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1.
Int J Mol Sci ; 23(20)2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2082320

ABSTRACT

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Sepsis , Humans , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Antithrombins/therapeutic use , COVID-19/complications , Anticoagulants/therapeutic use , Anticoagulants/pharmacology , Blood Coagulation Disorders/complications , Sepsis/complications , Antithrombin III , Biomarkers
2.
Int J Mol Sci ; 23(18)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2071501

ABSTRACT

In SARS-CoV-2-infected humans, disease progression is often associated with acute respiratory distress syndrome involving severe lung injury, coagulopathy, and thrombosis of the alveolar capillaries. The pathogenesis of these pulmonary complications in COVID-19 patients has not been elucidated. Autopsy study of these patients showed SARS-CoV-2 virions in pulmonary vessels and sequestrated leukocytes infiltrates associated with endotheliopathy and microvascular thrombosis. Since SARS-CoV-2 enters and infects target cells by binding its spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2), and there is evidence that vascular endothelial cells and neutrophils express ACE2, we investigated the effect of S-proteins and cell-cell communication on primary human lung microvascular endothelial cells (HLMEC) and neutrophils expression of thrombogenic factors and the potential mechanisms. Using S-proteins of two different SARS-CoV-2 variants (Wuhan and Delta), we demonstrate that exposure of HLMEC or neutrophils to S-proteins, co-culture of HLMEC exposed to S-proteins with non-exposed neutrophils, or co-culture of neutrophils exposed to S-proteins with non-exposed HLMEC induced transcriptional upregulation of tissue factor (TF), significantly increased the expression and secretion of factor (F)-V, thrombin, and fibrinogen and inhibited tissue factor pathway inhibitor (TFPI), the primary regulator of the extrinsic pathway of blood coagulation, in both cell types. Recombinant (r)TFPI and a thiol blocker (5,5'-dithio-bis-(2-nitrobenzoic acid)) prevented S-protein-induced expression and secretion of Factor-V, thrombin, and fibrinogen. Thrombomodulin blocked S-protein-induced expression and secretion of fibrinogen but had no effect on S-protein-induced expression of Factor-V or thrombin. These results suggests that following SARS-CoV-2 contact with the pulmonary endothelium or neutrophils and endothelial-neutrophil interactions, viral S-proteins induce coagulopathy via the TF pathway and mechanisms involving functional thiol groups. These findings suggest that using rTFPI and/or thiol-based drugs could be a viable therapeutic strategy against SARS-CoV-2-induced coagulopathy and thrombosis.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Angiotensin-Converting Enzyme 2 , Cell Communication , Endothelial Cells/metabolism , Endothelium/metabolism , Fibrinogen , Humans , Lipoproteins , Lung/metabolism , Neutrophils/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Sulfhydryl Compounds , Thrombin , Thrombomodulin , Thromboplastin , Thrombosis/etiology
3.
Int J Mol Sci ; 23(19)2022 Sep 29.
Article in English | MEDLINE | ID: covidwho-2066128

ABSTRACT

COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (ß2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X and von Willebrand factor (vWF). Different combinations of autoantibodies associate with different coagulopathies. Previous research revealed similarities between proteins with blood clotting functions and SARS-CoV-2 proteins, adenovirus, and bacterial proteins associated with moderate-to-severe COVID-19 infections. This study investigated whether polyclonal antibodies (mainly goat and rabbit) against these viruses and bacteria recognize human blood-related proteins. Antibodies against SARS-CoV-2 and adenovirus recognized vWF, PDE and PF4 and SARS-CoV-2 antibodies also recognized additional antigens. Most bacterial antibodies tested (group A streptococci [GAS], staphylococci, Escherichia coli [E. coli], Klebsiella pneumoniae, Clostridia, and Mycobacterium tuberculosis) cross-reacted with CL and PF4. while GAS antibodies also bound to F2, Factor VIII, Factor IX, and vWF, and E. coli antibodies to PDE. All cross-reactive interactions involved antibody-antigen binding constants smaller than 100 nM. Since most COVID-19 coagulopathy patients display autoantibodies against vWF, PDE and PF4 along with CL, combinations of viral and bacterial infections appear to be necessary to initiate their autoimmune coagulopathies.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Adenoviridae , Animals , Antibodies, Bacterial , Antigens, Bacterial , Autoantibodies , Bacterial Proteins , Blood Coagulation Factors , Capsid Proteins , Cardiolipins , Escherichia coli/metabolism , Factor IX , Factor VIII , Humans , Phosphoric Diester Hydrolases , Platelet Factor 4/metabolism , Prothrombin , Rabbits , SARS-CoV-2 , Serum Albumin , beta 2-Glycoprotein I , von Willebrand Factor
4.
J Thromb Haemost ; 20(10): 2171-2172, 2022 10.
Article in English | MEDLINE | ID: covidwho-2063871

ABSTRACT

Coagulopathy is inextricably linked to the field of hemostasis and thrombosis. In the same manner hemostasis and thrombosis may deal with bleeding and clot formation, coagulopathy also may be connected to bleeding or thrombosis, depending on the circumstances. However, when the same designation, "coagulopathy," may represent two clinically distinct presentations, it can create confusion. It is our obligation as hemostasis and thrombosis specialists to scotch this dubiety and direct the correct usage of coagulopathy.


Subject(s)
Blood Coagulation Disorders , Thrombosis , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , Hemorrhage , Hemostasis , Humans , Thrombosis/diagnosis
5.
Int J Environ Res Public Health ; 19(18)2022 Sep 19.
Article in English | MEDLINE | ID: covidwho-2043699

ABSTRACT

Since the very beginning of the COVID-19 pandemic, numerous researchers have made an effort to determine the molecular composition of the SARS-CoV-2 virus, and the exact pathomechanism through which the virus exerts such a devastating effect on the host/infected organism. Recent scientific evidence highlights the affinity of the virus towards ACE2 receptors, which are widespread in multiple human systems, including the central nervous system (CNS) and cerebral vessels. Such an affinity may explain endothelial dysfunction and damage that is observed in COVID-positive patients in histopathological studies, with subsequent dysregulation of the cerebral circulation leading to transient or acute cerebrovascular accidents. In this paper, we aimed to evaluate the effects of COVID-related hypoxemia and direct viral invasion on the cerebral circulation, with special respect to the postulated pathomechanism, vulnerable groups of patients, clinical course and outcomes, as well as diagnostic imaging findings.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Angiotensin-Converting Enzyme 2 , COVID-19/complications , Humans , Hypoxia , Pandemics , SARS-CoV-2
6.
Cardiovasc Hematol Agents Med Chem ; 20(3): 178-188, 2022.
Article in English | MEDLINE | ID: covidwho-2039581

ABSTRACT

The post-COVID neurological syndrome has been coined, which describes the functional and structural sequelae of coronavirus infection disease-19 (COVID-19) in the brain. Mild/severe manifestations of the post-COVID neurological syndrome have been identified in approximately 33.00% of COVID-19 survivors. The presence of neurological complications after COVID allowed neuropathologists to investigate in-depth the role of viral infection in neurons. The pathophysiology of the post-COVID neurological syndrome involved the development of a systematic response, including coagulopathy characterized by the formation of microthrombi. Coagulopathy, an old term for a new disease, describes the discrepancy between pro-coagulant and anticoagulant systems due to overexpression of pro-coagulant substances and or their receptors in addition to suppression of the anticoagulant molecules and or their receptors. Vascular endothelial cells and hepatocytes play a central role in the regulation of hemostasis that is disrupted during the acute phase response (APR) of coronavirus-19 (COVID-19). Currently, coagulopathy and inflammation are termed together since both form a complementary system, indicated by the elevation of inflammatory biomarkers (APR) and fibrinolysis biomarkers (D-dimer/fibrin). The later events of the post-COVID neurological syndrome are primarily induced by coagulopathy and direct viral tropism. Therefore, the paper introduces the hypothesis of coagulopathy induced post-COVID neurological syndrome.


Subject(s)
Blood Coagulation Disorders , Brain Injuries , COVID-19 , Anticoagulants , Biomarkers , Blood Coagulation Disorders/etiology , Brain Injuries/complications , COVID-19/complications , Endothelial Cells , Humans , SARS-CoV-2
7.
PLoS One ; 17(8): e0272216, 2022.
Article in English | MEDLINE | ID: covidwho-1993485

ABSTRACT

BACKGROUND: COVID-19 is a viral disease caused by a new strain of corona virus. Currently, prognosis and risk stratification of COVID-19 patients is done by the disease's clinical presentation. Therefore, identifying laboratory biomarkers for disease prognosis and risk stratification of COVID-19 patients is critical for prompt treatment. Therefore, the main objective of this study was to assess the risk stratification and prognostic value of basic coagulation parameters and factors associated with disease severity among COVID-19 patients at the Tibebe Ghion Specialized Hospital, COVID-19 treatment center, Northwest Ethiopia. METHODS: A follow-up study was conducted among conveniently recruited COVID-19 patients attended from March to June 2021. Socio-demographic and clinical data were collected using a structured questionnaire and checklist, respectively. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were analyzed by the HUMACLOT DUE PLUS® machine. Descriptive statistics were used to summarize the socio-demographic and clinical characteristics of study participants. Kruskal Wallis tests were used to compare the difference between parametric and non-parametric continuous variables, respectively. The area under the receiver operating characteristic curve (AUC) was used to evaluate the value of PT and APTT in the risk stratification and disease prognosis of COVID-19 patients. Ordinal logistic regression was used to identify the factors associated with disease severity and prognosis. A P-value < 0.05 was defined as statistically significant for all results. RESULT: Baseline PT at a cut-off value ≥ 16.25 seconds differentiated severe COVID-19 patients from mild and moderate patients (AUC: 0.89, 95% CI: 0.83-0.95). PT also differentiated mild COVID-19 patients from moderate and severe patients at a cut-off value ≤ 15.35 seconds (AUC: 0.90, 95% CI: 0.84-0.96). Moreover, alcohol drinkers were a 3.52 times more likely chance of having severe disease than non-drinkers (95% CI: 1.41-8.81). A one-year increment in age also increased the odds of disease severity by 6% (95% CI: 3-9%). An increment of ≥ 0.65 seconds from the baseline PT predicted poor prognosis (AUC: 0.93, 0.87-0.99). CONCLUSIONS AND RECOMMENDATIONS: Prolonged baseline PT was observed in severe COVID-19 patients. Prolonged baseline PT was also predicted to worsen prognosis. An increase from the baseline PT was associated with worsen prognosis. Therefore, PT can be used as a risk stratification and prognostic marker in COVID-19 patients.


Subject(s)
Blood Coagulation Disorders , COVID-19 , COVID-19/diagnosis , COVID-19/drug therapy , Follow-Up Studies , Humans , Partial Thromboplastin Time , Prognosis , Prothrombin Time , Retrospective Studies , Risk Assessment
8.
Clin Lab ; 68(8)2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1988445

ABSTRACT

BACKGROUND: According to recent studies, thrombotic complications frequently occur in Coronavirus Disease-19 (COVID-19) and are associated with increasing disease severity and poor prognosis. However, conventional coagulation assays are unable to identify these patients' hypercoagulable states, raising questions about the appropriate assessment tool. We aimed to evaluate coagulation abnormalities in patients with different severity of CO-VID-19 using viscoelastic tests. METHODS: This was a single center retrospective observational study in a group of 50 adult patients with SARS-COV-2 infection and different severity of pneumonia (20 moderate, 30 severe). Coagulation status was evaluated using rotational thromboelastometry (ROTEM®) in conjunction with conventional coagulation assays (platelet count, PT, aPTT, fibrinogen, and D-dimer levels). RESULTS: Shorter than normal EXTEM CFT, higher than normal A10 and MCF in INTEM, EXTEM, and FIBTEM and higher than normal α-angle were classified as markers of hypercoagulable state. Forty-four (88%) patients had at least two hypercoagulable ROTEM parameters. Seven patients developed thromboembolic complications. All were classified as having severe COVID-19 pneumonia. With increment increases in disease severity, we observed an increase in the number of patients with hypercoagulable parameters and higher INTEM, EXTEM, and FIBTEM MCF but without being statistically significant. On the other hand, we noted a significant decrement of PT (p = 0.039), higher fibrinogen (p = 0.001), higher D dimer (p < 0.001), and shorter CT EXTEM (p < 0.001). CONCLUSIONS: Our findings support the presence of a hypercoagulable state in COVID-19 patients, especially in the severe forms. It also highlights the role of viscoelastic tests in assessing COVID-19 coagulopathy and, therefore, their potential use in thrombophrophylactic management.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Adult , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , COVID-19/complications , COVID-19/diagnosis , Fibrinogen , Humans , SARS-CoV-2 , Thrombelastography , Thrombophilia/complications , Thrombophilia/diagnosis
9.
Nat Rev Immunol ; 22(10): 639-649, 2022 10.
Article in English | MEDLINE | ID: covidwho-1984398

ABSTRACT

COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Animals , Blood Coagulation Disorders/etiology , COVID-19/complications , Endothelium, Vascular , SARS-CoV-2 , Thrombosis/etiology
10.
Crit Care Med ; 48(10): e989-e990, 2020 10.
Article in English | MEDLINE | ID: covidwho-1383266
11.
Biosci Trends ; 16(4): 307-311, 2022 Sep 17.
Article in English | MEDLINE | ID: covidwho-1969709

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with increases in abnormal coagulation, and particularly D-dimer (D-D) levels. Heparin therapy has been recommended as pharmacologic thromboprophylaxis in patients hospitalized with COVID-19; however, data on its efficacy are lacking. The current study retrospectively analyzed changes in blood coagulation and the impact of heparin therapy. Medical records of 593 patients with confirmed COVID-19 were collected. On admission, elevated fibrinogen (Fg) levels were noted in with 42.2% (250/593) of patients, followed by increases in D-D (28.5%) and a prolonged prothrombin time (PT) (23.9%). Patients with severe/critical COVID-19 had a higher proportion of abnormal coagulation parameters than patients with mild/ordinary COVID-19. Dynamic changes in coagulation parameters were plotted on timeline charts for 97 patients with COVID-19 after heparin treatment. These changes, when combined with Fg, PT, D-D, and other indicators, may provide a relatively comprehensive description of coagulation abnormalities. Heparin seems to be important in the treatment of patients with COVID-19 based on the current findings. The efficacy of heparin in the treatment of COVID-19 should be confirmed by randomized controlled trials (RCTs) as soon as possible.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Anticoagulants/therapeutic use , COVID-19/drug therapy , Fibrinogen , Heparin/therapeutic use , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2
12.
Sci Rep ; 12(1): 13155, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1967619

ABSTRACT

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Blood Coagulation , Fibrin Fibrinogen Degradation Products , Humans , Partial Thromboplastin Time , Prospective Studies
14.
Diabetes Metab Res Rev ; 38(7): e3565, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1925908

ABSTRACT

AIMS: Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID-19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID-19 pneumonia only accounts for a part of COVID-19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well-known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients. MATERIALS AND METHODS: In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID-19 admitted to a third-level Hospital in Milan. RESULTS: We found an increased mortality in subjects with COVID-19 and diabetes, together with an altered inflammatory profile. CONCLUSIONS: This may support the hypothesis that diabetes and COVID-19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794).


Subject(s)
Blood Coagulation Disorders , COVID-19 , Diabetes Mellitus , COVID-19/complications , Humans , Inflammation , SARS-CoV-2
15.
J Transl Med ; 20(1): 265, 2022 06 11.
Article in English | MEDLINE | ID: covidwho-1885321

ABSTRACT

BACKGROUND: Sepsis is a life-threatening syndrome eliciting highly heterogeneous host responses. Current prognostic evaluation methods used in clinical practice are characterized by an inadequate effectiveness in predicting sepsis mortality. Rapid identification of patients with high mortality risk is urgently needed. The phenotyping of patients will assistant invaluably in tailoring treatments. METHODS: Machine learning and deep learning technology are used to characterize the patients' phenotype and determine the sepsis severity. The database used in this study is MIMIC-III and MIMIC-IV ('Medical information Mart for intensive care') which is a large, public, and freely available database. The K-means clustering is used to classify the sepsis phenotype. Convolutional neural network (CNN) was used to predict the 28-day survival rate based on 35 blood test variables of the sepsis patients, whereas a double coefficient quadratic multivariate fitting function (DCQMFF) is utilized to predict the 28-day survival rate with only 11 features of sepsis patients. RESULTS: The patients were grouped into four clusters with a clear survival nomogram. The first cluster (C_1) was characterized by low white blood cell count, low neutrophil, and the highest lymphocyte proportion. C_2 obtained the lowest Sequential Organ Failure Assessment (SOFA) score and the highest survival rate. C_3 was characterized by significantly prolonged PTT, high SIC, and a higher proportion of patients using heparin than the patients in other clusters. The early mortality rate of patients in C_3 was high but with a better long-term survival rate than that in C_4. C_4 contained septic coagulation patients with the worst prognosis, characterized by slightly prolonged partial thromboplastin time (PTT), significantly prolonged prothrombin time (PT), and high septic coagulation disease score (SIC). The survival rate prediction accuracy of CNN and DCQMFF models reached 92% and 82%, respectively. The models were tested on an external dataset (MIMIC-IV) and achieved good performance. A DCQMFF-based application platform was established for fast prediction of the 28-day survival rate. CONCLUSION: CNN and DCQMFF accurately predicted the sepsis patients' survival, while K-means successfully identified the phenotype groups. The distinct phenotypes associated with survival, and significant features correlated with mortality were identified. The findings suggest that sepsis patients with abnormal coagulation had poor outcomes, abnormal coagulation increase mortality during sepsis. The anticoagulation effects of appropriate heparin sodium treatment may improve extensive micro thrombosis-caused organ failure.


Subject(s)
Blood Coagulation Disorders , Sepsis , Hematologic Tests , Heparin/pharmacology , Heparin/therapeutic use , Humans , Machine Learning , Prognosis , Retrospective Studies
16.
Cardiovasc Hematol Disord Drug Targets ; 22(2): 83-86, 2022.
Article in English | MEDLINE | ID: covidwho-1892463

ABSTRACT

A turbulent coagulation system is a prominent feature of Coronavirus Disease 2019 (COVID-19), with venous thromboembolism (VTE) a leading cause of death. Our hypothesis is that patients with inherited hypocoagulability, like congenital bleeding disorders (CBD), enjoy a protective effect against COVID-19-induced hypercoagulability and related fatal consequences. Our primary and follow-up observations revealed this effect, at least among patients with moderate to severe congenital bleeding disorders, particularly coagulation factor deficiencies. Theoretically, patients with inherited hypocoagulobility have only a potential protective effect against COVID-19-related hypercoagulability. Yet the lower rate of morbidity and mortality in patients with CBDs suggests that hypercoagulability and thrombotic events are the main cause of death in COVID-19. Therefore, appropriate and timely administration of anticoagulants could significantly decrease the rate of morbidity and mortality in COVID-19.


Subject(s)
Blood Coagulation Disorders, Inherited , Blood Coagulation Disorders , COVID-19 , Thrombophilia , Thrombosis , Venous Thromboembolism , Humans , COVID-19/complications , SARS-CoV-2 , Blood Coagulation Disorders/complications , Anticoagulants/therapeutic use , Blood Coagulation Disorders, Inherited/complications , Thrombophilia/chemically induced , Thrombophilia/complications , Venous Thromboembolism/complications , Morbidity
17.
Am Surg ; 88(7): 1689-1693, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1892040

ABSTRACT

BACKGROUND: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. METHODS: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. RESULTS: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. DISCUSSION: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.


Subject(s)
Blood Coagulation Disorders , Wounds and Injuries , Biomarkers , Humans , Retrospective Studies , Thrombelastography/methods , Trauma Centers , Wounds and Injuries/diagnosis , Wounds and Injuries/therapy
18.
Anesthesiology ; 137(1): 67-78, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1891065

ABSTRACT

BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS: Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS: In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS: Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Respiratory Distress Syndrome , Thrombophilia , Thrombosis , Blood Coagulation Disorders/complications , COVID-19/complications , Critical Illness , Fibrinolysis , Humans , Hypoxia/complications , Microcirculation , Oxygen , Plasminogen Activator Inhibitor 1 , Prospective Studies , Retrospective Studies , Thrombophilia/complications , Thromboplastin
19.
Clin Appl Thromb Hemost ; 28: 10760296221103864, 2022.
Article in English | MEDLINE | ID: covidwho-1879207

ABSTRACT

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Thrombosis , Venous Thromboembolism , Adult , COVID-19/complications , COVID-19/drug therapy , Cohort Studies , Critical Illness , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Retrospective Studies , Thrombosis/chemically induced , Thrombosis/etiology , Venous Thromboembolism/chemically induced , Venous Thromboembolism/etiology
20.
Crit Care Clin ; 38(3): 491-504, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1878087

ABSTRACT

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are prone to venous, cerebrovascular, and coronary thrombi, particularly those with severe coronavirus disease 2019 (COVID-19). The pathogenesis is multifactorial and likely involves proinflammatory cascades, development of coagulopathy, and neutrophil extracellular traps, although further investigations are needed. Elevated levels of D-dimers are common in patients with COVID-19 and cannot be used in isolation to predict venous thromboembolism in people with SARS-CoV-2. If given early in hospital admission, therapeutic-dose heparin improves clinical outcomes in patients with moderate COVID-19. To date, antithrombotics have not improved outcomes in patients with severe COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Anticoagulants/therapeutic use , COVID-19/complications , Heparin , Humans , SARS-CoV-2 , Thrombosis/etiology
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