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Article ; Online: Thromboinflammation and microcirculation damage in heatstroke.

Iba, Toshiaki / Maier, Cheryl L / Levi, Marcel / Levy, Jerrold H

2024

Abstract: Rising temperatures associated with climate change have significantly increased the risk of heatstroke. Unfortunately, the trend is anticipated to persist and increasingly threaten vulnerable populations, particularly older adults. According to Japan's ... ...

Abstract	Rising temperatures associated with climate change have significantly increased the risk of heatstroke. Unfortunately, the trend is anticipated to persist and increasingly threaten vulnerable populations, particularly older adults. According to Japan's environment ministry, over 1000 people died from heatstroke in 2021, and 86% of deaths occurred in those above 65. Since the precise mechanism of heatstroke is not fully understood, we examined the pathophysiology by focusing on the microcirculatory derangement. Online search of published medical literature through MEDLINE and Web of Science using the term "heatstroke," "heat-related illness," "inflammation," "thrombosis," "coagulation," "fibrinolysis," "endothelial cell," and "circulation." Articles were chosen for inclusion based on their relevance to heatstroke, inflammation, and thrombosis. Reference lists were reviewed to identify additional relevant articles. Other than preexisting conditions (genetic background, age, etc.), factors such as hydration status, acclimatization, dysregulated coagulation, and inflammation are the additional major factors that promote tissue malcirculation in heatstroke. The fundamental pathophysiologic mechanisms significantly overlap with those seen in the systemic inflammatory response to sepsis, and as a result, coagulation-predominant coagulopathy develops during heat stress. Although a bleeding tendency is not common, bleeding frequently occurs in the microcirculation, causing additional injury. Sterile inflammation is mediated by proinflammatory cytokines, chemokines, and other humoral mediators in concert with cellular factors, including monocytes, neutrophils, platelets, and endothelial cells. Excess inflammation results in inflammatory cell death, including pyroptosis and necroptosis, and the release of danger signals that further propagate systemic inflammation and coagulopathy. Consequently, thromboinflammation is the critical factor that induces microcirculatory disturbance in heatstroke.
Language	English
Publishing date	2024-01-19
Publishing country	Italy
Document type	Journal Article
ZDB-ID	123586-2
ISSN	1827-1669 ; 0026-4806
ISSN (online)	1827-1669
ISSN	0026-4806
DOI	10.23736/S0026-4806.23.08919-X
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Article ; Online: Anticoagulation Monitoring for Perioperative Physicians.

Maier, Cheryl L / Sniecinski, Roman M

Anesthesiology

2021 Volume 135, Issue 4, Page(s) 738–748

MeSH term(s)	Anticoagulants/administration & dosage ; Anticoagulants/adverse effects ; Blood Coagulation/drug effects ; Blood Coagulation/physiology ; Humans ; International Normalized Ratio/methods ; International Normalized Ratio/standards ; Monitoring, Intraoperative/methods ; Monitoring, Intraoperative/standards ; Perioperative Care/methods ; Perioperative Care/standards ; Physician's Role ; Physicians/standards ; Point-of-Care Testing/standards ; Prothrombin Time/methods ; Prothrombin Time/standards
Chemical Substances	Anticoagulants
Language	English
Publishing date	2021-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	269-0
ISSN	1528-1175 ; 0003-3022
ISSN (online)	1528-1175
ISSN	0003-3022
DOI	10.1097/ALN.0000000000003903
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Article ; Online: Towards characterized convalescent plasma for COVID-19: The dose matters.

Verkerke, Hans P / Maier, Cheryl L

EClinicalMedicine

2020 Volume 26, Page(s) 100545

Keywords	covid19
Language	English
Publishing date	2020-09-19
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2020.100545
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Article ; Online: Four years into the pandemic, managing COVID-19 patients with acute coagulopathy: what have we learned?

Iba, Toshiaki / Levy, Jerrold H / Maier, Cheryl L / Connors, Jean M / Levi, Marcel

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Coagulopathy alongside micro- and macrovascular thrombotic events were frequent characteristics of patients presenting with acute COVID-19 during the initial stages of the pandemic. However, over the past 4 years, the incidence and manifestations of ... ...

Abstract	Coagulopathy alongside micro- and macrovascular thrombotic events were frequent characteristics of patients presenting with acute COVID-19 during the initial stages of the pandemic. However, over the past 4 years, the incidence and manifestations of COVID-19-associated coagulopathy have changed due to immunity from natural infection and vaccination and the appearance of new SARS-CoV-2 variants. Diagnostic criteria and management strategies based on early experience and studies for COVID-19-associated coagulopathy thus require reevaluation. As many other infectious disease states are also associated with hemostatic dysfunction, the coagulopathy associated with COVID-19 may be compounded, especially throughout the winter months, in patients with diverse etiologies of COVID-19 and other infections. This commentary examines what we have learned about COVID-19-associated coagulopathy throughout the pandemic and how we might best prepare to mitigate the hemostatic consequences of emerging infection agents.
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.02.013
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines.

Iba, Toshiaki / Maier, Cheryl L / Helms, Julie / Ferrer, Ricard / Thachil, Jecko / Levy, Jerrold H

Annals of intensive care

2024 Volume 14, Issue 1, Page(s) 64

Abstract: Maintaining tissue perfusion in sepsis depends on vascular integrity provided by the endothelial glycocalyx, the critical layer covering the luminal surface of blood vessels. The glycocalyx is composed of proteoglycans, glycosaminoglycans, and functional ...

Abstract	Maintaining tissue perfusion in sepsis depends on vascular integrity provided by the endothelial glycocalyx, the critical layer covering the luminal surface of blood vessels. The glycocalyx is composed of proteoglycans, glycosaminoglycans, and functional plasma proteins that are critical for antithrombogenicity, regulating tone, controlling permeability, and reducing endothelial interactions with leukocytes and platelets. Degradation of the glycocalyx in sepsis is substantial due to thromboinflammation, and treatments for sepsis and septic shock may exacerbate endotheliopathy via additional glycocalyx injury. As a result, therapeutic strategies aimed at preserving glycocalyx integrity should be considered, including modifications in fluid volume resuscitation, minimizing catecholamine use, controlling hyperglycemia, and potential use of corticosteroids and anticoagulants. In this review, we explore treatment strategies aligned with the recommendations outlined in the Surviving Sepsis Campaign Guidelines 2021 with a special emphasis on evidence regarding glycocalyx protection.
Language	English
Publishing date	2024-04-24
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2617094-2
ISSN	2110-5820
ISSN	2110-5820
DOI	10.1186/s13613-024-01301-6
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Article ; Online: Interdisciplinary Approach to Thrombosis Management in COVID-19 at a Large Academic Center.

Gaddh, Manila / Maier, Cheryl L

JCO oncology practice

2021 Volume 17, Issue 9, Page(s) 517–521

Abstract: There is an increasing recognition of association of COVID-19 with a distinct coagulopathy and increased risk of thrombosis. Unfortunately, effective strategies to prevent and treat thrombosis in this patient population remain uncertain. In the setting ... ...

Abstract	There is an increasing recognition of association of COVID-19 with a distinct coagulopathy and increased risk of thrombosis. Unfortunately, effective strategies to prevent and treat thrombosis in this patient population remain uncertain. In the setting of a worsening pandemic, there is an urgent need to provide practical guidance to the clinicians on management of the coagulopathy, while waiting for the results from large systematic trials to establish best practices. At our institution, we convened an interdisciplinary group of 25 experts in the field of thrombosis from different medical specialties to review available literature and brainstorm management strategies. The group provided a 3-tiered anticoagulation algorithm for patients with COVID-19 along with a pathway for multidisciplinary review of difficult or refractory cases, which are described in this manuscript. In these unprecedented times where medical decision making is made difficult by both the novelty of the disease and paucity of robust data, clinical algorithms such as the one presented here may prove to be helpful for frontline providers caring for individual patients.
MeSH term(s)	Blood Coagulation Disorders ; COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; Thrombosis/prevention & control
Language	English
Publishing date	2021-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.20.01056
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Zs.A 7198: Show issues

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Article ; Online: The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy.

Iba, Toshiaki / Helms, Julie / Maier, Cheryl L / Levi, Marcel / Scarlatescu, Ecaterina / Levy, Jerrold H

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan ...

Abstract	Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan dysfunction. Sepsis-associated acute kidney injury (AKI) is a significant contributor to patient morbidity and mortality. The connection between AKI and thromboinflammation is largely due to unique aspects of the renal vasculature. Specifically, the interaction between blood cells with the endothelial, glomerular, and peritubular capillary systems during thromboinflammation reduces oxygen supply to tubular epithelial cells. Previous studies have focused on tubular epithelial cell damage due to hypoxia, oxidative stress, and nephrotoxins. Although these factors are pivotal in acute tubular injury or necrosis, recent studies have demonstrated that AKI in sepsis encompasses a mixture of tubular and glomerular damage subtypes. In cases of sepsis-induced coagulopathy, thromboinflammation within the glomerulus and peritubular capillaries is an important pathogenic mechanism for AKI. Unfortunately, and despite the use of renal replacement therapy, the development of AKI in sepsis continues to be associated with high morbidity, mortality, and clinical challenges requiring alternative approaches. This review introduces the important role of thromboinflammation in AKI pathogenesis and details innovative vascular-targeting therapeutic strategies.
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.02.006
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Risk stratification utilizing sequential organ failure assessment (SOFA) score, antithrombin activity, and demographic data in sepsis-associated disseminated intravascular coagulation (DIC).

Iba, Toshiaki / Maier, Cheryl L / Tanigawa, Tomoki / Levy, Jerrold H

Scientific reports

2023 Volume 13, Issue 1, Page(s) 22502

Abstract: Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be appropriate for certain patients with DIC, particularly those with increased disease ... ...

Abstract	Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be appropriate for certain patients with DIC, particularly those with increased disease severity and deficiency in the physiologic anticoagulant antithrombin. We retrospectively analyzed post-marketing survey data from 1562 patients with sepsis-associated DIC and antithrombin activity of 70% or less. All the patients were treated with antithrombin concentrates. Baseline sequential organ failure assessment (SOFA) score, DIC score, and antithrombin activity were assessed. Cox multivariate regression analysis, Kaplan-Meier curve analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the performance of variables used to assess mortality. Furthermore, a decision tree was constructed to classify the risk of 28-day mortality. COX multivariate regression analysis demonstrated a significant association of age, sex, baseline SOFA score, baseline antithrombin activity, and the presence of pneumonia or skin/soft tissue infection with increased mortality. The area under the curve of SOFA score or antithrombin activity for mortality was 0.700 and 0.614, respectively. Kaplan-Meier analysis demonstrated that mortality was significantly higher in patients with SOFA score ≥ 12 and antithrombin activity < 47%. The decision tree analysis accurately classified the risk of death into high (> 40%), medium (40%-20%), and low (< 20%) categories in 86.1% of the cohort. Twenty eight-day mortality can be strongly predicted using baseline SOFA score, antithrombin activity, infection site, age, and sex as variables in the clinical decision tree for patients with sepsis-associated disseminated intravascular coagulation (DIC).
MeSH term(s)	Humans ; Antithrombins/therapeutic use ; Organ Dysfunction Scores ; Disseminated Intravascular Coagulation/etiology ; Retrospective Studies ; Anticoagulants/therapeutic use ; Antithrombin III ; Sepsis ; Risk Assessment ; Demography
Chemical Substances	Antithrombins ; Anticoagulants ; Antithrombin III (9000-94-6)
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-49855-y
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Article ; Online: Alloantigen Copy Number as a Critical Factor in RBC Alloimmunization.

Patel, Seema R / Maier, Cheryl L / Zimring, James C

Transfusion medicine reviews

2022 Volume 37, Issue 1, Page(s) 21–26

Abstract: RBC alloimmunization remains a significant barrier to ongoing transfusion therapy leading to morbidity, and in extreme cases mortality, due to delayed or insufficient units of compatible RBCs. In addition, the monitoring and characterization of ... ...

Abstract	RBC alloimmunization remains a significant barrier to ongoing transfusion therapy leading to morbidity, and in extreme cases mortality, due to delayed or insufficient units of compatible RBCs. In addition, the monitoring and characterization of alloantibodies, often with multiple specificities in a single patient, consumes substantial health care resources. Extended phenotypic matching has mitigated, but not eliminated, RBC alloimmunization and is only logistically available for specialized populations. Thus, RBC alloimmunization remains a substantial problem. In recent decades it has become clear that mechanisms of RBC alloimmunization are distinct from other antigens and lack of mechanistic understanding likely contributes to the fact that there are no approved interventions to prevent RBC alloimmunization from transfusion. The combination of human studies and murine modeling have identified several key factors in RBC alloimmunization. In both humans and mice, immunogenicity is a function of alloantigen copy number on RBCs. Murine studies have further shown that copy number not only changes rates of immunization but the mechanisms of antibody formation. This review summarizes the current understanding of quantitative and qualitative effects of alloantigen copy number on RBC alloimmunization.
MeSH term(s)	Humans ; Mice ; Animals ; Isoantigens ; DNA Copy Number Variations ; Erythrocytes ; Blood Transfusion ; Isoantibodies
Chemical Substances	Isoantigens ; Isoantibodies
Language	English
Publishing date	2022-12-23
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639107-2
ISSN	1532-9496 ; 0887-7963
ISSN (online)	1532-9496
ISSN	0887-7963
DOI	10.1016/j.tmrv.2022.12.009
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Zs.A 2239: Show issues

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Article ; Online: Iron deficiency anemia and bleeding management in pediatric patients with Bernard-Soulier syndrome and Glanzmann Thrombasthenia: A single-institution analysis.

Lee, Annika / Maier, Cheryl L / Batsuli, Glaivy

Haemophilia : the official journal of the World Federation of Hemophilia

2022 Volume 28, Issue 4, Page(s) 633–641

Abstract: Introduction: Frequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard-Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily ... ...

Abstract	Introduction: Frequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard-Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily treated with platelet transfusions or recombinant activated factor VII (rFVIIa) infusions. The impact of IDA on bleeding management and disease outcomes is understudied. Aim: To evaluate bleeding management, outcomes, and any association with IDA in pediatric patients with BSS and GT. Methods: Retrospective chart-review of pediatric patients with BSS or GT followed at a single hemophilia treatment center between 2007 and 2019. Results: We identified 14 patients with BSS (n = 2) or GT (n = 12). Patients received rFVIIa (7%), platelet transfusions (7%), or a combination of both (57%) for SBE. Eleven patients (79%) had IDA requiring oral and/or intravenous iron replacement and 50% required red blood cell transfusions. Due to recurrent SBE and refractory IDA, three patients (21%) received rFVIIa prophylaxis at 90 μg/kilogram 2-3 times/week for ≥15 months. Patients initiated on rFVIIa prophylaxis had a median baseline hemoglobin of 9.8 g/dL (min-max: 8.0-10.7 g/dL) compared to 11.7 g/dL (8.4-13.8 g/dL) for patients treated on-demand. Following initiation of rFVIIa prophylaxis, median hemoglobin and ferritin increased by 1.3 g/dL (0.7-2.5 g/dL) and 14.6 ng/mL (0.2-42.9 ng/mL), respectively, and bleeding rates were reduced by 7-78%. Conclusion: IDA is a known complication of recurrent bleeding events in individuals with inherited bleeding disorders. Routine monitoring for IDA may help improve bleeding management and reduce bleed burden in BSS/GT.
MeSH term(s)	Anemia/complications ; Bernard-Soulier Syndrome ; Blood Platelet Disorders/complications ; Child ; Hemophilia A/drug therapy ; Hemorrhage/complications ; Hemorrhage/prevention & control ; Humans ; Iron Deficiencies ; Recombinant Proteins/therapeutic use ; Retrospective Studies ; Thrombasthenia/complications
Chemical Substances	Recombinant Proteins
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14559
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