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2.
Medicina (Kaunas) ; 58(11)2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2116272

ABSTRACT

Background and Objectives: Aspirin (ASA) is a commonly used antithrombotic drug that has been demonstrated to reduce venous thromboembolism. The aim was to analyze if geriatric COVID-19 patients undergoing a 100 mg/day Aspirin (ASA) treatment prior to hospitalization differ in hospital outcome compared to patients without previous ASA therapy. Materials and Methods: An observational retrospective study was carried out using an anonymized database including geriatric COVID-19 patients (March to April 2020) admitted to Madrid Hospitals Group. A group of COVID-19 patients were treated with low ASA (100 mg/day) prior to COVID-19 infection. Results: Geriatric ASA-treated patients were older (mean age over 70 years; n = 41), had higher frequency of hypertension and hyperlipidemia, and upon admission had higher D-dimer levels than non-ASA-treated patients (mean age over 73 years; n = 160). However, patients under ASA treatment did not show more frequent pulmonary thromboembolism (PE) than non-ASA-treated patients. ASA-treated geriatric COVID-19-infected patients in-hospital < 30 days all-cause mortality was more frequent than in non-ASA-treated COVID-19 patients. In ASA-treated COVID-19-infected geriatric patients, anticoagulant therapy with low molecular weight heparin (LMWH) significantly reduced need of ICU care, but tended to increase in-hospital < 30 days all-cause mortality. Conclusions: Prior treatment with a low dose of ASA in COVID-19-infected geriatric patients increased frequency of in-hospital < 30 days all-cause mortality, although it seemed to not increase PE frequency despite D-dimer levels upon admission being higher than in non-ASA users. In ASA-treated geriatric COVID-19-infected patients, addition of LMWH therapy reduced frequency of ICU care, but tended to increase in-hospital < 30 days all-cause mortality.


Subject(s)
Aspirin , COVID-19 , Humans , Aged , Aspirin/therapeutic use , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Retrospective Studies , Hospitals
3.
Chirurgia (Bucur) ; 117(5): 526-534, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2100672

ABSTRACT

Background: Spontaneous retroperitoneal hematoma is a severe and potentially fatal complication that appears in the course of anticoagulation therapy. Therapeutic doses of low molecular weight heparin (LMWH) are used for the prevention of thrombosis in patients seriously ill with Covid-19. Methods: We describe 27 (0.14%) patients with retroperitoneal hematomas who required emergency surgery out of 19108 patients with Covid-19 who were hospitalized in Batajnica COVID Hospital between March 2021 and March 2022. All the patients were on therapeutic doses of LMWH. The existence of retroperitoneal hematoma was confirmed by abdominal ultrasound and computed tomography scans. Results: Open surgery was performed on 27 patients with spontaneous retroperitoneal hematomas (12 female and 15 male). The mean age of the study population was 71.6+-11.9 years. D-dimer was significantly elevated two days before the surgery in comparison with the values on the day of surgery (p=0.011). Six patients (22.23%) survived, while 21 (77.77%) patients died. Conclusion: Bleeding in Covid-19 patients treated by LMWH is associated with an increased risk of developing retroperitoneal hematoma. Open surgery for retroperitoneal hematoma in Covid-19 patients on anticoagulation therapy is a procedure associated with a high rate of mortality.


Subject(s)
COVID-19 , Peritoneal Diseases , Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Heparin, Low-Molecular-Weight , Anticoagulants , Treatment Outcome , Hematoma , Gastrointestinal Hemorrhage
4.
Turk J Ophthalmol ; 52(5): 324-330, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2100078

ABSTRACT

Objectives: Retinal vascular complications have been described in patients with coronavirus disease 2019 (COVID-19). This study aimed to analyze retinal microvascular changes and their correlations with clinical findings. Materials and Methods: This case-controlled study was conducted in a university hospital. The right eyes of 52 otherwise healthy patients recovered from COVID-19 and 42 healthy controls were examined with optical coherence tomography angiography. Mann-Whitney U test was used to compare vessel density (VD) and foveal avascular zone (FAZ) parameters. Associations with treatment choices, pneumonia, and laboratory findings were analyzed. Results: Twenty-nine patients (56%) and 18 healthy controls (43%) were men. Mean age of the COVID-19 group was 39.00±13.04 years. Twenty-two patients had pneumonia, 18 (35%) received hydroxychloroquine (HCQ), 17 (33%) received HCQ plus low-molecular-weight heparin (LMWH), and 10 (19%) received favipiravir. The patient group had lower parafoveal VD in the superficial capillary plexus (SCP) and lower parafoveal VD and perifoveal VD in the deep capillary plexus (DCP) than controls (p=0.003, p=0.004, p=0.001). FAZ area did not differ significantly (p=0.953). Perifoveal VD in the DCP was also significantly lower in the HCQ+LMWH group than the HCQ group (p=0.020) and in the presence of pneumonia (p=0.040). C-reactive protein (CRP) and ferritin levels were negatively correlated with perifoveal VD in the DCP (r=-0.445, p=0.023; r=-0.451, p=0.040). Ferritin was also negatively correlated with parafoveal VD in the SCP (r=-0.532, p=0.013). Conclusion: Parafoveal and perifoveal VD was found to be lower in the COVID-19 group. Presence of pneumonia, need for LMWH prophylaxis, and levels of CRP and ferritin were found to be negatively associated with retinal VD. Large-scale studies are needed to evaluate the clinical importance.


Subject(s)
COVID-19 , Tomography, Optical Coherence , Male , Humans , Adult , Middle Aged , Female , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Fovea Centralis , COVID-19/complications , Heparin, Low-Molecular-Weight , Hydroxychloroquine/therapeutic use , Ferritins
5.
Medicine (Baltimore) ; 101(37): e30367, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2077953

ABSTRACT

In patients with coronavirus disease 2019 (COVID-19), anticoagulation was suggested as a mitigating strategy. However, little research has been conducted on the adverse consequences of anticoagulant medication. This study aimed to investigate the adverse effect of low molecular weight heparin (LMWH) on hemoglobin fall in COVID-19 treatment. The electronic medical records of COVID-19 patients with pneumonia were collected (including clinical characteristics, vaccination status, complete blood count, coagulation profile, inflammatory cytokines, serum biochemical indicators, and computerized tomography imaging score). Whether they received LMWH, patients were divided into the LMWH group and the control group. Count data were represented as frequency distribution, and a 2-tailed test was used to compare the 2 groups. Spearman rank correlation was used to evaluate the interrelation between changes in hemoglobin and LMWH. The confounding factors were excluded by logistic regression analysis. A total of 179 COVID-19 pneumonia patients were enrolled (81 in the LMWH group and 98 in the control group). The change in hemoglobin was -6.0g/L (IQR -10.8 to 1.0) in the LMWH group and -2.0g/L (IQR -7.0 to 4.0) in the control group (P < .001, between-group difference, -5.0 g/L; 95% confidence interval, -7.0 to -3.0, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). The results of multivariate regression analysis showed that after adjusting for confounding factors, LMWH use was not associated with a decrease in hemoglobin (P > .05). In nonsevere COVID-19 patients with pneumonia, the preventive use of LMWH did not lower hemoglobin.


Subject(s)
COVID-19 , Pneumonia , Anticoagulants/therapeutic use , COVID-19/drug therapy , Cytokines , Hemoglobins , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pneumonia/drug therapy
6.
S Afr Med J ; 112(7): 472-477, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-2073605

ABSTRACT

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/adverse effects , Cross-Sectional Studies , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , South Africa/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
7.
Semin Thromb Hemost ; 48(7): 850-857, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2050627

ABSTRACT

Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.


Subject(s)
COVID-19 , Hemostatics , Humans , Heparin, Low-Molecular-Weight/therapeutic use , Enoxaparin/therapeutic use , COVID-19/drug therapy , Critical Illness , C-Reactive Protein , Anticoagulants/therapeutic use , Heparin/adverse effects , Viper Venoms , Antithrombins , Factor Xa Inhibitors
8.
J Hematol Oncol ; 15(1): 116, 2022 08 26.
Article in English | MEDLINE | ID: covidwho-2021317

ABSTRACT

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Thrombosis , Venous Thromboembolism , Aged , Anticoagulants , COVID-19/drug therapy , COVID-19 Testing , Hemorrhage , Heparin, Low-Molecular-Weight , Humans , SARS-CoV-2
9.
Expert Rev Clin Pharmacol ; 15(9): 1095-1105, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2004912

ABSTRACT

INTRODUCTION: The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED: We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION: The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKA therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKA therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.


Subject(s)
Atrial Fibrillation , COVID-19 , Venous Thromboembolism , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/adverse effects , Humans , Venous Thromboembolism/chemically induced , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
10.
Blood Coagul Fibrinolysis ; 33(6): 342-347, 2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2001485

ABSTRACT

Immunosuppressive treatment and bypassing agents are used to treat acquired haemophilia A (AHA). On the other hand, COVID-19 infection induces a hypercoagulable state. Managing bleeding, risk of thrombosis, bypassing agents, active infection and immunosuppressive treatment can be challenging. A 72-year-old man was diagnosed with acquired hemophilia A. He received steroids, rituximab and recombinant activated factor VII (rFVIIa). He developed severe SARS-CoV-2 infection. Due to thrombotic risk, he received low-molecular-weight heparin (LMWH) and developed an iliopsoas hematoma. Because of the risk of thrombosis, treatment with recombinant porcine FVIII (rpFVIII) was requested. Tocilizumab was administered for treatment of SARS-CoV-2 infection and unexpected improvement of FVIII levels was noted. Concluding, rpFVIII treatment was well tolerated and effective, easy to monitor and to administer. Tocilizumab may play a role as immunosuppressive treatment for AHA. The role of LMWH remains to be established in patients with coagulopathies.


Subject(s)
COVID-19 , Hemophilia A , Pneumonia , Animals , COVID-19/complications , COVID-19/drug therapy , Factor VIII/therapeutic use , Hemophilia A/complications , Hemophilia A/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Pneumonia/complications , Recombinant Proteins/therapeutic use , SARS-CoV-2 , Swine
11.
Ann Transplant ; 27: e935874, 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1988529

ABSTRACT

BACKGROUND COVID-19 disease, caused by the SARS-CoV-2 virus, has been one of the greatest challenges in modern medicine. It is mostly known to affect the pulmonary system, leading to pneumonia and acute respiratory distress syndrome, but there is a growing body of evidence of extrapulmonary manifestations of COVID-19 disease. CASE REPORT This article presents 3 cases of various extrapulmonary symptoms of COVID-19 disease and a literature review of similar clinical cases. Two patients had a medical history of living-donor kidney transplantation, and 1 patient was a kidney donor. We present symptoms, diagnostic processes, laboratory and imaging results, and treatment approach. Patient 1 was 29-year-old woman with new-onset diabetes mellitus due to SARS-CoV-2, which required temporary insulin treatment. Patient 2 was a 34-year-old man with fever, chronic fatigue, back pain, and abdominal pain. Imagining showed acalculous cholecystitis, epiploic appendagitis of the right colic flexure, and inflammation of pericardial fat pad in the left cardiophrenic angle. Coagulopathy due to COVID-19 was the most probable cause of the described processes. Therapeutic doses of low-molecular-weight heparin were administered. Patient 3 was a 68-year-old male kidney donor who had painless, nodular, reddening lesions on both shins, accompanied by itching on both shins and recurrent fever. The diagnosis of erythema nodosum during COVID-19 was made. After treatment with low-molecular-weight heparin, significant decreases of symptoms were observed. CONCLUSIONS We conclude that SARS-CoV-2 infection can have a varied course and can involve other systems and organs. Physicians should be aware of possible extrapulmonary symptoms associated with infection with this virus. Correct diagnosis is a prerequisite for proper treatment and prevention of unexpected complications.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , COVID-19/complications , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male
12.
PLoS One ; 17(8): e0270195, 2022.
Article in English | MEDLINE | ID: covidwho-1974308

ABSTRACT

INTRODUCTION: There are no clear data about the incidence and the prophylactic strategies of arterial and venous thromboembolic events (TE) in COVID-19 ambulatory patients. Thus, we conducted this study to analyze thromboembolic complications in this setting and to assess thromboprophylaxis management and outcomes in the real life. PATIENTS AND METHODS: This is an observational study including Covid-19 ambulatory patients. We assessed incidence of venous and arterial TE events as well as thromboprophylaxis outcomes and hemorrhagic complications. We defined high risk thrombo-embolic factor according to the Belgian guidelines which are the only guidelines that described thromboprophylaxis in COVID-19 ambulatory patients. RESULTS: We included 2089 patients with a mean age of 43±16 years. The incidence of 30 days venous and arterial TE complications in our cohort was 1%. Venous thromboembolic complications occurred in 0.8% and arterial thromboembolic complications occurred in 0.3%.We noted at least one high-risk TE factor in 18.5% of patients but thromboprophylaxis was prescribed in 22.5% of the cases, LMWH in 18.1%, and Rivaroxaban in 3.7%. Hemorrhagic events occurred in eight patients (0.3%): five patients showed minor hemorrhagic events and three patients showed major ones (0.14%). CONCLUSIONS: Our study showed that the incidence of thromboembolic complications is very low in COVID-19 ambulatory patients. Paradoxically, there is an over prescription of thrombo-prophylaxis in this population.


Subject(s)
COVID-19 , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Incidence , Middle Aged , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
13.
Clin Appl Thromb Hemost ; 28: 10760296221116350, 2022.
Article in English | MEDLINE | ID: covidwho-1974064

ABSTRACT

Objective: To compare Anti-Xa directed thromboprophylaxis using low molecular weight heparin (LMWH) (anti-Xa peak goal 0.2-0.5 IU/mL) to alternative anticoagulation strategies in critically ill COVID-19 patients. Methods: This was a retrospective, multicenter, single health-system study. Primary outcomes were thromboembolic events and clinically important bleeding events. Secondary outcomes included dosing comparisons between LMWH cohorts. Main Results: A total of 695 patients were included. No differences were found in the incidence of thrombotic events with any of the dosing strategies. The incidence of major bleeding was significantly higher in the standard dose thromboprophylaxis, intermediate dose subcutaneous heparin (SQH), and therapeutic anticoagulation cohorts. Forty-nine percent of patients within the anti-Xa directed group had their first anti-Xa peak at goal, while 43% were above goal. Patients who had levels above goal had dose modifications made, therefore anti-Xa directed LMWH resulted in significantly lower total daily doses compared to intermediate dose LMWH. Conclusions: Anti-Xa directed LMWH dosing provided comparable thromboprophylaxis with lower total daily doses of LMWH in critically ill COVID-19 patients. Further randomized controlled trials are needed to confirm our findings.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants , Critical Illness , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
14.
Eur Heart J Qual Care Clin Outcomes ; 8(8): 909-918, 2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-1973139

ABSTRACT

AIMS: This study aimed to compare the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. METHODS AND RESULTS: We systematically searched several databases and included observational studies or clinical trials that compared the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. A total of nine studies comprising 9637 patients were included. Metanalysis showed that LMWH administration was associated with a lower in-hospital mortality and 28/30-day mortality compared with UFH administration {[relative risk (RR) 0.44; 95% confidence interval (95% CI) 0.32-0.61; I2: 87.9%] and (RR 0.45; 95% CI 0.24-0.86; I2: 78.4%), respectively}. Patient with LMWH had shorter duration of hospital and ICU length of stay compared with UFH {[weighted mean difference (WMD) -2.20; 95% CI -3.01 to -1.40; I2:0%] and (WMD -1.41; 95% CI -2.20 to -0.63; I2: 0%), respectively}. The risk of ICU admission or mechanical ventilation was lower in patients who received LMWH than in those who received UFH (RR 0.67; 95% CI 0.55-0.81; I2: 67.3%). However, there was no difference in the incidence of bleeding with LMWH compared with UFH (RR 0.27; 95% CI 0.07-1.01; I2: 64.6%). CONCLUSION: Our meta-analysis showed that administration of LMWH was associated with better outcomes compared with UFH in hospitalized COVID-19 patients. Prospective cohorts and RCTs are urgently needed to explore the definitive effect of LMWH to provide direct high-certainty evidence. PROSPERO registration number: CRD42021271977.


Subject(s)
COVID-19 , Venous Thromboembolism , Humans , Heparin, Low-Molecular-Weight/therapeutic use , Heparin/adverse effects , Anticoagulants/therapeutic use , COVID-19/epidemiology , Prospective Studies , Venous Thromboembolism/drug therapy
15.
J Thromb Thrombolysis ; 54(3): 420-430, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1971785

ABSTRACT

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I2 = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I2 = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/adverse effects , COVID-19/drug therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Thrombosis/prevention & control
16.
J Cardiothorac Surg ; 17(1): 108, 2022 May 07.
Article in English | MEDLINE | ID: covidwho-1951270

ABSTRACT

INTRODUCTION: Extracorporeal circulation (ECC) in cardiac surgery is performed under systemic heparinization. Adequacy of heparin therapy and anticoagulation during ECC is assessed by activated clotting time (ACT), although there are concerns regarding the reliability of this measure. The ACT can be affected by factors other than heparin anticoagulation. A novel factor that should be considered is the influence of a COVID-19 infection. More than half of the hospitalized COVID-19 patients develop coagulation abnormalities with dysregulated coagulation test results. Patients recently recovered from COVID-19 may still demonstrate some forms of coagulation disorder affecting the ACT. This case describes an inaccurate point-of-care ACT testing in a patient with previous COVID-19 infection undergoing cardiac surgery with ECC and the alternative coagulation testing performed. CASE PRESENTATION: A 77-years-old Caucasian male presented with symptomatic severe mitral valve regurgitation for which he underwent surgery. Medical history revealed a COVID-19 infection one month before surgery. Pre-operative hematological lab results were normal and baseline ACT during surgery was 100 s. To achieve an adequate ACT of > 400 s, multiple doses of heparin were needed and after administration of a triple dose (75,000 IE heparin in total) this adequate ACT was achieved. In the meanwhile we measured anti-Xa level and APTT, which were at adequate levels when ACT was still < 400 s. DISCUSSION: This case emphasizes the need of alternative methods for monitoring heparin therapy in case ACT does not respond adequately. Another point to highlight in this case is the poorly correlated relation between ACT and APTT and anti-Xa in light of the recent COVID-19 infection. Although studies have shown that COVID-19 infection can cause coagulopathy and altered hemostatic parameters, ACT has never been investigated in COVID-19 patient. Understanding the correlation between ACT, APTT and anti-Xa in COVID-19 patients is mandatory.


Subject(s)
COVID-19 , Cardiopulmonary Bypass , Aged , Anticoagulants/therapeutic use , Heparin/therapeutic use , Heparin, Low-Molecular-Weight , Humans , Male , Point-of-Care Systems , Reproducibility of Results , Whole Blood Coagulation Time
17.
Saudi Med J ; 43(7): 715-722, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1955133

ABSTRACT

OBJECTIVES: To assess the effect of different thromboprophylaxis regimens on clinical outcomes and mortality of critical ill patients with coronavirus disease -19 (COVID-19). METHODS: We investigated the medical records of patients with positive COVID-19 (using polymerase chain reaction test) who were admitted to the intensive care unit (ICU) at Sakarya University Hospital, Sakarya, Turkey, from March 2020 to January 2021. We included patients under anticoagulant therapy in the clinical course. The patients were allocated to 3 groups: Group A - low-dose (prophylactic) low-molecular-weight-heparin (LMWH) therapy, Group B - high-dose (therapeutic) LMWH therapy, and patients that received aspirin additional to the high-dose (therapeutic) LMWH as Group C. Primary outcomes were overall mortality rates and length of stay (LOS) in ICU. Secondary outcomes were rates of major hemorrhagic and thrombotic events. RESULTS: Records of 475 patients were reviewed and 164 patients were included. No significant difference was detected in mortality rates between groups (p=0.135). Intensive care unit stay was 13 (9-24.5) days in Group A, 11 (8.75-23) days in Group B, and 13 (9-17) days in Group C without a significant difference (p=0.547). No significant difference was detected between groups in terms of thrombotic (p=0.565) and hemorrhagic events (p=0.615). CONCLUSION: A high-dose anticoagulation therapy and addition of aspirin to LMWH therapy did not decrease the mortality rates and LOS in ICU in critical ill COVID-19 patients. In addition, it did not increase the incidence of major hemorrhage and major thrombotic events.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Aspirin/therapeutic use , Critical Illness/therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
18.
BMJ ; 378: e070022, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1932663

ABSTRACT

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.


Subject(s)
Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Bayes Theorem , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Hospitals , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy
19.
J Thromb Haemost ; 20(10): 2214-2225, 2022 10.
Article in English | MEDLINE | ID: covidwho-1927616

ABSTRACT

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.


Subject(s)
COVID-19 , Heparin, Low-Molecular-Weight , Aftercare , Anticoagulants/adverse effects , Fibrinolytic Agents/adverse effects , Heparin/adverse effects , Humans , Patient Discharge , Platelet Aggregation Inhibitors/adverse effects , Rivaroxaban
20.
Anticancer Res ; 42(7): 3261-3274, 2022 07.
Article in English | MEDLINE | ID: covidwho-1924868

ABSTRACT

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.


Subject(s)
COVID-19 , Neoplasms , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Endothelial Cells , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Neoplasms/complications , Neoplasms/drug therapy , Prospective Studies , RNA, Viral , Risk Factors , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
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