Thrombotic Dysfunction Research Articles

Clinical characteristics, multiorgan dysfunction and outcomes of patients with COVID-19: a prospective case series.

Background:Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre.Methods:We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar. 17 to June 18, 2020, during the first wave of the pandemic. We recorded patients’ baseline characteristics, physiologic parameters, measures of organ function and therapies administered during hospitalization among patients in the intensive care unit (ICU) and in non-ICU settings, and compared the characteristics of hospital survivors and nonsurvivors. Finally, we recorded follow-up thoracic computed tomography (CT) and echocardiographic findings after hospital discharge.Results:We enrolled 100 consecutive patients (47 women) hospitalized with COVID-19, including 32 patients who received ICU care and 68 who received treatment in non-ICU settings. Respiratory sequelae were common: 23.0% received high-flow oxygen by nasal cannula, 9.0% received noninvasive ventilation, 24.0% received invasive mechanical ventilation and 2.0% received venovenous extracorporeal membrane oxygenation. Overall, 9.0% of patients had cerebrovascular events (3.0% ischemic stroke, 6.0% intracranial hemorrhage), and 6.0% had pulmonary embolism. After discharge, 11 of 19 patients had persistent abnormalities on CT thorax, and 6 of 15 had persistent cardiac dysfunction on echocardiography.Interpretation:This study provides further evidence that COVID-19 is a multisystem disease involving neurologic, cardiac and thrombotic dysfunction, without evidence of hepatic dysfunction. Patients have persistent organ dysfunction after hospital discharge, underscoring the need for research on long-term outcomes of COVID-19 survivors.

Repurposing low-dose naltrexone for the prevention and treatment of immunothrombosis in COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by striking dysregulation of the immune system, with evidence of hyperinflammation, an impaired induction of interferons, and delayed adaptive immune responses. In addition to dysfunctional immune responses, thrombosis is a hallmark of severe COVID-19. Because traditional anticoagulation strategies are associated with increased bleeding, novel strategies that address both the immune and thrombotic dysfunction associated with COVID-19 would be of tremendous benefit. In this commentary, we discuss the unique properties of low dose naltrexone (LDN) which could be leveraged to reduce the immune-mediated thrombotic complications in COVID-19. Mechanistically, LDN can blunt innate immune responses and Toll-like receptor (TLR) signaling, reducing interleukin1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon (IFN) levels. Because of the immune-mediated thrombotic mechanisms that underlie COVID-19, we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.

Correlation of chest CT severity score with D-dimer levels in patients with COVID-19

Abstract Background Coronavirus disease 2019 (COVID 19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) predominantly affects lungs and leads to COVID-19 pneumonia. Studies have shown that COVID 19 is hypercoagulative prothrombotic state. The innate tropism of SARS CoV-2 for vascular endothelial cells and their consequent damage, together with the intense activation of inflammatory responses and of coagulation pathways, may explain the intense pro-coagulative state. It ultimately predisposes to systemic micro-thrombotic alterations and gives rise to the consistent rate of multi-organ failure, DIC and ARDS in severe COVID-19 patients. Purpose Aims of this retrospective study were to determine the correlation between a CT-based semi-quantitative score of pulmonary involvement in COVID-19 pneumonia with D-dimer and CRP levels. Materials and methods 174 symptomatic SARS-CoV-2 patients were enrolled from August 4 to October 12, 2020, for this single-center analysis in rural India and chest CT examinations were retrospectively evaluated. The COVID 19 positivity was defined on the basis of RTPCR done at ICMR (Indian Council of Medical Research) approved laboratory. A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1: <5%; 2: 5–25%; 3: 26–50%; 4: 51–75%; 5: >75%; range 0–5; global score 0–25). D-dimer and CRP were done at the time of admission. One way ANOVA and post hoc Tukey test were performed to compare the variables of Chest CT score in percentage to various other variables. Results CT score had significant positive correlation with D-dimer levels (p=0.002, r: 0.237). CT score was significantly correlated with CRP (p<0.001, r: 0.392) levels. Subgroup analysis by post hoc Tukey test further showed that D-dimer levels were significantly elevated in 51–75% and >75% lobar involvement groups on Chest CT with statistically significant p value of <0.001. Conclusions This study data suggests that CT score has significant positive correlation with D-dimer and CRP. D-dimer is significantly elevated in the group where lobar involvement is more significant on Chest CT. D-dimer is an indirect marker of active coagulation and thrombin formation. Elevated D-dimer represents activation of endovascular thrombotic processes. This hypercoagulative infection-induced state is systemic, and may lead to various clinical manifestations such as myocardial infarction, stroke, limb ischemia and DIC. Monitoring of pro-thrombotic activity of SARS-CoV-2 with tests such as D-dimer, with consequent labelled administration of adjusted doses of anticoagulants are of paramount importance in order to prevent worsening of global conditions due to vascular parenchymal or systemic thrombotic dysfunction in COVID-19 patients. Funding Acknowledgement Type of funding sources: None.

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study. Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function. 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis. Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis. ClinicalTrials.gov Identifier: NCT02036255.

The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction.

Platelet activation provides a critical link between inflammation and thrombosis. Sulforaphane (SFN), a naturally occurring isothiocyanate, has been shown to display both anti-inflammatory and anti-thrombotic actions in the systemic microvasculature. As inflammation promotes thrombosis and vice versa, in this study we investigated whether SFN is able to reduce inflammatory potentiation of thrombotic events, suppress platelet activation and thrombus formation in the cerebral microvasculature. Thrombosis was induced in the murine brain using the light/dye-injury model, in conjunction with LPS treatment, with and without SFN treatment. In vitro and in vivo platelet assays (aggregation, flow and other functional tests) were also employed, using both human and murine platelets. SFN was found to reduce LPS-mediated enhancement of thrombus formation in the cerebral microcirculation. In tail-bleed experiments, LPS treatment prolonged bleeding time, and SFN treatment was found to protect against this LPS-induced derangement of platelet function. SFN inhibited collagen-mediated platelet aggregation in vitro and in vivo and the associated adhesion and impaired calcium signalling. Furthermore, glycoprotein VI was shown to be involved in the protective effects observed with SFN treatment. The data presented here provide evidence for the use of SFN in preventing stroke in selected high-risk patient cohorts.

Urokinase-containing locking solution in the prevention of dialysis catheter dysfunction: a double blind randomized controlled trial.

The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction. Patients with a history of at least two separate TCC thrombotic dysfunctions treated with urokinase lock during the 6 months preceding inclusion are recruited in eight Belgian dialysis units. Patients are randomized in two groups: the control group receiving Taurolock™-HEP500 (heparin 500 IU/mL, taurolidine, citrate 4%) after each hemodialysis session and the treatment group receiving Taurolock-U 25,000 (urokinase 25,000, taurolidine, citrate 4%) once a week and the standard Taurolock-HEP500 at the end of the two others sessions. The primary outcome is the incidence rate of TCC thrombotic dysfunction defined by the use of urokinase. The secondary outcomes are the incidence rate of TCC removal and systemic thrombolysis. For the study, both patients and healthcare staff are blinded to treatment allocation. The present trial is the first to investigate the effect of Taurolock-U 25,000 catheter lock once a week as secondary prevention in hemodialysis patients with the highest risk of TCC-related thrombotic dysfunction. ClinicalTrials.gov Identifier: NCT02036255.

Long-term Outcome of Peripherally Implanted Venous Access Ports in the Forearm in Female Cancer Patients.

The aim of this retrospective study was to analyze the long-term outcome of peripherally implanted venous access ports in the forearm at our institution in a female patient collective. Between June 2002 and May 2011, a total of 293 female patients with an underlying malignancy had 299 forearm ports implanted in our interventional radiology suite. The mean age of the cohort was 55 ± 12 years (range 26-81 years). The majority of women suffered from breast (59.5 %) or ovarian cancer (28.1 %). Complications were classified as infectious complications, thrombotic and nonthrombotic catheter dysfunction (dislocation of the catheter or port chamber, fracture with/without embolization or kinking of the catheter, port occlusion), and others. We analyzed a total of 90,276 catheter days in 248 port systems (47 patients were lost to follow-up). The mean device service interval was 364 days per catheter (range 8-2,132, median 223 days, CI 311-415, SD 404). Sixty-seven early (≤ 30 days from implantation) or late complications (>30 days) occurred during the observation period (0.74/1,000 catheter days). Common complications were port infection (0.18/1,000 days), thrombotic dysfunction (0.12/1,000 days), and skin dehiscence (0.12/1,000 days). Nonthrombotic dysfunction occurred in a total of 21 cases (0.23/1,000 days) and seemed to cumulate on the venous catheter entry site on the distal upper arm. Peripherally implanted venous access ports in the forearm are a safe alternative to chest or upper-arm ports in female oncology patients. Special attention should be paid to signs of skin dehiscence and nonthrombotic dysfunction, especially when used for long-term treatment.

Comparison of Tesio and LifeCath Twin Permanent Hemodialysis Catheters: The VyTes Randomized Trial

Central venous catheters for maintenance hemodialysis (HD) are designed to attain the required dialysis dose through sustained high blood flow rates (BFR). The authors studied the immediate and long-term performance and complications of two twin-catheter systems, the Tesio catheter (TC) and the LifeCath Twin (LC), to inform clinical practice. This single-center randomized controlled parallel-group trial allocated 80 incident patients (1:1) to receive either a TC (MedComp) or LC (Vygon). Patients were dialyzed to target BFR 450 mL/min and followed up for 12 months. The primary outcome was achievement of target BFR during the first HD session. Secondary outcomes included thrombotic dysfunction, displacement and catheter-related infection. Catheter dysfunction was defined by a BFR ≤ 250 mL/min. More LCs reached the primary endpoint (44% vs. 10%, p=0.001) delivering a higher BFR (mean 383±82 vs. 277±79 mL/min, p<0.001). Significant differences in BFR persisted until the fourth dialysis session. Rates of catheter-related bacteremia (0.40 vs. 0.51/1,000 catheter days, p=0.7) and exit site infection were similar between groups (0.24 vs. 0.09/1,000 catheter days, p=0.4). Overall rates of catheter dysfunction were 2.8/1,000 catheter days (95% CI 2.1-3.5), with no differences in thrombolytic lock use although the LC group required more thrombolytic infusions (6 vs. 0, p=0.01). The LC can deliver greater BFRs in the first three HD sessions following insertion although this did not translate into differences in performance, dialysis adequacy or complication rates with long-term use. Both catheter types can consistently deliver high BFRs over an extended period of time.

Thrombotic dysfunction of mechanical mitral valve

Thrombotic dysfunction of mechanical mitral valve

Nonconvulsive seizures and renal failure after intracerebral hemorrhage

Nonconvulsive seizures (NCSZ) and periodic epileptiform discharges (PEDs) are common and associated with poor outcome after intracerebral hemorrhage (ICH). Our objective is to describe the frequency of renal, liver, metabolic and thrombotic dysfunction after ICH and its association with non-convulsive status epilepticus (NCSE), NCSZ and PEDs.

Successful thrombolysis on a mechanical tricuspid prosthesis

Recombinant tissue-type plasminogen activator (rt-PA) is presently used for the treatment of different clinical entities, mostly myocardial infarction. Its use for treatment of thrombotic dysfunction of prosthetic cardiac valves is more recent and has been only rarely reported. A 33-year-old woman with a St Jude Medical prosthesis in the tricuspid position, had suffered from thrombotic dysfunction of her prosthesis for more than 2 months. She was treated with rt-PA, and after infusion of 70 mg, the prosthesis functioned normally. She showed a moderate systemic fibrinolytic state associated with mild bleeding complications.