Publications
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Arachchillage DJ, Thachil J, Anderson JAM, et al., 2024, Diagnosis and management of heparin-induced thrombocytopenia: Third edition., Br J Haematol, Vol: 204, Pages: 459-475
Randi AM, Jones D, Peghaire C, et al., 2023, Mechanisms regulating heterogeneity of hemostatic gene expression in endothelial cells., J Thromb Haemost, Vol: 21, Pages: 3056-3066
The hemostatic system involves an array of circulating coagulation factors that work in concert with platelets and the vascular endothelium to promote clotting in a space- and time-defined manner. Despite equal systemic exposure to circulating factors, bleeding and thrombotic diseases tend to prefer specific sites, suggesting an important role for local factors. This may be provided by endothelial heterogeneity. Endothelial cells differ not only between arteries, veins, and capillaries but also between microvascular beds from different organs, which present unique organotypic morphology and functional and molecular profiles. Accordingly, regulators of hemostasis are not uniformly distributed in the vasculature. The establishment and maintenance of endothelial diversity are orchestrated at the transcriptional level. Recent transcriptomic and epigenomic studies have provided a global picture of endothelial cell heterogeneity. In this review, we discuss the organotypic differences in the hemostatic profile of endothelial cells; we focus on 2 major endothelial regulators of hemostasis, namely von Willebrand factor and thrombomodulin, to provide examples of transcriptional mechanisms that control heterogeneity; finally, we consider some of the methodological challenges and opportunities for future studies.
Altmann DM, Whettlock EM, Liu S, et al., 2023, The immunology of long COVID (vol 23, 618, 2023), NATURE REVIEWS IMMUNOLOGY, Vol: 23, Pages: 697-697, ISSN: 1474-1733
Arachchillage DJ, Weatherill A, Rajakaruna I, et al., 2023, Thrombosis, major bleeding, and survival in COVID-19 supported by VV- ECMO in the first vs second wave- multicentre observational study in the UK, Journal of Thrombosis and Haemostasis, Vol: 21, Pages: 2735-2746, ISSN: 1538-7836
BACKGROUND: Bleeding and thrombosis are major complications of veno-venous extracorporeal membrane (VV-ECMO). OBJECTIVES: To assess thrombosis, major bleeding (MB) and 180-day in patients supported by VV-ECMO between first (1st March-31st May 2020) and second (1st June 2020-30th June 2021) waves of the COVID-19 pandemic. PATIENTS/METHODS: Observational study of 309 consecutive patients (≥18years) with severe COVID-19 supported by VV-ECMO in four nationally commissioned ECMO centres, UK. RESULTS: Median age was 48 (19-75)years and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8%(123/309) and 30%(93/309). In multivariate analysis, age >55 years (HR 2.29 [1.33-3.93],p=0.003) and elevated creatinine (HR 1.91 [1.19-3.08],p=0.008) were associated with increased mortality. Corrected for duration of VV-ECMO support, arterial thrombosis alone (HR 3.0 [95% CI1.5-5.9], P= 0.002) or circuit thrombosis alone (HR 3.9 [95% 2.4-6.3], P<0.001), but not venous thrombosis, increased mortality. MB during ECMO had 3-fold risk (95% CI 2.6-5.8, P<0.001) of mortality. The first wave cohort had more males (76.7% vs 64%, p=0.014), higher 180-day survival (71.1% vs 53.3% p=0.003), more venous thrombosis alone (46.4% vs 29.2%, p=0.02) and lower circuit thrombosis (9.2% vs 28.1%, p<0.001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%], p<0.0001) and Tocilizumab (20/150 [13.3%] vs 4/159 [2.5%] p=0.005). CONCLUSIONS: MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality whilst venous thrombosis alone had no effect. MB during ECMO support increased mortality 3.9-fold.
Arachchillage DJ, Rajakaruna I, Odho Z, et al., 2023, Impact of thromboprophylaxis on hospital acquired thrombosis following discharge in patients admitted with COVID-19: multicentre observational study in the UK, British Journal of Haematology, Vol: 202, Pages: 485-497, ISSN: 0007-1048
Post-discharge thromboprophylaxis in patients admitted with COVID-19 remains controversial. We aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in patients (≥18 years) discharged following admission for COVID-19 in an observational study across 26 NHS Trusts in the UK (01.04.2020-31.12.2021). Overall, 8895 patients were included to the study: 971 patients were discharged with thromboprophylaxis and propensity score matched (PSM) with a desired ratio of 1:1, from patients discharged without thromboprophylaxis. Patients with heparin induced thrombocytopenia, major bleeding during admission and pregnant women were excluded. As expected from 1:1 PSM, no difference was observed in parameters between the two groups, including duration of hospital stay, except the thromboprophylaxis group had a significantly higher proportion who had received therapeutic dose anticoagulation during admission. There were no differences in the laboratory parameters especially D-dimers between the two groups at admission or discharge. Median duration of thromboprophylaxis following discharge from hospital was 4 weeks (1-8 weeks). No difference was found in HAT in patients discharged with TP versus no TP (1.3% vs. 0.92%, p = 0.52). Increasing age and smoking significantly increased the risk of HAT. Many patients in both cohorts had raised D-dimer at discharge but D-dimer was not associated with increased risk of HAT.
Altmann DM, Whettlock EM, Liu S, et al., 2023, The immunology of long COVID, Nature Reviews Immunology, ISSN: 1474-1733
Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing-remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.
Garfield BE, Bianchi P, Arachchillage DJ, et al., 2023, A comparison of long-term outcomes in patients managed with venovenous extracorporeal membrane oxygenation in the first and second waves of the COVID-19 pandemic in the United Kingdom.., Critical Care Medicine, Vol: 51, Pages: 1064-1073, ISSN: 0090-3493
OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ2, 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in
Arachchillage DJ, Pericleous C, 2023, Evolution of Antiphospholipid Syndrome, SEMINARS IN THROMBOSIS AND HEMOSTASIS, Vol: 49, Pages: 295-304, ISSN: 0094-6176
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- Citations: 3
Arachchillage DJ, Laffan M, Pericleous C, 2023, Hydroxychloroquine as an Immunomodulatory and Antithrombotic Treatment in Antiphospholipid Syndrome, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 24
Jayakody Arachchillage D, Rajakaruna I, Pericleous C, et al., 2022, Autoimmune disease and COVID-19- a multicentre observational study in the United Kingdom, Rheumatology, Vol: 61, Pages: 4643-4655, ISSN: 1462-0324
ObjectiveTo establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) in comparison to a propensity matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK.MethodsThis is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a pre-designed standardised case record form. Adult patients (≥18 years) admitted between 1st of April 2020 and 31 July 2020 were included.ResultsOverall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with systemic lupus erythematosus, rheumatoid arthritis or antiphospholipid syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia: 240(60.91%) vs 206(52.28%), p= 0.015, raised LDH 150(38.08%) vs 43(10.92%), p< 0.001 and raised creatinine 122(30.96%) vs 86(21.83%), p= 0.01 respectively. A significantly higher proportion of patients with severe rheumatologic AD had raised CRP : 77(96.25%) vs 70(87.5%), p= 0.044 and LDH 20(25%) vs 6(7.5%), p= 0.021. Patients with severe rheumatologic AD had significantly higher mortality [32/80(40%)] compared with propensity matched cohort of patients without AD [20/80(25%)], p= 0.043. However, there was no difference in 180-day mortality between propensity matched cohorts of patients with or without AD in general, p= 0.47.ConclusionsPatients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and raised LDH were more frequent in patients with any AD whilst raised CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19.
Arachchillage DJ, Crossette-Thambiah C, Asmar N, et al., 2022, Cerebral vein thrombosis after ChAdOx1 nCov-19 vaccination: Long-term outcome of four patients, RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, Vol: 6
Bekono-Nessah I, Rosenburg A, Bowles CT, et al., 2022, Bleeding and thrombotic complications and their impact on mortality in patients supported with left ventricular assist device for cardiogenic shock, PERFUSION-UK, ISSN: 0267-6591
Arachchillage DJ, Mackillop L, Chandratheva A, et al., 2022, Guidelines for thrombophilia testing: A British Society for Haematology guideline, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 198, Pages: 443-458, ISSN: 0007-1048
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- Citations: 9
Vandenbriele C, Arachchillage DJ, Frederiks P, et al., 2022, Anticoagulation for percutaneous ventricular assist device-supported cardiogenic shock, Journal of the American College of Cardiology, Vol: 79, Pages: 1949-1962, ISSN: 0735-1097
Interest in the use of mechanical circulatory support for patients presenting with cardiogenic shock is growing rapidly. The Impella (Abiomed Inc), a microaxial, continuous-flow, short-term, ventricular assist device (VAD), requires meticulous postimplantation management. Because systemic anticoagulation is needed to prevent pump thrombosis, patients are exposed to increased bleeding risk, further aggravated by sepsis, thrombocytopenia, and high shear stress–induced acquired von Willebrand syndrome. The precarious balance between bleeding and thrombosis in percutaneous VAD–supported cardiogenic shock patients is often the main reason that patient outcomes are jeopardized, and there is a lack of data addressing optimal anticoagulation management strategies during percutaneous VAD support. Here, we present a parallel anti-Factor Xa/activated partial thromboplastin time-guided anticoagulation algorithm and discuss pitfalls of heparin monitoring in critically ill patients. This review will guide physicians toward a more standardized (anti)coagulation approach to tackle device-related morbidity and mortality in this critically ill patient group.
Crossette-Thambiah C, Pericleous C, Asmar N, et al., 2022, Clinical and biological features of cerebral venous sinus thrombosis following ChAdOx1 nCov-19 vaccination, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 93, Pages: 445-448, ISSN: 0022-3050
Vaccines for COVID-19were developed with unprecedented speedand since January 2021, the AstraZeneca/Oxford University ChAdOx1 nCoV-19 vaccine has been administered to over 400 million people globally1. In April 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA)reported a possible association between ChAdOx1 nCoV-19 and a rare syndrome of unusual site thrombosis combined with thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT).Frequency of VITT varies across age groups. Overall 411 cases of VITT have been reported to Medicine & Healthcare prodcuts Regulatory Agency (MHRA) by 21st of July 2021 with fatality rate of 17.76% (73/411)2.
Kefalogianni R, Kamani F, Gaspar M, et al., 2022, Complement activation during cardiopulmonary bypass and association with clinical outcomes., EJHaem, Vol: 3, Pages: 86-96
In this prospective, single-centre observational study of 30 patients undergoing cardiopulmonary bypass (CPB), the effect of unfractionated heparin (UFH), CPB surgery and protamine sulphate on complement and on post-operative blood loss were assessed. Although C3 and C4 levels decreased significantly immediately following the administration of UFH, C3a, C5a, Bb fragment and SC5b-9 remained unchanged. During CPB, C3 and C4 continued to fall whilst both alternative and classical pathways activation markers, Bb, C3a, C5a and SC5b-9 increased significantly. Protamine sulphate had no effect on classical pathway components or activation markers but decreased alternative pathway activation marker Bb. Over the 12-24 h post-surgery, both classical and alternative pathway activation markers returned to baseline, whilst C3 and C4 levels increased significantly but not to baseline values. Total drain volume 24 h after the surgery showed a moderate inverse correlation with post-protamine C3 (r = -0.46, p = 0.01) and C4 (r = -0.57, p = 0.0009) levels, whilst a moderate positive correlation was observed with post-protamine C3a (r = 0.46, p = 0.009), C5a (r = 0.37, p = 0.04) and SC5b-9 (r = 0.56, p = 0.001) levels but not with Bb fragment (r = 0.25, p = 0.17). Thus, inhibition of complement activation may be a therapeutic intervention to reduce post-operative blood in patients undergoing CPB.
Arachchillage DJ, Rajakaruna I, Scott I, et al., 2022, Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 196, Pages: 566-576, ISSN: 0007-1048
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- Citations: 21
Arachchillage DJ, Rajakaruna I, Odho Z, et al., 2022, Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 196, Pages: 79-94, ISSN: 0007-1048
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- Citations: 6
Crossette-Thambiah C, Nicolson P, Rajakaruna I, et al., 2021, The clinical course of COVID-19 in pregnant <i>versus</i> non-pregnant women requiring hospitalisation: results from the multicentre UK CA-COVID-19 study, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 195, Pages: 85-89, ISSN: 0007-1048
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Garfield B, Bianchi P, Arachchillage D, et al., 2021, Six month mortality in patients with COVID-19 and non-COVID-19 viral pneumonitis managed with veno-venous extracorporeal membrane oxygenation, ASAIO Journal, Vol: 67, Pages: 982-988, ISSN: 1058-2916
A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score [8.76 vs. 10.42, p = 0.004]), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS.
Mirsadraee S, Gorog DA, Mahon CF, et al., 2021, Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning, CRITICAL CARE MEDICINE, Vol: 49, Pages: 804-815, ISSN: 0090-3493
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Ranger A, Gaspar M, Elkhatteb A, et al., 2021, The heparin-von Willebrand factor interaction and conventional tests of haemostasis - the challenges in predicting bleeding in cardiopulmonary bypass, British Journal of Haematology, Vol: 192, Pages: 1073-1081, ISSN: 0007-1048
Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single‐centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen‐binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non‐significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase‐thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti‐Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.
Memtsas VP, Arachchillage DRJ, Gorog DA, 2021, Role, Laboratory Assessment and Clinical Relevance of Fibrin, Factor XIII and Endogenous Fibrinolysis in Arterial and Venous Thrombosis, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22
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Chang KW, Owen S, Gaspar M, et al., 2021, Outcome of major hemorrhage at a major cardiothoracic center in patients with activated major hemorrhage protocol versus nonactivated protocol., Seminars in Thrombosis and Hemostasis, Vol: 47, Pages: 74-83, ISSN: 0094-6176
This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data were collected retrospectively from patient electronic records and hospital transfusion databases recording issue of blood products from January 2016 to December 2018. Of 134 patients with MH, 24 had activated MHP and 110 did not have activated MHP. Groups were similar for age, sex, baseline hemoglobin, platelet count, coagulation screen, and renal function with no difference in the baseline clinical characteristics. The total number of red cell units (median and [IQR]) transfused was no different in the patients with activated (7.5 [5-11.75]) versus nonactivated (9 [6-12]) MHP (p = 0.35). Patients in the nonactivated MHP group received significantly higher number of platelet units (median: 3 vs. 2, p = 0.014), plasma (median: 4.5 vs. 1.5, p = 0.0007), and cryoprecipitate (median: 2 vs. 1, p = 0.008). However, activation of MHP was associated with higher mortality at 24 hours compared with patients with nonactivation of MHP (33.3 vs. 10.9%, p = 0.005) and 30 days (58.3 vs. 30.9%, p = 0.01). The total RBC and platelet (but not fresh frozen plasma [FFP]) units received were higher in deceased patients than in survivors. Increased mortality was associated with a higher RBC:FFP ratio. Only 26% of patients received tranexamic acid and these patients had higher mortality at 30 days but not at 24 hours. Deceased patients at 30 days had higher levels of fibrinogen than those who survived (median: 2.4 vs. 1.8, p = 0.01). Patients with activated MHP had significantly higher mortality at b
Price LC, Garfield B, Bleakley C, et al., 2020, Rescue therapy with thrombolysis in patients with severe COVID-19 ARDS, Pulmonary Circulation, Vol: 10, Pages: 1-5, ISSN: 2045-8940
Acute respiratory distress syndrome (ARDS) in patients with Coronavirus disease 19 (COVID-19) is associated with an unusually high incidence of pulmonary embolism (PE) and microthrombotic disease, with evidence for reduced fibrinolysis. We describes even patients requiring invasive ventilation for COVID-19 ARDS with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular (RV) dysfunction on echocardiography, who were treated with alteplaseas fibrinolytic therapy. All patients were non-smokers, 6 (86%) were male and median age was 56.7 (50-64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n=4), inhaled nitric oxide (n=5) and nebulised epoprostenol (n=2). The median duration of mechanical ventilation prior to thrombolysis was 7 (5-11) days.Systemic alteplase was administered to 6 patients (50mg or 90mg bolus over 120 minutes) at 16 (10-22) days after symptom onset. All received therapeutic heparin pre-and post-thrombolysis, without intracranial haemorrhageor other major bleeding. Alteplase improvedPaO2/FiO2(PF) ratio (from 97.0 (86.3-118.6) to 135.6 (100.7-171.4), p=0.03) and ventilatory ratio (from 2.76 (2.09 -3.49) to 2.36 (1.82 –3.05), p=0.011) at twenty-four hours.Echocardiographic parameters at 2 (1-3) days (n=6) showed RVSP was 63 (50.3-75) then 57 (49-66) mmHgpost-thrombolysis (p=0.26), TAPSE was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p=0.56)and RV fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1) %, p=0.09). At7 (1-13) days after thrombolysis,using DECT imaging(n=3),average relative peripheral lung enhancement increased from 12.6 to 21.6% (p=0.06).Conclusion:Thrombolysis improved PF ratio and ventilatory ratio at 24h as rescue therapy in patients with RV dysfunction due to COVID-19 ARDS despite maximum therapy
Arachchillage DJ, Desai SR, Devaraj A, et al., 2020, Reply to: Sanfilippo et al Caviedes et al., American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 261-263, ISSN: 1073-449X
Ridge CA, Desai SR, Jeyin N, et al., 2020, Dual-energy CT pulmonary angiography (DECTPA) quantifies vasculopathy in severe COVID-19 pneumonia, Radiology: Cardiothoracic Imaging, Vol: 2, ISSN: 2638-6135
BackgroundThe role of dual energy computed tomographic pulmonary angiography (DECTPA) in revealing vasculopathy in coronavirus disease 2019 (COVID-19) has not been fully explored.PurposeTo evaluate the relationship between DECTPA and disease duration, right ventricular dysfunction (RVD), lung compliance, D-dimer and obstruction index in COVID-19 pneumonia.Materials and MethodsThis institutional review board approved this retrospective study, and waived the informed consent requirement. Between March-May 2020, 27 consecutive ventilated patients with severe COVID-19 pneumonia underwent DECTPA to diagnose pulmonary thrombus (PT); 11 underwent surveillance DECTPA 14 ±11.6 days later. Qualitative and quantitative analysis of perfused blood volume (PBV) maps recorded: i) perfusion defect ‘pattern’ (wedge-shaped, mottled or amorphous), ii) presence of PT and CT obstruction index (CTOI) and iii) PBV relative to pulmonary artery enhancement (PBV/PAenh); PBV/PAenh was also compared with seven healthy volunteers and correlated with D-Dimer and CTOI.ResultsAmorphous (n=21), mottled (n=4), and wedge-shaped (n=2) perfusion defects were observed (M=20; mean age=56 ±8.7 years). Mean extent of perfusion defects=36.1%±17.2. Acute PT was present in 11/27(40.7%) patients. Only wedge-shaped defects corresponded with PT (2/27, 7.4%). Mean CTOI was 2.6±5.4 out of 40. PBV/PAenh (18.2 ±4.2%) was lower than in healthy volunteers (27 ±13.9%, p = 0.002). PBV/PAenh correlated with disease duration (β = 0.13, p = 0.04), and inversely correlated with RVD (β = -7.2, p = 0.001), persisting after controlling for confounders. There were no linkages between PBV/PAenh and D-dimer or CTOI.ConclusionPerfusion defects and decreased PBV/PAenh are prevalent in severe COVID-19 pneumonia. PBV/PAenh correlates with disease duration and inversely correlates with RVD. PBV/PAenh may be an important marker of vasculopathy in severe COVID-19 pneumonia
Padley GJ, Desai SS, Weaver C, et al., 2020, Catheter-Directed Thrombolysis in a Patient with Severe COVID-19 Pneumonia on Extracorporeal Membrane Oxygenation, SEMINARS IN THROMBOSIS AND HEMOSTASIS, Vol: 46, Pages: 850-852, ISSN: 0094-6176
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Arachchillage DJ, Remmington C, Rosenberg A, et al., 2020, Anticoagulation with argatroban in patients with acute antithrombin deficiency in severe COVID‐19, British Journal of Haematology, Vol: 190, Pages: e286-e288, ISSN: 0007-1048
Arachchillage DJ, Stacey A, Akor F, et al., 2020, Thrombolysis restores perfusion in COVID-19 hypoxia, British Journal of Haematology, Vol: 190, Pages: E270-E274, ISSN: 0007-1048
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