The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing ...COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy.
Bleeding following transcatheter aortic valve replacement (TAVR) has important prognostic implications. This study sought to evaluate the impact of baseline mean platelet volume (MPV) on bleeding ...events after TAVR.
Patients undergoing TAVR between February 2010 and May 2019 were included. Low MPV (L-MPV) was defined as MPV ≤10 fL and high MPV (H-MPV) as MPV >10 fL. The primary endpoint was the occurrence of major/life-threatening bleeding complications (MLBCs) at one-year follow-up. Among 1,111 patients, 398 (35.8%) had L-MPV and 713 (64.2%) had H-MPV. The rate of MLBCs at 1 year was higher in L-MPV patients compared with H-MPV patients (22.9% vs. 17.7% respectively, p = 0.034). L-MPV was associated with vascular access-site complications (36.2% vs. 28.9%, p = 0.012), early (<30 days) major bleeding (15.6% vs. 9.4%, p<0.01) and red blood cell transfusion >2 units (23.9% vs. 17.5%, p = 0.01). No impact of baseline MPV on overall death, cardiovascular death and ischemic events (myocardial infarction and stroke) was evidenced. Multivariate analysis using Fine and Gray model identified preprocedural hemoglobin (sHR 0.84, 95%CI 0.75-0.93, p = 0.001), preprocedural L-MPV (sHR 1.64, 95%CI 1.16-2.32, p = 0.005) and closure time adenosine diphosphate post-TAVR (sHR 2.71, 95%CI 1.87-3.95, p<0.001) as predictors of MLBCs.
Preprocedural MPV was identified as an independent predictor of MLBCs one year after TAVR, regardless of the extent of platelet inhibition and primary hemostasis disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress ...syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected.
Results
One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 IQR 51; 70 years and 47 IQR 37; 63 points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 0.14–0.94, p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 0.03–0.81; DVT: 0.13 0.01–0.89, stroke: 0.06 0–0.68, all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05).
Conclusion
Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.
Unfractionated heparin (UFH) is used as an anticoagulant during the atrial fibrillation (AF) ablation procedure to prevent the occurrence of thromboembolic events. Guidelines recommend an activated ...clotting time (ACT) greater than 300 s (s) based on studies of patients treated with vitamin K antagonist (VKA) for their AF. However, direct oral anticoagulants (DOACs) have supplanted VKAs in AF and are now used as first-line therapy. It is recommended not to interrupt them during the procedure, which could interfere with the ACT measures.
To assess the real-life relationship between ACT, DOAC concentrations, and UFH anti-Xa activity in patients treated by uninterrupted DOAC therapy.
We conducted a single-center retrospective study. We analyzed consecutive patients with AF who underwent catheter ablation under DOAC therapy.
In total, 40 patients were included, including 15 (37.5%), 20 (50.0%), and 5 (12.5%) on rivaroxaban, apixaban, and dabigatran, respectively. Baseline ACT was significantly lower in the apixaban group. ACT was linearly correlated with the residual concentration of apixaban and dabigatran but not with rivaroxaban. After UFH injection, ACT was linearly correlated with the anti-Xa activity, regardless of DOAC. Patients in the apixaban group received a higher total dose of UFH during the procedure to achieve a target ACT > 300 s, which resulted in significantly higher anti-Xa activity during the procedure.
Our results raise the question of optimal management of intra-procedural heparin therapy and highlight the limitations of the ACT test, particularly in patients on apixaban.
Abstract
Background
Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine ...diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF.
Methods
We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds.
Results
Patients with AF had a higher incidence of MLBCs (20 vs. 12%,
p
= 0.002), MACCE (29 vs. 20%,
p
= 0.002), and all-cause mortality (15 vs. 8%,
p
= 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment.
Conclusion
In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.
Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute ...to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events.
This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU).
Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 (
= 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50-4.86);
< 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 (
< 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27-4.93);
= 0.008).
In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.
Among the distinctive features of coronavirus disease 2019 (COVID-19), numerous reports have stressed the importance of vascular damage associated with coagulopathy onset 1. Histological analysis of ...pulmonary vessels in patients with COVID-19 revealed severe endothelial injury associated with intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and disrupted endothelial cell membranes together with widespread thrombosis and occlusion of alveolar capillaries. Microparticles (MPs) shed by apoptotic/stimulated cells of various cellular lineages, including platelets, leukocytes, macrophages or endothelial cells, are reliable markers of vascular damage 2 released upon pro-inflammatory conditions and behave as active participants in the early steps of clot formation 3. Circulating MPs promote procoagulant responses due to the exposure of tissue factor, the physiological activator of the coagulation cascade, and of negatively charged phospholipids, such as phosphatidylserine, required for the assembly of the tenase and prothrombinase coagulation complexes ultimately leading to thrombin generation, through which they can precisely be quantified 4. MPs carry angiotensin-converting enzyme (ACE)1 and upregulate ACE1 expression in neighbouring endothelial cells 5. By contrast, exosomes were recently reported to convey ACE2, the cell-entry receptor for SARS-CoV-2 4, in the vasculature 6. ACE2 converts angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7), which by virtue of its actions on the Mas receptor, limits the noxious effects of Ang II. Pioneering data have demonstrated that the renin–angiotensin system has a crucial role in severe acute injury and that ACE2 has a protective role in acute lung injury mediated by SARS-CoV 7. According to this paradigm, the loss of ACE2 function following binding by SARS-CoV-2 may contribute to unopposed Ang II accumulation that further exacerbates tissue injury and promotes inflammation, MPs release and thrombosis. During SARS-CoV-2 infection, we hypothesised that various factors including inflammatory burden, Ang II, altered shear stress and hypoxic vasoconstriction, could enhance MPs shedding by various cell lineages including the alveolar vascular endothelium and contribute to clot formation.
Procoagulant microparticles are associated with the extent of lung injuries in #COVID19 and pulmonary thrombosis
https://bit.ly/3eX2LPc
Introduction. Acute pulmonary embolism (APE) is a frequent condition in patients with COVID-19 and is associated with worse outcomes. Previous studies suggested an immunothrombosis instead of a ...thrombus embolism, but the precise mechanisms remain unknown. Objective. To assess the determinants and prognosis of APE during COVID-19. Methods. We retrospectively included all consecutive patients with APE confirmed by computed tomography pulmonary angiography hospitalized at Strasbourg University Hospital from 1 March to 31 May 2019 and 1 March to 31 May 2020. A comprehensive set of clinical, biological, and imaging data during hospitalization was collected. The primary outcome was transfer to the intensive care unit (ICU). Results. APE was diagnosed in 140 patients: 59 (42.1%) with COVID-19, and 81 (57.9%) without COVID-19. A 812% reduction of non-COVID-19 related APE was registered during the 2020 period. COVID-19 patients showed a higher simplified pulmonary embolism severity index (sPESI) score (1.15 ± 0.76 vs. 0.83 ± 0.83, p = 0.019) and were more frequently transferred to the ICU (45.8% vs. 6.2%, p < 0.001). No difference regarding the most proximal thrombus localization, Qanadli score (8.1 ± 6.9 vs. 9.0 ± 7.4, p = 0.45), the proportion of subsegmental (10.2% vs. 11.1%, p = 0.86), and segmental pulmonary embolism (35.6% vs. 24.7%, p = 0.16) was evidenced between COVID-19 and non-COVID-19 APE. In COVID-19 patients with subsegmental or segmental APE, thrombus was, in all cases (27/27 patients), localized in areas with COVID-19-related lung injuries. Marked inflammatory and prothrombotic biological markers were associated with COVID-19 APE. Conclusions. APE patients with COVID-19 have a particular clinico–radiological and biological profile and a dismal prognosis. Our results emphasize the preeminent role of inflammation and a prothrombotic state in these patients.
Purpose
Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.
Methods
All patients ...referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.
Results
150 COVID-19 patients were included (122 men, median age 63 53; 71 years, SAPSII 49 37; 64 points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (
n
= 145) confirmed that COVID-19 ARDS patients (
n
= 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%,
p
< 0.008). Coagulation parameters significantly differed between the two groups.
Conclusion
Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
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