Recent Advances in Thrombosis and Hemostasis—Part XIII

“Life is like riding a bicycle. To keep your balance, you must keep moving.”

― Albert Einstein (1879–1955)

Keeping the balance can also be to find the way in between too much of the good and the bad. However, in medicine, we often have to navigate the care of our patients between two bad outcomes. Perhaps the most poignant example in our specialty is anticoagulant management to avoid or at least minimize the risk of thromboembolic events as well as bleeding complications. This dilemma provides the title in articles such as “Between Scylla and Charybdis: Risks of early therapeutic anticoagulation for venous thromboembolism after acute intracranial hemorrhage.”[1]

Another situation, as described in the first review in this compilation of Seminars in Thrombosis and Hemostasis (STH), is when a patient with a bleeding disorder has been treated to achieve normalization of hemostasis and is then subjected to risk factors for thrombosis, or when the deficient hemostatic factor has been overcompensated. In the first contribution to this theme issue, Franchini et al review the risk factors for arterial and venous thrombotic events as well as the potential negative side effects of replacement therapy and newer non-replacement therapy for hemophilia.[2] They also discuss risk reduction and management of thromboembolic events in patients with hemophilia.

Another congenital blood disorder, most common in the Mediterranean, South and Southeast Asia, the Middle East, and Africa, is thalassemia. Danilatou et al, from the Steering Committees of Hemostasis and Erythrocyte and Hemoglobinopathies Study Groups, Hellenic Society of Haematology, present here a position statement focusing on transfusion-dependent thalassemia, which is associated with an increased risk of thrombosis.[3] They review the pathophysiology and risk factors, and then provide guidance, based on studies with mostly low-quality evidence, on prevention and treatment of venous thromboembolism in various clinical scenarios.

Thereafter, the reader will find two review articles addressing patients with stroke. In the first, Wang et al have performed a systematic review and network meta-analysis of various pharmacologic and mechanical thromboprophylaxis methods studied in 33 randomized trials with patients suffering from ischemic stroke.[4] They conclude that low-molecular-weight heparin or heparinoids are effective in reducing venous thromboembolism, but with the downside of more extracranial hemorrhage.

In the second stroke-related article, Wichaiyo and Suthisisang penetrate the biological and pharmacological characteristics of the thrombolytic agents alteplase, tenecteplase, and reteplase.[5] They review how fibrin specificity, resistance to plasminogen activator inhibitor-1, clot penetration and retention, as well as off-target effects, are important to understand for finding the best balance between clot resolution and hemorrhagic complications.

From the brain, we move over to the gut, which contains the largest microbial ecosystem in our body. Tsante et al review here the important metabolites produced by the gut microbiota.[6] The most established association is between trimethylamine-N-oxide and platelet activation, discussed in detail here. Additional metabolites and their effects are also reviewed. This leads the authors to an analysis of the metabolites as diagnostic tools, prognostic indicators, and targets for intervention.

The use of artificial intelligence in the risk assessment and diagnosis of venous thromboembolism is accumulating interest. Gurumurthy et al have reviewed studies on machine learning for the diagnosis of pulmonary embolism, and for the prediction of risk of venous thromboembolism after surgery and in patients with cancer.[7] They found that although many studies boast excellent C-statistics, there is often a lack of external validation, transparency, and standardized reporting, and problems with “black box” algorithms.

Another novel topic is the use of other drugs than anticoagulants to prevent venous thromboembolism. These alternatives might be less effective but a better choice for patients at a high risk of bleeding or with other contraindications. In a back-to-back article, Gurumurthy and Thachil discuss, here, the data rendering potential support for these agents, including aspirin (not so new), statins, antidiabetic agents, hydroxychloroquine, proprotein convertase subtilisin/kexin type 9 inhibitors, and renin–angiotensin–aldosterone system inhibitors.[8] They conclude that many uncertainties remain in this area.

The first of two original articles in this issue is a retrospective cohort study of almost 10,000 children with central venous catheter(s). Sochet et al analyzed the frequency of thrombolytic agent use, the occurrence of new, hospital-acquired deep vein thrombosis and pulmonary embolism, and risk factors for this.[9] The use of a thrombolytic agent to manage dysfunction of the catheter was independently associated with hospital-acquired venous thromboembolism.

The second study also involves device-related thrombosis, in this case, in the inferior vena cava after insertion of a filter. Gong et al were interested in evaluating the predictive value of composite inflammatory parameters.[10] Those were the ratios of neutrophils/lymphocytes, platelets/lymphocytes, lymphocytes/monocytes, and monocytes/high-density lipoprotein cholesterol, all measured within 24 hours after the filter insertion. The best discrimination was obtained with the neutrophil/lymphocyte ratio.

A commentary by Fan et al reviews available data on red light therapy and effects on platelets, endothelium, and vascular tone.[11] Although photomodulation has been shown to reduce platelet activation and von Willebrand factor activity, there are concerns about insufficient tissue penetration. It remains to be shown if this non-pharmacological method has any role in patients at very high risk of or with active bleeding to prevent or treat thrombosis.

Finally, we have two letters to the Editor. Mattiuzzi and Lippi performed a database analysis to explore whether the increasing use of anticoagulants to prevent venous thromboembolism after femur fracture has had any effect on mortality.[12] For the period of 2018 to 2024, they could not identify any significant change in mortality.

The second letter comments on a study on venous pulmonary embolism, published by Trocchia et al in this Journal.[13] Lee and Wang are concerned that the filter used for patient age was not appropriate and that the results, therefore, became incorrect.[14]

With this variety of topics, we hope that every reader will find one or several articles of interest. Submissions of good quality on new topics related to venous thromboembolism are welcome to this theme issue series. As opposed to other issues in STH, the manuscript does not have to be solicited. However, please be aware that few unsolicited original studies, as opposed to reviews, are accepted for publication.

Conflict of Interest

None declared.

• References

• 1 Nguyen T, Sharma M, Crooks P. et al. Between Scylla and Charybdis: Risks of early therapeutic anticoagulation for venous thromboembolism after acute intracranial hemorrhage. Br J Neurosurg 2022; 36 (02) 251-257
• 2 Franchini M, Focosi D, Mannucci PM. Thrombotic complications in hemophilia: An intricate conundrum. Semin Thromb Hemost 2025; 52 (02) 164-173
• 3 Danilatou V, Papadakis E, Kyriakou E, Nomikou E, Delicou S, Girtovitis F. Transfusion-dependent thalassemia and venous thromboembolism management: Position statement from the Steering Committees of Hemostasis and Erythrocyte and Hemoglobinopathies Study Groups-Hellenic Society of Haematology. Semin Thromb Hemost 2025; 52 (02) 174-185
• 4 Wang C, Han M, Ren L. et al. Comparative study of venous thromboembolic prophylaxis strategies for patients with ischemic stroke: A systematic review and network meta-analysis of randomized controlled trials. Semin Thromb Hemost 2025; 52 (02) 186-198
• 5 Wichaiyo S, Suthisisang C. Current understandings on biological characteristics of thrombolytics in acute ischemic stroke. Semin Thromb Hemost 2025; 52 (02) 199-208
• 6 Tsante K, Petrou E, Tsalas S. et al. Do we have the gut to beat thrombosis?. Semin Thromb Hemost 2025; 52 (02) 209-218
• 7 Gurumurthy G, Kisiel F, Reynolds L. et al. Machine learning in venous thromboembolism - why and what next?. Semin Thromb Hemost 2025; 52 (02) 219-235
• 8 Gurumurthy G, Thachil J. Nonanticoagulant strategies for venous thromboembolism prophylaxis. Semin Thromb Hemost 2025; 52 (02) 236-247
• 9 Sochet AA, Le MQ, Goldenberg NA, Betensky M. Thrombolytic instillation for central venous catheter dysfunction and venous thromboembolism risk among critically ill children. Semin Thromb Hemost 2025; 52 (02) 248-255
• 10 Gong M, Jiang R, He X, Gu J. Association of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, monocyte-to-high-density lipoprotein cholesterol ratio with in-situ vena cava thrombosis. Semin Thromb Hemost 2025; 52 (02) 256-265
• 11 Fan BE, Pasalic L, Hew YY, Lippi G, Favaloro EJ. Red light therapy in thrombosis and hemostasis. Semin Thromb Hemost 2025; 52 (02) 266-272
• 12 Mattiuzzi C, Lippi G. Pulmonary embolism-related mortality in femur fracture patients: a recent retrospective epidemiological analysis. Semin Thromb Hemost 2025; 52 (02) 273-274
• 13 Trocchia C, Ashour D, Mosha M. et al. Venous thromboembolism occurrence and association with gastrointestinal disorders in children with cystic fibrosis: An analysis from the TriNetX Research Network Global Multicenter Real-World Dataset. Semin Thromb Hemost 2025; 51 (07) 736-744
• 14 Lee C-S, Wang J. Research design concerns in a TriNetX analysis of venous thromboembolism in pediatric cystic fibrosis patients. Semin Thromb Hemost 2025; 52 (02) 275-276

Publication History

Received: 07 November 2025

Accepted: 12 November 2025

Article published online:
10 February 2026