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

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.

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Thrombotic Events with Neisseria Meningitidis Vaccination in Patients with Paroxysmal Nocturnal Hemoglobinuria, UK Experience

Blood ◽

10.1182/blood-2020-141769 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 35-36

Author(s):

Louise Arnold ◽

Richard Kelly ◽

Talha Munir ◽

Petra Muus ◽

Alexandra Pike ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Research Funding ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Intravascular Hemolysis ◽

Material Support ◽

Vein Thrombosis ◽

Number Of Patients ◽

Change In Practice ◽

Pnh Clone ◽

Support Research

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic and thrombotic condition. Patients can experience severe anemia due to intravascular hemolysis, thrombotic events, renal impairment and pulmonary hypertension. Symptomatic patients are treated with complement inhibitors either in clinical trials or with eculizumab the only licensed treatment in the UK. Due to the mechanism of action of eculizumab, it increases susceptibility to Neisseria infection, including Neisseria meningitidis. To reduce this risk of infection, worldwide practice is for patients to be vaccinated at least 2 weeks prior to receiving eculizumab (serogroups A, C, Y, W 135 and B). It was noted within the PNH National Service at Leeds (UK) that a small number of patients deteriorated with enhanced intravascular hemolysis and thrombosis during the period between vaccination and eculizumab, leading to a review of practice. We report five of 121 patients with events in the intervening 2 weeks between vaccination and commencement of eculizumab from 2002-2012:A 44 year female presented with hemolysis and hemoglobinuria, with a granulocyte PNH clone of 99.4%. She was transfusion dependent and on anticoagulation. She consented to the PNH pilot eculizumab study, undergoing meningococcal vaccination as per protocol. Twenty two days later, she suffered an ischemic stroke with left hemiplegia and permanent weakness, resulting in exclusion from the study. Two years later she received eculizumab in the TRIUMPH study.A 37 year male presented with hemoglobinuria and fatigue with a granulocyte PNH clone of 99.58%. He had significant hemolysis, managed initially with warfarin and blood transfusions. He consented to start eculizumab and received meningococcal vaccination. 4 days later he presented with a symptomatic right hepatic vein thrombosis, promptly commenced eculizumab.A 29 year male, with abdominal pain and hemoglobinuria for 3 years developed a stroke and portal vein thrombosis leading to a diagnosis of PNH, with a granulocyte PNH clone of 84.99%. He commenced anticoagulation. Four months after the stroke he received meningococcal vaccination in preparation for scheduled commencement with eculizumab. He experienced a left central retinal vein thrombosis 15 days after its administration prior to starting eculizumab.A 47 year old male, was diagnosed with haemolytic PNH but only had mild symptoms and anaemia. Twenty four years later, he developed increasing hemolysis and symptoms; granulocyte PNH clone of 96.45%. Eculizumab was planned and he received meningococcal vaccination, but presented ten days later with acute renal failure secondary to massive intravascular haemolysis, necessitating emergency eculizumab therapy.A 35 year female, with a granulocyte PNH clone of 99.87%. Although she had active intravascular hemolysis, eculizumab was declined, and anticoagulation commenced. Four years later she consented to start eculizumab, receiving meningococcal vaccination. She was admitted 24 hours later with a stroke and commenced eculizumab the same day, but has persistent neurological impairment to date. See Table 1 Discussion: The close time proximity of these serious events to the patients' vaccinations raised concern that the complement system was being activated by administration of the vaccine, precipitating complications of PNH. It is also concerning that 4 of the 5 patients experienced thrombotic events despite therapeutic anticoagulation, confirming that anticoagulation only partially mitigates the risk of thrombosis in patients with PNH. The decision was taken to administer the vaccination immediately after the first dose of eculizumab, with therapeutic doses of antibiotic (ciprofloxacin 500mg bd) for the first 14 days post vaccination, followed by long term meningococcal prophylaxis (penicillin V or erythromycin 500mg bd) whilst receiving a complement inhibitor. Since this change in practice in 2012 we have commenced eculizumab therapy in 211 patients with no similar complications as described. Thus the change in practice appears to reduce the occurrence of these severe complications associated with vaccinations prior to initiating anti-complement therapy. Whilst it is possible these events could have been caused by the underlying condition of PNH, we would advise colleagues to also adopt a change in practice to reduce potentially significant complications. Disclosures Arnold: Alexion Pharmaceuticals: Honoraria. Kelly:Alexion: Honoraria. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Pike:Apellis: Research Funding. Riley:Alexion: Honoraria. Griffin:Alexion Pharmaceuticals: Honoraria, Other: Conference Support; Biocryst: Membership on an entity's Board of Directors or advisory committees. Hillmen:Acerta: Other: Financial or material support; Roche: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; Pharmacyclics: Other: Financial or material support, Research Funding; Janssen: Consultancy, Other: Financial or material support, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Apellis: Consultancy, Research Funding, Speakers Bureau; Alexion: Consultancy, Research Funding, Speakers Bureau; Gilead: Other: Financial or material support, Research Funding.

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

Blood ◽

10.1182/blood.v126.23.625.625 ◽

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.

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

Circulation ◽

10.1161/circ.125.suppl_10.ap254 ◽

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.

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

Blood ◽

10.1182/blood-2020-136782 ◽

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.

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Venous Thromboembolism

10.2310/fm.1102 ◽

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

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Anticoagulation Treatment in Venous Thromboembolism: Options and Optimal Duration

Current Pharmaceutical Design ◽

10.2174/1381612827666211111150705 ◽

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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Predictors of venous thromboembolism development before and during chemotherapy for advanced germ cell tumor

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyz177 ◽

2020 ◽

Vol 50 (3) ◽

pp. 338-343

Author(s):

Satoshi Nitta ◽

Koji Kawai ◽

Tomokazu Kimura ◽

Takashi Kawahara ◽

Shuya Kandori ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Lactate Dehydrogenase ◽

Germ Cell ◽

Germ Cell Tumor ◽

Vena Cava ◽

Significant Risk ◽

Cell Tumor ◽

Vein Thrombosis ◽

The Right

Abstract Objective We retrospectively analyzed the incidence and localization of venous thromboembolism in patients undergoing chemotherapy for advanced germ cell tumor and separately evaluated the risk factors for venous thromboembolism development before and during chemotherapy. Methods We included 121 patients treated with cisplatin-based chemotherapy between 2005 and 2018. Venous thromboembolism was defined as venous thrombosis diagnosed using radiological imaging with or without thromboembolic symptoms. We analyzed the clinical parameters for identifying the possible venous thromboembolism risk factors. Khorana score was used to calculate the venous thromboembolism risk. Results Thirteen patients showed prechemotherapy venous thromboembolism and 13 developed venous thromboembolism during chemotherapy. The most common venous thromboembolism was deep vein thrombosis (10 patients), followed by inferior vena cava thrombus (eight patients) and pulmonary thrombus (six patients). Compared to the group without venous thromboembolism, the group with prechemotherapy venous thromboembolism showed higher proportion of patients with tumors originating in the right testis (10 out of 13), significantly higher lactate dehydrogenase levels (828 IU/L versus 436 IU/L, P = 0.013), significantly higher proportion of patients with retroperitoneal lymph node (RPLN) metastases >5 cm in diameter (76.9% versus 33.7%, P = 0.003) and slightly higher proportion of patients with high-risk Khorana score (≥ 3; 30.8% versus 11.6%). No significant differences were observed between the clinical characteristics of patients with venous thromboembolism developed during chemotherapy and patients without venous thromboembolism. Conclusions We show that both RPLN mass > 5 cm and high lactate dehydrogenase levels are significant risk factors for prechemotherapy venous thromboembolism but not for venous thromboembolism development during chemotherapy.

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Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival

Blood ◽

10.1182/blood-2008-08-175745 ◽

2009 ◽

Vol 113 (17) ◽

pp. 3911-3917 ◽

Cited By ~ 85

Author(s):

Grace H. Ku ◽

Richard H. White ◽

Helen K. Chew ◽

Danielle J. Harvey ◽

Hong Zhou ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Venous Catheter ◽

Population Based ◽

Older Age ◽

Myelogenous Leukemia ◽

Vein Thrombosis ◽

Chronic Comorbidities

Abstract A population-based cohort was used to determine the incidence and risk factors associated with development of venous thromboembolism (VTE) among Californians diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep vein thrombosis in both the lower and upper extremities, pulmonary embolism, and mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events occurred within 3 months of AML diagnosis. In AML patients, female sex, older age, number of chronic comorbidities, and presence of a catheter were significant predictors of development of VTE within 1 year. A diagnosis of VTE was not associated with reduced survival in AML patients. Among 2482 cases with acute lymphoblastic leukemia (ALL), the 2-year incidence of VTE in ALL was 4.5%. Risk factors for VTE were presence of a central venous catheter, older age, and number of chronic comorbidities. In the patients with ALL, development of VTE was associated with a 40% increase in the risk of dying within 1 year. The incidence of VTE in acute leukemia is appreciable, and is comparable with the incidence in many solid tumors.

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Pregnancy and Venous Thromboembolism: Risk Factors, Trends, Management, and Mortality

BioMed Research International ◽

10.1155/2020/4071892 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Mohammed A. Alsheef ◽

Alhanouf M. Alabbad ◽

Rowida A. Albassam ◽

Rawan M. Alarfaj ◽

Abdul Rehman Z. Zaidi ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Retrospective Chart Review ◽

Leg Pain ◽

Vein Thrombosis ◽

Saudi Women ◽

Randomized Design ◽

Potential Factors ◽

Lower Leg Pain ◽

And Control

Background. Pregnancy is one of the major risk factors for the development of venous thromboembolism (VTE). Objective. To elucidate the circumstances surrounding pregnancy-induced deep vein thrombosis (DVT) and pulmonary embolism (PE), assess potential factors triggering thrombosis (e.g., thrombophilia, obesity, age, parity, and family history), initial and long-term management, and assess recurrence rate and mortality for VTE in pregnant Saudi women. Methods. A retrospective chart review of 180 patients with objectively confirmed VTE (DVT, PE, or both) that occurred during pregnancy, or the postpartum period was conducted. All patients who experienced episodes of objectively confirmed VTE were included. Results. Overall, 180 patients were included. Further, 60% (n=109) and 40% (n=71) of the VTE cases occurred during the postpartum and antenatal periods, respectively. Cesarean section was the most prevalent risk factor among study participants (n=86 (47.8%)), followed by obesity (n=73 (40.6%)). The most common clinical presentations were lower leg pain (57.2%) and lower limb swelling (54.4%). VTE recurrences were observed in approximately 11% of the participants, and maternal mortality occurred in 2 (1.1%) cases. Conclusion. Pregnancy was the most common provoking factor for VTE in our study. Pregnant women should undergo formal, written assessments of risk factors for VTE at the first visit and delivery. Larger studies with a randomized design, and control groups are required to confirm the current findings.

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