Ashrani, Aneel A.

Abstract To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N = 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and time-dependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT ≥ 0.2 anti-Xa U/mL and on warfarin with an INR ≥ 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose ≥ 30 000 U/d, the median proportion of time with an APTT ≥ 0.2 anti-Xa U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin anticoagulation are effective in preventing VTE recurrence.

The role of venous stasis syndrome (VSS) mechanisms (i.e. venous outflow obstruction [VOO] and venous valvular incompetence [VVI]) on quality of life (QoL) and activities of daily living (ADL) is unknown. The objective of this study was to test the hypotheses that venous thromboembolism (VTE),VSS,VOO and VVI are associated with reduced QoL and ADL. This study is a follow-up of an incident VTE case-control study nested within a population-based inception cohort of residents from Olmsted County, MN, USA, between 1966 and 1990. The study comprised 232 Olmsted County residents with a first lifetime VTE and 133 residents without VTE. Methods included a questionnaire and physical examination for VSS; vascular laboratory testing for VOO and VVI; assessment of QoL by SF36 and of ADL by pertinent sections from the Older Americans Resources and Services (OARS) and Arthritis Impact Measurement Scales (AIMS2) questionnaires. Of the 365 study participants, 232 (64%), 161 (44%), 43 (12%) and 136 (37%) had VTE, VSS, VOO and VVI, respectively. Prior VTE was associated with reduced ADL and increased pain, VSS with reduced physical QoL and increased pain, and VOO with reduced physical QoL and ADL.VVI was not associated with QoL or ADL. In conclusion,VSS and VOO are associated with worse physical QoL and increased pain. VOO and VTE are associated with impaired ADL. We hypothesize that rapid clearance of venous outflow obstruction in individuals with acute VTE will improve their QoL and ADL.

Abstract Venous stasis syndrome may complicate deep vein thrombosis (DVT; i.e. post-phlebitic syndrome), but, in most cases, venous stasis syndrome is not post-phlebitic. The objective of this study was to determine the risk factors (including prior DVT) for venous stasis syndrome, and to assess venous outflow obstruction and venous valvular incompetence as possible mechanisms for venous stasis syndrome. This was a case–control study nested within a population-based inception cohort. The study population consisted of 232 Olmsted County, MN residents with a first lifetime venous thromboembolism (VTE) and 133 residents without VTE. Measurements included a questionnaire and physical examination for venous stasis syndrome; strain gauge outflow plethysmography, venous continuous wave Doppler ultrasonography and passive venous drainage and refill testing for venous outflow obstruction and venous valvular incompetence. Altogether, 161 (44%), 43 (12%), and 136 (38%) subjects respectively, had venous stasis syndrome, venous outflow obstruction and venous valvular incompetence. Independent risk factors for venous stasis syndrome included increasing patient age and body mass index (BMI), prior DVT, longer time interval since DVT, and varicose veins. Both venous outflow obstruction ( p = 0.003) and venous valvular incompetence ( p < 0.0001) were strongly associated with venous stasis syndrome. Increasing age and prior DVT were significantly associated with venous outflow obstruction, while prior DVT, varicose veins and venous stasis syndrome diagnosed prior to the incident DVT were significantly associated with venous valvular incompetence. The risks of venous outflow obstruction, venous valvular incompetence and venous stasis syndrome were higher with left leg DVT. In conclusion, increasing patient age and BMI, prior DVT (particularly left leg DVT), longer time interval since DVT and varicose veins are independent risk factors for venous stasis syndrome. Venous stasis syndrome related to DVT is due to venous outflow obstruction and venous valvular incompetence, while venous stasis syndrome related to older age and to varicose veins is due to venous outflow obstruction and to venous valvular incompetence, respectively.

Objective— Although diabetes mellitus is reported as a risk factor for venous thromboembolism (VTE), persons with diabetes are frequently hospitalized for medical illness or surgery, or confined to a nursing home, all major VTE risk factors. Consequently, we tested diabetes for an independent association with incident VTE. Methods and Results— Using Rochester Epidemiology Project resources, we identified all Olmsted County, Minn residents who met objective criteria for incident VTE over the 25-year period, 1976 to 2000 (n=1922), and 1 to 2 resident controls per case, matched on age, gender, and length of medical history (n=2115). Complete medical histories in the community were reviewed for previously identified independent VTE risk factors and diabetes-related variables. We tested diabetes and diabetes complications (retinopathy, nephropathy or neuropathy, and ketoacidosis) as potential VTE risk factors, both alone and after adjusting for VTE risk factors. Univariately, diabetes by clinical diagnosis or by stricter criteria (fasting ambulatory blood glucose ≥140 mg/dL or antidiabetic drug therapy), and diabetes complications, were associated with overall incident VTE. However, after controlling for hospitalization for major surgery or medical illness and nursing home confinement, diabetes was no longer associated with VTE. Conclusion— Diabetes mellitus and diabetes complications are not independent risk factors for incident VTE.