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The outcome of anticoagulation for cancer-associated venous thromboembolism (Ca-VTE) differs according to cancer location, but data are limited and inconsistent.Patients with acute venous thromboembolism (VTE) enrolled between 03/01/2013 and 04/30/2021 were followed prospectively to assess VTE recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and death.There were 1702 (45.3 %) patients with Ca-VTE including: gastrointestinal (n = 340), pancreatic (n = 223), hematologic (n = 188), genitourinary (n = 163), lung (n = 139), ovarian (n = 109), breast (n = 97), renal (n = 75), prostate (n = 73), hepatobiliary (n = 70), brain (n = 57), and other cancers (n = 168); 2057 VTE patients had no cancer (NoCa-VTE). Hepatobiliary cancer had the highest VTE recurrence (all rates 100 person-years) of all cancers and higher compared to NoCa-VTE (13.69, p = 0.01), while the MB rate, although numerically higher (15.91), was not different (p = 0.09). Another 3 cancers had higher VTE recurrence but similar MB rates compared to NoCa-VTE: genitourinary [(9.59, p = 0.01) and (7.03, p = 1.0)], pancreatic [(9.74, p 0.001) and (5.47, p = 1.00)], and hematologic [(5.29, p = 0.05) and (3.59, p = 1.0)]. Renal cancer had the highest rate of MB among all cancers and was higher than that of NoCa-VTE (16.49; p 0.001), with no difference in VTE recurrence (1.62; p = 1.0). VTE recurrence and MB rates were not significantly different between NoCa-VTE and gastrointestinal, lung, breast, prostate, and brain cancers. CRNMB rates were similar and mortality higher in Ca-VTE patients, except for prostate and breast cancer, compared to NoCa-VTE.Significant differences in clinical outcomes indicate that anticoagulation strategies may need to be tailored to the primary cancer location.

Popliteal cysts (PC) result from distension of the gastrocnemio-semimembranosous bursa. Published reports indicate coincident PC and deep vein thrombosis (DVT). Whether the presence of PC increase the risk of deep vein thrombosis (DVT) remains unclear.Lower extremity venous Duplex ultrasound (DUS) reports were evaluated across the Mayo Clinic Enterprise (Rochester, Minnesota, Jacksonville, Florida, Scottsdale, Arizona, and the Mayo Clinic Health System) in patients ≥ 18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute lower extremity DVT and PC from these reports. To determine whether there is a link between PC and lower extremity DVT, the frequency of PC among cases (ultrasounds with acute DVT) were compared to controls (ultrasounds without acute DVT).A total of 357,703 lower extremities venous DUS were performed in 237,052 patients (mean age 63.3 ± 16.6, 54.4% were female) between 1992 and 2021. Acute DVT was identified in 32,572 (9.1%) DUS, and PC in 32,448 (9.1%). PC were seen in a lower frequency (8.0%) of ultrasounds with acute DVT than those without (9.2%) acute DVT (OR: 0.85, 95% CI: 0.82 to 0.89, p 0.001). In a multivariate logistic regression model after adjusting for age, sex, and race, PCs were not positively associated with acute DVT (adjusted OR: 0.84, 95% CI: 0.81 to 0.88).PC are an incidental finding or an alternative diagnosis on lower extremity venous DUS, a finding that increases significantly with age. PC were not a risk factor in the development of lower extremity DVT.

Background: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. Methods: Consecutive patients (4/8/2015 – 12/31/2020) undergoing rest and postexercise ankle–brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 – 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. Results: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92–0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91–0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). Conclusion: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.

Background The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort. Methods COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise. Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms. Results A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients. Conclusion We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013–8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p

To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight 60 kg, 60-120 kg, and 120 kg.Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight 60 kg, and 230 (8.9%) had bodyweight 120 kg. Patients with bodyweight 60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight 120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01).Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight 60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight 120 kg on rivaroxaban.

Background/objectves Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). Methods Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies. Results Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. Conclusion In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.

Background: Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with UE-DVT. Limited observational data has been published on outcomes in this setting and no direct comparison to traditional anticoagulation has been performed. Objective: Evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT compared to low-molecular weight (LWMH) and warfarin. Methods: Consecutive patients with VTE were enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and July 22, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received either rivaroxaban, apixaban, LMWH or warfarin within the first 14 days after diagnosis and who completed at least 3 months of anticoagulant therapy or had an outcome event in that period were included into the analysis. Recurrent VTE, major bleeding, clinical relevant non-major bleeding (CRNMB), and death were assessed at 3 months, in person whenever feasible, or by mailing a written questionnaire or a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board. Results: One hundred and thirty-four patients with acute UE-DVT were included. Forty-one were treated with apixaban, 32 with rivaroxaban, and 61 with LWMH and/or warfarin. The mean age was 58.3 years, mean BMI was 28.2, and 59% were male (Table 1). Patients treated with LMWH / warfarin were older (61.3 vs 55.8, p=0.04) and had a lower BMI (27.1 vs 29.0, p=0.0496). Twenty-six (19%) patients had catheter-associated UE-DVT, 93 (69.4%) had a diagnosis of malignancy, and 16 (11.9%) had concurrent pulmonary embolism, which were similar between groups. More patients on apixaban /rivaroxaban were receiving chemotherapy (53.4% vs 47.5%, p=0.04) and had recent surgery (13.7% vs 3.3%, p=0.04) compared to LMWH / warfarin. At 3 months of follow up, 1 recurrent VTE occurred in patients treated with LMWH /warfarin and none of those treated with apixaban /rivaroxaban (p=0.27). Major bleeding occurred in 2 patients treated with LMWH /warfarin and in none of those treated with apixaban /rivaroxaban (p=0.12). CRNMB occurred in 1 patient treated with LWMH /warfarin and 5 patients treated with apixaban / rivaroxaban (p=0.15). Two of the CRNMBs occurred with rivaroxaban and 3 occurred with apixaban. Death occurred in 5 patients treated with LMWH /warfarin and in none of the apixaban /rivaroxaban treated patients (p=0.01). Conclusion: This single institution prospective study adds to the limited experience with apixaban and rivaroxaban for acute UE-DVT. Treatment of UE-DVT with rivaroxaban and apixaban appears to be as safe and effective as LMWH/warfarin after 3 months of anticoagulation. Disclosures McBane: BMS: Research Funding.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013-8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p 0.001), surgery (30.0% vs. 38.0%; p = 0.03), or trauma (3.7% vs. 19.9%; p 0.001). The four most common cancers included hematologic malignancies (20.6%), lung (11.5%), gastrointestinal (10.3%), and ovarian/GYN (9.1%). Nearly half of patients had metastatic disease (43.8%) and 57% were receiving chemotherapy. VTE recurrence rates were similar for patients with (7.1%) and without cancer (4.0%; p = 0.105). Major bleeding (6.3% vs. 2.3%; p = 0.007) were greater for cancer patients while clinical relevant non major bleeding rates did not differ (7.1% vs. 4.6%; p = 0.159). In this retrospective analysis, cancer patients with calf DVT have similar rates of VTE recurrence but higher major bleeding outcomes compared to patients without cancer.

Background P-selectin - a biomarker of platelet and endothelial cell activation is elevated in patients with non-valvular atrial fibrillation (NVAF). However, the association between sP-selectin level and thromboembolic complications in NVAF patients remains controversial. We tested the hypothesis that plasma soluble P-selectin (sPSL) level correlates with the measures of left atrial blood stasis in NVAF. Methods Plasma sPSL concentration was measured using solid-phase ELISA in 103 NVAF patients (age 63 ± 14 years; 26% women) and 48 normal sinus rhythm controls (NSR; age 64 ± 14 years; 41% women) who were not on aspirin. Within the group of NVAF cases, 27 had no spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography, 31had mild SEC, 15 moderate, 20 severe, and 10 patients had left atrial appendage thrombus (LAAT). Results The median soluble sPSL level was higher in NVAF cases compared to NSR controls [(interquartile range) 26 (20−32) ng/mL vs 22 (15–29) ng/mL, p = 0.0045]. Only NVAF patients with CHA2DS2-VASc score ≥ 1 had higher sPSL level compared to NSR controls. Patients with severe SEC had significantly higher sPSL levels [32 (24–38) ng/mL] compared to all other NVAF patients (p = 0.0042) and to NSR controls (p Conclusions There is a direct correlation between p-selectin level and severe blood stasis in the left atrium. Only NVAF patients with CHA2DS2-VASc score ≥ 1 or with LAAT had higher sPSL level compared to NSR controls.

Background Low molecular weight heparin (LMWH) is the guideline-endorsed treatment for cancer-associated venous thromboembolism (cVTE). Study objectives were to compare the efficacy and safety of rivaroxaban and enoxaparin in cVTE. Methods Using a cohort study design, consecutive patients with cVTE (3/1/2013-7/31/2016), enrolled in the Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry, were compared to contemporary cancer patients receiving enoxaparin. The cumulative incidence of venous thromboembolism (VTE) recurrence, major and clinically relevant non-major bleeding, and survival were assessed at 3 and 12 months. Results Ninety-eight patients received rivaroxaban (51% female, mean age 63 ± 12 years) and 168 enoxaparin (34.5% female, mean age 62 ± 15 years). The most common cancers included gastrointestinal/pancreatic, genitourinary and hematologic cancers. More than half of patients had pulmonary emboli at presentation. More than half had metastases, and two-thirds were receiving chemotherapy. At 3 months, there were no differences in VTE recurrence (rivaroxaban 1.0% vs enoxaparin 4.2%; P = .15), major bleeding (rivaroxaban 5.1% vs enoxaparin 3.6%; P = .55), or all-cause mortality (rivaroxaban 4.1% vs enoxaparin 8.9%; P = .14). At 12 months, these outcomes did not differ by treatment strategy. Conclusion The results of this "real-world" experience with cVTE suggest that rivaroxaban may offer a safe and effective alternative to LMWH.

INTRODUCTION Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes. METHODS AND RESULTS Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9 vs. 5.7 ± 1.6, P

Aims Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR). Methods and Results RNA from isolated platelets were reverse transcribed, assayed against 15 genes using real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin-like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold-lower (17.0±2.8 vs 12.5±3.8, P

The pathophysiologic relevance of PFO shunt flow direction as a mechanism of stroke in conditions associated with elevation of left ventricular filling pressures such as atrial fibrillation (AF) is unknown. We analyzed 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing TEE

Background Obesity is a risk factor for non-valvular atrial fibrillation (NVAF), diabetes mellitus, and hypertension. Adiponectin, a unique biomarker of adipose tissue, has antiinflammatory, insulin-sensitizing, and antiatherogenic properties and is known to be higher in women. The relationship between adiponectin, gender, and thromboembolic risk in atrial fibrillation however is unknown. Methods The relationship between gender, adiponectin levels, and echocardiographic measures of blood stagnation and left atrial appendage thrombus (LAAT) was assessed in 209 patients with NVAF (55 women and 154 men; mean age 63±14years) compared to 70 normal sinus rhythm controls (29 women and 41 men; mean age 64±14years). Total adiponectin was measured by solid-phase ELISA. Demographic and clinical variables of CHADS 2 and CHA2DS2-VASc were collected, and spontaneous echocardiographic contrast (SEC), left atrial appendage emptying velocity (LAAEV) and left atrium volume index (LAVI) were measured prospectively. Results Elevated adiponectin was associated with advanced cardiovascular pathology and permanent arrhythmia but only in men with NVAF. In NVAF men, a step-wise increase in adiponectin levels was noted relative to increasing intensity of SEC and decreasing LAAEV. Adiponectin level >16657ng/ml predicted LAAT (OR: 3.66; 95% Cl: 1.21–11.48; p=0.022) after adjustment for CHADS2 score in men but not in women with NVAF. Conclusions There is a direct correlation between elevated adiponectin level and the degree of left atrial blood stasis in men but not in women with NVAF. High adiponectin levels can be used as an important variable in the prediction of LAAT.

SummaryAdrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had “spontaneous HIT” with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Purpose: To assess retrospectively 30-day, 1-year, and 3-year patency of chronically occluded iliofemoral venous thrombotic lesions treated with stent placement in a case series from a single institution. Materials and Methods: Records of 189 consecutive patients treated by interventional radiology for iliofemoral venous occlusions between March 1, 2003, and December 1, 2008, were retrospectively reviewed. A total of 89 patients (27 men; median age, 46.2 y) with chronic iliac or iliofemoral deep vein thrombosis without involvement of the inferior vena cava met criteria for analysis. Results: All patients (91 limbs) successfully underwent placement of venous self-expanding stents. Patency rate at discharge was 100%. Following the index procedure, mean pressure gradient across the lesion decreased from 5.63 mm Hg (95% CI, 3.51–7.75) to 0.71 mm Hg (95% CI, 0.08 –1.34; P .0001). There were no bleeding complications. Median follow-up was 11.3 months (range, 0.8 –72.4 mo). Follow-up at 30 days demonstrated 90 of 91 limbs to be patent. Primary patency rates of treated limbs at 1 and 3 years were 81% and 71%, respectively. Primary patency was lost in 17 cases (19.1%); interventions to maintain or restore stent patency were performed in 13 cases (14.6%). Primary assisted limb patency rates at 1 and 3 years were 94% and 90%, respectively; secondary patency rate was 95%. Conclusions: Angioplasty with stent placement for treatment of chronically thrombosed iliofemoral veins is a low-risk procedure with acceptable patency rates for as long as 3 years. The outcomes in patients treated in a quaternary referral center are similar to those reported by other centers.

The mechanistic paradigm underlying venous thrombosis at atypical locations stems from the observation that most events occur as a result of pathology of the organ system drained by the involved venous segment. Cerebral venous sinus thrombosis stands apart as an exception to this general rule. Although brain and sinus pathology are well established causes, these combined variables account for approximately one third of cases. The marked female preponderance and strong association with gender specific risk factors including hormonal manipulation, pregnancy and the puerperium are particularly notable. Factor V Leiden and prothrombin G20210A mutations and hyperhomocysteinemia represent important risk factors particularly when combined with acquired variables. The association with oral contraception use and the prothrombin G20210A gene mutation may offer insights into the anatomic predilection for cerebral venous sinus involvement as compared to venous thrombosis of the lower extremities. The intent of this review is to summarize the corporate literature of both acquired and congenital risk factors associated with cerebral venous sinus thrombosis in order to assist clinicians in their search for underlying mechanisms and to risk stratify patients for anticoagulation treatment duration and risk of recurrent thrombosis.

The aim of the study was to determine whether CHADS(2) score is predictive of left atrial appendage thrombus (LAAT) in nonvalvular atrial fibrillation (AF). Strategies for effective stroke prevention in AF require tools capable of identifying those patients at greatest risk for embolization of LAAT and most likely to benefit from warfarin. Nearly half of strokes in AF are due to noncardioembolic mechanisms for which antiplatelet therapy would be more appropriate. Previous attempts to develop such tools have been limited by including patients without proven cardioembolism.Nonanticoagulated, nonvalvular AF patients with (cases) or without (controls) LAAT by transesophageal echocardiography were identified using Mayo Clinic Echocardiography and Cardioversion Unit Databases (Rochester, MN). Type and duration of AF, CHADS(2) score, and echocardiography measures were compared to determine variables predictive of LAAT.The CHADS(2) score was significantly higher for cases (n = 110, mean +/- SD 2.8 +/- 1.6) compared to controls (n = 387, 1.6 +/- 1.3). By multivariate analysis, independent predictors of LAAT included heart failure (HR 5.78, P0001), prior stroke/transient ischemic attack (HR 3.94, P.0001), diabetes mellitus (HR 1.98, P = .015), permanent AF (HR 3.02, P.05), AF duration (HR 2.24, P.05), and spontaneous echocardiographic contrast (HR 4.35, P = .005). Using these elements, a new scoring system provided cleaner case-control separation (C-index 0.90) and higher predictive power compared to CHADS(2) (C-index 0.71).The CHADS(2) score predicts the presence of LAAT in AF patients. Some, but not all, variables within this score are predictive of LAAT. By including only echo and clinical variables predictive of LAAT, our novel scoring system better identified those AF patients at greatest cardioembolic risk.

Nonbacterial thrombotic endocarditis (NBTE) is rare and the role of the new oral anticoagulants (NOAC) as treatment is uncertain. A 50-year old woman with a history of migraines complained of worsening headaches over the last 12 months accompanied by neurologic deficits and altered mental status.

A 50-year-old woman had a lifelong history of painful ulcerations as a result of livedoid vasculopathy. She was a heterozygous carrier of factor V Leiden and prothrombin gene mutations and was receiving hormone replacement therapy. The ulcers healed after warfarin therapy, which has been reported to be effective in only one previous patient with this condition.

Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available oral anticoagulant, but now several DOACs are available and their use has become more prevalent in recent years. In spite of this increased use, many physicians remain reluctant to prescribe DOACs due to concerns about bleeding and reversibility.

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear.aCLa were measured by double ELISA in patients with TAO (n=47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n=48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p=0.01) or healthy individuals (2%; p,0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p=0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals.TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.

Background: Segmental arterial mediolysis (SAM) is a rare non-inflammatory non-atherosclerotic disease characterized by lysis of the arterial media. The clinical presentation varies from acute self-limiting pain to organ infarction and death from arterial dissection. The natural history and risk of

Several characteristics of thromboangiitis obliterans are unique and confirm the existence of the disease as a distinct pathological entity. Its predilection for young smoking males, peripheral type of vascular involvement, recurrences of superficial thrombophlebites, and typical histolopathology form the principals of the disease although the etiology remains unknown. The authors report the unusual finding of Buerger's disease occurring in two brothers, one of whom had occlusion of the left external iliac and femoral arteries. All other clinical characteristics of these two cases were typical for thromboangiitis oblit erans. Presentation of some peculiarities of the disease, particularly the lack of familial association, may help to unravel the pathogenesis of thromboangiitis obliterans.

Historically, warfarin had been the standard anticoagulant for prevention of stroke in patients with non-valvular atrial fibrillation (AF) since 1954. Recently several novel oral anticoagulants (NOACs) have been approved as alternatives to warfarin with the potential advantage of improved short-term

Low molecular weight heparin (LMWH) is the guideline endorsed treatment of choice for cancer associated venous thromboembolism (VTE). Rivaroxaban offers a convenient potential alternative to LMWH; however there are no data comparing either the efficacy or safety of these two therapies in this

OBJECTIVE To test active cancer for an association with venous thromboembolism (VTE) location. PATIENTS AND METHODS Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N=3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N=1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors. RESULTS In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P =.01), intra-abdominal DVT (OR, 2.22; P =.004), and bilateral leg DVT (OR, 2.09; P =.02), but not pulmonary embolism (OR, 0.93). CONCLUSION Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.

To characterize differences in the prevalence of thrombophilic variables in a large cohort of patients with cerebral venous sinus thrombosis (CVST) and lower extremity deep vein thrombosis (DVT).An inception cohort of individuals was identified with first lifetime incident CVST between 1995 and 2005 for whom comprehensive thrombophilia testing was available. To test the hypothesis that thrombophilia prevalence differs with respect to thrombus location, test results were compared to a randomly selected group of patients with lower extremity DVT with comprehensive thrombophilia testing.During this time period, 163 patients with CVST were identified who underwent comprehensive thrombophilia testing. Thrombophilia results were abnormal in 29% including anticardiolipin antibodies (17%), heterozygous factor V Leiden (10%), and heterozygous prothrombin G20210A mutation (n = 14/122; 11%). The prothrombin mutation was more than twice as common in patients with CVST (p = 0.04). Activated protein C resistance, factor V Leiden, and protein C deficiency were more common in patients with DVT (p0.05 for each comparison). The anticardiolipin antibodies in patients with CVST were primarily low titer IgM isotype.The prevalence of selected thrombophilia factors differs comparing patients with cerebral venous sinus thrombosis and deep vein thrombosis. These differences may offer insights into mechanisms governing the geographic distribution of venous thrombosis.

A 61-year-old man was admitted to an outside medical facility with left leg deep vein thrombosis and bilateral pulmonary emboli. His clinical course was complicated by hypotension, azotemia and declining mental status. Positive blood cultures for gram-positive cocci prompted transfer to our institution. Despite broad-spectrum antibiotics (vancomycin, cefepime, and ciprofloxacin), the patient remained febrile (temperature 39.4°C) with persistent leukocytosis. An echocardiogram revealed no valvular vegetations. Bacteremia persisted with methicillin-sensitive Staphylococcus aureus despite antimicrobial therapy. In the absence of a clear source of infection, an indium-111labeled white blood cell (WBC) scan was performed, revealing radiotracer enhancement of the left popliteal, femoral, and common femoral veins (Panels A and B) corresponding to thrombus location as assessed by ultrasound (Panels C and D). Radiotracer uptake within these Images in Vascular Medicine

Thromboangiitis obliterans (TAO) has been reported to become less common in general population but more common in women, and in elderly patients. The authors looked at the clinical characteristics of TAO in Poland where there was no significant decrease of smoking and the extent of aging of the general population is less profound. They retrospectively reviewed the records of 377 patients with the diagnosis of TAO hospitalized in their institution from 1970 to 1995. If young smoking males demonstrated distal-extremity ischemia with no bruits audible over major arteries, upper limbs involvement, or superficial thrombophlebitis, the diagnosis of TAO was considered certain. When at least one of those criteria was missed, and in men older than 35 years, but in all females, typical arteriographic findings were required for the diagnosis of TAO. Connective-tissue disease, hyperlipidemia, diabetes, and hypercoagulable state were excluded. Three hundred forty-two men (91%), and 35 (9%) women had a mean age of 29.5 years at the onset of the disease (the oldest patient was 50 years old). The prevalence of TAO in southwest Poland is 8.1/100,000 and the incidence of the disease steadily declines; there was no increase of TAO in women. Three hundred thirty-seven (89%) experienced rest pain, 321 (85%) had ischemic necrosis, and 233 (62%) thrombophlebitis at some (continued on next page) time in the course of the disease. Raynaud's phenomenon occurred in only 39 patients (10%). Those patients who had quit smoking had a 50% decrease of the disease recurrences compared to their smoking period. Because the cause of declining incidence of TAO is obscure, the authors critically evaluated previously used explanations of this phenomenon. They did not confirm the observation of a change in the TAO clinical spectrum: occurrence in women did not increase, the aging of the TAO population was not observed. In Poland TAO is still a disease affecting the peripheral circulation of young smoking males with recurrent episodes of superficial thrombophlebitis and common involvement of the upper extremities; Raynaud's phenomenon is rather infrequent. Smoking cessation ameliorates the course of the disease but does not invariably stop further exacerbations.