Thomas Gary

Platelet-to-Lymphocyte Ratio: A Novel Marker for Critical Limb Ischemia in Peripheral Arterial Occlusive Disease Patients

Background Platelet-to-Lymphocyte Ratio (PLR) is an easily applicable blood test. An elevated PLR has been associated with poor prognosis in patients with different oncologic disorder. As platelets play a key role in atherosclerosis and atherothrombosis, we investigated PLR and its association with critical limb ischemia (CLI) and other vascular endpoints in peripheral arterial occlusive disease (PAOD) patients. Methods and Findings We evaluated 2121 PAOD patients treated at our institution from 2005 to 2010. PLR was calculated and the cohort was categorized into tertiles according to the PLR. An optimal cut-off value for the continuous PLR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort occurrence of CLI significantly increased with an increase in PLR. As an optimal cut-off value, a PLR of 150 was identified. Two groups were categorized, one containing 1228 patients (PLR≤150) and a second group with 893 patients (PLR>150). CLI was more frequent in PLR>150 patients (410(45.9%)) compared to PLR≤150 patients (270(22.0%)) (p<0.001), as was prior myocardial infarction (51(5.7%) vs. 42(3.5%), p = 0.02). Regarding inflammatory parameters, C-reactive protein (median 7.0 mg/l (3.0–24.25) vs. median 5.0 mg/l (2.0–10.0)) and fibrinogen (median 457 mg/dl (359.0–583.0) vs. 372 mg/dl (317.25–455.75)) also significantly differed in the two patient groups (both p<0.001). Finally, a PLR>150 was associated with an OR of 1.9 (95%CI 1.7–2.1) for CLI even after adjustment for other well-established vascular risk factors. Conclusions An increased PLR is significantly associated with patients at high risk for CLI and other cardiovascular endpoints. The PLR is a broadly available and cheap marker, which could be used to highlight patients at high risk for vascular endpoints.

A high CHA2DS2-VASc score is associated with a high risk for critical limb ischemia in peripheral arterial occlusive disease patients

BACKGROUND The CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years (doubled), type 2 diabetes, previous stroke, transient ischemic attack, or thromboembolism (doubled), vascular disease, age 65-75 years, and sex category) score was published as a predictive scoring model for stroke in atrial fibrillation patients. As multiple vascular risk factors are included in this score we evaluated the occurrence of critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients according to their CHA(2)DS(2)-VASc score independent of a coexisting atrial fibrillation. METHODS We evaluated 2237 PAOD patients treated at our institution from 2005 to 2010. CHA(2)DS(2)-VASc score was calculated and the occurrence of CLI was investigated. Furthermore all constituents of the score were investigated concerning association with CLI. RESULTS Frequency of CLI was higher in patients with a high CHA(2)DS(2)-VASc score. Age ≥ 75 years was associated with an increased risk for CLI (OR 3.0), as was age 65-75 years (OR 1.8), type 2 diabetes (OR 2.8), and the factor previous stroke, transient ischemic attack, or thromboembolism (OR 1.4). The occurrence of arterial hypertension was protective for CLI (OR 0.6). Sex and congestive heart failure were not associated with an increased CLI risk. CONCLUSION High CHA(2)DS(2)-VASc score is associated with a high CLI risk. As not all constituents are equally associated with CLI and some are even protective, a new score including only some of the factors should be evaluated for the prediction of CLI.

Impaired Endothelial-Dependent and Endothelium-Independent Vasodilatation in Patients With Thromboangiitis Obliterans

Background: Endothelial dysfunction is the key process in the development of atherosclerosis. The aim of our study was to evaluate endothelial dysfunction measured by the noninvasive technique of Celermajer that plays a role in the pathogenesis of thrombangitis obliterans. Methods: A total of 36 patients with thrombangitiis obliterans ([TAO]; mean age 44.9 ± 1.3 years) were compared with 30 healthy individuals (mean age 36.1 ± 1.8 years). High frequency ultrasound was used to measure changes in response to reactive hyperemia (leading to flow-mediated endothelium-dependent dilatation) and in response to 0.4 mg sublingual nitroglycerin ([NTG]; leading to NTG-induced, endothelium-independent dilatation). Results: Patients with TAO showed a lower but statistically not significant flow-mediated dilatation and a statistically significant reduced NTG-induced vasodilatation than the control group. Conclusion: Our results suggest that both mechanisms play a role in patients with TAO, the endothelium-independent impaired vasodilatation even in a more significant way than the impaired endothelium-dependent vasodilatation.

Acute wiiitis representing as thrombosis of the inferior vena cava and left pelvic veins

Deep venous thrombosis as a result of venous wall injury provoked by trauma is a common finding. It often occurs in patients with sportive overstraining, caused by over fatigue of the body structures. In 2007, the entity of “acute wiiitis” was first described in a letter to the New England Journal of Medicine. Acute wiiitis sums up all affections, mainly skeletal and muscle affections, provoked by playing Nintendo Wii, a very common and loved video-game system. Deep venous thrombosis as a consequence of Nintendo Wii has not been described so far. We present a patient with a massive free floating thrombus of the left pelvic veins originating from the gluteal veins and reaching into the inferior vena cava after playing Nintendo Wii.

Primary antiphospholipid antibody syndrome—one further aspect of thrombophilia in overweight and obese patients with venous thromboembolism

Objective: Overweight and obesity are established risk factors for venous thromboembolism (VTE). We examined the difference in the frequency of primary antiphospholipid antibody syndrome (PAPS) in VTE patients according to their BMI.

Association of the Derived Neutrophil-Lymphocyte Ratio With Critical Limb Ischemia.

Neutrophil and leukocyte counts are laboratory parameters that reflect the systemic inflammatory response in patients with atherosclerotic diseases. Based on the means of these parameters, the derived neutrophil–lymphocyte ratio (dNLR) can be calculated. We investigated a possible association of critical limb ischemia (CLI) and the dNLR in patients with peripheral arterial disease (PAD). We performed a retrospective data analysis including 1995 patients with PAD treated at our department in the years 2005 to 2010. The cohort was divided into tertiles according to dNLR. Higher dNLR values were associated with an increased CLI rate. In the tertile with lowest dNLR, the CLI rate was 20.4%, in the second tertile the CLI rate was 26.1%, and in the third tertile the CLI rate was 36.1%. Statistical significance was shown using a Jonckheere-Terpstra test (P < .001). A high dNLR is associated with an increased rate of CLI in patients with PAD. This might be a useful parameter to highlight patients at increased risk of CLI.

Unusual deep vein thrombosis sites: magnetic resonance venography in patients with negative compression ultrasound and symptomatic pulmonary embolism

Objectives To evaluate the clinical characteristics of patients with pulmonary embolism (PE), negative compression ultrasound (CUS) of the lower limbs and detection of unusual deep vein thrombosis (DVT) sites by means of magnetic resonance (MR) venography. Methods A retrospective data analysis of PE patients hospitalized at our institution from April 2009 to 2011. Results From April 2009 to 2011, a total of 762 PE patients were treated at our institution. In 169 of these patients CUS for DVT was negative. In these patients MR venography was performed for further evaluation. We found venous thrombosis at unusual sites in 12 of these patients. Due to free floating thrombus masses and fear of life-threatening PE progression we inserted an inferior vena cava filter in three of these 12 patients. The leading venous thromboembolism risk factor in our patients was immobilization (5 patients, 41.7%). Conclusions We conclude that especially in patients with PE and negative CUS of the lower limbs a thrombosis of the pelvic veins should be considered in case of symptoms for venous thrombosis in this area. Further diagnostic work-up with MR venography should be scheduled in these patients especially in patients with risk factor immobilization as therapeutic consequences might occur.

Low mean platelet volume is associated with critical limb ischemia in peripheral arterial occlusive disease

Mean platelet volume (MPV) was recently published as a possible marker of coronary artery disease in patients at high risk for major adverse cardiac events. Because platelets play an important role in atherosclerosis, we examined the relationship between critical limb ischemia (CLI) and MPV in patients with peripheral arterial occlusive disease (PAOD). Our study comprised 2124 PAOD patients. Univariate logistic regression was performed to analyze potential predictors for CLI. Nagelkerke’s R² is reported. Cross validation was performed using the leave-one-out principle. ROC analyses were performed to identify the best cut off value for MPV predicting CLI; to this end, Youden’s index was calculated. For CLI diabetes (p < 0.001, OR 2.44, 95% CI 1.97–3.02), hsCRP (p < 0.001, OR 1.01, 95% CI 1.01–1.01), age (p < 0.001, OR 1.05, 95% CI 1.04–1.06), thrombocytosis (p = 0.025, OR 1.84, 95%CI 1.08–3.14), and MPV (p = 0.003, OR 0.84, 95% CI 0.75–0.94) were significant independent predictors for CLI. ROC analysis (AUC: 0.55, 95% CI 0.52–0.58, p < 0.001) showed ≤10.2 as the best cut off value for MPV to predict CLI. As there is a significant relationship between low MPV and a high risk for CLI in PAOD patients, MPV can be used to identify patients who are likely to develop CLI.

Safety and Efficacy of Periprocedural Anticoagulation With Enoxaparin in Patients Undergoing Peripheral Endovascular Revascularization

Background: Periprocedural anticoagulation is primarily used in endovascular procedures to prevent acute reocclusion of the target vessel, but periprocedural anticoagulation might also have an impact on long-term outcome. Consecutive bleeding events are feared complications. Despite changes in peripheral endovascular revascularizations (EVRs), the periprocedural management has remained unchanged for years. Unfractionated heparin is still the treatment of choice during and immediately after EVR. Materials and Methods: We performed a prospective, single-center, open-label phase III study comparing 2 different regimes of enoxaparin peri-interventional to peripheral EVR stratified into low- and high-risk groups according to the acute and long-term reocclusion risk due to their vessel morphology. In both groups, 0.5 mg/kg of enoxaparin as a bolus was administered intravenously 10 to 15 minutes before the start of the procedure. In the low-risk group, 40 mg of enoxaparin were administered once daily for 7 days; whereas in the high-risk group, 1 mg/kg of enoxaparin was administered subcutaneously (sc) 2 times a day for 48 hours after the procedure and afterward 40 mg of enoxaparin was administered sc once daily for 5 days. Results: For the analysis of the per protocol population, 44 patients remained in the low-risk group and 140 in the high-risk group. Concerning the primary safety end point, a total of 25 (13.59%) bleeding events occurred until day 30; 5 (11.36%) of them in the low-risk group and 20 (14.29%) in the high-risk group (P = .809 for low vs high risk). None of the bleeding events observed were major according to Thrombolysis In Myocardial Infarction criteria. Concerning our primary efficacy end point, none of the patients showed an acute reocclusion classified as a significant decrease in ankle–brachial index (ABI) or elevated peak systolic velocity ratio confirmed by duplex sonography until day 30. Concerning the second end point of prevention of chronic reobstruction, at day 180 ABI has decreased in the low-risk group from mean 0.94 at day 30 to mean 0.89 and from 1.28 at day 30 to 0.85 after 6 months in the high-risk group. No significant reobstruction was found in the low-risk group, whereas 5 significant reobstruction events were objectified in the high-risk group, all of them in the femoropopliteal arterial segment at day 180. Conclusion: We conclude that low-molecular-weight heparin either in a low-dose or high-dose regime during a peripheral EVR is safe concerning bleeding complications and acute reobstructions. The long-term follow-up showed no significant difference between our high- and low-risk groups concerning reobstruction. The periprocedural anticoagulation seems to have no influence on the long-term patency rate after peripheral EVR.

Massive pulmonary embolism caused by internal iliac vein thrombosis with free-floating thrombus formation in the inferior vena cava.

Nowadays, compression ultrasonography (CUS) is the gold standard for the routine diagnosis of deep venous thrombosis (DVT). The drawback of CUS is the low sensitivity concerning the diagnosis of isolated pelvic vein thrombosis, especially referring to isolated internal iliac vein and ovarian vein thromboses. Therefore, magnetic resonance (MR) venography has become a valuable alternative. We present the case of a 45-year-old female patient with a massive pulmonary embolism with the indication for thrombolytic therapy due to severe right ventricular overload. We were not able to detect a DVT in the lower limbs of this patient with CUS. However, further DVT workup by MR venography showed a free-floating thrombus formation originating from the right internal iliac veins into the inferior vena cava. Owing to the fact that this thrombus was free floating, surgical removal of the thrombus was scheduled and performed successfully. In some patients it might be important to look for so-called rare causes of pulmonary embolism, even when CUS of the lower limbs does not reveal any DVTs. The diagnostic procedure of choice for these patients seems to be MR phlebography, as iliac and pelvic veins can be evaluated without radiation exposure with this procedure.