Review
Cardiac & Cardiovascular Systems
Stephan Nopp, Daniel Kraemmer, Cihan Ay
Summary: While anticoagulation therapy has made progress, thrombosis remains a leading cause of death worldwide. Direct oral anticoagulants dominate clinical practice, but bleeding risk is still significant. Therefore, research focuses on developing safer anticoagulants, with factor XI (FXI) inhibition as a promising target.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Alina Scridon
Summary: This article comprehensively explores the complex role of platelets in hemostasis and thrombosis, discussing their importance in clinical medicine, and studying hemostatic platelet-related disorders and antithrombotic therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Antonio Greco, Claudio Laudani, Marco Spagnolo, Federica Agnello, Denise Cristiana Faro, Simone Finocchiaro, Marco Legnazzi, Maria Sara Mauro, Placido Maria Mazzone, Giovanni Occhipinti, Carla Rochira, Lorenzo Scalia, Davide Capodanno
Summary: Therapeutic anticoagulation is used to prevent or treat blood clots, but it can increase the risk of bleeding. Inhibitors of Factor XI (FXI) show promise in reducing the adverse events of anticoagulation. Large-scale phase 3 clinical trials are needed to confirm the role of FXI inhibitors and determine their clinical indications.
Article
Hematology
Hilary Whitworth, Helen Havens Clark, Rebecca A. Hubbard, Char Witmer, Charles E. Leonard, Leslie Raffini
Summary: This study examined the incidence rate of recurrent VTE in pediatric patients with unprovoked VTE, evaluated potential risk factors for recurrence, and described anticoagulation regimens and bleeding in this population. The results showed that age ≥ 12 years and inherited thrombophilia were significantly associated with recurrent VTE. Future research should focus on the efficacy of prolonged anticoagulation for this population.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Ophira Salomon, David Gailani
Summary: Therapeutic inhibitors targeting FXI(a) are being evaluated as potential treatments for preventing thrombosis, with the expectation of having a smaller impact on hemostasis than current anticoagulants targeting thrombin or factor Xa. However, some patients on these inhibitors may still experience abnormal bleeding or require emergent surgery, necessitating the development of strategies to address these situations. Treatment with antifibrinolytic agents and low doses of recombinant factor VIIa has been effective in preventing abnormal bleeding in FXI-deficient patients, suggesting a potential strategy for patients on therapeutic FXI(a) inhibitors experiencing bleeding or requiring invasive procedures.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Medicine, General & Internal
Omri Cohen, Samuela Pegoraro, Walter Ageno
Summary: Cerebral venous thrombosis is a rare but leading cause of stroke in young adults, with diagnosis, treatment, and risk factors similar to other venous thrombosis. Early recognition and timely treatment are crucial.
Review
Cardiac & Cardiovascular Systems
Steven P. Grover, Nigel Mackman
Summary: Appropriate activation of coagulation requires a balance between procoagulant and anticoagulant proteins in blood. SERPIN anticoagulants function by forming irreversible inhibitory complexes with target coagulation proteases. Mutations in SERPIN family members can cause hereditary thrombophilias, and low plasma levels of SERPINs are associated with an increased risk of thrombosis. Engineered SERPINs hold potential as novel therapies for the treatment of thrombotic pathologies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Hematology
Alisa S. Wolberg, Yaqiu Sang
Summary: This article discusses the pathogenesis of venous thromboembolism and focuses on the role of fibrinogen and factor XIII in thrombus formation and resolution, providing insights for the development of new anticoagulant strategies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Clinical Neurology
Shadi Yaghi, Liqi Shu, Ekaterina Bakradze, Setareh Salehi Omran, James A. Giles, Jordan Y. Amar, Nils Henninger, Marwa Elnazeir, Ava L. Liberman, Khadean Moncrieffe, Jenny Lu, Richa Sharma, Yee Cheng, Adeel S. Zubair, Alexis N. Simpkins, Grace T. Li, Justin Chi Kung, Dezaray Perez, Mirjam Heldner, Adrian Scutelnic, David Seiffge, Bernhard Siepen, Aaron Rothstein, Ossama Khazaal, David Do, Sami Al Kasab, Line Abdul Rahman, Eva A. Mistry, Deborah Kerrigan, Hayden Lafever, Thanh N. Nguyen, Piers Klein, Hugo Aparicio, Jennifer Frontera, Lindsey Kuohn, Shashank Agarwal, Christoph Stretz, Narendra Kala, Sleiman El Jamal, Alison Chang, Shawna Cutting, Han Xiao, Adam de Havenon, Varsha Muddasani, Teddy Wu, Duncan Wilson, Amre Nouh, Syed Daniyal Asad, Abid Qureshi, Justin Moore, Pooja Khatri, Yasmin Aziz, Bryce Casteigne, Muhib Khan, Yao Cheng, Brian Mac Grory, Martin Weiss, Dylan Ryan, Maria Cristina Vedovati, Maurizio Paciaroni, James E. Siegler, Scott Kamen, Siyuan Yu, Christopher R. Leon Guerrero, Eugenie Atallah, Gian Marco De Marchis, Alex Brehm, Tolga Dittrich, Marios Psychogios, Ronald Alvarado-Dyer, Tareq Kass-Hout, Shyam Prabhakaran, Tristan Honda, David S. Liebeskind, Karen Furie
Summary: The study compared the effectiveness of DOACs and warfarin in treating CVT, showing similar outcomes in recurrent venous thrombosis, death, and partial/complete recanalization rates between the two groups, but lower risk of major hemorrhage in the DOACs treatment group.
Review
Hematology
Laura Girardi, Tzu-Fei Wang, Walter Ageno, Marc Carrier
Summary: Patients with cancer have a higher risk of developing venous thromboembolism (VTE) due to specific risk factors and thrombotic and hemostatic pathophysiological pathways. Managing cancer-associated VTE can be challenging due to increased risk of recurrent events and bleeding complications. Direct oral anticoagulants have shown effectiveness, safety, and convenience compared to low-molecular-weight heparin in managing cancer-associated VTE. However, there are still unmet needs and potential solutions, such as factor XI inhibitors, to address bleeding risk, drug interactions, and liver dysfunction.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Johan Holm, Buster Mannheimer, Rickard E. Malmstrom, Erik Eliasson, Jonatan D. Lindh
Summary: The study found an increased risk of any severe bleed when NOAC treatment was combined with drugs affecting bleeding. Increased risk was evident for combinations with apixaban (hazard ratio (HR) 1.47; 95% CI 1.33-1.63), rivaroxaban (HR 1.7; 95% CI 1.49-1.92), and dabigatran (HR 1.26; 95% CI 1.05-1.52).
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Kaidireyahan Wumaier, Wenqian Li, Jiuwei Cui
Summary: Venous thromboembolism (VTE) in cancer patients is associated with increased morbidity and mortality, decreased quality of life, and higher economic burden. Low molecular weight heparin (LMWHs) has been the standard treatment for cancer-associated VTE, but the introduction of new oral anticoagulants (NOACs) offers another option for some cancer patients with thrombosis. A more comprehensive understanding of drug properties, efficacy and safety, and economic analysis is needed to choose the most appropriate treatment.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Review
Hematology
Dimitrios Rafail Kalaitzopoulos, Anastasios Panagopoulos, Saurabhi Samant, Natasha Ghalib, Jona Kadillari, Angelos Daniilidis, Nicolas Samartzis, Janaki Makadia, Leonidas Palaiodimos, Damianos G. Kokkinidis, Nikolaos Spyrou
Summary: Venous thromboembolism (VTE) in pregnancy is a significant cause of maternal mortality. Differentiating between physiological changes and symptoms of VTE can be challenging, and timely and accurate diagnosis is crucial. Systemic anticoagulation is a key aspect of VTE prevention and therapy.
THROMBOSIS RESEARCH
(2022)
Review
Hematology
Brandon Lui, Benjamin Wee, Jeffrey Lai, Zille Khattak, Anna Kwok, Cynthia Donarelli, Prahlad Ho, Hui Yin Lim
Summary: The study found that the treatment outcomes for VTE improved over time, with reduced rates of thrombotic recurrence and clinically significant bleeding complications in the DOAC era compared to the warfarin era.
THROMBOSIS RESEARCH
(2022)
Article
Hematology
Anne Hege Aamodt, Thor Wakon Skattor
Summary: Cerebral venous thrombosis (CVT) is a rare form of stroke that primarily affects younger individuals, particularly reproductive-age females. Due to its vague clinical and radiological presentation, CVT is often overlooked. Magnetic resonance venography and computed tomography venography can confirm the diagnosis of CVT. Anticoagulation with low-molecular-weight heparin is the main treatment, while endovascular intervention remains controversial. This review provides an overview of the epidemiology, diagnosis, and treatment of CVT in adults, as well as discusses the increased occurrence of CVT in patients with COVID-19 or following COVID-19 vaccination.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2022)
Review
Cardiac & Cardiovascular Systems
Steven P. Grover, Nigel Mackman
Article
Hematology
Steven P. Grover, Tatianna M. Olson, Brian C. Cooley, Nigel Mackman
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2020)
Article
Multidisciplinary Sciences
Joni M. Prasad, Oscar Negron, Xinli Du, Eric S. Mullins, Joseph S. Palumbo, Jessica M. Gilbertie, Magnus Hook, Steven P. Grover, Rafal Pawlinski, Nigel Mackman, Jay L. Degen, Matthew J. Flick
Summary: This study identifies the essential role of the fibrinogen in combating Staphylococcus aureus infection, which relies on the coagulant function of thrombin. The bacteria-derived prothrombin activator vWbp is crucial for the fibrinogen-mediated bacterial clearance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Hematology
Yohei Hisada, Kenison B. Garratt, Anaum Maqsood, Steven P. Grover, Tomohiro Kawano, Brian C. Cooley, Jonathan Erlich, Florian Moik, Matthew J. Flick, Ingrid Pabinger, Nigel Mackman, Cihan Ay
Summary: This study investigated the association of active Lys-PG in plasma and VTE in pancreatic cancer patients, as well as the impact of human pancreatic tumors expressing Lys-PG on venous thrombus resolution in mice. The results suggest that Lys-PG may contribute to the development of VTE in pancreatic cancer.
Review
Hematology
Steven P. Grover, Yohei M. Hisada, Raj S. Kasthuri, Brandi N. Reeves, Nigel Mackman
Summary: Cancer patients are at a higher risk of arterial and venous thrombotic events compared to the general population, with factors such as cancer site and stage, treatment-related factors, and cytotoxic effects of chemotherapeutic agents contributing to this increased risk. Despite advancements in targeted therapies, some anticancer agents still carry a risk of thrombosis, necessitating a better understanding of the mechanisms involved to develop effective treatment strategies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Letter
Hematology
Nigel Mackman, Yohei Hisada, Steven P. Grover, Axel Rosell, Sebastian Havervall, Fien von Meijenfeldt, Katherina Aguilera, Ton Lisman, Charlotte Thalin
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Hematology
Nigel Mackman, Steven P. Grover, Silvio Antoniak
Summary: TF expression is increased during viral infections, particularly in lung epithelial cells of COVID-19 patients. Increased TF expression associated with viral infections may contribute to thrombosis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Cardiac & Cardiovascular Systems
Steven P. Grover, Taylor Coughlin, Salma M. Fleifil, Jens J. N. Posma, Henri H. M. Spronk, Stefan Heitmeier, A. Phillip Owens, Nigel Mackman
Summary: Contrary to the hypothesis, the combination of aspirin and rivaroxaban did not show a greater reduction of atherosclerosis in Ldlr(-/-) mice compared to using each agent alone. However, all treatment groups (aspirin, rivaroxaban, and combination) reduced macrophage content and apoptosis in the lesions compared to control group. The expression of a small number of proteins in the aorta and plasma was altered in mice treated with aspirin and/or rivaroxaban.
Letter
Hematology
Steven P. Grover, Linda Sundler Bjorkman, Arne Egesten, Stephan Moll, Nigel Mackman
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Steven P. Grover, Tomohiro Kawano, Jun Wan, Pansakorn Tanratana, Zsofia Polai, Young J. Shim, Omri Snir, Sigrid Braekkan, Sophia Dhrolia, Rohan R. Kasthuri, Pavan K. Bendapudi, Keith R. McCrae, Alisa S. Wolberg, John-Bjarne Hansen, Henriette Farkas, Nigel Mackman
Summary: C1INH is a serine protease inhibitor that regulates multiple biological pathways. Deficiency of C1INH is associated with hereditary angioedema (HAE) and increased risk of coagulation activation and thrombosis.
Article
Hematology
Jun Wan, Pansakorn Tanratana, Mark Roest, Andras Gruber, Rafal Pawlinski, Alisa S. Wolberg, Nigel Mackman, Steven P. Grover
Summary: This study describes a novel mouse whole blood TG assay to assess the amplifying roles of intrinsic pathway factors in mouse coagulation. The assay has enhanced sensitivity to FXI and FIX-dependent amplification of coagulation, suggesting an important role of blood cells in this process.
Article
Hematology
Steven P. Grover, Vanthana Bharathi, Jens J. Posma, John H. Griffin, Joseph S. Palumbo, Nigel Mackman, Silvio Antoniak
Summary: The chemotherapeutic drug doxorubicin is cardiotoxic and can cause irreversible heart failure. In addition, it induces the activation of coagulation. Thrombin-mediated activation of protease-activated receptor 1 (PAR1) has been found to contribute to doxorubicin-induced cardiac injury.
Letter
Cardiac & Cardiovascular Systems
Prakash Saha, Clemens Gutmann, Jack Kingdon, Alexandru Dregan, Laura Bertolaccini, Steven P. Grover, Ashish S. Patel, Bijan Modarai, Oliver Lyons, Christian Schulz, Marcelo E. Andia, Alkystis Phinikaridou, Rene M. Botnar, Alberto Smith
Article
Hematology
Robert A. Campbell, Yohei Hisada, Frederik Denorme, Steven P. Grover, Emma G. Bouck, Elizabeth A. Middleton, Alisa S. Wolberg, Matthew T. Rondina, Nigel Mackman
Summary: Patients with COVID-19 had significantly higher levels of D-dimer, EVTF activity, and active PAI-1 compared with healthy controls, while patients with sepsis had significantly higher levels of D-dimer and EVTF activity compared with healthy controls. High levels of both EVTF activity and active PAI-1 in COVID-19 patients may promote thrombosis due to simultaneous activation of coagulation and inhibition of fibrinolysis, and the high levels of active PAI-1 may explain the lower levels of D-dimer in COVID-19 patients compared with sepsis patients.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Steven P. Grover, Clare M. Schmedes, Alyson C. Auriemma, Emily Butler, Molly L. Parrish, Adam Miszta, Audrey C. Cleuren, Mayken Visser, Stefan Heitmeier, Jens J. Posma, Henri M. Spronk, Silvio Antoniak, Alisa S. Wolberg, Rafal Pawlinski, David Gailani, Nigel Mackman