a thromboinflammatory disease, where thrombotic coagulopathy and intravascular coagulation are closely linked to mortality and clinical outcomes.[1] [2] [3] [4] As thrombocytopenia, systemic microvascular thrombosis, and elevated D-dimer levels reflect COVID-19 severity,[1] [2] [3] [4] cellular effectors of hemostasis and thrombosis—especially platelets—likely participate in COVID-19 pathogenesis. However, specific roles for platelets in COVID-19 as disease drivers, biomarkers, and therapeutic targets remain unspecified. Here, we highlight how platelets may be affected by COVID-19 in a manner supporting pathology, which offers insights into COVID-19 susceptibility, progression, and resolution. Like other viral infections and inflammatory states, COVID-19 likely involves alterations in platelet number, form, and function, or “platelet heterogeneity.”[5] [6] Knowledge gained over the past decade detailing mechanisms of platelet heterogeneity in inflammation and immune responses may help to gain ground in the battle against COVID-19. In turn, a surge of collaborative studies around COVID-19 pathogenesis may result in unique insights into platelet function critical to understanding and managing other inflammatory disease states.

Severe COVID-19 Is a Microvascular Disease.

Severe COVID-19 Is a Microvascular Disease.

Severe aortic stenosis patient risk during the COVID-19 pandemic.

Aortic stenosis (AS) is a progressive aortic valve disease that can lead to heart failure, syncope and sudden death if not treated. Severe AS currently affects more than 2 million people over 65 years of age in the USA. The only treatment option for AS is valve replacement by either surgical aortic valve replacement (AVR) or the less invasive transcatheter aortic valve replacement (TAVR), also called transcatheter aortic valve implantation (TAVI). AVR requires intensive care unit (ICU) admission, whereas TAVR can be performed in a non-ICU setting. Both procedures are commonly associated with complications, such as stroke.1 Bleeding and thrombosis are also potential complications of these procedures. Given the considerable morbidity and mortality, patients with these postoperative complications are admitted to the ICU for management. SARS-CoV-2, which causes COVID-19, has become a pandemic and has caused high mortality rates among the elderly. Currently, there is no vaccine against SARS-CoV-2, and there is no effective treatment to treat patients with severe COVID-19. More than 730 000 people worldwide and over 160 000 in the USA have died from COVID-19 as of 10 August 2020 according to Johns Hopkins Coronavirus Resource Center; these figures are expected to continue to rise until there are effective vaccines and therapies. Treating patients with COVID-19 during this pandemic requires many medical resources. Importantly, acute respiratory distress syndrome and multiorgan failures, believed to be due to systemic and pulmonary thrombosis,2 3 are common symptoms of severe COVID-19 that require treatment in the ICU. Therefore, government officials have recommended ceasing almost all elective surgeries until the COVID-19 pandemic is under control.4 Although many patients with symptomatic AS can delay procedures intended to alleviate their symptoms, some may require life-saving procedures. In cases where life-saving procedures (AVR or TAVR) are required, …

COVID-19 induced systemic thrombosis

COVID-19 induced systemic thrombosis

Characteristics of Large-Vessel Occlusion Associated with COVID-19 and Ischemic Stroke.

The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Large-vessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke.

Evaluation of Remote Pharmacist-Led Outpatient Service for Geriatric Patients on Rivaroxaban for Nonvalvular Atrial Fibrillation During the COVID-19 Pandemic.

ObjectiveThis study was designed to evaluate the efficacy of remote medication management of rivaroxaban by pharmacists for geriatric patients with nonvalvular atrial fibrillation during the COVID-19 pandemic.MethodsA single-site, prospective cohort study was conducted among patients with non-valvular atrial fibrillation who received rivaroxaban therapy from July 2019 to December 2019. Patients in the pharmacist-led education and follow-up service (PEFS) group were managed remotely by a pharmacist. In contrast, those in the usual care (UC) group were managed by other providers. Data of routine blood tests, coagulation function tests, which also included cardiac function parameters were collected. The number and type of provider encounters, interventions related to rivaroxaban therapy, the occurrence of thromboembolism or bleeding, and the time of the first outpatient visit after discharge were recorded.ResultsA total of 600 patients were recruited, and results of 381 patients were analyzed in the end, of which 179 patients were from the PEFS group and 202 were from the UC group. There was no significant difference between the two groups in terms of the occurrence ratio of systemic thrombosis, heart failure (LVEF < 40%), and left atrial dilation, which was defined as enlargement of left atrial diameter (LAD) > 40 mm. The cumulative incidences of bleeding complications, such as gastrointestinal tract and skin ecchymosis, were significantly higher in the UC group (12.4% vs. 6.1%, P=0.038; 4.5% vs. 0.6%, P=0.018). There was no significant difference after pharmacist intervention in terms of thrombosis occurrence ratio between the two groups (P = 0.338, HR: 0.722, 95% CI: 0.372-1.405). Remote instruction by a pharmacist reduced outpatient service frequency within the first 30 days after discharge (23.7% vs. 1.1%, P < 0.001). However, more patients in the PEFS group presented for the first outpatient revisit later than 40 days post-discharge (12.8% vs. 21.3%, P < 0.001).ConclusionRemote pharmacist-led medication instruction of rivaroxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.

Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity.

Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity.

Effect of COVID-19 on the Organs.

The COVID-19 pandemic that first became apparent in Wuhan, China, is now infecting millions all over the world. This is a review of COVID-19's extensive effects on virtually all the organs. It causes inflammation, endotheliitis, vasoconstriction, hypercoagulability, and edema. Lymphocytopenia, elevated D-dimer, elevated fibrin degradation products (FDPs), and disseminated intravascular coagulation (DIC) are observed. Deep vein thrombosis (DVT), venous thromboembolism, pulmonary embolism (PE), systemic and pulmonary arterial thrombosis and embolism, ischemic stroke, and myocardial infarction (MI) are reported.In the heart it can cause acute coronary syndrome, congestive heart failure, myocarditis, and arrhythmias. Kidney injury is usually secondary to systemic abnormalities. Stroke occurs even in young patients. Delirium and seizures are common. Anosmia and impaired sense of taste are reported. Psychological problems are common among patients as well as providers. Stool may contain virus. Lactate dehydrogenase may be elevated. Various skin manifestations including patchy erythematous rash are reported.

Will Complement Inhibition Be the New Target in Treating COVID-19-Related Systemic Thrombosis?

Will Complement Inhibition Be the New Target in Treating COVID-19-Related Systemic Thrombosis?

Antithrombotics after Intracranial Hemorrhage in Patients with Left Ventricular Assist Devices

Decisions regarding if or when to resume antithrombotics (anticoagulation or antiplatelets) after intracranial hemorrhage (ICH) in patients with left ventricular devices (LVADs) remain controversial and available data to guide management is limited. We aim to explore antithrombotic practices following ICH in LVAD patients and identify most effective strategies. Using a retrospective analysis of our institutional LVAD database between 11/2012 and 5/2018, we identified all patients who suffered ICH. We recorded type and timing of antithrombotic resumed following ICH. Primary outcome events included subsequent ischemic stroke or TIA, pump thrombosis, systemic thrombosis, re-hemorrhage, and extracranial bleeding; death was a secondary outcome. Other variables collected included age, sex, and year of LVAD placement. Descriptive and nonparametric survival analyses were performed. A total of 36 adult patients met our criteria. Median age was 54.5 years (IQR 38-56), 28% were women, and 25% non-white. Forty-four percent of procedures occurred after 2014 and ICH occurred a median of 266 days (IQR 110-689) after LVAD implantation. Antiplatelets were held in 83% of patients for a median duration of 20 days (IQR 5.5 days to never restarted) and anticoagulation held in 92% for a median of 5 days (IQR 3-27). After ICH, 19 patients suffered 25 outcome events including 19 primary events (3 ischemic strokes/TIAs, 3 pump thromboses, 4 systemic thrombotic events, 7 re-hemorrhage, and 2 systemic hemorrhages). Kaplan-Meier survival free of a primary outcome was 89%, 72% and 58% at 7, 14 and 30 days post-ICH, respectively. Most of the 36 patients died (n=26, 72%), 12 within 90 days of the index ICH. There were no significant associations between survival free of a primary event and timing of anticoagulation, age > 60, sex, or LVAD placement before vs after 2014. Ischemic and hemorrhagic complications occurred at similar, high rates following intracranial hemorrhage in LVAD patients, with no evidence of increased risk of re-hemorrhage with early anticoagulation. Future study is necessary to identify specific risk factors for rebleeding and re-thrombosis in these patients to reduce levels or morbidity and mortality following intracranial hemorrhage.

Acute Anticoagulation after Ischemic Stroke in Patients with Left Ventricular Assist Devices

Despite reductions in major adverse events with the latest generation of left ventricular assist devices (LVADs), the incidence of stroke remains high. The timing of anticoagulation resumption is controversial. We aim to explore practices of anticoagulation management following ischemic stroke in LVAD patients and identify optimal strategies. We retrospectively analyzed our LVAD database between 11/2012 and 5/2018. Patients who suffered ischemic stroke were categorized into 3 groups based on the timing of anticoagulation resumption post-stroke: anticoagulation immediately continued (A), held 1-4 days (B), held >4 days (C). Primary outcome events included recurrent ischemic stroke or TIA, pump thrombosis, systemic thrombosis, and intracranial or extracranial bleeding within 90 days. Descriptive and nonparametric survival analyses were performed. Of the 38 patients identified as having an ischemic stroke, 22 experienced 37 primary outcomes including 5 recurrent ischemic strokes/TIAs, 3 pump thromboses, 15 systemic embolic events, 9 intracranial and 5 systemic hemorrhages. We found no significant association between timing of anticoagulation resumption and incidence of subsequent ischemic events (Group A= 39%, B= 22%, C= 17%) or intracranial bleeding (Group A= 17%, B= 33%, C= 33%). Kaplan-Meier survival free of a primary outcome for all patients was 65%, 56% and 50% at 7, 14 and 30 days post ischemic stroke, respectively. There was no association between survival and timing of anticoagulation, sex, LVAD type or placement before vs after 2014. We found a high rate of early outcomes after ischemic stroke in LVAD patients, with no evidence of increased risk with continued anticoagulation. Accepting the limitations of a retrospective study, these data suggest that anticoagulation may not need to be held acutely to prevent hemorrhagic conversion. Risk factors for these post ischemic stroke outcomes however were not identified. Further research is needed to identify approaches to decrease these secondary complications.