Unprovoked Venous Thromboembolism Research Articles

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study.

Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. The RIETE and SOME scores aim to identify patients with acute VTE at high risk of occult cancer. In the present study, we evaluated the performance of both scores. The scores were evaluated in a retrospective cohort from two centers. The area under the receiver-operating characteristics curve (AUC) evaluated the discriminatory performance. The RIETE score was applied to 815 patients with provoked and unprovoked VTE, of whom 56 (6.9%) were diagnosed with cancer. Of the 203 patients classified as high-risk, 18 were diagnosed with cancer, representing 32.1% (18/56) of the total cancer diagnoses. In the group of 612 low-risk patients, 67.9% of the cancer cases were diagnosed (38/56). Sensitivity, specificity, negative and positive predictive values, and AUC were 32%, 76%, 94%, 9%, and 0.430 (95% confidence interval [CI], 0.38‒0.47), respectively. The SOME score could be calculated in 418 patients with unprovoked VTE, of whom 33 (7.9%) were diagnosed with cancer. Of the 45 patients classified as high-risk, three were diagnosed with cancer, representing 9.1% (3/33) of the total cancer diagnoses. In the group of 373 low-risk patients, 90.9% of the cancer cases were diagnosed (30/33). Sensitivity, specificity, negative and positive predictive values, and AUC were 33%, 88%, 94%, 20%, and 0.351 (95% CI, 0.27‒0.43), respectively. The performance of both scores was poor. Our results highlight the need to develop new models to identify high-risk patients who may benefit from an extensive cancer screening strategy.

Venous Thromboembolism Characteristics and Outcomes Among RIETE Patients Tested & Untested for Inherited Thrombophilia

Inherited thrombophilia (IT) workup is commonly pursued in venous thromboembolism (VTE) patients. Recent American Society of Hematology (ASH) guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large prospective RIETE registry was analyzed to compare VTE risk factors, management and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and following its discontinuation. Among 103,818 patients enrolled in RIETE, 21,089 (20.3%) were tested for IT, 8,422 (8.1%) tested positive, and 82,729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors, and less common in those with major risk factors like surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However IT-negative patients with pregnancy or postpartum-related VTE, had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates post-treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities.

Inpatient thrombophilia workup; does hematology consult prevent unnecessary testing?

Hypercoagulable disorders are best described as a group of acquired and hereditary conditions that increase the risk for the development of thrombi within veins or arteries. In the setting of an unprovoked venous thromboembolism, common practice in the inpatient setting has been further investigation via a thrombophilia workup to establish an underlying cause. Current Hematology-Oncology guidelines argue against inpatient workup as the results rarely influence inpatient management. Following American Society of Hematology guidelines (Middledorp), the current study found that only 15% (11/72) of patients met appropriate criteria for thrombophilia testing. There was no relationship between appropriate thrombophilia testing and diagnosis of thrombophilia or initiation of anticoagulation. There was a relationship between appropriate thrombophilia testing and Hematology-Oncology consultation. This demonstrates the need for expert consultation if thrombophilia testing is being considered. The current study provides more evidence that a strong recommendation against inpatient testing should be made as testing does not aid in diagnosis or change management and is an overutilization of healthcare resources.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Viewpoint: Provoked thrombosis in antiphospholipid syndrome.

Unprovoked thrombosis (thrombosis occurring without an established environmental factor favouring the episode) is a classic feature of APS. In the general population, provoked venous thromboembolism (VTE) is clearly defined and has clinical and therapeutic differences compared with unprovoked VTE. Whether provoked VTE in the context of APS may lead to a limited treatment duration is not well established. Therefore, careful clinical and laboratory evaluation is needed to identify patients eligible for a limited duration of anticoagulation treatment after provoked VTE. Given the uncertainties of available data, the risks and benefits of treatment decisions should be clearly explained. Decisions should be shared by both the patient and physician. Cardiovascular risk factors are common in patients with APS with arterial thrombosis. There are insufficient data suggesting that cardiovascular risk factor control would allow the cessation of anticoagulation. In most instances, arterial thrombosis will require prolonged anticoagulants. A careful analysis of clinical characteristics and laboratory evaluation, particularly the aPL antibody profile, is needed to make decisions on a case-by-case basis.

Qualitative experiences, values, and decisional needs of patients with unprovoked venous thromboembolism who suffer bleeding—“This pill will keep you alive tonight”

BackgroundContemporary guidelines recommend extended-duration anticoagulation among patients with a first unprovoked venous thromboembolism (VTE). Little is known about whether this recommendation aligns with patient values after a bleeding complication. ObjectivesTo explore the experiences, values, and decisional needs of patients with unprovoked VTE related to extended-duration treatment after an anticoagulant-associated bleed. MethodsIn this descriptive, qualitative study, face to face online semistructured interviews were conducted with patients with unprovoked VTE who had experienced bleeding and continued anticoagulant treatment in one academic hospital in Canada. Data were analyzed using directed content analysis to identify themes. Themes were mapped onto the Ottawa Decisional Support Framework to identify decisional needs. ResultsBetween September and December 2021, 14 patients were interviewed (age 41-69 years; 9 females). Many patients were not aware of the option to stop anticoagulation and had limited understanding of the decision about treatment duration. Despite the negative quality-of-life impact of clinically relevant bleeding during VTE treatment, the majority continued anticoagulation due to emotional trauma of VTE diagnosis, a perception that bleeding would be more manageable than VTE recurrence, a desire to maintain a connection to subspecialty care or non-VTE related benefits (eg, cancer diagnosis, protection from COVID-19). Patients’ decisional needs included lack of choice awareness, inadequate support for participation, lack of personalized risk stratification, and inadequate information on monitoring and managing heavy menstrual bleeding. ConclusionDespite the impact of anticoagulant-associated bleeding on quality of life, patients preferred continuing with anticoagulation for reasons extending beyond secondary VTE prevention. Effective decision-support interventions are needed to address unmet decisional needs.

High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: the HUNT study

AbstractMicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study. Incident VTE cases (n = 510) and a subcohort (n = 1890) were derived from the third survey of the Trøndelag Health Study (HUNT3), a population-based cohort. The expression levels of miR-145 were measured in plasma samples obtained at baseline. The study population was divided into quartiles based on miR-145 levels in participants in the subcohort, and weighted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE (HR, 0.51; 95% CI, 0.38-0.68) than those with miR-145 in the lowest quartile in age- and sex-adjusted analysis, and the inverse association was most pronounced for unprovoked VTE (HR, 0.39; 95% CI, 0.25-0.61). Risk estimates remained virtually the same after further adjustment for body mass index, and cancer and arterial cardiovascular disease at baseline. In conclusion, elevated expression levels of miR-145 in plasma were associated with decreased risk of future incident VTE. The protective role of miR-145 against VTE is consistent with previous experimental data and suggests that miR-145 has the potential to be a target for VTE prevention.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry

IntroductionAlthough older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. MethodsWe analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. ResultsFrom January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22–1.52) and major bleeding (OR, 2.08; 95%CI, 1.85–2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54–0.71). ConclusionsCompared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.

Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

Recurrent venous thrombosis - an unusual first presentation of autoimmune polyendocrinopathy syndrome type 3B.

A 45-year-old female presented with unprovoked recurrent venous thromboembolism (VTE), in unusual sites, and pancytopenia, posing a complex diagnostic challenge. Work-up for inherited thrombophilia, antiphospholipid syndrome (APLS) and paroxysmal nocturnal haemoglobinuria were unremarkable. Investigations revealed autoimmune thyroid disease, and a mixed iron/vitamin B12 deficiency due to pernicious anaemia and resultant atrophic gastritis. Hyperhomocysteinaemia due to vitamin B12 deficiency was identified as a potential contributor to her recurrent VTE. This case highlights the unusual initial presentation of autoimmune polyendocrinopathy syndrome type 3B (APS-3B) with recurrent thromboembolism, and emphasises the importance of considering hyperhomocysteinaemia in unprovoked and atypical VTE cases.

Provoked vs minimally provoked vs unprovoked VTE: does it matter?

Venous thromboembolism (VTE) is a multifactorial disease, and its risk depends on exposure to risk factors and predisposing conditions. Based on their strength of association with a VTE episode, risk factors are classified as major or minor and determined using a temporal pattern to be transient or persistent. All patients with VTE should receive anticoagulant treatment for at least 3 months in the absence of an absolute contraindication. Beyond this period, selected patients may be candidates for an extended phase of anticoagulation aimed at secondary VTE prevention. The risk of recurrent VTE if anticoagulation is discontinued is probably the main driver of decision-making regarding extended treatment. The risk of recurrence after VTE associated with major risk factors is low if the risk factor is no longer present. In this case, treatment can be discontinued. If the major risk factor is persistent, anticoagulation should be continued. After VTE occurring in the absence of risk factors, anticoagulation should probably be continued indefinitely if the risk for bleeding is low and preferably with minimal effective doses of anticoagulants. VTE occurring after exposure to minor risk factors is probably the most challenging situation, especially if the clinical manifestation was acute pulmonary embolism. Understanding the actual role of minor risk factors in the occurrence of VTE helps in estimating the risk of recurrence and avoiding the dangers associated with unnecessary anticoagulation. The availability of safer strategies for anticoagulation could allow personalized strategies for secondary prevention of VTE.

The Choice of Anticoagulant at First Recurrence Does Not Alter the Risk for the Second Recurrence

Introduction : Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major public health hazard, with up to 30-50% of patients with unprovoked VTE experiencing a recurrent VTE event. These recurrent VTE events are associated with significant morbidity and mortality. However, transition strategies to second-line anticoagulation regimens following the first recurrence on anticoagulation have not been well studied. We sought to examine whether rates of the second VTE recurrence were different in those patients who changed their anticoagulation regimen from those who did not . Methods: With an IRB approval for the study, we created a database of all patients 18 years and older diagnosed with the first recurrent VTE at a large tertiary academic hospital between January 1, 2010, and December 31, 2019. The collected data was de-identified and compiled in a secure, standardized institutional database. We assessed the anticoagulation status at the time of and immediately following the first VTE recurrence, and identified patients who were switched to a different anticoagulant regimen. We used Fisher's exact test to evaluate proportions. Statistical significance was set at p&amp;lt;0.05. Results:We identified 138 patients with the first VTE recurrence. Of these patients, 114 (83%) developed DVT, 7 (5%) PE, and 17 (12%) both DVT and PE. Mean age was 63 years at the time of first VTE; 70 (51%) were female. Racial/ethnic representation was 84 (61%) White, 46 (33%) Black, and 133 (96%) non-Hispanic. The majority of patients had cardiovascular risk factors, including hypertension 80 (58%), hyperlipidemia 44 (32%), ordiabetes 40 (29%). Among 138 patients, 32 (23%) had active cancer, May-Thurner syndrome or inferior vena cava (IVC) atresia were reported in 13 (9%) of cases, and 21 (17%) underwent IVC filter placement at the time of the first VTE recurrence. The median follow-up time after diagnosis of a second VTE was 5 years. Following the first VTE recurrence, 19 (14%) of patients switched to a different anticoagulant agent, 7 (5%) had the dose of the anticoagulant adjusted, 1 (0.7%) was given a different INR target, and one had a change in the frequency of administration. The second VTE occurred in 49 (46%) patients who remained on the same anticoagulation regimen and in 3 (16%) who had the agent changed, in 5 who had dose of anticoagulant changed, in 1 (100%) each who had frequency or INR target changed. The association between unprovoked first VTE and the development of the second VTE was not significant (p= 0.85, Fisher's exact test). 49 (36%) of patients had at least one bleeding episode requiring the interruption of anticoagulation or hospitalization. Of those, 43 (88%) occurred while on an anticoagulant. Conclusion: The choice of an anticoagulant regimen after the first VTE recurrence does not impact the rate of the second recurrence.

Increased Activated Protein C Response Rates to Thrombin Formation in Asymptomatic Factor V Leiden Carriers Are Driven By the Endothelium

Background The thrombophilic factor V Leiden (FVL) mutation shows a highly variable clinical expressivity. We have shown in vivo that asymptomatic FVL carriers respond to extrinsic coagulation activation with higher activated protein C (APC) formation rates than those with a history of venous thromboembolism (VTE). Recently we have established an ex vivo model for personalized assessment of the protein C (PC) pathway combining endothelial colony forming cells (ECFCs) and autologous plasma. Aim of this study was to investigate potential modulating factors of the APC response in the endothelium unraveling the enigma of the variable expressivity of the FVL phenotype. Methods ECFCs were isolated from FVL carriers with (FVL VTE+) or without (FVL VTE-) a history of unprovoked VTE and healthy controls (non-FVL) (n=7 each). Quality control of cultured cells included cobblestone morphology as examined by light microscopy, positive staining for CD31, CD309, CD201, and CD141, CD34, and negative staining for CD45 analyzed by flow cytometry. We either added autologous or pooled normal defibrinated plasma to the confluent cell culture and inititated thrombin formation by addition of tissue factor (1 pmol/L) and CaCl 2 (16.6 mmol/L) ( Fig. 1A). Thrombin and APC formation were measured over time using oligonucleotide-based enzyme capture assays (OECAs) and the ratio between the area under the curve (AUC) of APC formation and the AUC of thrombin formation was calculated as measure for APC response to thrombin. Moreover, we quantified thrombomodulin (TM) and endothelial protein C receptor (EPCR) expression in cell-based enzyme-linked immunosorbent assays (cell-ELISAs) and measured activation of purified PC on ECFCs in the APC-OECA. Results ECFC morphology in light microscopy and characteristic surface marker expression in flow cytometry did not differ between non-FVL, FVL VTE-, and FVL VTE+ subgroups. In the ECFC-based ex vivo model, the APC response in plasma on autologous cells was significantly higher in asymptomatic FVL VTE- carriers compared to non-FVL carriers (P = .0072) and compared to the FVL VTE+ subgroup (P = .0292) whereas it did not differ significantly between non-FVL and FVL VTE+ carriers. EPCR expression on ECFCs measured by cell-ELISA was higher in non-FVL carriers compared to FVL VTE+ subjects (P = .0374) but did not differ significantly when comparing non-FVL versus FVL VTE-, and FVL VTE+ versus FVL VTE-. Similarly, we showed that TM expression as well as activation of purified PC on ECFCs did not differ between cohorts. However, when the APC response was assessed on FVL VTE- and FVL VTE+ ECFCs using non-FVL plasma, the difference in the APC response between asymptomatic FVL carriers and FVL carriers with a history of VTE persisted (P = .0111) ( Fig. 1B). Conclusion Consistent with previous in vivo experiments, APC response rates to thrombin formation were increased on ECFCs obtained from asymptomatic FVL carriers compared to those from FVL carriers with a history of VTE in autologous plasma. Although TM and EPCR expression did not differ between both groups, we showed that the endothelial APC response in asymptomatic FVL carriers remained increased when using plasma from healthy controls. Our observations suggest that the increased APC response to thrombin in asymptomatic FVL carriers is driven by the endothelium. Further studies are warranted to elucidate the underlying mechanism for a better understanding of endogenous protective factors in FVL carriers. These findings may pave the way towards personalized, precision medicine approaches for managing the thrombotic risk in FVL and other disorders related to the PC pathway.

Balancing risks of recurrent venous thromboembolism and bleeding with extended anticoagulation: a decision analysis

BackgroundA decision to stop or continue anticoagulation after 3 months of anticoagulation for venous thromboembolism (VTE) should be made by weighing individual risks of recurrence and bleeding. ObjectivesTo determine the optimal ratio of recurrence risk reduction to increase the risk of bleeding in terms of maximizing quality-adjusted life years (QALYs) gained. MethodsUsing a microsimulation model, outcomes within 5 years were simulated after assigning extended treatment if absolute recurrence risk reduction outweighed absolute increase in clinically relevant bleeding risk (International Society on Thrombosis and Haemostasis definition), weighted by a certain ratio. Data were simulated based on the Bleeding Risk Study, a prospective cohort including patients after ≥3 months of anticoagulation for unprovoked VTE or provoked VTE with history of VTE. The VTE-PREDICT risk score was used to estimate 5-year risks of recurrent VTE and clinically relevant bleeding. ResultsAmong 10,000 individuals (mean age, 60.2 years, 36% female), the ratio of 0.90 (95% CI, 0.51-3.40; ie, bleeding is considered 0.90 the severity of recurrent VTE), with 99% of patients assigned extended anticoagulation, was considered optimal and resulted in 93 (95% CI, −23 to 203) additional QALYs compared with the least favorable ratio (5.10, 0% extended anticoagulation). At the optimal ratio, treatment based on VTE-PREDICT yielded 44 (95% CI, −69 to 157) additional QALYs versus standard of care. ConclusionWith the current evidence, the optimal ratio between relevant bleeding risk and absolute recurrence risk reduction remains uncertain. Our results confirm that clinical equipoise exists regarding the decision to stop or continue anticoagulation after initial VTE treatment, emphasizing the importance of shared decision-making.

Baseline characteristics and outcomes of extended oral anticoagulant treatment in patients with venous thrombosis: a retrospective cohort study in France

Abstract Background Guidelines recommend anticoagulant (AC) extended treatment for patients with unprovoked VTE or VTE provoked by permanent risk factors (ESC 2019, CHEST 2021). A recent observational study has shown that apixaban extended treatment (&amp;gt;6 months) vs no extended treatment in patients with venous thromboembolism (VTE), regardless of risk factors, is associated with decreased risk of recurrent VTE (rVTE), with no increase in major bleeding. A better safety profile for patients receiving apixaban vs those receiving vitamin K antagonists (VKAs) was also observed. Purpose To describe characteristics of patients with VTE receiving AC extended treatment (&amp;gt;6months) vs those receiving acute treatment only (&amp;lt;6 months). Outcomes among patients receiving extended treatment with apixaban and VKAs were also reported. Methods The presence of risk factors were assessed in a nationwide retrospective cohort study of AC treatment-naïve adult patients (identified via the French national health data system: SNDS) with VTE, who were prescribed VKAs or apixaban from 2013 to 2018. Descriptive statistics for patients receiving AC extended treatment vs those receiving only acute treatment are presented. Risk of bleeding (based on principal diagnoses of hospital stays), rVTE (based on principal diagnosis of hospital stays and specified procedures), and all-cause mortality were assessed 18 months following the initiation of extended treatment using inverse probability treatment weighted (IPTW) analysis to balance baseline socio-demographic and clinical characteristics. Results 21,215 VTE patients who initiated AC treatment were included: 10,775 VKAs (41.5% acute vs 58.5% extended treatment) and 10,440 apixaban (44.5% acute vs and 55.5% extended treatment). A higher proportion of apixaban and VKA patients with permanent risk factors (apixaban: 57.7%; VKAs: 57.7%) or unprovoked VTE (apixaban: 56.8%; VKAs: 59.7%) received extended treatment vs acute treatment only. Table 1 shows the adverse clinical outcomes assessed during extended treatment in IPTW balanced cohorts. Compared to patients treated with VKAs (n=6151), patients treated with apixaban (n=5682) had lower rates of rVTE (1.89 vs 2.84 per 100 person-years), bleeding (1.11 vs 1.69 per 100 person-years) and all-cause mortality (2.70 vs 6.74 per 100 person-years). Conclusions A slightly higher proportions of patients with permanent VTE risk factors and unprovoked VTE received extended treatment compared to acute treatment. Consistent with guidelines, there persists a need to increase these rates when clinically indicated to improve patient outcomes. Clinical event rates were numerically lower for apixaban compared to VKAs, which suggests clinical benefit for apixaban. However, more robust confirmatory analyses are required.

OC 46.1 Absolute Quantitative Proteomics for Occult Cancer Screening in Patient with Unprovoked Venous Thromboembolism: Results from the Prospective PLATO-VTE Study

OC 46.1 Absolute Quantitative Proteomics for Occult Cancer Screening in Patient with Unprovoked Venous Thromboembolism: Results from the Prospective PLATO-VTE Study

PB1411 Study of Endothelial Dysfunction in Patients with Unprovoked Venous Thromboembolism through Endothelial Colony-Forming Cell In Vitro Characterization

PB1411 Study of Endothelial Dysfunction in Patients with Unprovoked Venous Thromboembolism through Endothelial Colony-Forming Cell In Vitro Characterization

PB0479 The ABC-Bleeding Score for Prediction of On-Treatment Clinically Relevant Bleeding in Patients with Unprovoked Venous Thromboembolism: Results from the Prospective PLATO-VTE Study

PB0479 The ABC-Bleeding Score for Prediction of On-Treatment Clinically Relevant Bleeding in Patients with Unprovoked Venous Thromboembolism: Results from the Prospective PLATO-VTE Study

PB0463 Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project

PB0463 Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project

OC 40.5 Risk of All-Cause Mortality Following Anticoagulant Cessation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-Analysis

OC 40.5 Risk of All-Cause Mortality Following Anticoagulant Cessation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-Analysis