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Thromboembolic Disease and Antithrombotic Therapy
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Thromboembolic Disease and Antithrombotic Therapy

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 7226

Special Issue Editor

Dr. Prahlad Ho

E-Mail Website
Guest Editor
1. Northern Clinical Diagnostics and ThrombovAscular Research (NECTAR) Center, Northern Health, Epping, Melbourne, VIC 3076, Australia
2. Diagnostic Services, Northern Health, Epping, Australia
3. Australian Centre for Blood Diseases, Monash University, Prahran, Melbourne, Australia
4. Department of Medicine, Northern Health, University of Melbourne, Epping, Australia
Interests: thrombosis; anticoagulation; venous thromboembolism; pulmonary embolism; hematology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Venous thromboembolism is a common disorder affecting up to 1 in 12 individuals in their lifetime, with substantial healthcare and socioeconomic costs due to its recurrence and complications. The introduction of direct oral anticoagulant in the last decade marked a paradigm shift in the management of VTE, although there remains significant disease burden represented by chronic complications such as post thrombotic syndrome and chronic thromboembolic pulmonary hypertension, risk of recurrent thrombosis, bleeding risk associated with anticoagulation and substantial mortality. Despite improved acute VTE management, the management of chronic complications remains inadequate. More recently, Factor XI and XII have emerged as potential new targets for novel anticoagulants.

The next challenge in thrombosis management is the development of effective risk stratification methods using novel biomarkers to encompass the multifactorial contributors to thrombosis, including the various components of Virchow’s triad and taking into account epigenetic mechanisms in modulating VTE. Much refinement is still required to ensure the equilibrium between thrombotic and bleeding risk is carefully maintained. These biomarkers, when identified, will allow the transition of traditional thrombosis care into personalised medicine, and facilitate the development of specific targeted therapies for this heterogenous disease. 

This Special Issue aims to bring together a body of literature which discusses the latest research in thromboembolic disease and antithrombotic therapy as we move towards personalised VTE therapy.

Dr. Prahlad Ho
Guest Editor

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Keywords

  • thrombosis
  • pulmonary embolism
  • manticoagulation
  • DOAC (direct oral anticoagulants)
  • DVT (deep vein thrombosis)
  • novel anticoagulants (factor XIa inhibitors)
  • thrombin
  • fibrin generation
  • risk stratification
  • biomarkers
  • Virchow’s triad
  • post thrombotic syndrome

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Published Papers (5 papers)

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Research

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17 pages, 1394 KiB  
Article
A Pilot Study to Evaluate an International Normalized Ratio-Derived Formula in Combination with Heparin-Calibrated Anti-Xa Activity in Calculating a Plasma Edoxaban Level
by Chun-Fung Sin, Pui-Yee Chan, Yi-Teng Hoo, Wang-Ho Yuen and Hoi-Ching Wong
J. Clin. Med. 2025, 14(3), 1006; https://doi.org/10.3390/jcm14031006 - 5 Feb 2025
Viewed by 705
Abstract
Introduction: A drug-specific chromogenic assay is not immediately available, so it hampers the treatment of patients who present in a clinical emergency. In this pilot study, we aimed to create a formula to predict a plasma edoxaban level based on the international normalized [...] Read more.
Introduction: A drug-specific chromogenic assay is not immediately available, so it hampers the treatment of patients who present in a clinical emergency. In this pilot study, we aimed to create a formula to predict a plasma edoxaban level based on the international normalized ratio (INR) and heparin-calibrated anti-Xa activity and derive a novel workflow for routine laboratory diagnosis. Method: Forty-two patients prescribed edoxaban were recruited and randomized to a testing or validation cohort. Plasma levels from the testing cohort were used to create a prediction formula that was then validated in a validation cohort and real-world clinical requests. Results: The INR-derived formula had high sensitivity (95.8–100%) to predict the plasma edoxaban level > 50 ng/mL and >100 ng/mL but with low specificity. However, the specificity of predicting the plasma edoxaban level of ≥100 ng/mL was 100% by using an INR ≥ 1.5 as cut-off. Heparin-calibrated anti-Xa-derived formula had a high sensitivity (90.9–100%) and specificity (93.8–100%) in real clinical situations. A two-tier approach of combining INR-derived and heparin-calibrated anti-Xa-derived formulae can overcome the low specificity and utilize the advantages of wide availability and a short turnaround time of the INR-derived formula. Conclusions: Both INR-derived and heparin-calibrated anti-Xa-derived formulae can be applied to calculate the plasma edoxaban level. A two-tier workflow of combining these two formulae greatly helps streamline the treatment of patients prescribed edoxaban who present in a clinical emergency. Adoption of this framework is feasible for routine diagnostic laboratories. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)
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11 pages, 239 KiB  
Article
A 12-Year Review of Upper Extremity Deep Vein Thrombosis—Are They the Same as Lower Extremity Deep Vein Thrombosis?
by Patrick Leung, Brandon Lui, Julie Wang, Prahlad Ho and Hui Yin Lim
J. Clin. Med. 2024, 13(21), 6440; https://doi.org/10.3390/jcm13216440 - 27 Oct 2024
Cited by 2 | Viewed by 1338
Abstract
Background: Upper extremity deep vein thrombosis (UEDVT) is uncommon but not insignificant. The current literature is limited, and the management is largely extrapolated from the treatment of lower extremity DVTs (LEDVT). Methods: A retrospective review was conducted on patients diagnosed with UEDVT [...] Read more.
Background: Upper extremity deep vein thrombosis (UEDVT) is uncommon but not insignificant. The current literature is limited, and the management is largely extrapolated from the treatment of lower extremity DVTs (LEDVT). Methods: A retrospective review was conducted on patients diagnosed with UEDVT at Northern Health, Victoria, Australia, between December 2010 and December 2022. Medical records were reviewed to assess baseline characteristics and treatment outcomes. The results were compared to our previously collected data for LEDVTs. Results: 137 patients with UEDVT were identified (52.6% females; median age 62 years, IQR 46–74 years). A total of 105 patients (76.6%) had at least one provoking factor at the time of diagnosis, most commonly malignancy (45.7%) and/or indwelling venous devices (58.1%). Fourteen patients (10.1%) were subsequently diagnosed with Paget–Schroetter syndrome, with nine receiving endovascular or surgical intervention. A total of 109 patients (79.6%) received limited therapeutic anticoagulation (median 3 months, IQR 1.5–6.0 months) with enoxaparin, the most common anticoagulant used. Six patients had major bleeding (5.2/100-patient-years), and seven developed clot progression while on anticoagulation (6.0/100-patient-years). Ten patients had recurrent VTE following anticoagulation cessation (4.6/100-patient-years). There were no significant differences seen in the complication rate between catheter-related UEDVT and other UEDVTs. Compared to LEDVT, UEDVT was more likely provoked with comparable complication rates. Conclusions: UEDVTs were commonly associated with a provoking factor, with indwelling catheters and/or malignancies being the most common. Interestingly, catheter-related UEDVT had comparable clot progression/recurrence and major bleeding compared to other UEDVTs and LEDVTs, which may be confounded by relatively high rates of malignancy. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)

Review

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30 pages, 3837 KiB  
Review
Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide
by Giuseppe Miceli, Anna Maria Ciaccio and Antonino Tuttolomondo
J. Clin. Med. 2025, 14(9), 2914; https://doi.org/10.3390/jcm14092914 - 23 Apr 2025
Viewed by 1583
Abstract
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant [...] Read more.
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)
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10 pages, 379 KiB  
Review
Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Cancer Patients with Central Venous Catheters: A Literature Review
by Hikmat Abdel-Razeq and Mohammed J. Al-Jaghbeer
J. Clin. Med. 2024, 13(6), 1660; https://doi.org/10.3390/jcm13061660 - 14 Mar 2024
Cited by 2 | Viewed by 2161
Abstract
Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory [...] Read more.
Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory settings. The endothelial injury associated with the use of these catheters adds to the risk of VTE to already high-risk patients. The introduction of direct oral anticoagulants (DOACs), with its proven efficacy and safety in multiple clinical indications, have renewed the attention to VTE prophylaxis in cancer patients with CVC. Several clinical trials and meta-analyses had shown that both apixaban and rivaroxaban are effective in lowering the risk of VTE, without increasing the risk of bleeding. Several risk assessment models (RAM) have utilized patient-related, tumor-related, and treatment-related factors, in addition to widely available biomarkers, like Hemoglobin (Hb) level, white blood cell (WBC) and platelets counts to stratify patients into two or three VTE risk levels. In this manuscript, we review the published clinical trials and meta-analyses that attempted to study the efficacy and safety of anticoagulants, mostly the DOACs, in cancer patients with CVCs. We will also propose a practical risk-directed approach to enhance VTE prophylaxis rate. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)
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Other

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11 pages, 1162 KiB  
Systematic Review
Safety and Efficacy of Direct Oral Anticoagulants Apixaban and Rivaroxaban Versus Standard Therapy for VTE Prophylaxis Post Cancer Surgery—A Network Meta-Analysis of Randomized Clinical Trials
by Alaa Shahbar, Abdulaziz Alawlqi, Abdullah Alhifany, Afnan Noor, Abdulaali R. Almutairi and Mohammed Alnuhait
J. Clin. Med. 2025, 14(6), 1811; https://doi.org/10.3390/jcm14061811 - 7 Mar 2025
Viewed by 895
Abstract
Background/Objectives: Venous thromboembolism (VTE) is a major risk for cancer patients undergoing surgery due to hypercoagulability and surgical stress. Traditional low-molecular-weight heparins (LMWHs) are used as the standard of care for VTE prophylaxis, but subcutaneous administration often leads to suboptimal patient adherence. [...] Read more.
Background/Objectives: Venous thromboembolism (VTE) is a major risk for cancer patients undergoing surgery due to hypercoagulability and surgical stress. Traditional low-molecular-weight heparins (LMWHs) are used as the standard of care for VTE prophylaxis, but subcutaneous administration often leads to suboptimal patient adherence. Direct oral anticoagulants (DOACs) are being explored as more convenient and effective alternatives. This study employed a network meta-analysis approach to comparatively assess the safety and efficacy of DOACS and LMWH in preventing VTE among cancer patients undergoing oncologic surgery. Methods: A systematic review and network meta-analysis were conducted. The search strategy included randomized controlled trials (RCTs) retrieved from databases such as CLINICALTRIAL.GOV, MEDLINE, and EMBASE. The search encompassed studies published up to October 2023 and compared the efficacy and safety of DOACs with LMWHs in patients undergoing cancer surgery. The primary outcome was the incidence of VTE, and the secondary outcomes included the incidences of major bleeding events (MB) and clinically relevant non-major bleeding (CRNMB). Results: A network meta-analysis of four randomized controlled trials (RCTs) involving 1600 cancer surgery patients was conducted. No statistically significant differences in VTE rates were observed between DOACs and LMWHs. While rivaroxaban 10 mg once daily for 30 days significantly reduced VTE risk compared to placebo (RR: 0.27, 95% CI: 0.08–0.95), no significant differences were found in major or clinically relevant non-major bleeding risks between DOACs and LMWH or placebo. Conclusions: This network meta-analysis provides evidence supporting the use of DOACs, specifically apixaban and rivaroxaban, as safe and efficacious alternatives to LMWHs for VTE prophylaxis in cancer patients undergoing surgery. The oral administration and reduced monitoring requirements associated with DOACs address the limitations inherent to LMWHs, potentially improving patient adherence. These findings emphasize the need for additional head-to-head trials and long-term studies further to solidify their role in this high-risk patient population. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)
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