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1.
Clin Neurol Neurosurg ; 215: 107212, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763637

ABSTRACT

OBJECTIVE: To determine the level of compliance of The American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) for initiation of venous thromboembolism (VTE) prophylaxis after non-operative traumatic brain injury (TBI) and the explanation for the deviations. METHODS: A retrospective review from May 2018 to February 2020 in a Level II trauma center for patients with TBI and length of stay of more than 24 h. We performed an analysis of overall and subgroup compliance with guidelines. The ACS TQIP criteria for low and moderate-risk for hemorrhagic progression were used for subgroup classification. RESULTS: Of 393 patients, 239 (60.8%) patients received chemoprophylaxis in a mean of 64 (SD: +/-42) hours since admission. "Compliance" was achieved in 52.2% of patients. In subgroup analysis, 51.4% of patients in "low-risk" and 55.1% in "moderate-risk" were "compliant." The most common rationale for non-compliance in "low-risk" was a stay less than 48 h in 35.9% of patients. However, in "moderate-risk," the most common non-compliance was starting prophylaxis before the recommended 72 h from admission in 37% of cases. CONCLUSIONS: Guidelines streamline clinical practice to optimize outcomes, but there are scenarios in which deviation of the recommendations may be indicated based on clinical judgment. We show that a stay of less than 48 h was the most common rationale for not starting prophylaxis in "low-risk" patients. However, in the "moderate-risk" subgroup, the most common reason was starting chemoprophylaxis before the recommended time frame, which we called a "paradoxical" non-compliance.


Subject(s)
Brain Injuries, Traumatic , Venous Thromboembolism , Anticoagulants/therapeutic use , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Chemoprevention , Humans , Retrospective Studies , Trauma Centers , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
2.
Cardiovasc Hematol Agents Med Chem ; 20(2): 114-124, 2022.
Article in English | MEDLINE | ID: covidwho-1760080

ABSTRACT

Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa- direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients' physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.


Subject(s)
Atrial Fibrillation , Venous Thromboembolism , Administration, Oral , Anticoagulants/pharmacology , Atrial Fibrillation/drug therapy , Dabigatran , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
3.
JAMA ; 327(13): 1247-1259, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1750260

ABSTRACT

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19 , Venous Thromboembolism , Adult , Anticoagulants/therapeutic use , Aspirin/adverse effects , Bayes Theorem , Critical Illness/therapy , Female , Hemorrhage/chemically induced , Humans , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Respiration, Artificial , Venous Thromboembolism/drug therapy
4.
Eur Rev Med Pharmacol Sci ; 26(1): 54-58, 2022 01.
Article in English | MEDLINE | ID: covidwho-1636663

ABSTRACT

OBJECTIVE: Direct-acting oral anticoagulants (DOACs) have established indications, according to recent guidelines for the treatment and prevention of venous thromboembolism (VTE), including pulmonary embolism (PE), with a safer profile compared to vitamin K antagonist (VKA) in terms of a lower risk for major bleeding and no need of blood coagulation tests. However, DOACs are not indicated in the treatment of patients with triple-positive antiphospholipid syndrome (APS). This limitation is often extended in clinical practice to patients with isolated positivity. The COVID-19 pandemic has sometimes made it difficult to maintain a safe VKA treatment, due to the practical difficulties of performing INR. PATIENTS AND METHODS: We evaluated 39 patients with a previous unprovoked VTE/PE, who were no longer eligible for VKA treatment due to the difficulty of performing INR during the COVID-19 pandemic lockdown, in Italy. All patients had a positive LAC and refused a long-term anticoagulation with low molecular weight heparin. They were shifted to edoxaban. RESULTS: Any recurrence of VTE/PE occurred during the observation period (up to eight months of treatment), while only one minor bleeding event was recorded (Hazard ratio=0.06, 95% confidence interval 0.03-0.11, p=0.094). No arterial events occurred during the observation period. Hemoglobin, platelets, and creatinine were unchanged during the observation period. CONCLUSIONS: Edoxaban treatment may be safe and effective in preventing the recurrence of VTE/PE in patients with isolated LAC positivity, without the occurrence of arterial events.


Subject(s)
COVID-19/epidemiology , Factor Xa Inhibitors/therapeutic use , Lupus Coagulation Inhibitor/drug effects , Pandemics , Pulmonary Embolism/drug therapy , Pyridines/therapeutic use , Thiazoles/therapeutic use , Venous Thromboembolism/drug therapy , Adult , COVID-19/prevention & control , Factor Xa Inhibitors/adverse effects , Female , Humans , Italy , Male , Middle Aged , Pyridines/adverse effects , Quarantine , Thiazoles/adverse effects
5.
In Vivo ; 36(1): 381-383, 2022.
Article in English | MEDLINE | ID: covidwho-1592873

ABSTRACT

BACKGROUND/AIM: This study analyzed the characteristics of patients with COVID-19 with major events during the first days of hospitalization. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients admitted to two hospitals in Athens, Greece. The characteristics of patients with COVID-19 who suffered the primary endpoint (venous thromboembolic events, intubation, and death) during the first days of hospitalization were analyzed. RESULTS: Among 95 patients included in the analysis, 21 presented with major adverse events during a median follow-up of 13 days. More than 50% of these patients presented with a major event during the first 3 days. Anticoagulation treatment was inversely associated with the cumulative incidence of the primary endpoint [hazard ratio=0.16 (95% confidence interval=0.06-0.47)]. Patients with major events were older, with lower baseline SatO2, and higher number of Wells' criteria and Charlson comorbidity index. Among these patients, those with hypertension were at higher risk for early occurrence of events (≤ first three days of hospitalization). CONCLUSION: Major adverse events may occur early in hospitalized patients with COVID-19 with a high-risk profile. Anticoagulation treatment appears to reduce this risk and thus prompt thromboprophylaxis should be employed in these patients.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/adverse effects , Humans , Retrospective Studies , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Venous Thromboembolism/epidemiology
8.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
9.
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
11.
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
12.
J Thromb Thrombolysis ; 53(3): 646-662, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1439746

ABSTRACT

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.


Subject(s)
COVID-19 , Hemostatics , Thrombophilia , Thrombosis , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Factor VIII , Fibrinogen/analysis , Humans , Prospective Studies , Thrombelastography , Thrombophilia/diagnosis , Thrombophilia/etiology , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy , von Willebrand Factor
13.
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
15.
J Thromb Thrombolysis ; 53(2): 446-453, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1363762

ABSTRACT

Patients with COVID-19 are at higher risk of thrombosis due to the inflammatory nature of their disease. A higher-intensity approach to pharmacologic thromboprophylaxis may be warranted. The objective of this retrospective cohort study was to determine if a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol incorporating severity of illness, weight, and biomarkers decreased incidence of thrombosis in hospitalized patients with COVID-19. Included patients were hospitalized with COVID-19 and received thromboprophylaxis within 48 h of admission. Exclusion criteria included receipt of therapeutic anticoagulation prior to or within 24 h of admission, history of heparin-induced thrombocytopenia, extracorporeal membrane oxygenation, pregnancy, or incarceration. Per-protocol patients received thromboprophylaxis according to institutional protocol involving escalated doses of anticoagulants based upon severity of illness, total body weight, and biomarker thresholds. The primary outcome was thrombosis. Secondary outcomes included major bleeding, mortality, and identification of risk factors for thrombosis. Of 1189 patients screened, 803 were included in the final analysis. The median age was 54 (42-65) and 446 (55.5%) were male. Patients in the per-protocol group experienced significantly fewer thrombotic events (4.4% vs. 10.7%, p = 0.002), less major bleeding (3.1% vs. 9.6%, p < 0.001), and lower mortality (6.3% vs. 11.8%, p = 0.02) when compared to patients treated off-protocol. Significant predictors of thrombosis included mechanical ventilation and male sex. Post-hoc regression analysis identified mechanical ventilation, major bleeding, and D-dimer ≥ 1500 ng/mL FEU as significant predictors of mortality. A targeted pharmacologic thromboprophylaxis protocol incorporating severity of illness, body weight, and biomarkers appears effective and safe for preventing thrombosis in patients with COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19 , Thrombosis , Venous Thromboembolism , Adult , Aged , Body Weight , COVID-19/complications , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Thrombosis/chemically induced , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy
16.
Semin Thromb Hemost ; 48(1): 93-99, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1356595

ABSTRACT

The inflammatory process is strongly involved in the pathophysiology of venous thromboembolism (VTE) and has a significant role in disease prediction. Inflammation most probably represents a common denominator through which classical and nonclassical risk factors stimulate thrombotic process. Inflammation of the venous wall promotes the release of tissue factor, inhibits the release of anticoagulant factors, and hampers endogenous fibrinolysis. Systemic inflammatory response also inhibits restoration of blood flow in the occluded vessel. Recent studies indicate that increased inflammatory response ("cytokine storm") is related to prothrombotic state and thromboembolic events in patients with coronavirus disease 2019 (COVID-19). The growing evidence of involvement of inflammation in the pathogenesis of VTE indicates the importance of anti-inflammatory treatment and prevention of VTE. While aspirin was shown to be effective in prevention of recurrent venous thrombosis after treatment with anticoagulant drugs, some other anti-inflammatory drugs like nonsteroidal anti-inflammatory agents may have prothrombotic effect, thus potentially increasing the risk of VTE. Recently, new specific anti-inflammatory drug inhibitors of inflammatory markers that have been shown to be involved in the pathogenesis of VTE are being searched. As thrombogenesis is based on activation of coagulation provoked by inflammation, then prevention and treatment of VTE should include both anticoagulant and anti-inflammatory agents. Combined treatment is related to increased risk of bleeding complications, therefore subtherapeutic doses of both drugs should be used to improve the efficacy of management of VTE without increasing the risk of bleeding.


Subject(s)
COVID-19 , Venous Thromboembolism , Venous Thrombosis , Anticoagulants/therapeutic use , Humans , Inflammation/drug therapy , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thrombosis/drug therapy
18.
Shock ; 55(3): 316-320, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1304005

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our institution, many critically ill COVID-19-positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, Mass) in patients admitted to the intensive care unit over a period of 3 weeks. In 25 patients who had a ROTEM test, we found that 11 (44%) met criteria for fibrinolysis shutdown. Eight of 9 (73%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.


Subject(s)
COVID-19/complications , Fibrinolysis , Intensive Care Units , Thrombelastography , Thrombophilia/diagnosis , Thrombosis/diagnosis , Venous Thromboembolism/diagnosis , Adult , Aged , COVID-19/blood , COVID-19/diagnosis , Clinical Decision-Making , Female , Fibrinolysis/drug effects , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Patient Selection , Predictive Value of Tests , Retrospective Studies , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/blood , Thrombosis/drug therapy , Thrombosis/etiology , Venous Thromboembolism/blood , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
19.
Thromb Res ; 205: 1-7, 2021 09.
Article in English | MEDLINE | ID: covidwho-1284572

ABSTRACT

BACKGROUND: It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. METHODS: We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). RESULTS: 738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12-1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64-1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91-5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54-1.51; Log-Rank test p = 0.513). CONCLUSION: In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.


Subject(s)
COVID-19 , Venous Thromboembolism , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19 Testing , Factor Xa Inhibitors/therapeutic use , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Venous Thromboembolism/drug therapy
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