Bleeding events in Asian patients with cancer-associated thrombosis: a 10-year single-centre experience.

Introduction

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), represents the third leading cause of death globally [ 1 ]. Cancer is a well-established major risk factor for VTE, with patients suffering from malignancies facing an approximately 6.5-fold increased risk compared to individuals without cancer [ 1 ]. Research indicates that CAT occurs most frequently during the early stages of cancer or shortly after its diagnosis [ 2 ]. In a study conducted in Malaysia, there was 10.6% incidence of cancer-associated thrombosis recorded in solid organ tumours [ 3 ]. The presence of VTE in cancer patients is associated with significantly poorer outcomes, with mortality rates increasing by two to six times in this population [ 4 ]. Moreover, a diagnosis of VTE often correlates with a worse overall prognosis for cancer patients [ 5 ].

The pathogenesis of CAT is multifactorial, arising from a complex interplay of patient-specific, cancer-specific, and treatment-related risk factors [ 4 , 6 ]. Patient-related factors include advanced age, obesity, and a history of smoking [ 4 ]. Cancer-related determinants are primarily the site, stage, and histology of the tumour, with adenocarcinomas of the pancreas, stomach, and ovaries conferring the highest thrombotic risk, while cancers of the breast and prostate are associated with a relatively lower incidence [ 1 , 7 ]. Furthermore, therapeutic interventions such as major surgery, chemotherapy, and the use of central venous catheters significantly exacerbate this risk [ 1 , 4 , 6 ].

The management of CAT centres on anticoagulation therapy, with options including low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), vitamin K antagonist (VKAs), fondaparinux, and, more recently, direct oral anticoagulants (DOACs) [ 4 , 6 ]. For years, LMWH has been the cornerstone of treatment, endorsed by clinical guidelines for its superior efficacy and safety profile compared with VKAs in the cancer population [ 6 , 7 ]. However, the long-term requirement for daily subcutaneous injections presents a significant burden, often affecting patient compliance and quality of life [ 7 , 8 ]. DOACs have emerged as attractive alternatives due to their advantages, including rapid onset and offset of action, fixed-dosing regimens, fewer interactions with drugs and food, and the elimination of the need for routine laboratory monitoring [ 7 , 8 ]. Several clinical trials have investigated the safety and efficacy of DOACs in cancer-associated VTE [ 7 , 8 ].

Against this background, increasing attention has been directed towards evaluating the efficacy and safety of DOACs in CAT, particularly in comparison with the long-established use of LMWH. Both the SELECT-D and Hokusai VTE Cancer trials provide strong support for the non-inferiority of DOACs compared to LMWH in treating cancer-associated VTE. However, an increased risk of bleeding, particularly in gastrointestinal cancer patients, necessitates cautious use [ 9 – 11 ]. The advent of DOACs has revolutionised anticoagulation therapy, offering a rapid onset of action, fixed dosing, no need for routine monitoring, and an oral route of administration [ 7 , 8 ]. Their efficacy and safety in the general VTE population are unequivocal; however, their application in cancer patients requires specific validation due to the unique haemostatic challenges in this cohort. Landmark trials such as SELECT-D and HOKUSAI VTE Cancer were designed to address this precise question. The SELECT-D trial demonstrated that rivaroxaban was noninferior to dalteparin, with a lower rate of VTE recurrence (4% vs. 11%) but a higher rate of clinically relevant nonmajor bleeding (13% vs. 4%), particularly in patients with gastrointestinal malignancies [ 9 ]. Similarly, the HOKUSAI VTE Cancer trial found that edoxaban was effective, with a lower recurrence rate than dalteparin (7.9% vs. 11.3%) but a higher incidence of major bleeding (6.9% vs. 4.0%). A meta-analysis of these and other studies confirms that while DOACs are non-inferior to LMWH for preventing recurrent VTE, there was a statistically significant increased risk of major bleeding, especially in patients with gastroesophageal or genitourinary cancers [ 11 ].

Therefore, DOACs represent a promising and convenient alternative to LMWH and VKAs for managing cancer-associated VTE, demonstrating non-inferior efficacy and a manageable safety profile. However, the study populations in previous studies were predominantly composed of patients with solid tumours, with limited representation from haematological malignancies [ 9 , 10 ]. Additionally, studies focusing on Asian populations are relatively scarce.

The objectives of this study were (i) to determine the 6 months incidence of bleeding events among patients treated for cancer-associated thrombosis, (ii) to determine the pattern of anticoagulants used in the treatment for CAT in HCTM from January 2015-January 2025, (iii) to determine the bleeding events according to the type of anticoagulants, and (iv) to determine the factors associated with bleeding events in patients being treated for CAT.

Materials and methods

Study design

This was a single-centre, retrospective study conducted at Hospital Canselor Tuanku Muhriz (HCTM), a semigovernment tertiary teaching hospital in Malaysia with dedicated inpatient haematology and oncology wards, each comprising 28 beds, daycare services and weekly clinics. This study protocol has received approval from the Research Ethics Committee of Universiti Kebangsaan Malaysia (JEP-2025-137/FF-2025-118) to ensure compliance with ethical standards.

Study population

Inclusion criteria included patients with active malignancy, aged more than 18 years old, who presented with the first episode of VTE (lower limb DVT or PE) based on radiological findings from the period of January 2015 to January 2025, and were being treated with anticoagulants for at least 6 months (rivaroxaban, apixaban, dabigatran, edoxaban, warfarin, enoxaparin, fondaparinux). This study excluded cancer patients who received anticoagulant therapy for other reasons, such as atrial fibrillation; patients on antiplatelet therapy; patients who were prescribed fewer than seven days of anticoagulants; and patients who did not complete six months of therapy.

The sampling method was purposive, and all samples that met the inclusion and exclusion criteria were selected for the study. Given the retrospective nature of the study, informed consent was waived. However, patients’ confidentiality was strictly maintained by de-identifying data.

Data collection process

Cancer patients diagnosed with VTE from January 2015 to January 2025 were identified using discharge codes (International Classification of Diseases) and the pharmacy registry. Codes C00-C97 (neoplasm), I82 (deep vein thrombosis), and I26 (pulmonary embolism from the 10th revision of the International Classification of Diseases (ICD-10) were screened. The list of patients was retrieved from the International Centre for Casemix and Clinical Coding for HCTM database in Kuala Lumpur. A list of patients prescribed anticoagulants was obtained from the pharmacy record system. Clinical and laboratory data were extracted from HCTM’s electronic medical records and clinical records obtained via the Medical Record Department, HCTM. Cases of pulmonary embolism were identified through imaging, including computed tomography with pulmonary angiography (CTPA) or contrast-enhanced computed tomography of the thorax (CECT), via electronic medical records or clinical records from outside the study centre. Lower limb DVTs were identified from lower limb ultrasound Doppler imaging.

Data collected at the initial diagnosis of VTE include age, sex, ethnicity, type of VTE, and type of anticoagulant. Patients who were initially prescribed parenteral anticoagulants and later changed to DOACs during the initial 2 weeks were labelled as the DOAC group. The first episode of bleeding documented in HCTM after starting anticoagulants within the first six months was based on clinical notes of the event, assessed via the electronic medical record (e.g., discharge summaries, procedure reports, or imaging). Patients who developed a reduction in haemoglobin without any clinical, endoscopic, or radiologic evidence of bleeding were not counted as having a bleeding event. All bleeding events were independently adjudicated by at least 2 reviewers.

Data on evidence of severe thrombocytopenia (platelet count < 50 × 10 9 /L), prolonged INR (INR > 1.5), metastatic status, chemotherapy administration during the VTE treatment, renal insufficiency (CrCL < 60mL/min), and recent surgery (less than three months) were recorded and analysed for all patients with bleeding events. For non-bleeding patients, data were collected at the end of 6 months of treatment.

Operational definition

Active malignancy: Any diagnosis of cancer (solid or haematological), in the previous 6 months, or underwent cancer treatment over the last six months, recurrent or metastatic cancer, or cancer that was not in remission [ 9 ]. A bleeding event was defined according to the International Society on Thrombosis and Haemostasis (ISTH) [ 12 ]. The study excluded any recurrent bleeding during the study period. Major bleeding was defined as a bleeding event with either (i) a drop in haemoglobin of 2 g/dL, (ii) a required transfusion of two units of packed red blood cells, (iii) involving critical site bleeding (intracranial, intraspinal, intraocular, retroperitoneal or pericardial area), and (iv) contributing to death. Clinically relevant non-major bleeding was defined as a bleeding event that does not meet the criteria for major bleeding but is associated with medical intervention, interruption or continuation of anticoagulant treatment, or is accompanied by any discomfort or impairment of daily life activities. Prolonged INR was defined as a value of INR > 1.5. Renal insufficiency was defined as creatinine clearance < 60mL/min. Severe thrombocytopenia was defined as a level of platelet count < 50 × 10 9 /L.

Data for prolonged INR, severe thrombocytopenia, renal insufficiency, metastatic status, chemotherapy administration and recent surgery (less than 3 months) were taken at the bleeding event.

Statistical analysis

The statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) Version 29.0. For descriptive analysis, categorical data were presented as frequencies and percentages, and associations with bleeding were analysed using the chi-square test when appropriate. Continuous data were presented as medians with interquartile ranges, based on the data’s normality. The normality of data was determined using the Kolmogorov-Smirnov test. The incidence of major bleeding events and clinically relevant non-major bleeding events among patients who were treated for cancer-associated thrombosis in HCTM was reported as a percentage. The bleeding incidence among different types of anticoagulant classes was reported in percentage. The number of cancer patients who were converted from DOACs to LMWH during VTE treatment was reported as a percentage. The risk factors associated with bleeding events in cancer patients being treated for VTE with DOACs were analysed using logistic regression. A p-value < 0.05 was considered significant.

Results

We screened 415 cancer patients with VTE, and 203 were included in the final analysis (Fig. 1 ). Patients’ demographics, clinical characteristics, and their association with bleeding are summarised in Table 1 . Median age of our patients was 63 years (IQR 15). The majority of patients were aged ≥ 60 years (61.1%), female (61.1%), and Malay (53.2%), followed by Chinese (37.9%) and Indian (7.9%). The five most common non-haematology malignancies with VTE in our study were gynaecological (51, 25.1%), gastrointestinal (GI) (35, 17.2%), lung (31, 15.3%), genitourinary (GU) (18, 8.9%), and breast (17, 8.4%). Haematological malignancies with VTE included acute leukaemia (3, 1.5%), lymphoma (17, 8.4%) and multiple myeloma (4, 2.0%).

Associations between socio-clinical characteristics with bleeding outcomes

Fifty-one patients (25.1%) experienced bleeding events within the first six months of anticoagulation. No significant associations with bleeding outcomes were observed for age ( p = 0.540), sex ( p = 0.475), or race ( p = 0.392). Type of malignancy (haematological versus non-haematological, administration of chemotherapy and presence of metastatic disease were not significantly associated with bleeding. Prolonged INR during a bleeding event (INR > 1.5) was significantly associated with bleeding ( p = 0.014). Otherwise, other clinical data were not associated with bleeding, including severe thrombocytopenia, renal insufficiency, and recent surgery, p = 0.561, = 0.188 and = 0.158, respectively.

VTE and patterns of anticoagulants

In terms of VTE events, 109/203 (53.7%) had pulmonary embolism (PE), 66/203 (32.5%) had DVT, and 28/203 (13.8%) had both pulmonary embolism and deep vein thrombosis. The distribution of different anticoagulants used in the cohort is displayed in Fig. 2 . Rivaroxaban was the most frequently used anticoagulant, followed by enoxaparin; the least frequently used was edoxaban.

Of the 179 patients in the non-haematological cohort, 122 (68.2%) were treated with DOACs, 43 (24%) with LMWH, 12 (6.7%) with warfarin and 2 (1.1%) with fondaparinux. Among patients with GI malignancies ( n = 35), 23 (67%) received DOACs, 7 (20%) received LMWH (63.8%), 1 (2.9%) fondaparinux and 4 (11.4%) received warfarin. Among those with GU malignancies ( n = 18), 11 (61.1%) received DOACs, 5 (27.8%) received LMWH, and 2 (11.1%) received warfarin. Within the haematological malignancy cohort, DOACs remained the most commonly used anticoagulants (12/24, 50%), followed by LMWH (6/24, 25%) and fondaparinux (6/24, 25%), while no patients received warfarin.

Doses of the DOACs were administered as per international guideline standards: rivaroxaban 15 mg BD for 21 days, then 20 mg once daily (OD); dabigatran 150 mg twice daily (BD); and edoxaban 60 mg OD. As for apixaban, 5 of 16 patients were treated with 2.5 mg BD due to renal insufficiency (serum creatinine ≥ 133 µmol/L), while the remaining were treated with 5 mg BD. Another parenteral anticoagulant identified in the data was fondaparinux, which accounted for approximately 3.9% of the total cohort and is preferable due to its daily dosing regimen. Patients who were on warfarin were monitored regularly with an international normalised ratio (INR) ranging from two to three with appropriate dose adjustment.

The pattern of anticoagulants used for the treatment of CAT in our centre from 2015 until 2024 is shown in Fig. 3 . The graph demonstrated an increasing trend in rivaroxaban prescriptions over the years. Starting from low usage in 2015, the number of rivaroxaban prescriptions steadily increased and peaked in 2023, before experiencing a slight reduction in 2024. The use of enoxaparin fluctuated throughout the study period, with a slight peak in 2018, followed by a gradual decrease to fewer than five per year, as recorded in 2024. Other anticoagulants displayed minimal variation, maintaining stable trends over the ten-year study period.

Bleeding events and the associated risk factors

The bleeding incidence within the first six months of anticoagulant therapy was 25.1% (51/203), comprising 17 major bleeding and 34 clinically relevant non-major bleeding (CRNMB). The GI tract was the commonest site of bleeding (45.1%), followed by the genitourinary tract (21.6%). The incidence of bleeding events was 24% among patients with non-haematological malignancies, compared with 33.3% among those with haematological malignancies. According to malignancy type, the incidence of bleeding was 16/35 (45.7%) in GI, 15/51 (29.4%) in gynaecology, 4/31 (12.9%) in lungs, and 1/18 (5.6%) in GU.

Among patients with GI malignancies ( n = 35), 16 (45.7%) experienced bleeding events. Distribution of anticoagulants during the bleeding events was as follows: DOACs (10/23, 43.5%), LMWH (3/7, 42.9%), and warfarin (3/4, 75%). Five events occurred at the cancer sites, and all were on DOACs at the time of bleeding (Table 2 ).

When analysed by anticoagulant class (Fig. 4 ), bleeding was most frequently observed among patients receiving vitamin K antagonist, warfarin (41.6%), followed by parenteral anticoagulants (LMWH and fondaparinux) (33.3%), while the lowest proportion occurred among DOAC users (20.2%). Among parental anticoagulants, 15 bleeding events occurred with LMWH, while 4 occurred with fondaparinux. Both LMWH and Fondaparinux were each associated with 2 recorded major bleeding events. In total, 5 fatal bleedings were recorded in the cohort.

During therapy, among patients receiving DOACs, 8 (6%) required conversion to LMWH. The reasons were: four patients experienced bleeding events, while another four were converted from DOACs to LMWH for other clinical reasons, including worsening thrombocytopenia, anaemia with an unidentified bleeding source and acute renal injury.

The median time from the start of anticoagulation to the first bleeding episode was 31.5 days (IQR: 56 days). Figure 5 shows the distribution of timing for bleeding events within the first six months of anticoagulants.

Risk factors for bleeding events in cancer associated thrombosis

Associated risk factors for bleeding events in patients treated for CAT were analysed using a simple logistic regression method (Table 3 ). We found that prolonged INR during the bleeding event was shown to be an associated risk factor ( p = 0.016, OR 2.42), which was more than twofold risk of bleeding among cancer patients with VTE. Females had a lower odds of bleeding compared to males (OR: 0.79, 95% CI: 0.42–1.51, p = 0.475), while the Chinese race had the highest odds for bleeding (OR: 1.59, 95% CI: (0.82–3.07), p = 0.173); however, they were not significant. Other associated risk factors, such as metastatic disease, chemotherapy, renal insufficiency, and recent surgery, did not yield any statistically significant associations with the bleeding events.

Discussion

In our study, a total of 203 patients treated for cancer-associated thrombosis were identified during the 10-year study period. The incidence of bleeding events within six months of anticoagulation was 25.1% (51/203). This is notably higher than rates reported in pivotal randomised trials, including SELECT-D (12.1%) 9 , Hokusai-VTE Cancer [ 10 ] (16.3%), and Caravaggio [ 13 ] (10.9%). Differences in study design, patient selection, and anticoagulant type could also account for part of the discrepancy. Clinical trials often exclude patients with high bleeding risk, such as those with severe thrombocytopenia or recent major bleeding. In our study, we also determined whether severe thrombocytopenia was a risk factor for bleeding [ 9 , 10 , 13 ]. Furthermore, unlike those trials that focus on one or two anticoagulants, our real-world study encompassed a broader spectrum, including warfarin, parenteral anticoagulants (enoxaparin, fondaparinux) and multiple DOACs [ 1 , 2 , 8 ].

On the other hand, when compared with retrospective real-world cohorts, our findings are most comparable to Poenou et al., who reported a 6-month cumulative bleeding incidence of 26.7% among 110 cancer patients treated for VTE, whereby this diversity better reflects real-world prescribing among patients with cancer-associated thrombosis [ 14 ]. In contrast, another retrospective study by the TROLL Registry documented substantially lower rates, with a 12.7% bleeding incidence, among patients receiving LMWH (85.8%) 15 . These differences may be attributed to variations in anticoagulation use and ethnic background. In addition, similar to the landmark trials, the TROLL registry was conducted among a Western population, whereas our study population was predominantly Asian [ 15 ]. Ethnic variation may explain the discrepancy with our study as ethnic and genetic factors are known to influence anticoagulant metabolism and bleeding risk, particularly for DOACs and VKAs, as in differences in pharmacogenetics, cancer biology, comorbidities and healthcare systems have been shown to influence bleeding risk across populations [ 16 ].

Regarding anticoagulant distribution, our study showed a distinct pattern compared with the TROLL registry [ 15 ]. DOACs were the predominant agents used (66%) followed by parenteral anticoagulants (33.3%) and lastly warfarin (5.9%). Since this was a retrospective study, the exact reasons for choosing DOACs over LMWH were not documented. This contrasts with the TROLL Registry, where LMWH accounted for 85.8% of the initial anticoagulants used and DOACs for only 7.7%, reflecting an earlier treatment era (2005–2022) when LMWH was the recommended standard for CAT [ 15 ]. Nonetheless, the TROLL data showed a progressive increase in DOAC use over time, particularly in the later years of registry enrolment, which parallels the trend observed in our cohort [ 15 ]. This shared trajectory highlights the global shift towards DOAC-based therapy, aligning with contemporary international guidelines that now endorse DOACs as a preferred option for CAT treatment [ 4 , 17 , 18 ].

In relation to bleeding patterns, bleeding in our cohort occurred most frequently among patients treated with warfarin, while DOAC users experienced the lowest proportion of bleeding events. Regarding the site of bleeding, the gastrointestinal tract was the most common location (45%), with similar distribution between major and CRNMB. This finding is consistent with previous randomised studies, in which GI bleeding predominated, particularly among patients receiving DOACs [ 9 , 10 ]. Similarly, the retrospective study by Poenou et al. reported that 31% of all bleeding events were gastrointestinal in origin; however, the study focused predominantly on patients receiving LMWH and unfractionated heparin, which may limit direct comparison with contemporary DOAC-based cohorts [ 14 ]. Nevertheless, data from the TROLL Registry demonstrated a comparable pattern, with 33.3% of major bleeding events occurring at GI sites [ 15 ]. This can be due to several pathophysiological mechanisms, including tumour infiltration of the GI wall or mucosal ulceration, which can subsequently predispose to bleeding [ 19 ]. In our study, five bleeding events occurred at the tumour site in patients with GI malignancies, all of whom were on DOACS. Three of the events occurred before 2020–2021, when international guidelines began recommending against the use of DOACs in patients with luminal GI and GU cancers. These findings emphasise the importance of individualised anticoagulant selection and close monitoring in patients with GI malignancies or pre-existing mucosal pathology.

We further analysed the timing of bleeding events from the initiation of treatment. In the study, we found that most bleeding events occurred within the first 3 months of treatment, with fewer events thereafter. This pattern is consistent with previous studies, which have shown that the risk of bleeding is highest during the early treatment phase [ 14 ]. These findings suggest that early anticoagulation is a period of heightened risk, likely reflecting advanced tumour burden, treatment-related mucosal injury, and the effects of high-intensity initial anticoagulation, thereby highlighting the need for close monitoring during the initial phase of therapy [ 20 , 21 ].

With respect to anticoagulation eligibility, a total of 124 patients were not started on anticoagulation and were therefore excluded from this analysis, The most frequent reasons for this were high bleeding risk, advanced frailty or patient refusal This is consistent with findings from retrospective studies, such as the TROLL Registry, where approximately 10% of patients with cancer associated thrombosis did not receive anticoagulation, mainly due to recent major bleeding, thrombocytopenia or limited life expectancy [ 15 ]. As in another study, several patients were excluded due to contraindications to anticoagulants or palliative status, highlighting a shared real-world challenge in managing fragile populations [ 14 ]. This approach aligns with international guidelines that emphasise that treatment decisions should be carefully individualised, balancing thrombotic and bleeding risks with the overall clinical prognosis and the patient’s preference [ 4 , 18 ].

Another important outcome of this study was the evaluation of risk factors for bleeding events. In this study, prolonged INR at the time of bleeding (defined as an INR > 1.5) emerged as a significant associated risk factor for bleeding (OR 2.42, p = 0.016), accentuating the role of impaired haemostasis in amplifying anticoagulant-associated bleeding. However, there are limited retrospective studies that specifically assessed INR derangement as a risk factor for bleeding in cancer-associated thrombosis, making direct comparison challenging. One of the few studies addressing this relationship was conducted among 75 cancer patients on oral anticoagulants (warfarin), whereby 20% experienced bleeding and 30% were over-anticoagulated (INR > 4), alongside a trend towards higher INR values and older age among those who had bleeding complications [ 22 ]. Similarly, Bhardwaj et al. found that even mildly elevated INR levels predicted bleeding in patients treated with DOACs for venous thromboembolism, although the study did not distinguish between cancer and non-cancer populations [ 23 ]. In contrast, most available evidence has focused on clinical or treatment-related predictors of bleeding. In the COMMAND-VTE, chronic kidney disease was recognised as an independent predictor of bleeding [ 24 ]. Another study by the RIETY Registry otherwise identified recent major bleed, anaemia and metastatic disease as significant predictors of bleed among anticoagulated cancer patients [ 25 ]. The lack of significance in our study may reflect the limited number of cases recruited; the association between prolonged INR and bleeding provides valuable insight into the potential role of laboratory markers in identifying patients at higher risk.

This study has several limitations. Its retrospective, single-centre design may introduce selection bias and limit the generalisability of findings. Due to the retrospective nature of data collection, certain variables, such as smoking history, body mass index (BMI), and Eastern Cooperative Oncology Group (ECOG) performance status, were not consistently available or documented. These parameters may represent important contributors to bleeding risk and limit the ability to fully adjust for potential confounders or to identify additional predictors of bleeding in this cohort. Furthermore, bleeding events may have been under-reported due to incomplete documentation or management outside of the study centre, leading to an underestimation of bleeding incidence. In this study, the modest sample size restricted the statistical power to detect associations between associated risk factors and bleeding outcomes. The use of simple logistic regression, driven by sample size constraints, may have led to residual confounding due to the inability to adjust for multiple variables. In addition, transitions between anticoagulant therapies, such as switching from LMWH to DOACs, were not recorded, limiting assessment of their potential impact on bleeding outcomes. Lastly, treatment allocation was not randomised and reflected clinician preference, leading to heterogeneity in anticoagulant choice and potential confounding by indication.

The study’s strength lies in its inclusion of multiple anticoagulant classes, which provides a comprehensive picture of treatment patterns and outcomes beyond the narrower scope of randomised trials, which typically include a limited number of agents. This study also represents one of the few available cohorts of cancer-associated VTE managed with anticoagulation in an Asian population, addressing a gap in the literature where most trials were conducted among Western populations.

Conclusion

This study demonstrated that bleeding events are a significant complication among Asian patients with cancer-associated thrombosis, with a bleeding incidence of 25.1%. Analysis of treatment trends showed a progressive shift towards DOACs as the predominant therapy. Bleeding events occurred across all anticoagulant classes, with the highest proportion among patients receiving warfarin. Most bleeding events occurred in the gastrointestinal tract, with nearly half occurring within the first month of therapy. A minority of patients (6%) required conversion from DOACs to LMWH, mainly due to bleeding or increased bleeding risk, accentuating the continued relevance of parenteral anticoagulation. Among the risk factors examined, only prolonged INR (INR > 1.5) was independently associated with bleeding, whereas other demographic and clinical variables were not significant. In conclusion, this study provides important insights into the prevalence, patterns, and predictors of bleeding in cancer-associated VTE, reinforcing the need for vigilant monitoring and individualised anticoagulation strategies to optimise patient outcomes. Future multicentre studies integrating bleeding management strategies, including the prevalence and indications for transfusion, are warranted to provide deeper insight into the severity, clinical consequences, and healthcare resource impact of anticoagulant-related bleeding in cancer patients.

Author contributions

All authors contributed to the study conception and design. H.A. collected data. H.A. and Y.S.Q. analysed the data and prepared the figures and tables. H.A. wrote the first draft of the manuscript. N.R.T. and Y.S.Q. commented and edited on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

Open access funding provided by The Ministry of Higher Education Malaysia and Universiti Kebangsaan Malaysia

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

Data Citations

Zaboras Z, Jørgensen CT, Stensvold A, Pettersen HH, Galovic Grdinic A, Brækkan SK et al (2024) TH Open 8(1):e132–e140. 10.1055/s-0044-1782219. Real-world data on treatment patterns and bleeding in cancer-associated thrombosis: Data from the TROLL Registry

Data Availability Statement

No datasets were generated or analysed during the current study.