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1.
BMJ Case Rep ; 15(3)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1745765

ABSTRACT

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition related to a state of hypercoagulability in advanced neoplastic disease. Most of the time, arterial thromboembolic event precedes the diagnosis of NBTE. We report here a case of NBTE responsible for multiple ischaemic strokes, which leads to the diagnosis of metastatic pancreatic adenocarcinoma. Aortic and mitral valvular regurgitations secondary to NBTE appeared within 6 weeks despite therapeutic anticoagulation with direct oral anticoagulant (DOAC) in stroke prevention of paroxysmal atrial fibrillation. Bivalvular regurgitations resolved 8 weeks after therapeutic switch to low-molecular-weight heparin (LMWH) and chemotherapy. DOACs are a possible alternative to LMWH for the prevention of venous thromboembolism in patients with active neoplasia. There is a lack of evidence for a clinical efficiency for the prevention of arterial thromboembolism in NBTE. We propose here a short review of the efficacy of anticoagulant therapy for the prevention of arterial thromboembolism in NBTE.


Subject(s)
Adenocarcinoma , Endocarditis, Non-Infective , Pancreatic Neoplasms , Adenocarcinoma/drug therapy , Anticoagulants/therapeutic use , Endocarditis, Non-Infective/diagnosis , Endocarditis, Non-Infective/drug therapy , Endocarditis, Non-Infective/etiology , Heparin , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/drug therapy
2.
Semin Thromb Hemost ; 48(3): 309-317, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1692483

ABSTRACT

Cerebral venous thrombosis (CVT) is a rare form of stroke that often affects younger age groups, especially reproductive age group females. CVT is a potentially fatal neurological condition that can be frequently overlooked due to the vague nature of its clinical and radiological presentation. Headache is the most common presenting symptom. However, a wide range of symptoms can be present and the symptom onset can be acute, subacute, or chronic. Neuroimaging is mandatory in cases where CVT is suspected. Both magnetic resonance venography and computed tomography venography can confirm a diagnosis of CVT. Anticoagulation with low-molecular-weight heparin is the mainstay of treatment. Intracranial hemorrhage is not considered a contraindication to the use of anticoagulants in CVT. Endovascular intervention is still controversial but can be a treatment option for patients with neurological deterioration or thrombus progression, despite the use of anticoagulation or with development of new or worsening intracerebral hemorrhage. Patients with CVT have an increased risk of recurrence of CVT and other types of venous thromboembolism. This review provides an overview of the epidemiology, diagnosis, and treatment of CVT in adults. Commentary about increased presentation of CVT in patients with coronavirus disease 2019 (COVID-19), or after immunization against COVID-19, is also provided.


Subject(s)
COVID-19 , Intracranial Thrombosis , Venous Thrombosis , Adult , Anticoagulants/therapeutic use , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Intracranial Thrombosis/drug therapy , Intracranial Thrombosis/therapy , Venous Thrombosis/drug therapy , Venous Thrombosis/therapy
3.
Medicina (Kaunas) ; 58(2)2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1667242

ABSTRACT

Background: The frequent occurrence of thromboembolic events in patients infected with the severe acute respiratory syndrome CoV2 (SARS-CoV-2) virus is a well-recognized fact in the medical literature, but less data is available about possible hemorrhagic incidents. Methods: We report the case of a 76-year-old patient who suffered from a mild COVID-19 infection in September 2021 and after four weeks, experienced a completely spontaneous popliteal hematoma followed by deep vein thrombosis (DVT). Therapy with low molecular weight heparins (LMWH) was started, but subsequently, the patient developed a massive sub-pectoral and calf hematoma leading to moderate post-hemorrhagic anemia and acute kidney injury. This patient was treated completely conservatively. Conclusions: Considering the continuous spread of the infection with various, continuously evolving strains of this virus and the extended use of LWMH in clinical practice, such cases were seldom described in the medical literature, but should be considered as a potential cause for hemorrhagic events.


Subject(s)
COVID-19 , Venous Thrombosis , Aged , Hematoma/etiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , SARS-CoV-2 , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology
4.
J Thromb Haemost ; 20(4): 1008-1014, 2022 04.
Article in English | MEDLINE | ID: covidwho-1662290

ABSTRACT

BACKGROUND: Hypercoagulability and endothelial dysfunction are hallmarks of coronavirus disease 2019 (COVID-19) and appear to predict disease severity. A high incidence of thrombosis despite thromboprophylaxis is reported in patients with moderate to severe COVID-19. Recent randomized clinical trials suggest that therapeutic-intensity heparin confers a survival benefit in moderate-severity COVID-19 compared to standard-intensity heparin, potentially by harnessing heparin-mediated endothelial-stabilizing and anti-inflammatory effects. OBJECTIVE: We hypothesized that patients with moderate-severity COVID-19 exhibit enhanced hypercoagulability despite standard-intensity thromboprophylaxis with low molecular weight heparin (LMWH) compared to non-COVID-19 hospitalized patients. METHODS: Patients with moderate COVID-19 and a control group (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-negative hospitalized patients) receiving LMWH thromboprophylaxis were recruited. Markers of endothelial damage and plasma thrombin generation parameters were assessed. RESULTS: Tissue plasminogen activator levels were significantly increased in the COVID-19 group (8.3 ± 4.4 vs. 4.9 ± 2.4 ng/ml; P = .02) compared to non-COVID-19-hospitalized patients. Despite thromboprophylaxis, mean endogenous thrombin potential was significantly increased among COVID-19 patients (1929 ± 448 vs. 1528 ± 460.8 nM*min; P = .04) but lag time to thrombin generation was significantly prolonged (8.1 ± 1.8 vs. 6.2 ± 1.8 mins; P = .02). While tissue factor pathway inhibitor (TFPI) levels were similar in both groups, in the presence of an inhibitory anti-TFPI antibody, the difference in lag time between the groups was abrogated. CONCLUSIONS: Collectively, these data demonstrate that COVID-19 of moderate severity is associated with increased plasma thrombin generation and endothelial damage, and that hypercoagulability persists despite standard LMWH thromboprophylaxis. These findings may be of clinical interest given recent clinical trial data which suggest escalated heparin dosing in non-severe COVID-19 may be associated with improved clinical outcomes.


Subject(s)
COVID-19 , Thrombophilia , Venous Thromboembolism , Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , SARS-CoV-2 , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Tissue Plasminogen Activator , Venous Thromboembolism/epidemiology
5.
Cardiovasc Res ; 117(14): 2807-2820, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1596913

ABSTRACT

AIMS: Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. METHODS AND RESULTS: Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6-24) vs. 9 (interquartile range: 5-16) days, P = 0.009]. CONCLUSION: Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , /virology , Aged , Anticoagulants/pharmacology , Austria/epidemiology , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/mortality , Female , Hemostasis , Heparin, Low-Molecular-Weight/pharmacology , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , SARS-CoV-2/drug effects , /prevention & control
6.
Thromb Haemost ; 122(2): 295-299, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1595734

ABSTRACT

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.


Subject(s)
COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Pneumonia/drug therapy , SARS-CoV-2/physiology , Aged , COVID-19/mortality , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Male , Middle Aged , Pneumonia/mortality , Respiration, Artificial , Severity of Illness Index , Survival Analysis , Treatment Outcome
7.
Med Sci Monit ; 27: e935379, 2021 Dec 30.
Article in English | MEDLINE | ID: covidwho-1593238

ABSTRACT

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.


Subject(s)
COVID-19/diagnosis , COVID-19/drug therapy , Hospitalization/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Aged , Aged, 80 and over , Aspirin/therapeutic use , Betamethasone/therapeutic use , Cohort Studies , Dietary Supplements , Early Diagnosis , Female , Flavonoids/therapeutic use , Follow-Up Studies , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Indomethacin/therapeutic use , Italy , Male , Middle Aged , Omeprazole/therapeutic use , Patient Acuity , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Time , Treatment Outcome
8.
PLoS One ; 16(3): e0248009, 2021.
Article in English | MEDLINE | ID: covidwho-1575841

ABSTRACT

INTRODUCTION: Since the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death. METHODS AND FINDINGS: We conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk. CONCLUSIONS: We evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.


Subject(s)
COVID-19/pathology , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/administration & dosage , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Dyspnea/etiology , Female , Fever/etiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Mental Disorders/complications , Mental Disorders/pathology , Neoplasms/complications , Neoplasms/pathology , Nursing Homes , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Sex Factors , Survival Rate
9.
Anaesthesist ; 70(8): 662-670, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1575534

ABSTRACT

BACKGROUND: In the context of sepsis and septic shock, coagulopathy often occurs due to the close relationship between coagulation and inflammation. Sepsis-induced coagulopathy (SIC) is the most severe and potentially fatal form. Anticoagulants used in prophylactic or therapeutic doses are discussed to potentially exert beneficial effects in patients with sepsis and/or SIC; however, due to the lack of evidence recent guidelines are limited to recommendations for drug prophylaxis of venous thromboembolism (VTE), while treatment of SIC has not been addressed. METHODS: In order to determine the status quo of VTE prophylaxis as well as treatment of SIC in German intensive care units (ICU), we conducted a Germany-wide online survey among heads of ICUs from October 2019 to May 2020. In April 2020, the survey was supplemented by an additional block of questions on VTE prophylaxis and SIC treatment in coronavirus disease 2019 (COVID-19) patients. RESULTS: A total of 67 senior doctors took part in the survey. The majority (n = 50; 74.6%) of the responses were from ICU under the direction of an anesthesiologist and/or a department of anesthesiology. Most of the participants worked either at a university hospital (n = 31; 47.8%) or an academic teaching hospital (n = 27; 40.3%). The survey results show a pronounced heterogeneity in clinical practice with respect to the prophylaxis of VTE as well as SIC treatment. In an exemplary case of pneumogenic sepsis, low molecular weight heparins (LMWH) were by far the most frequently mentioned group of medications (n = 51; 76.1% of the responding ITS). In the majority of cases (n = 43; 64.2%), anti-FXa activity is not monitored with the use of LMWH in prophylaxis doses. Unfractionated heparin (UFH) was listed as a strategy for VTE prophylaxis in 37.3% of the responses (n = 25). In an exemplary case of abdominal sepsis 54.5% of the participants (n = 36; multiple answers possible) stated the use of UFH or LMWH and UFH with dosage controlled by PTT is used on two participating ICUs. The anti-FXa activity under prophylactic anticoagulation with LMWH is monitored in 7 participating clinics (10.6%) in abdominal sepsis. Systematic screening for sepsis-associated coagulation disorders does not take place in most hospitals and patterns in the use of anticoagulants show significant variability between ICUs. In the case of COVID-19 patients, it is particularly noticeable that in three quarters of the participating ICUs the practice of drug-based VTE prophylaxis and SIC treatment does not differ from that of non-COVID-19 patients. CONCLUSION: The heterogeneity of answers collected in the survey suggests that a systematic approach to this topic via clinical trials is urgently needed to underline individualized patient care with the necessary evidence.


Subject(s)
Anticoagulants , Blood Coagulation Disorders , Heparin, Low-Molecular-Weight/therapeutic use , Sepsis , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Germany , Heparin/therapeutic use , Humans , Intensive Care Units , Sepsis/complications
11.
Bosn J Basic Med Sci ; 22(2): 270-279, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1529055

ABSTRACT

The aim of this study was to investigate the patient characteristics and laboratory parameters for COVID-19 non-survivors as well as to find risk factors for major bleeding complications. For this retrospective study, the data of patients who died with COVID-19 in our intensive care unit were collected in the period of March 20 - April 30, 2020. D-dimer, platelet count, C-reactive protein (CRP), troponin, and international normalized ratio (INR) levels were recorded on the 1st, 5th, and 10th days of hospitalization in order to investigate the possible correlation of laboratory parameter changes with in-hospital events. A total of 161 non-survivors patients with COVID-19 were included in the study.  The median age was 69.8±10.9 years, and 95 (59%) of the population were male. Lung-related complications were the most common in-hospital complications. Patients with COVID-19 had in-hospital complications such as major bleeding (39%), hemoptysis (14%), disseminated intravascular coagulation (13%), liver failure (21%), ARDS (85%), acute kidney injury (40%), and myocardial injury (70%). A multiple logistics regression analysis determined that age, hypertension, diabetes mellitus, use of acetylsalicylic acid (ASA) or low molecular weight heparin (LMWH), hemoglobin, D-dimer, INR, and acute kidney injury were independent predictors of major bleeding. Our results showed that a high proportion of COVID-19 non-survivors suffered from major bleeding complications.


Subject(s)
COVID-19 , Heparin, Low-Molecular-Weight , Aged , Aged, 80 and over , COVID-19/complications , Hemorrhage/etiology , Heparin, Low-Molecular-Weight/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies
12.
Viruses ; 13(11)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1481019

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control , Anticoagulants/administration & dosage , Delphi Technique , Duration of Therapy , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Venous Thromboembolism/complications , Venous Thromboembolism/diagnosis
13.
Cardiovasc Res ; 117(14): 2807-2820, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1450385

ABSTRACT

AIMS: Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. METHODS AND RESULTS: Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6-24) vs. 9 (interquartile range: 5-16) days, P = 0.009]. CONCLUSION: Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , /virology , Aged , Anticoagulants/pharmacology , Austria/epidemiology , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/mortality , Female , Hemostasis , Heparin, Low-Molecular-Weight/pharmacology , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , SARS-CoV-2/drug effects , /prevention & control
14.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Article in English | MEDLINE | ID: covidwho-1448131

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2 , Thrombophilia/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Consensus , Critical Illness , Disease Management , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/analysis , Fondaparinux/adverse effects , Fondaparinux/therapeutic use , Hemorrhage/chemically induced , Heparin/adverse effects , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inpatients , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Pregnancy Complications, Infectious/blood , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk , Thrombophilia/etiology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
15.
Curr Hematol Malig Rep ; 16(5): 455-463, 2021 10.
Article in English | MEDLINE | ID: covidwho-1442179

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is associated with a high rate of respiratory failure, thromboembolism, bleeding, and death. Patients with myeloproliferative neoplasms (MPNs) are prone to both thrombosis and bleeding, calling for special care during COVID-19. We reviewed the clinical features of MPN patients with COVID-19, suggesting guidance for treatment. RECENT FINDINGS: One study by the European LeukemiaNet collected 175 MPN patients with COVID-19 during the first wave of the pandemic, from February to May 2020. Patients with primary myelofibrosis (PMF) were at higher risk of mortality (48%) in comparison with essential thrombocythemia (ET) (25%) and polycythemia vera (19%); the risk of death was higher in those patients who abruptly discontinued ruxolitinib. In patients followed at home, in regular wards, or in ICU, the thrombosis rate was 1.0%, 2.8%, and 18.4%, respectively. Independent risk factors for thrombosis were ET phenotype, transfer to ICU, and neutrophil/lymphocyte ratio; major bleeding occurred in 4.3% of patients, particularly those with PMF. MPN patients with non-severe COVID-19 treated at home should continue their primary or secondary antithrombotic prophylaxis with aspirin or oral anticoagulants. In the case of hospitalization, patients assuming aspirin should add low molecular weight heparin (LMWH) at standard doses. In contrast, LMWH at intermediate/therapeutic doses should replace oral anticoagulants prescribed for atrial fibrillation or previous venous thromboembolism. Intermediate/high doses of LMWH can also be considered in ICU patients with ET, particularly in the case of a rapid decline in the number of platelets and progressive respiratory failure.


Subject(s)
COVID-19 , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/complications , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/diagnosis , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/epidemiology , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/therapy , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/epidemiology , Myeloproliferative Disorders/therapy , Pandemics , SARS-CoV-2/physiology , Thrombosis/epidemiology
16.
Semin Reprod Med ; 39(5-06): 186-193, 2021 11.
Article in English | MEDLINE | ID: covidwho-1440502

ABSTRACT

Thrombosis in pregnancy is a major cause of maternal and fetal morbidity and mortality. Risk stratification of venous thromboembolism (VTE) during pregnancy is complex. The hypercoagulability observed in pregnant women can reduce bleeding during childbirth, but may cause thrombosis especially in the presence of additional prothrombotic risk factors such as antiphospholipid antibodies or genetic thrombophilic defects. The availability of large datasets allows for the identification of additional independent risk factors, including assisted reproductive technologies (ARTs), endometriosis, and recurrent pregnancy loss. Data on the risk of VTE linked to COVID-19 in pregnant women are very limited, but suggest that infected pregnant women have an increased risk of VTE. Current guidelines on the prevention and treatment of VTE in pregnancy are based on available, albeit limited, data and mainly present expert opinion. Low-molecular-weight heparins (LMWHs) are the mainstay of anticoagulation to be employed during pregnancy. Administration of LMWH for VTE treatment in pregnancy should be based on the personalized approach, taking into account a weight-based adjusted scheme. During gestation, due to physiological changes, in women at high risk of VTE, monitoring of anti-Xa activity is performed to ensure adequate LMWH dosing. As for the treatment duration for pregnant women with acute VTE, guidelines suggest that anticoagulation should be continued for at least 6 weeks postpartum for a minimum total duration of therapy of 3 months.


Subject(s)
COVID-19 , Venous Thromboembolism , Antibodies, Antiphospholipid , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pregnancy , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
17.
Viruses ; 13(10)2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438739

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/physiopathology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Blood Coagulation Disorders/drug therapy , COVID-19/drug therapy , Endothelial Cells , Factor Xa Inhibitors/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inflammation/drug therapy , Male , Middle Aged , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Thrombosis/drug therapy , Thrombosis/immunology
18.
Cardiol J ; 28(5): 758-766, 2021.
Article in English | MEDLINE | ID: covidwho-1431057

ABSTRACT

The coronavirus pandemic disease 2019 (COVID-19) has changed the face of contemporary medicine. However, each and every medical practitioner must be aware of potential early and late complications of COVID-19, its impact on chronic diseases - especially ones as common as atrial fibrillation (AF) - and the possible interactions between patients' chronic medications and pharmacotherapy of COVID-19. Patients with AF due to comorbidities and, often, elderly age are assumed to be at a higher risk of a severe course of COVID-19. This expert consensus summarizes the current knowledge regarding the pharmacotherapy of AF patients in the setting of the COVID-19 pandemic. In general, anticoagulation principles in quarantined or asymptomatic individuals remain unchanged. Nevertheless, it is advisable to switch from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants (NOACs) whenever possible due to their consistent benefits and safety with fixed dosing and no monitoring. Additionally, in AF patients hospitalized due to mild or moderate COVID-19 pneumonia, we recommend continuing NOAC treatment or to switching to low-molecular-weight heparin (LMWH). On the other hand, in severely ill patients hospitalized in intensive care units, intravenous or subcutaneous dosing is preferable to oral, which is why the treatment of choice is either LMWH or unfractionated heparin. Finally, particularly in critical scenarios, the treatment strategy in COVID-19 patients with AF should be individualized based on possible interactions between anticoagulants, antiarrhythmics, antivirals, and antibiotics. In this consensus, we also discuss how to safely perform COVID-19 vaccination in anticoagulated AF patients.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Administration, Oral , Aged , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , COVID-19 Vaccines , Heparin , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pandemics , SARS-CoV-2 , Vitamin K
19.
Chest ; 161(2): 418-428, 2022 02.
Article in English | MEDLINE | ID: covidwho-1363121

ABSTRACT

BACKGROUND: Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population. RESEARCH QUESTION: What is the comparative efficacy and safety of prophylaxis agents for prevention of VTE in critically ill adults? STUDY DESIGN AND METHODS: Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. RESULTS: We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 [95% credible interval [CrI], 0.33-0.90]; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 [95% CrI, 0.47-1.37]; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 [95% CrI, 0.46-0.98]; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 [95% CrI, 0.50-1.50]). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty). INTERPRETATION: Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pharmacologic therapy and mechanical compressive devices were unclear. TRIAL REGISTRY: Open Science Framework; URL: https://osf.io/694aj.


Subject(s)
Anticoagulants/therapeutic use , Critical Illness , Intermittent Pneumatic Compression Devices , Venous Thromboembolism/prevention & control , Adult , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pulmonary Embolism/prevention & control , Randomized Controlled Trials as Topic
20.
Sao Paulo Med J ; 140(1): 123-133, 2022.
Article in English | MEDLINE | ID: covidwho-1362119

ABSTRACT

BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic-dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.


Subject(s)
COVID-19 , Venous Thromboembolism , Adult , Aged , Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inpatients , SARS-CoV-2
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