Risk Factors Predictive of Occult Cancer Detection in Patients with Unprovoked Venous Thromboembolism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 625-625
Author(s):  
Ryma Ihaddadene ◽  
Daniel J Corsi ◽  
Alejandro Lazo-Langner ◽  
Sudeep Shivakumar ◽  
Vicky Tagalakis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Cancer Screening ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Hazard Ratio ◽  
Vein Thrombosis ◽  
Occult Cancer ◽  
Occult Malignancy ◽  
Cox Proportional Hazard Models

Abstract Background: Venous thromboembolism (VTE) may be the earliest sign of cancer. Risk factors associated with the presence of an occult cancer in patients with a first acute unprovoked VTE are unknown. We sought to assess the risk factors predictive of occult cancer detection in patients with a first unprovoked symptomatic VTE. Methods: Post-hoc, pre-defined analyses of the multicenter open-label randomized controlled trial - Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial (Carrier M et al. N Engl J Med 2015). The trial compared comprehensive computed tomography (cCT) of the abdomen and pelvis in addition to limited occult-cancer screening (complete history and examination, basic laboratory testing, chest radiography, and breast, cervical and prostate cancer screening) with limited occult-cancer screening alone in patients with a first unprovoked episode of VTE. Cox proportional hazard models were used to analyze the effect of specific risk factors on the outcome of occult cancer within 12 months of a diagnosis of unprovoked VTE. Multivariable analysis was performed using Cox proportional hazard models that included all variables that achieved a p value of < 0.20 in univariate analyses. Results: A total of 854 patients were randomized to limited occult cancer screening only, or limited occult cancer screening in combination with a cCT. The mean age was 54 years and 67.4% were males. A total of 33 (3.9%; 95% C.I. 2.8-5.4) patients received a new diagnosis of cancer at 12 months follow-up. Age ≥ 60 years, compared to age < 60 years, was a predictor of cancer with a corresponding hazard ratio (HR) of 2.90 (95% C.I. 1.44-5.83, p=0.003). A previous provoked VTE in patients was also associated with a higher risk of developing cancer (HR=3.57, 95% C.I. 1.38-9.25, p=0.009). Patients with an unprovoked deep vein thrombosis (DVT), compared to either those with a pulmonary embolism (PE) only or both DVT and PE, seemed more likely to have a diagnosis of cancer. However, this trend was not statistically significant. (Table 1) These results were confirmed on multivariable analysis. Patients exhibiting one of these characteristics had a three-fold higher risk of occult cancer compared with patients without these characteristics. (Table 1) Conclusion: Age at unprovoked VTE diagnosis (≥ 60 years) and prior provoked VTE are predictors of occult cancer, and could potentially be used to identify a group of patients with unprovoked VTE at high risk of underlying cancer. Table 1.Risk factors of occult malignancy among patients with a first unprovoked symptomatic VTE.Patients without cancer (%) (n = 821)Patients with cancer (%) (n = 33)Univariate analysis Hazard Ratio (95% C.I.)P valueMultivariable analysis Hazard Ratio (95% C.I.)P valueAge at diagnosis ≥ 60 years288 (35.1)20 (60.6)2.90 (1.44-5.83)0.0033.0 (1.47-5.99)0.002Male sex555 (67.6)21 (63.6)0.72 (0.35-1.46)0.358--Prior provoked VTE42 (5.1)5 (15.2)3.57 (1.38-9.25)0.0093.8 (1.46-10.03)0.006Type of current VTEDVT only444 (54.3)24 (72.7)1.91 (0.89-4.12)0.0972.1 (0.97-4.51)0.061PE only271 (33.1)7 (21.2)0.60 (0.26-1.38)0.229--DVT + PE103 (12.6)2 (6.1)0.54 (0.13-2.24)0.392--Baseline medicationsOral contraceptive pill48 (5.8)0 (0.0)----Exogenous estrogen18 (2.2)1 (3.0)1.51 (0.21-11.07)0.685--Antiplatelet agent39 (4.8)1 (3.0)0.62 (0.09-4.56)0.641--Oral anticoagulant688 (83.8)26 (78.8)0.66 (0.29-1.53)0.337--LMWH391 (47.7)15 (45.5)0.68 (0.34-1.36)0.275--VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; LMWH, low molecular weight heparin Disclosures Lazo-Langner: Pfizer: Honoraria, Other: Participated in studies funded by this organization, Speakers Bureau; LEO Pharma: Honoraria, Other: Participated in studies funded by this organization; Boehringer Ingelheim: Honoraria, Other: Participated in studies funded by this organization; Bayer: Honoraria, Other: Participated in studies funded by this organization; Daiichi-Sankyo: Other: Participated in studies funded by this organization; Novartis: Other: Participated in studies funded by this organization; Celgene: Other: Participated in studies funded by this organization; Alexion: Research Funding. Shivakumar:Bayer: Honoraria. Routhier:Sanofi-Aventis: Research Funding. Douketis:Janssen: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Honoraria; Sanofi-Aventis: Honoraria; Daiichi-Sankyo: Consultancy; Actelion: Consultancy; Biotie: Other: Advisory board; The Medicines Company: Other: Advisory board; Bayer: Consultancy; Boehringer Ingelheim: Consultancy, Honoraria. Carrier:LEO Pharma: Consultancy, Research Funding; BMS: Research Funding; Bayer: Consultancy; Pfizer: Consultancy.

scholarly journals Detection of Paroxysmal Nocturnal Hemoglobinuria Clones in Patients with Idiopathic Venous Thromboembolism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1532-1532
Author(s):  
Alejandro Lazo-Langner ◽  
Michael J. Kovacs ◽  
Ben Hedley ◽  
Fatimah Al-Ani ◽  
Michael Keeney ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Research Funding ◽  
Secondary Outcome ◽  
Flow Cytometric Assay ◽  
Color Flow ◽  
Vein Thrombosis ◽  
Flow Cytometric ◽  
Number Of Patients ◽  
Pnh Clone

Abstract Background. Paroxsymal Nocturnal Hemoglobinuria (PNH) is an uncommon disease with an estimated population prevalence of 0.002%, however the estimated prevalence of venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) or pulmonary embolism (PE), in PNH patients is 25 to 33%. Small PNH clones have been identified in patients with unexplained splanchnic vein thrombosis and in people with apparently normal blood counts and might predispose these patients to thrombosis. Furthermore, only about 40-50% of idiopathic VTE patients are affected by one or more thrombophilias. The presence of PNH clones as a contributing factor to a hypercoagulable state has never been examined in this population. Patients and Methods. In order to determine the prevalence of PNH clones in patients with prevalent idiopathic DVT/PE we conducted a cross-sectional study at the Thrombosis Clinic of the London Health Sciences Centre in London, Ontario, Canada, between May 2011 and June 2014. We included patients with at least one episode of objectively demonstrated DVT or PE according to previously published criteria. Patients were excluded if they had: a) a previous diagnosis of PNH, b) well established predisposing risk factors for VTE in the 3 months preceding the VTE, c) active cancer other than non-melanoma skin cancer within 6 months of VTE, or if they were unable to provide written informed consent. Clinical and laboratory information was abstracted from the patient charts. Patients were screened for PNH using a high sensitivity flow cytometric assay which can detect at least 0.01% GPI deficient erythrocytes using CD235a and CD59 in a 2 color assay. Additionally, a modification of our previously developed fluorescent aerolysin (FLAER) assay was used to detect GPI deficient neutrophils using FLAER, the GPI linked protein CD24, CD45 and CD15 (a mature neutrophil marker) in a 4 color flow cytometric assay. A control group of 30 normal donors was used to standardize, determine and validate the level of sensitivity of both the red and white cell assays. The primary outcome of the study was the presence of a PNH clone >0.02% in erythrocytes or neutrophils. Secondary outcome was the presence a PNH clone of any size. Assuming an underlying PNH proportion in the population of 0.002%, we estimated that a sample size of 402 patients achieved 80% power to detect a proportion of 0.4%. Confidence intervals for proportions were calculated using the Wilson score method. Results We included 394 patients of which 388 had samples available for flow cytometry. The characteristics of the included patients are shown in Table 1. One patient (0.26%; 95% CI 0.05 to 1.45) had a detectable PNH clone in the neutrophil population (0.02%) whereas another patient had a detectable PNH clone below the positivity threshold (<0.01%). Neither patient had evidence of hemolysis or cytopenias. Conclusion Very small PNH clones can be detected in a small proportion of patients with unexplained VTE but without clinical manifestations of hemolytic PNH. Their relation with the development of VTE is yet to be determined. Table 1. Patients’ characteristics Demographics [n/N (%; 95% CI)] Age (years) [Mean (SD)] 57(16.6) Body Mass Index [Mean (SD)] 31.5 (8.5) Male Gender 216/388 (55.7;50.7-60.5) Caucasian ethnicity 365/388 (94.1;91.3-96.0) Family History of VTE 102/370 (27.6;23.3-32.3) Comorbidities [n/N (%; 95% CI)] Hypertension 125/386 (32.4;27.9-37.2) Diabetes 48/386 (12.4;9.5-16.1) Coronary artery disease 33/381 (8.7;6.2-11.9) Stroke / TIA 33/381 (8.7;6.2-11.9) Dyslipidemia 104/340 (30.6;25.9-35.7) COPD 22/380 (5.8;3.9-8.6) Peripheral vascular disease 35/310 (11.3;8.2-15.3) Inflamatory bowel disease 13/383 (3.4;2.0-5.7) Rheumatic disease 100/362 (27.6;23.3-32.4) Risk factors for VTE [n/N (%; 95% CI)] Oral contraceptive use 43/171 (25.1;19.2-32.1) Hormone replacement therapy 14/171 (8.2;4.9-13.3) Thrombophilia 127/388 (32.7;28.3-37.6) Diagnosis [n/N (%; 95% CI)] DVT 175/388 (45.1;40.2-50.1) PE 148/388 (38.1;33.4-43.1) DVT + PE 63/388 (16.2;12.9-20.2) Upper extremity DVT 2/388 (0.5;0.1-1.9) n, Number of patients with risk factor; N, number of patients with valid information; SD standard deviation; CI confidence interval Disclosures Lazo-Langner: Alexion Pharmaceuticals: Research Funding. Keeney:Alexion Pharmaceuticals: Research Funding. Chin-Yee:Alexion Pharmaceuticals: Research Funding.

scholarly journals Long-Term Risk Factors for Occult Cancer Detection in Patients with Unprovoked Venous Thromboembolism: A Post-Hoc Analysis of the Reverse Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1230-1230
Author(s):  
Nathan Cantor ◽  
Marc Carrier ◽  
Marc A. Rodger ◽  
Gabrielle Veillet-Lemay ◽  
Elham Sabri ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Cancer Diagnosis ◽  
Research Funding ◽  
Anticoagulation Therapy ◽  
Post Hoc Analysis ◽  
Occult Cancer ◽  
Post Hoc ◽  
D Dimer

Abstract Background: The diagnosis of an unprovoked (i.e., in the absence of any risk factors) venous thromboembolism (VTE) may be a sign of an underlying cancer. Previous estimates of the incidence rate of occult cancer in patients with unprovoked VTE are as high as 5-10%. However, screening methods to detect cancer early in these patients are of limited clinical value and previous identification of risk factors focused on short-term cancer diagnosis. Therefore, this study will assess the long-term incidence and risk factors of cancer in unprovoked VTE patients. Methods: This retrospective study is a post-hoc analysis of the REVERSE (Recurrent Venous Thromboembolism Risk Stratification Evaluation) study. Patient data was collected following an initial six-month course of anticoagulation therapy and were followed for a mean time period of 5.0 years (range 1 month-8 years). We performed univariable analysis to test the strength of association between each potential predictor variable and occult cancer diagnosis. Furthermore, using forward model selection we created a multivariable model with optimal predictive value for cancer diagnosis. Results: Among 663 patients presenting with unprovoked VTE, 38 (5.7%) subsequently developed a new cancer diagnosis during the follow-up period. The most common types of cancers diagnosed were prostate (21%) and colorectal cancer (16%). Univariate analysis revealed age > 65 (OR 2.59; 95% CI 1.31-4.49, P= 0.0036), elevated D-Dimer (OR 2.71; 95% CI 1.38-5.31, P=0.026) and pulmonary vein obstruction (PVO) score (OR 4.34 95% CI 1.26-14.92, P=0.023) as the strongest predictors of occult cancer. Only D-Dimer (Adj.-OR 2.72 95% CI 1.39-5.32) remained in the multivariate model and no other factor significantly improved the model's fit. Conclusion: Patients with an unprovoked VTE remain at an elevated risk of developing cancer following anticoagulation therapy. Age > 65 years old, elevated D-Dimer, and PVO in pulmonary embolism patients are among potential risk factors for developing occult cancer. More studies are needed to validate these potentially important risk factors. Disclosures Carrier: BMS: Honoraria, Research Funding; Leo Pharma: Research Funding; Pfizer: Honoraria; Bayer: Honoraria. Rodger:Biomerieux: Research Funding. Kovacs:Daiichi Sankyo Pharma Development: Research Funding; Bayer: Research Funding.

scholarly journals Role of age, sex, and specific provoking factors on the distal versus proximal presentation of first symptomatic deep vein thrombosis: analysis of the SWIss Venous ThromboEmbolism Registry (SWIVTER)

2021 ◽  
Author(s):  
David Spirk ◽  
Tim Sebastian ◽  
Jürg Hans Beer ◽  
Lucia Mazzolai ◽  
Drahomir Aujesky ◽  
...  
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Acute Infection ◽  
Multivariable Analysis ◽  
Lower Limbs ◽  
Vein Thrombosis ◽  
Male Sex ◽  
Deep Vein ◽  
The Impact

AbstractWe aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80–4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20–3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33–3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29–5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.

scholarly journals Screening for Cancer in Patients with Acute Venous Thromboembolic Disease

2021 ◽  
Vol 41 (01) ◽  
pp. 042-047
Author(s):  
Marc Blondon
Keyword(s):  
Cancer Screening ◽  
Whole Body ◽  
Care Providers ◽  
Vein Thrombosis ◽  
Risk Assessment Models ◽  
Occult Cancer ◽  
Pet Ct ◽  
Venous Thromboembolic ◽  
Deep Vein ◽  
Active Cancer

AbstractActive cancer causes approximately 25% of all acute events of venous thromboembolism (VTE). While most of the cancer diagnoses are known or clinically apparent at the time of VTE, care providers and patients may be worried about the 3 to 8% risk of occult cancer occurring in the year after VTE. Several studies have compared limited to extensive cancer screening after acute VTE, especially with the addition of abdominal computed tomography (CT) or whole-body PET-CT, with the hope to shorten the time to cancer diagnosis and lead to less advanced cancer stages. These studies have not shown improved clinical outcomes with an extensive screening, and have led to current recommendations of limited screening for cancer in patients with acute VTE, including unprovoked cases. Several risk assessment models have been developed to identify patients at greatest risk of occult cancer, however, with low discriminative performances and no current clinical usefulness. Some clinical situations may empirically deserve a more thorough cancer screening, such as unprovoked upper extremity deep vein thrombosis (DVT), bilateral leg DVT, descending leg DVT, or recurrent VTE during anticoagulation.

Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients

2005 ◽  
Vol 93 (01) ◽  
pp. 76-79 ◽  
Author(s):  
Alain Leizorovicz ◽  
Alexander Cohen ◽  
Alexander Turpie ◽  
Carl-Gustav Olsson ◽  
Samuel Goldhaber ◽  
...  
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Mortality Rates ◽  
Hazard Ratio ◽  
Group Iii ◽  
Vein Thrombosis ◽  
Group I ◽  
Compression Ultrasound ◽  
The Difference ◽  
Deep Vein

SummaryThe clinical importance of asymptomatic proximal and distal deep vein thrombosis (DVT) remains uncertain and controversial. The aim of this retrospective,post-hoc analysis was to examine mortality and risk factors for development of proximal DVT in hospitalized patients with acute medical illness who were recruited into a randomized, prospective clinical trial of thromboprophylaxis with dalteparin (PREVENT).We analyzed 1738 patients who had not sustained a symptomatic venous thromboembolic event by Day 21 and who had a complete compression ultrasound of the proximal and distal leg veins on Day 21. We examined the 90-day mortality rates in patients with asymptomatic proximal DVT (Group I, N = 80), asymptomatic distal DVT (Group II, N = 118) or no DVT (Group III, N = 1540).The 90-day mortality rates were 13.75%, 3.39%, and 1.92% for Groups I–III, respectively. The difference in mortality between Group I and Group III was significant (hazard ratio 7.63, 95% CI = 3.8–15.3;p < 0.0001),whereas the difference between Groups II and III did not reach significance (hazard ratio 1.36, 95% CI = 0.41–4.45).The association of asymptomatic proximal DVT with increased mortality remained highly significant after adjusting for differences in baseline demographics and clinical variables. Risk factors significantly associated with the development of proximal DVT included advanced age (p = 0.0005), prior DVT (p = 0.001), and varicose veins (p = 0.04). In conclusion, the high mortality rate in patients with asymptomatic proximal DVT underscores its clinical relevance and supports targeting of asymptomatic proximal DVT as an appropriate endpoint in clinical trials of thromboprophylaxis.

Abstract P254: Risk Factors For Venous Thromboembolism in a Cohort of French Women

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Martin Lajous ◽  
Laura Tondeur ◽  
Agnes Fournier ◽  
Francoise Clavel-Chapelon
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Venous Thromboembolism ◽  
Fruits And Vegetables ◽  
Smoking Status ◽  
Premenopausal Women ◽  
Prior History ◽  
Inverse Association ◽  
Vein Thrombosis

Background: There is controversy over whether cardiovascular disease and venous thromboembolism (VTE) share risk factors. Prospective information on risk factors for VTE in otherwise healthy individuals is limited. Methods and Results We evaluated the relation between known risk factors for cardiovascular disease and incidence of VTE among 65,272 French women in the E3N prospective cohort study with no prior history of VTE and who were free of cardiovascular disease or cancer in 1993. All information was self-reported via mailed questionnaires and diet and physical activity were assessed using previously validated instruments. Between 1993 and 2007, 766 cases of deep vein thrombosis or pulmonary embolism were first identified through self-reports and validated using medical records and information from treating physicians. Cases were considered valid if the diagnosis was based on an imaging procedure. We evaluated the following risk factors: education, menopause, postmenopausal hormone use, treated hypercholesterolemia and hypertension, diabetes, body mass index (BMI), physical activity, smoking status and intake of alcohol, red meat, fish, fruits and vegetables, fiber and coffee. In a multivariable model with age as the time scale, we found that, compared to women with a BMI <22 kg/m2, the HR (95%CI) was 1.35 (1.14, 1.60) for 22–24.9 kg/m2, 2.11 (1.73, 2.57) for 25–29.9 kg/m2 and 2.88 (2.08, 3.98) for ≥30 kg/m2 and the p-trend was <0.0001. Menopause was found to be inversely associated with VTE risk [HR=0.60 (95%CI 0.45–0.80); postmenopausal vs. premenopausal women]. In analyses restricted to postmenopausal women, relative to never users current use of postmenopausal hormones was significantly associated to VTE risk [HR=1.44 (95%CI 1.18–1.74)]. No significant association was found with dietary and other cardiovascular risk factors. Conclusion In this large prospective study only some risk factors for cardiovascular disease were associated to VTE incidence. We observed a strong inverse association between menopause and VTE.

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism

2013 ◽  
Vol 109 (01) ◽  
pp. 79-84 ◽  
Author(s):  
Sylvia Reitter-Pfoertner ◽  
Thomas Waldhoer ◽  
Michaela Mayerhofer ◽  
Ernst Eigenbauer ◽  
Cihan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Multivariable Analysis ◽  
Factor V Leiden ◽  
Arterial Disease ◽  
Factor V ◽  
Term Survival ◽  
Long Term Survival ◽  
History Of

SummaryData on the long-term survival following venous thromboembolism (VTE) are rare,and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 outpatients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

scholarly journals Incidence, Management and Outcomes of Arterial and Venous Thromboembolism after Chimeric Antigen Receptor Modified T Cells for B-Cell Lymphoma and Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Anna L. Parks ◽  
Swetha Kambhampati ◽  
Bita Fakhri ◽  
Charalambos Andreadis ◽  
Lissa Gray ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
T Cells ◽  
Venous Thromboembolism ◽  
B Cell ◽  
Research Funding ◽  
Vte Prophylaxis ◽  
Therapeutic Anticoagulation ◽  
Car T ◽  
History Of

Introduction: Chimeric antigen receptor modified T Cell (CAR-T) therapy is a rapidly developing treatment for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Although this population is at high risk for thrombosis, there are few data about rates of venous thromboembolism (VTE) and arterial thromboembolism (ATE) with CAR-T. Additionally, treatment with anticoagulation is complicated because of the prevalence of thrombocytopenia following CAR-T. Our goal was to determine the incidence, associated risk factors, management and outcomes of VTE and ATE in the 60 days following CAR-T therapy. Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events. Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies. For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively. In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE-3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE-1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation. Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies. Disclosures Fakhri: University of California San Francisco: Current Employment. Andreadis:Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong:Janssen: Research Funding; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; GSK: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

Venous Thromboembolism

2020 ◽  
Author(s):  
Samuel Z. Goldhaber
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Antithrombotic Agents ◽  
Vein Thrombosis ◽  
Recurrent Venous Thrombosis ◽  
Deep Vein ◽  
D Dimer ◽  
In Pregnancy

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites).  This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Anticoagulation Treatment in Venous Thromboembolism: Options and Optimal Duration

2021 ◽  
Vol 27 ◽  
Author(s):  
Stavrianna Diavati ◽  
Marios Sagris ◽  
Dimitrios Terentes-Printzios ◽  
Charalambos Vlachopoulos
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Clinical Genetic ◽  
Vein Thrombosis ◽  
Anticoagulation Treatment ◽  
Molecular Pathophysiology ◽  
Deep Vein

: Venous thromboembolism (VTE), clinically presenting as deep-vein thrombosis (DVT) or pulmonary embolism (PE), constitutes a major global healthcare concern with severe complications, long-term morbidity and mortality. Although several clinical, genetic and acquired risk factors for VTE have been identified, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. Anticoagulation has been the cornerstone of therapy for decades, but there still are uncertainties regarding primary and secondary VTE prevention, as well as optimal therapy duration. In this review we discuss the role of factor Xa in coagulation cascade and the different choices of anticoagulation therapy based on patients’ predisposing risk factors and risk of event recurrence. Further, we compare newer agents to traditional anticoagulation treatment, based on most recent studies and guidelines.

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