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1.
Blood Coagul Fibrinolysis ; 33(5): 239-256, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1891118

ABSTRACT

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.


Subject(s)
COVID-19 , Sepsis , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Arginine/analogs & derivatives , Critical Illness , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pipecolic Acids , Sepsis/drug therapy , Sulfonamides , Thrombocytopenia/chemically induced , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/drug therapy
2.
Wien Klin Wochenschr ; 133(23-24): 1237-1247, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1756805

ABSTRACT

BACKGROUND: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients. METHODS: This multicenter prospective register study included all patients with a SARS-CoV­2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic. RESULTS: Overall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort. CONCLUSION: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.


Subject(s)
COVID-19 , Aged , Austria , Critical Illness , Humans , Intensive Care Units , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314287

ABSTRACT

Introduction: On February 25 th , 2020, the first two patients were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Tyrol, Austria. Based on alarming reports from the neighboring region Lombardy in Italy, rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease 2019 (COVID-19) patients. Methods: A coordinated county wide step-up approach ensured adequate ICU bed availability for COVID-19 patients avoiding shortage of mechanical ventilation capacity. All patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the region of Tyrol, Austria were recorded in the Tyrolean COVID-19 Intensive Care Registry. Data were censored on July 17 th , 2020. Results: From March 9 th , 2020 to July 17 th , 2020, 106 critically ill patients with COVID-19 were admitted to an ICU. Median age was 64 (interquartile range [IQR], 54-74) years and the majority of patients were male (76 patients [71.7%]). Median simplified acute physiology score III (SAPS III) was 56 (IQR, 49-64) points. The median duration from appearance of first symptoms to ICU admission was 8 (IQR, 5-11) days. Frequently observed comorbidities were arterial hypertension in 71 patients (67.0%), cardiovascular (45 patients [42.5%]) and renal comorbidities (21 patients [19.8%]). Invasive mechanical ventilation was required in 72 patients (67.9%), 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 (IQR, 5-31) days, median hospital LOS was 27 (IQR, 13-49) days.ICU mortality was 21.7% (23 patients), while only one patient (0.9%) died after ICU discharge on a general ward (hospital mortality 22,6%). As of July 17 th , 2020, two patients are still hospitalized, one in an ICU, one on a general ward. Conclusions: Critically ill COVID-19 patients admitted to an ICU in the region of Tyrol, Austria, showed a high severity of disease often requiring complex treatments with increased lengths of ICU- and hospital stay. Despite that, we found ICU and hospital mortality in this cohort to be remarkably low. Adaptive surge response providing sufficient ICU resources presumably has contributed to the overall favorable outcome.

4.
J Clin Med ; 11(3)2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674681

ABSTRACT

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

5.
Wien Klin Wochenschr ; 133(23-24): 1237-1247, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1474017

ABSTRACT

BACKGROUND: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients. METHODS: This multicenter prospective register study included all patients with a SARS-CoV­2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic. RESULTS: Overall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort. CONCLUSION: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.


Subject(s)
COVID-19 , Aged , Austria , Critical Illness , Humans , Intensive Care Units , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
7.
Wien Klin Wochenschr ; 132(21-22): 653-663, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-996403

ABSTRACT

INTRODUCTION: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus­2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. METHODS: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. RESULTS: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54-74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49-64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5-11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5-31 days), median hospital LOS was 27 days (IQR 13-49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. CONCLUSION: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Aged , Austria , COVID-19 , Cohort Studies , Coronavirus Infections/therapy , Critical Illness/therapy , Female , Humans , Intensive Care Units , Male , Middle Aged , Pneumonia, Viral/therapy , SARS-CoV-2 , Treatment Outcome
8.
Br J Anaesth ; 126(3): 590-598, 2021 03.
Article in English | MEDLINE | ID: covidwho-965444

ABSTRACT

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor. METHODS: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT. RESULTS: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test. CONCLUSION: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Critical Illness/epidemiology , Fibrinolysis/drug effects , Thrombophilia/blood , Thrombophilia/epidemiology , Adult , Aged , Anticoagulants/administration & dosage , Blood Coagulation Tests/methods , COVID-19/diagnosis , Female , Fibrinolysis/physiology , Humans , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Tissue Plasminogen Activator/administration & dosage
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