The Hypercoagulable Profile of Organ Donors with Intravascular Clots Has a Similar Profile to COVID-19 and ICU Patients with Thrombotic Complications

A test's negative predictive value-the probability that a negative result is a true negative result-is dependent on the prevalence of the condition. The present pandemic circumstances present us with unique challenges. False negatives in current testing methodology are to be expected.[1] Thus, a rigorous and contextual interpretation of a negative test result is necessary. Blood hypercoagulability and the risk of thrombosis are well documented in cases of the novel SARS-CoV-2 coronavirus (COVID-19) pandemic.[2] The systemic inflammatory response is associated with endothelial upregulation of proinflammatory mediators that lead to in situ thrombi, as well as a generalized disseminated intravascular coagulation. As many as 31% of ICU patients with COVID-19 have been reported to have thrombotic complications. More specifically, cerebral thrombotic complications confined to the arterial bed have been well described.[3, 4]. The case described shows that milder forms of coronavirus infection may lead to other types of critical and unusual thrombotic complications. An otherwise healthy 47-year-old Caucasian woman developed fever and respiratory signs and symptoms consistent with a possible case of COVID-19 infection in late March of 2020. Interstitial opacities were seen on radiographic examination. Two COVID-19 PCR nasopharyngeal tests were negative, and she recovered at home over the following 2 weeks. Three weeks later, she developed headaches, expressive aphasia, and a generalized tonic-clonic seizure. The patient was treated for a possible ischemic stroke with alteplase thrombolysis at a local hospital. After subsequent transfer and evaluation, a diagnosis of a left transverse and sigmoid sinus thrombosis with adjacent cortical edema was made. On review of her history, the patient denied taking any form of hormonal contraception, and did not have personal, or family history indicative of thrombophilia. She recovered fully after anticoagulation with enoxaparin and subsequent dabigatran. Prior to discharge a COVID-19, IgG antibody test was reported as positive. Decontextualized and overly simplistic interpretation of COVID-19 negative tests amidst a pandemic is problematic. In addition to the obvious infection control issues associated with the resulting lack of isolation and contract tracing, it may deprive some patients of the opportunity to receive antithrombotic therapy. Prophylactic and therapeutic regimens for hospitalized patients are in evolution, and have been associated with improved clinical outcomes.[5] We are aware that the role of anticoagulation in outpatient cases is not well studied, but we believe it deserves proper investigation. References: West, C.P., V.M. Montori, and P. Sampathkumar,COVID-19 Testing: The Threat of False Negative Results.Mayo Clin Proc, 2020.Thachil, J., et al.,ISTH interim guidance on recognition and management of coagulopathy inCOVID-19.J Thromb Haemost, 2020.18(5): p. 1023-1026.Oxley, T.J., et al.,Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young.N Engl J Med, 2020.Klok, F.A., et al.,Confirmation of the high cumulative incidence of thrombotic complications incritically ill ICU patients with COVID-19: An updated analysis.Thromb Res, 2020.Paranjpe, I., et al.,Association of Treatment Dose Anticoagulation with In-Hospital SurvivalAmong Hospitalized Patients with COVID-19.J Am Coll Cardiol, 2020. Disclosures No relevant conflicts of interest to declare.

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Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Thrombosis Research ◽

10.1016/j.thromres.2020.04.013 ◽

2020 ◽

Vol 191 ◽

pp. 145-147 ◽

Cited By ~ 1078

Author(s):

F.A. Klok ◽

M.J.H.A. Kruip ◽

N.J.M. van der Meer ◽

M.S. Arbous ◽

D.A.M.P.J. Gommers ◽

...

Keyword(s):

Critically Ill ◽

Icu Patients ◽

Thrombotic Complications

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Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis

Thrombosis Research ◽

10.1016/j.thromres.2020.04.041 ◽

2020 ◽

Vol 191 ◽

pp. 148-150 ◽

Cited By ~ 392

Author(s):

F.A. Klok ◽

M.J.H.A. Kruip ◽

N.J.M. van der Meer ◽

M.S. Arbous ◽

D. Gommers ◽

...

Keyword(s):

Critically Ill ◽

Cumulative Incidence ◽

Icu Patients ◽

Thrombotic Complications

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Non-Overt Coagulopathy in Non-ICU Patients with Mild to Moderate COVID-19 Pneumonia

Journal of Clinical Medicine ◽

10.3390/jcm9061781 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1781 ◽

Cited By ~ 4

Author(s):

Daniela Mazzaccaro ◽

Francesca Giacomazzi ◽

Matteo Giannetta ◽

Alberto Varriale ◽

Rosa Scaramuzzo ◽

...

Keyword(s):

Respiratory Distress ◽

Early Stage ◽

Characteristic Curve ◽

Thrombotic Complication ◽

Chi Square ◽

Icu Patients ◽

Non Invasive Ventilation ◽

Chi Square Test ◽

Thrombotic Complications ◽

Better Than

Introduction: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. Materials and methods: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. Results: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). Conclusions: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.

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Activated Platelets Harbour SARS-CoV-2 During Severe COVID-19

Thrombosis and Haemostasis ◽

10.1055/a-1683-8455 ◽

2021 ◽

Author(s):

Ejaife O. Agbani ◽

Prism Schneider ◽

Braedon McDonald ◽

Leslie Skeith ◽

Man-Chiu Poon ◽

...

Keyword(s):

3D Imaging ◽

State Of The Art ◽

Platelet Rich Plasma ◽

Icu Patients ◽

Blood Samples ◽

Passive Mechanism ◽

Activated Platelets ◽

Imaging Approach ◽

Thrombotic Complications ◽

Underlying Mechanisms

Clinical SARS-CoV-2 infection (COVID-19) is characterised by a hyperinflammatory and procoagulant state that increases the risk of thrombosis and death. Despite thromboprophylaxis at least at the conventional doses, incidence as high as 31% has been reported for thrombotic complications in Intensive Care Unit (ICU) patients with COVID-19 infections. Still, it remains unclear how SARS-Cov-2 may initiate and or perpetuates the intractable thrombo-inflammatory states in COVID-19; and the need to understand the underlying mechanisms is urgent. In this image report, we utilised a state-of-the-art high-resolution 3D imaging approach to examine the interactions of SARS-CoV-2 with platelets, erythrocytes and leucocytes in blood samples obtained from COVID-19 patients in our ICU; and we visualised platelet procoagulant activity and the spatial localisation of SARS-CoV-2 in platelet-rich-plasma reconstituted to contain erythrocytes and leucocytes. Strikingly, we observed that activated platelets harboured SARS-Cov-2 during severe COVID-19 in our patient that eventually succumbed to the infection. SARS-Cov-2 internalisation into the cytosol was probably via a passive mechanism, as we have previously established that actin cytoskeleton remodelling and increased membrane permeability occurred during platelet transformation to the procoagulant phenotype. More work is needed to understand platelets’ role in the recalcitrant thrombotic states of COVID-19.

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Platelet aggregates, a marker of severe COVID-19 disease

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206933 ◽

2020 ◽

pp. jclinpath-2020-206933

Author(s):

Alexandros Rampotas ◽

Sue Pavord

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Respiratory Failure ◽

Blood Film ◽

Platelet Activity ◽

Icu Patients ◽

Thrombotic Complications ◽

Platelet Aggregates

Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure.

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Continuation of therapeutic anticoagulation before and during hospitalization is associated with reduced mortality in COVID-19 ICU patients

Journal of Lung Pulmonary & Respiratory Research ◽

10.15406/jlprr.2021.08.00263 ◽

2021 ◽

Vol 8 (3) ◽

pp. 120-130

Author(s):

Rachel L. Choron ◽

Stephen Iacono ◽

Karishma Maharaja ◽

Christopher D. Adams ◽

Christopher A. Butts ◽

...

Keyword(s):

Critically Ill ◽

Lower Risk ◽

Multivariable Analysis ◽

Underlying Mechanism ◽

Icu Patients ◽

Risk Of Death ◽

Therapeutic Anticoagulation ◽

Significant Difference ◽

Thrombotic Complications ◽

Prophylactic Anticoagulation

Background: Literature has well established COVID-19 associated coagulopathy with resulting thrombotic complications including microthrombi as an underlying mechanism leading to severe respiratory disease. Therapeutic anticoagulation (TAC) for COVID-19 patients has therefore been widely trialed to combat COVID-19’s coagulopathic effects. However, literature has yet to define which population of patients TAC benefits; the most current randomized controlled trials (RCTs) reveal TAC to be possibly beneficial to moderately-ill hospitalized COVID-19 patients, whereas benefits did not outweigh risks in critically-ill ICU patients. Importantly, these studies excluded patients who received prehospital TAC. We examined outcomes in critically ill COVID-19 ICU patients who received TAC vs prophylactic anticoagulation (PAC) and specifically whether prehospital TAC effected outcomes. Methods: Retrospective cohort study of 132 COVID-19 ICU patients admitted March-June, 2020. Initial clinical practice provided PAC, as literature demonstrating COVID-19 associated coagulopathy and increased thromboembolic complications emerged, a TAC protocol was initiated. Results: 130 patients were included in the study, 95 of whom received TAC and 35 PAC. There was 50.8% overall mortality, with lower mortality in the TAC vs PAC group (46.3% vs 62.9%, p=0.094). There were few thromboembolic and hemorrhagic complications, with no significant difference between TAC and PAC patients. Of 24 patients anticoagulated prior to and during hospitalization, only 1 (4.2%) died, whereas the mortality was 60.6% among patients therapeutically anticoagulated during hospitalization only (p<0.001). Multivariable analysis revealed patients who received prehospital and in hospital TAC had a 92% lower risk of death (p=0.008) compared to in hospital only TAC and PAC patients. Conclusions: Overall, therapeutic anticoagulation did not result in mortality benefit to COVID-19 ICU patients compared to prophylactic anticoagulation. However, a sub-population of patients who received TAC both prior to and during hospitalization had a 12-fold lower risk of death. This suggests a protective effect of TAC when it is continued before and during hospitalization. RCTs are needed to specifically examine this subset of COVID-19 patients.

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LOX-1+ immature neutrophils predict severe COVID-19 patients at risk of thrombotic complications

10.1101/2020.09.15.293100 ◽

2020 ◽

Author(s):

Béhazine Combadiere ◽

Lucille Adam ◽

Paul Quentric ◽

Pierre Rosenbaum ◽

Karim Dorgham ◽

...

Keyword(s):

At Risk ◽

Point Of Care ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Clinical Severity ◽

Icu Patients ◽

Neutrophil Lymphocyte Ratio ◽

Density Lipoprotein Receptor ◽

Patients At Risk ◽

Thrombotic Complications

AbstractRationalLymphopenia and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 (COVID-19) severity.ObjectiveWe sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 patients based on Intensive Care Units (ICU) and non-ICU admission.MethodsWe developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 phenotypes in critical and severe patients.ResultsOur results showed that 80% of ICU patients develop strong myelemia with CD10−CD64+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or the Interleukin-3 receptor alpha (CD123), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm (IL-1β, IL-6, IL-8, TNFα), and with intravascular coagulation. Importantly, high proportions of LOX-1+-immature neutrophils are associated with high risks of severe thrombosis.ConclusionsTogether these data suggest that point of care enumeration of LOX-1-immature neutrophils might help distinguish patients at risk of thrombosis complication and most likely to benefit from intensified anticoagulant therapy.

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Assessment of Hematologic and Coagulation Parameters As Predictive Value in COVID-19 with Unfavourable Evolution

Blood ◽

10.1182/blood-2020-134153 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 13-13

Author(s):

Viola Maria Popov ◽

Lelia Iliescu ◽

Marius Ioan Balea ◽

Daniela Georgeta Georgescu ◽

Mihaela Andreescu ◽

...

Keyword(s):

Conflicts Of Interest ◽

Ferritin Level ◽

Hematological Parameters ◽

Severe Pneumonia ◽

Protein S ◽

Coefficient Of Determination ◽

Icu Patients ◽

Coagulation Parameters ◽

Thrombotic Complications ◽

A Prospective Study

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious disease. The pathogenic mechanism of COVID-19 pneumonia involved excessive immune reaction in the host - a "cytokine storm", that determined extensive tissue damage associated with coagulation abnormalities. Severity of this disease is associated with comorbidities such as hypertension, obesity, pulmonary disease or age. Thrombotic complications are reported during COVID-19 evolution even with prophylaxis. OBJECTIVE: In this study, we evaluate hematological and coagulation parameters in order to obtain predictors for an unfavourable evolution of the patient. DESIGN AND SETTING: We performed a prospective study that included all patients admitted in our hospital in Hematology, Pneumology, and Intensive Care Unit (ICU) Department at Colentina Clinical Hospital during April - July 2020. The study group included 144 patients that were split into ICU and non-ICU patients. All patients were SARS-CoV-2-positive by molecular test. The distribution according to gender was as follows: 67 male with median age: 61 (min 22, max 88) and 77 female with median age: 57 (min 17, max 92). RESULTS: Age is an important risk factor for the severity; 50 patients admitted in ICU with median age 67 (min 34, max 92) and 94 non-ICU patients with median age 52.5 (min 17, max 92), p=0.00003. Associated comorbidities were important and were present in both groups. In ICU patients, we obtained lower level of lymphocytes compared with non ICU group median: 1 x 103/L (min 0.04 x 103/L max 3.28 x 103/L) vs 1.57 x 103/L (min 0.39 x 103/L max 23.35 x 103/L), p=0.0001. There are no significant differences between groups for the rest of hematological parameters. The neutrophil/lymphocytes ratio (NLR) is with statistical difference between ICU and non-ICU groups: 2.34 (min 1.06, max 31.90) vs 7.94 (min 2.18, max 90.04), p<0.000001. This indicator seems to be predictor for severe evolution; a high correlation with IL-6 level (r=0.73, p< 0.001) was obtained. NLR in association with IL-6, CRP and ferritin level are important factors in severe evolution of COVID-19 (severe pneumonia-more than 50% of lung evaluated by CT-scan and presence of any complications during COVID-19 evolution), coefficient of determination-R2 =0.69, R2 - adjusted 0.67, p<0.0001). The ICU patients with unfavourable evolution had a higher level of D-Dimers at the admission in hospital compared with ICU patients who were discharged from the hospital (3.42 mg/ml FEU vs 1.09 mg/ml FEU, p=0.01). Patients with thrombosis (stroke, myocardial infarction, deep venous thrombosis, thromboembolism) during COVID-19 evolution have higher level of D Dimers compared with patients without thrombotic complications (7.35 mg/ml FEU vs 0.82 mg/ml FEU), p=0.0001. There are no difference for another coagulation tests (APTT, Quick time) or Protein C, Protein S and Antithrombin III level. CONCLUSIONS: We conclude that NLR in association with feritin, CRP and IL-6 assessment are important to be evaluated in COVID-19 patient in order to expect a severe evolution of the disease. D- Dimer should be an important parameter to be evaluated for all COVID-19 patients in order to identify COVID-19 patients with high risk of thrombotic complications. Disclosures No relevant conflicts of interest to declare.

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Die Aplasie der Vena cava inferior als Ursache rezidivierender Bein- und Beckenvenenthrombosen

VASA ◽

10.1024/0301-1526.28.4.289 ◽

1999 ◽

Vol 28 (4) ◽

pp. 289-292 ◽

Cited By ~ 16

Author(s):

Tiesenhausen ◽

Amann ◽

Thalhammer ◽

Aschauer

Keyword(s):

Inferior Vena Cava ◽

Inferior Vena ◽

Heart Defects ◽

Vena Cava ◽

Clinical Signs ◽

Vena Cava Inferior ◽

Caval Vein ◽

Rare Finding ◽

Thrombotic Complications ◽

Asplenia Syndrome

Congenital anomalies of the caval vein are often associated with other abnormities such as heart defects, situs inversus or a polysplenia-asplenia-syndrome. An isolated, congenital malformation like aplasia of the inferior vena cava is a rare finding. A review of the embryology and abnormities, diagnostics, clinical signs and treatment is given together with the histories of two patients having thrombosis of the lower extremities and pelvic veins, caused by aplasia of the inferior vena cava. After thrombotic complications caused by vena cava aplasia there is high risk of recurrence. Those patients should be anticoagulated for lifetime.

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