- Email: [email protected]
Hemodynamic Effect of Stenting in Post-Thrombotic Iliofemoral Venous Obstruction
150 Abstracts
JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS January 2016
The Functional Examination of Lymphedema: Advantage and Limitation of SPECT/CT Lymphoscintigraphy and Near-Infrared Fluorescence Lymphography S. Matsubara, J. Maegawa, T. Mikami, Y. Yabuki. Department of PRS, Yokohama City University, Yokohama, Japan Background: The evaluation of the lymphatic function and existence of the lymphatic vessels in lower limb lymphedema patient is important. We investigate them usually by lymphoscintigraphy (LS) and nearinfrared fluorescence lymphography (NIF). However, the detected lymph vessels are different according to the point that tracers or indocyanine green were injected. This is a preliminary study to understand the dynamics of lymphatic flow, using SPECT/CT lymphoscintigraphy (SPECT) and NIF. Methods: From 2013 to 2014, 248 patients with lymphedema of the lower extremities who were examined by SPECT and/or NIF were evaluated as outpatients or in the operating room. In two-dimensional images of LS, we define colateral lymphatic flow as unusual linear uptake of isotope on the out of medial side of the lower extremities. In SPECT, the uptake of isotope was colored by gradation and fused with CT images. We define deep lymphatic flow as uptake of isotope under the fascia in axial images. The percentage of colateral lymphatic flow and deep flow were investigated. In NIF, the dye was injected each interdigital space and checked by PDE camera. The linear pattern and dermal back flow (DBF) were detected in realtime fashion. In some cases, their clinical findings were different from SPECT images; the dye was injected in the paramalleolar area. Results: There is colateral lymphatic flow in 66% patients on the lateral superficial area or deep area, and 71% of limbs, in which there is no symptom of lymphedema, have colateral lymphatic flow. In axial images of SPECT, 80% limbs have the deep lymphatic flow. There are 9% limbs without superficial lymphatic flow and 20% limbs without deep flow. In NIF, the linear pattern and DBF was easily detected below knee. However in the low lymphatic function of dorsum, the linear pattern was checked under injection into the paramalleolar area. Conclusions: Our LS and SPECT are useful to detect the functional lymphatic vessels. NIF is also useful to repeat examination for search them. To understand their correct location makes it possible to improve both the conservative and surgical treatment of the lymphedema. Author Disclosures: S. Matsubara: Nothing to disclose; J. Maegawa: Nothing to disclose; T. Mikami: Nothing to disclose; Y. Yabuki: Nothing to disclose.
Resourcing of Heparin and Low-Molecular-Weight Heparins from Bovine, Ovine, and Porcine Origin: Studies to Demonstrate the Biosimilarities D. Hoppensteadt, E. Kalodiki, P. Maia, A. Silva de Castro, E. Kumar, N. Guler, W. Jeske, D. Kahn, J. Walenga, E. Coyne, J. Fareed. Loyola University Medical Centre, Chicago, Ill Background: The currently used unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) are mostly derived from porcine mucosal tissue, but a shortage of their supply is anticipated. Resourcing of heparins using bovine (cow) and ovine (sheep) tissues is discussed at regulatory and pharmaceutical levels. The aim of the study is to compare five individual batches of UFH obtained from porcine, bovine, and origin and their depolymerized products, enoxaparins. Methods: The molecular profile of the heparins and enoxaparins from various sources were determined using the size exclusion method. A narrow-range calibration method was used for comparing the molecular weight of heparin, whereas the EP method was used to cross-reference the molecular weight of enoxaparins. Activated partial thromboplastin time (aPTT) and thrombin time (TT) measured the anticoagulant potency. Anti-Xa and anti-IIa activities (Hyphen Biomedical, Ohio) determined the USP potency. The interaction between AT and heparins/enoxaparin were investigated in a purified biochemical system, using AT supplemented buffered assay. Thrombin generation inhibition was studied with fluorometry (Technoclone, Vienna, Austria). The relative interaction of heparins/enoxaparins with heparin-induced thrombocytopenia (HIT) antibody induced aggregation of platelets was investigated using serum pool obtained from clinically confirmed HIT cases using aggregometry. Results: The molecular profile of bovine, ovine, porcine heparins and enoxaparin were almost identical. Porcine and ovine heparin produced consistently comparable anticoagulant effects with PT and aPTT, which were stronger vs the bovine. In contrast, the enoxaparins derived from these three sources showed minimal differences. In the anti Xa and IIa assays, both ovine and porcine heparins produced similar inhibition, whereas the
bovine heparin exhibited lower activity. In the purified system, the porcine and ovine preparations consistently showed lower IC50 values for both the thrombin and Xa inhibition in contrast to bovine heparin. The USP potency of the porcine and ovine heparins ranged from 180 to190 u/mg, whereas the bovine was 130 to 140 u/mg. The anti-Xa-to-IIa ratio for the heparins were comparable. The ovine and porcine enoxaparin exhibited comparable potencies, which ranged from 94 to 110 u/mg, whereas bovine enoxaparin was slightly lower at 80 to 87 u/mg. However, the anti-Xa and anti-IIa ratios were comparable. The AT-mediated inhibition of factor Xa and anti-IIa was stronger with heparins vs enoxaparins. Similarly, heparins produced stronger inhibition of thrombin generation vs enoxaparin. In the HIT screening, there was no difference between the HIT responses in the heparins or enoxaparins from different species. Conclusions: While bovine, ovine, and porcine heparins and enoxaparins exhibit comparable molecular profiles, in some of the functional assays, bovine heparin and enoxaparin exhibited somewhat lesser potencies, especially in the pharmacopeial assays. No differences were noted in the HIT antibody interactions among heparins and enoxaparins from different species. These studies demonstrate that ovine and porcine heparins are biosimilar and can be developed as such for clinical purposes. The bovinederived heparins exhibit slightly weaker potencies in functional assays despite comparable molecular profile. Potency adjustment for in vivo usage may be required to obtain comparable anticoagulant responses for the bovine heparin and enoxaparin. Author Disclosures: D. Hoppensteadt: Nothing to disclose; E. Kalodiki: Nothing to disclose; P. Maia: Nothing to disclose; A. Silva de Castro: Nothing to disclose; E. Kumar: Nothing to disclose; N. Guler: Nothing to disclose; W. Jeske: Nothing to disclose; D. Kahn: Nothing to disclose; J. Walenga: Nothing to disclose; E. Coyne: Nothing to disclose; J. Fareed: Nothing to disclose.
Hemodynamic Effect of Stenting in Post-Thrombotic Iliofemoral Venous Obstruction R. L. M. Kurstjens, M. de Wolf, I. Toonder, R. de Graaf, C. Wittens. Maastricht University Medical Center, Maastricht, The Netherlands Background: Good clinical success can be achieved when treating post-thrombotic iliofemoral deep venous obstruction by percutaneous transluminal angioplasty and stenting. Although research has shown that intravenous pressures are significantly elevated in post-thrombotic limbs, little is known about the hemodynamic effect of stenting. The aim of this study was to determine whether venous hypertension can be reduced by stenting of iliofemoral deep venous obstruction. Methods: Twenty-two patients with unilateral post-thrombotic iliofemoral venous obstruction were included. Common femoral vein and dorsal foot vein pressures were invasively and continuously measured while patients underwent a standardized treadmill test the day before treatment. This test was repeated 3 months after treatment. Results: Mean age was 43 6 12 years, 19 patients were female, and 20 had left-sided obstruction. Venous claudication was present in all patients. Three patients decided not to undergo the second treadmill test, and pressure measurements in three patients could not be obtained during the second treadmill test because it was decided to stent into the deep femoral vein. After stenting, common femoral vein pressure during the treadmill test was reduced by 22.3 6 24.8 mm Hg in diseased limbs (P ¼ .003, paired-samples t-test). No difference in effect of stenting was observed between diseased and control limbs at the level of the dorsal foot vein (P ¼ .940). Pain-free walking distance increased by 224 6 283 meters (P ¼ .014), and maximum walking distance increased by 235 6 245 meters (P ¼ .001). Conclusions: Common femoral vein pressure is significantly reduced by stenting in patients with post-thrombotic deep venous obstruction of the iliofemoral tract. Additionally, walking distance significantly increases, suggesting an association between venous claudication and venous hypertension. Author Disclosures: R. L. M. Kurstjens: Nothing to disclose; M. de Wolf: Nothing to disclose; I. Toonder: Nothing to disclose; R. de Graaf: Nothing to disclose; C. Wittens: Nothing to disclose.
Is Routine Follow-up Surveillance of Iliac Vein Stents for Iliocaval Venous Obstruction Necessary? R. Abdul-Haqq, Z. Novak, B. Pearce, T. Matthews, M. Patterson, W. Jordan, M. Passman. University of Alabama, Birmingham, Ala Background: Although iliac vein stenting has emerged as effective treatment for iliocaval venous obstruction (ICVO), the role of surveillance
JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS January 2016
The Functional Examination of Lymphedema: Advantage and Limitation of SPECT/CT Lymphoscintigraphy and Near-Infrared Fluorescence Lymphography S. Matsubara, J. Maegawa, T. Mikami, Y. Yabuki. Department of PRS, Yokohama City University, Yokohama, Japan Background: The evaluation of the lymphatic function and existence of the lymphatic vessels in lower limb lymphedema patient is important. We investigate them usually by lymphoscintigraphy (LS) and nearinfrared fluorescence lymphography (NIF). However, the detected lymph vessels are different according to the point that tracers or indocyanine green were injected. This is a preliminary study to understand the dynamics of lymphatic flow, using SPECT/CT lymphoscintigraphy (SPECT) and NIF. Methods: From 2013 to 2014, 248 patients with lymphedema of the lower extremities who were examined by SPECT and/or NIF were evaluated as outpatients or in the operating room. In two-dimensional images of LS, we define colateral lymphatic flow as unusual linear uptake of isotope on the out of medial side of the lower extremities. In SPECT, the uptake of isotope was colored by gradation and fused with CT images. We define deep lymphatic flow as uptake of isotope under the fascia in axial images. The percentage of colateral lymphatic flow and deep flow were investigated. In NIF, the dye was injected each interdigital space and checked by PDE camera. The linear pattern and dermal back flow (DBF) were detected in realtime fashion. In some cases, their clinical findings were different from SPECT images; the dye was injected in the paramalleolar area. Results: There is colateral lymphatic flow in 66% patients on the lateral superficial area or deep area, and 71% of limbs, in which there is no symptom of lymphedema, have colateral lymphatic flow. In axial images of SPECT, 80% limbs have the deep lymphatic flow. There are 9% limbs without superficial lymphatic flow and 20% limbs without deep flow. In NIF, the linear pattern and DBF was easily detected below knee. However in the low lymphatic function of dorsum, the linear pattern was checked under injection into the paramalleolar area. Conclusions: Our LS and SPECT are useful to detect the functional lymphatic vessels. NIF is also useful to repeat examination for search them. To understand their correct location makes it possible to improve both the conservative and surgical treatment of the lymphedema. Author Disclosures: S. Matsubara: Nothing to disclose; J. Maegawa: Nothing to disclose; T. Mikami: Nothing to disclose; Y. Yabuki: Nothing to disclose.
Resourcing of Heparin and Low-Molecular-Weight Heparins from Bovine, Ovine, and Porcine Origin: Studies to Demonstrate the Biosimilarities D. Hoppensteadt, E. Kalodiki, P. Maia, A. Silva de Castro, E. Kumar, N. Guler, W. Jeske, D. Kahn, J. Walenga, E. Coyne, J. Fareed. Loyola University Medical Centre, Chicago, Ill Background: The currently used unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) are mostly derived from porcine mucosal tissue, but a shortage of their supply is anticipated. Resourcing of heparins using bovine (cow) and ovine (sheep) tissues is discussed at regulatory and pharmaceutical levels. The aim of the study is to compare five individual batches of UFH obtained from porcine, bovine, and origin and their depolymerized products, enoxaparins. Methods: The molecular profile of the heparins and enoxaparins from various sources were determined using the size exclusion method. A narrow-range calibration method was used for comparing the molecular weight of heparin, whereas the EP method was used to cross-reference the molecular weight of enoxaparins. Activated partial thromboplastin time (aPTT) and thrombin time (TT) measured the anticoagulant potency. Anti-Xa and anti-IIa activities (Hyphen Biomedical, Ohio) determined the USP potency. The interaction between AT and heparins/enoxaparin were investigated in a purified biochemical system, using AT supplemented buffered assay. Thrombin generation inhibition was studied with fluorometry (Technoclone, Vienna, Austria). The relative interaction of heparins/enoxaparins with heparin-induced thrombocytopenia (HIT) antibody induced aggregation of platelets was investigated using serum pool obtained from clinically confirmed HIT cases using aggregometry. Results: The molecular profile of bovine, ovine, porcine heparins and enoxaparin were almost identical. Porcine and ovine heparin produced consistently comparable anticoagulant effects with PT and aPTT, which were stronger vs the bovine. In contrast, the enoxaparins derived from these three sources showed minimal differences. In the anti Xa and IIa assays, both ovine and porcine heparins produced similar inhibition, whereas the
bovine heparin exhibited lower activity. In the purified system, the porcine and ovine preparations consistently showed lower IC50 values for both the thrombin and Xa inhibition in contrast to bovine heparin. The USP potency of the porcine and ovine heparins ranged from 180 to190 u/mg, whereas the bovine was 130 to 140 u/mg. The anti-Xa-to-IIa ratio for the heparins were comparable. The ovine and porcine enoxaparin exhibited comparable potencies, which ranged from 94 to 110 u/mg, whereas bovine enoxaparin was slightly lower at 80 to 87 u/mg. However, the anti-Xa and anti-IIa ratios were comparable. The AT-mediated inhibition of factor Xa and anti-IIa was stronger with heparins vs enoxaparins. Similarly, heparins produced stronger inhibition of thrombin generation vs enoxaparin. In the HIT screening, there was no difference between the HIT responses in the heparins or enoxaparins from different species. Conclusions: While bovine, ovine, and porcine heparins and enoxaparins exhibit comparable molecular profiles, in some of the functional assays, bovine heparin and enoxaparin exhibited somewhat lesser potencies, especially in the pharmacopeial assays. No differences were noted in the HIT antibody interactions among heparins and enoxaparins from different species. These studies demonstrate that ovine and porcine heparins are biosimilar and can be developed as such for clinical purposes. The bovinederived heparins exhibit slightly weaker potencies in functional assays despite comparable molecular profile. Potency adjustment for in vivo usage may be required to obtain comparable anticoagulant responses for the bovine heparin and enoxaparin. Author Disclosures: D. Hoppensteadt: Nothing to disclose; E. Kalodiki: Nothing to disclose; P. Maia: Nothing to disclose; A. Silva de Castro: Nothing to disclose; E. Kumar: Nothing to disclose; N. Guler: Nothing to disclose; W. Jeske: Nothing to disclose; D. Kahn: Nothing to disclose; J. Walenga: Nothing to disclose; E. Coyne: Nothing to disclose; J. Fareed: Nothing to disclose.
Hemodynamic Effect of Stenting in Post-Thrombotic Iliofemoral Venous Obstruction R. L. M. Kurstjens, M. de Wolf, I. Toonder, R. de Graaf, C. Wittens. Maastricht University Medical Center, Maastricht, The Netherlands Background: Good clinical success can be achieved when treating post-thrombotic iliofemoral deep venous obstruction by percutaneous transluminal angioplasty and stenting. Although research has shown that intravenous pressures are significantly elevated in post-thrombotic limbs, little is known about the hemodynamic effect of stenting. The aim of this study was to determine whether venous hypertension can be reduced by stenting of iliofemoral deep venous obstruction. Methods: Twenty-two patients with unilateral post-thrombotic iliofemoral venous obstruction were included. Common femoral vein and dorsal foot vein pressures were invasively and continuously measured while patients underwent a standardized treadmill test the day before treatment. This test was repeated 3 months after treatment. Results: Mean age was 43 6 12 years, 19 patients were female, and 20 had left-sided obstruction. Venous claudication was present in all patients. Three patients decided not to undergo the second treadmill test, and pressure measurements in three patients could not be obtained during the second treadmill test because it was decided to stent into the deep femoral vein. After stenting, common femoral vein pressure during the treadmill test was reduced by 22.3 6 24.8 mm Hg in diseased limbs (P ¼ .003, paired-samples t-test). No difference in effect of stenting was observed between diseased and control limbs at the level of the dorsal foot vein (P ¼ .940). Pain-free walking distance increased by 224 6 283 meters (P ¼ .014), and maximum walking distance increased by 235 6 245 meters (P ¼ .001). Conclusions: Common femoral vein pressure is significantly reduced by stenting in patients with post-thrombotic deep venous obstruction of the iliofemoral tract. Additionally, walking distance significantly increases, suggesting an association between venous claudication and venous hypertension. Author Disclosures: R. L. M. Kurstjens: Nothing to disclose; M. de Wolf: Nothing to disclose; I. Toonder: Nothing to disclose; R. de Graaf: Nothing to disclose; C. Wittens: Nothing to disclose.
Is Routine Follow-up Surveillance of Iliac Vein Stents for Iliocaval Venous Obstruction Necessary? R. Abdul-Haqq, Z. Novak, B. Pearce, T. Matthews, M. Patterson, W. Jordan, M. Passman. University of Alabama, Birmingham, Ala Background: Although iliac vein stenting has emerged as effective treatment for iliocaval venous obstruction (ICVO), the role of surveillance