JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Thrombotic risk determined by CREB3L1 variants in a population-based cohort study: linkage disequilibrium with prothrombin mutation
Manderstedt E, Halldén C, Lind-Halldén C, Elf J, Svensson PJ, Engström G, Melander O, Baras A, Lotta LA, Zöller B and
Trends in home treatment and early discharge of patients with low-risk pulmonary embolism
Farmakis IT, Christodoulou KC, Hobohm L, Giannakoulas G, Keller K, Lurz P, Valerio L, Barco S and Konstantinides SV
Recent guidelines recommend a strategy of home treatment or early discharge in low-risk pulmonary embolism (PE). Contemporary rates of the implementation of this approach in everyday clinical practice are unknown.
Effect of direct oral anticoagulants in cirrhosis: an in vitro study
Pereira Portela C, Calderara DB, Mdawar-Bailly E, Aliotta A, Veuthey L, Gautier LA, Moradpour D, Fraga M, Zermatten MG and Alberio L
Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of DOAC in patients with cirrhosis is limited. Our aim was to explore the in vitro effect of DOAC on thrombin generation (TG) in plasma from patients with cirrhosis compared to healthy controls.
"Reversal of direct oral anticoagulants: Guidance from the SSC of the ISTH": Reply
Levy JH, Shaw JR, Connors JM, Douketis J and Weitz JI
Unconventional interaction of the zebrafish thrombopoietin receptor with Mapk14a determines thrombocyte development and function
Thakkar KJ, Naseer S, Chowdhury S, Mondal S, Shrivastva S, Ribeyron L, Menon MB, Kapuria V, Minocha S and Roy A
Thrombopoietin receptor signalling permits the thrombocyte lineage development in human, mice as well as zebrafish. While the sequence, structure, signalling, and function of TpoR is well-conserved in humans and mice, the zebrafish thrombopoietin receptor (zTpoR) remains less understood.
Causal insights into the role of metabolites in venous thromboembolism pathogenesis: A metabolome-wide mendelian randomization study
Hu W, Bei Y, Chen G, Xu J, Yang M, Yu L, He W, Hu Y, Mao F, Chen S, Xu D and Dai H
Venous thromboembolism (VTE) is a significant global health burden, and metabolic alterations play a key role in its pathogenesis. However, previous studies have been constrained by several limitations, hindering clarification of the causal role of metabolites.
Discerning Specific Thrombolytic Activities and Blood Clot Degradomes of Diverse Snake Venoms with Untargeted Peptidomics
Smith CF, Baldé MA, French S, Modahl CM, Bahrabadi L, Amponsah-Asamoah M, Larson KY, Maroney SP, Ceja Galindo D, Millimouno M, Camara N, Benjamin J, Brandehoff NP, McCabe MC, Cohen MJ, Jackson K, Baldé C, Castoe TA, Mackessy SP, Hansen KC and Saviola AJ
Many snake venoms have been shown to possess thrombolytic activity. However, it remains unclear if actions on other clot-stabilizing proteins beyond fibrin chains contribute significantly to venom-induced thrombolysis because the clot-wide targets of venom proteases and the mechanisms responsible for thrombolysis are not well understood.
Risks of incident venous thromboembolism, recurrent thromboembolism, and use of antithrombotic therapies among children with congenital heart disease undergoing cardiac surgery: a global multicenter analysis of real-world data
Kiskaddon AL, Do NL, Amankwah EK, Witt DM, Ignjatovic V, Giglia TM, Woods GM, Whitworth HB, Stock AC and Goldenberg NA
Data on the characteristics and antithrombotic treatments of venous thromboembolism (VTE) among children with congenital heart disease undergoing cardiac surgery are limited.
Plasminogen and plasmin induce specialized pro-resolving mediators and promote efferocytosis via 5-lipoxygenase
Perucci LO, Carneiro FS, Souza JC, Grossi LC, Souza JAM, Zaidan I, Cardoso C, Lara ES, Felix FB, Baik N, Tavares LP, Soriani FM, Teixeira MM, Parmer RJ, Miles LA and Sousa LP
The plasminogen (Plg)/plasmin (Pla) system has been recognized for its pro-resolving actions, such as promoting efferocytosis. However, the role of specialized pro-resolving mediators (SPMs) in these Plg/Pla effects remains unexplored.
Consensus protocol for platelet desialylation (β-galactose exposure) quantification using lectins by flow cytometry: Communication from the ISTH SSC Subcommittee on Platelet Physiology
Kauskot A, Ramstrom S, Nipoti T and van der Wal DE
Platelets contain many heterogeneous carbohydrates (glycans): often capped by sialic acid. The removal of sialic acid (desialylation) is important for platelet function and clearance, leading to novel diagnostic markers. Platelet desialylation can be easily measured using inexpensive, user-friendly lectins, and flow cytometry.
Enhancing hemostasis potency in hemophilia with a small interfering RNA targeting protein S
Eladnani RP, Schaeper U, Diab R, Aretz J, Vrotniakaite-Bajerciene K, Çaku S, Yasmin R, Li B, Reina Caro MD, Dames S, Eisermann M, Löffler K, Martinez A, de Laat B, Brodard J, Casini A, Kremer Hovinga JA, Allam R, Fernández JA, Griffin JH, Laffan MA, Majumder R, Ahnström J and Angelillo-Scherrer A
One hemophilia treatment concept focuses on rebalancing coagulation and anticoagulation to restore normal blood clotting. Targeting the coagulation regulator, protein S (PS), in hemophilia shows promise to increase the generation of thrombin-a critical enzyme in the clotting process.
Maternal platelet-derived factors induce trophoblastic LAIR2 expression to promote trophoblast invasion and inhibit platelet activation at the fetal-maternal interface
Lyssy F, Forstner D, Guettler J, Kupper N, Ujčič K, Neuper L, Daxboeck C, El-Heliebi A, Kummer D, Krappinger JC, Vejzovic D, Rinner B, Cvirn G, Wernitznig S, Moser G, Valdes DS, Herse F, Höbler AL, Pollheimer J, James JL, Feichtinger J and Gauster M
During human placentation extravillous trophoblasts (EVTs), arising from cell column trophoblasts (CCT) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs but their physiological role remained unclear so far.
The Incidence and Risk Of Venous thromboembolism in patients with Active Malignancy and Isolated Superficial Venous Thrombosis: A systematic review and meta-analysis. (The IROVAM-iSVT review)
Bailey AJM, Luo OD, Zhou SQ and Wells PS
The management of cancer-associated isolated superficial venous thrombosis (iSVT) remains controversial as cancer patients are at higher risk of bleeding and venous thromboembolism (VTE).
Corticosteroid use to mitigate transaminitis-associated decline in FVIII levels following valoctocogene roxaparvovec gene therapy: clinical practice guidance
Konkle BA, Peyvandi F, Foster GR, Hermans C, La Mura V, Leavitt AD, Lillicrap D, Mahlangu J, Ozelo MC, Pipe S, Recht M, Srivastava A, Young G and Miesbach W
Valoctocogene roxaparvovec is the only factor VIII (FVIII) gene therapy currently approved for adults with severe hemophilia A in Europe and the USA. Elevated alanine transaminase (transaminitis) has been the most common adverse event observed during valoctocogene roxaparvovec clinical trials. Typically mild and transient, this marker of hepatocyte injury coincides, in some patients, with reduced FVIII levels and is generally managed with a reactive course of corticosteroids. An essential step in optimizing outcomes for patients who receive valoctocogene roxaparvovec is to review the extensive evidence currently available on this topic to determine practices for managing transaminitis, if it occurs. This forum article provides practical guidance based on the available clinical data and expert opinion for evaluating and managing transaminitis with corticosteroids to mitigate potential declines in FVIII activity levels in adults with severe hemophilia A who have received valoctocogene roxaparvovec.
The critical role of platelet adenylyl cyclase 6 in haemostasis and thrombosis
Webb BA, Cheah LT, Khalil JS, Hindle MS, McKay M, Turner NA, Kearney MT, Ariens RAS, Duval C and Naseem KM
Platelet activation is constrained by endothelial-derived prostacyclin (PGI) through cyclic adenosine-5'-monophosphate (cAMP) signalling involving multiple isoforms of adenylyl cyclase (AC). The roles of specific AC isoforms in controlling haemostasis remain unclear and require clarification.
The thrombin generation potential increases after feminizing gender-affirming hormone treatment, decreases after masculinizing gender-affirming hormone treatment, and is determined by the hormone treatment regimen
Bøgehave M, Glintborg D, Christensen LL, T'Sjoen G, Vervalcke J, Wiepjes CM, den Heijer M, Andersen MS and Bladbjerg EM
The effects of gender-affirming hormone therapy (GAHT) on the overall coagulation potential are not clarified. The global thrombin generation (TG) assay addresses the combined effect of coagulation factors and inhibitors.
Factor Activity Levels and Bleeding Scores in Hemophilia Carriers: Apparent Paradoxes
Puetz J
Multiple studies report abnormal bleeding in hemophilia carriers with normal factor activity levels. Other studies report the lack of abnormal bleeding in carriers with hemophilia. In addition, limited data suggests that the bleeding risk in carriers increases with age while at the same time, factor activity levels are rising. Potential explanations for these paradoxical findings include inadequate data, inadequate measures of bleeding, inadequate measures of factor activity, or uncharacterized biological modifiers.
Importance of Tubulin Detyrosination in Platelet Biogenesis
Moog S, Mallo L, Eckly A, Janke C, Pujol A, Iruzubieta P, López de Munain A, Moutin MJ, Strassel C, Lanza F and Kimmerlin Q
The functional diversity of microtubules is regulated through the expression of distinct α- and β-tubulin isotypes together with several post-translational modifications, a concept known as tubulin code. Tubulin detyrosination is a reversible post-translational modification which consists in the removal of the genetically encoded C-terminal tyrosine residue of most α-tubulins. While this modification has been observed in the megakaryocyte lineage, its importance remains poorly understood in platelet biogenesis.
Anticoagulation and Other Risk Factors for Clinically Relevant Bleeding after Medical Hospitalization: The Medical Inpatient Thrombosis and Hemostasis Study
Gergi M, Wilkinson K, Sparks A, Roetker NS, Al-Samkari H, Smith NL, Plante TB, Cushman M, Repp AB, Holmes CE, Martin K and Zakai NA
Clinically relevant Bleeding after discharge from a medical hospitalization is associated with increased morbidity and mortality. There is limited knowledge of the risk factors for this bleeding.
Hereditary antithrombin deficiency and venous thrombosis in pregnancy - results of a retrospective multicenter study
Dybedal I, Iversen N, Jacobsen AF, Bjørge L, Chaireti R, Henriksson CE, Schultz NH, Hvas AM, Sandset PM, Weedon-Fekjær H, Bremme K and Abildgaard U
The optimal anticoagulant regimen to prevent pregnancy-related venous thrombosis (VT) in women with antithrombin (AT) deficiency is unknown.
Refractory autoimmune heparin-induced thrombocytopenia following cardiac surgery
Zlamal J, Bohnert BN, Althaus K, Tilly R, Häberle H, Schlensak C, Rosenberger P and Bakchoul T
Autoimmune heparin-induced thrombocytopenia (aHIT) is a severe subtype of HIT characterized by persistent thrombocytopenia and prothrombotic condition even though anticoagulation with heparin has been discontinued. Here we report on a patient with a previous history of aHIT where re-exposure to heparin during cardiac surgery resulted in recurrent aHIT with pulmonary embolism. Alternative anticoagulants as well as high dose intravenous immunoglobulin were ineffective, and only multiple cycles of therapeutic plasma exchange (TPE) restored platelet counts and prevented further thrombosis progression. The therapy was guided by an ex vivo model of anti-platelet factor 4 (PF4)-mediated thrombosis that showed accurate performance in predicting the clinical outcome. Most importantly, the ability to induce thrombus formation was mainly caused by anti-PF4 (heparin-independent) antibodies. Our paper provides the first description of recurrent aHIT with translational evidence that pathogenic heparin-independent anti-PF4 Abs can be specifically targeted by TPE, emphasizing the clinical use in refractory cases of aHIT.