Takashi Shibuya

Hemostasis activation during sclerotherapy of lower extremity varices

The influence of compression sclerotherapy upon hemostasis activation was investigated in 41 consecutive patients with lower extremity varices by serial measurement of thrombin-antithrombin III complexes (TAT), D-dimer, fibrinogen and C-reactive protein (CRP). Blood sampling was carried out before operation and on the 7th and 28th post-operative day in patients randomly assigned to either the control group (n = 18), in which high ligation of sapheno-femoral junction and local excision of varices were performed, or the sclerotherapy group (n = 23) in which the comparable surgical intervention and compression sclerotherapy using hypertonic saline were performed simultaneously. In both groups, the TAT, D-dimer and fibrinogen concentrations at day 7 were significantly elevated compared to the value before operation while CRP showed no significant change during the observation period. In the sclerotherapy group, higher incidence of superficial thrombosis was observed and the TAT concentration at day 7 was significantly higher than that in the control group (p < 0.01), and the TAT at day 28 was still significantly elevated compared to the pre-operative level (p < 0.05). However, no relationship between TAT and D-dimer concentrations and the extent of superficial thrombosis was observed. We conclude that compression sclerotherapy for lower extremity varices causes latent activation of coagulation system and can be a risk factor for venous thromboembolism.

An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread

OBJECTIVE To develop an infection-resistant polytetrafluoroethylene (PTFE) vascular graft for potential clinical use in grafting in sites of bacterial contamination and in replacement of the infected grafts. SETTING Experimental study in rabbits. MATERIALS AND METHODS An antibiotic ofloxacin (OFLX) was bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine threads. The in-vitro antibacterial activity of OFLX-PTFE thread was determined by measuring the zone of growth inhibition against Escherichia coli. The thread was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft. OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC) of rabbits and the entire graft was covered with fibrin containing a fixed number of E. coli. Three or 7 days after the grafting, the grafts with perigraft tissue were harvested and subjected to bacteriological studies. RESULTS In spite of early phase rapid elution of OFLX, a significant antibacterial activity was retained for more than 2 weeks. The antibacterial activity of OFLX-PTFE threads implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to approximately 1% after a week. The swab culture of all the control grafts was positive, while only one of 13 PTFE-OFLX grafts was positive. The number of viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in comparison with that of control grafts. Thus, the OFLX-PTFE grafts exhibited a marked in-vivo antibacterial activity. CONCLUSION By a unique method, it was possible to furnish PTFE graft with an excellent infection-resistant property, without affecting the original biological behaviour.

The coagulofibrinolytic state of patients with primary varicose veins of the lower legs.

The relationship between a local hypercoagulable state and primary varicose veins of the lower legs was investigated by measuring the plasma levels of D-dimer (DD) and the thrombin-antithrombin-III complex (TAT) in 122 consecutive patients before treatment, and in 46 patients after surgical intervention and compression sclerotherapy. Elevated levels of DD and TAT were found in 25% and 20%, respectively, of the 122 patients, being significantly elevated in the patients with thrombophlebitis compared to the patients with no dermal symptoms, pigmentation, or stasis dermatitis. There was no significant difference in either parameter among eight groups of patients classified according to their valvular incompetence. The levels of DD and TAT were elevated before treatment in 25% and 20%, respectively, of 45 treated patients, but became significantly reduced after treatment. These results indicate that even though the local hypercoagulable state in varicose veins without thrombophlebitis is too subtle to be detected by systemic parameters such as DD and TAT, a local hypercoagulable state can be detected in a certain proportion of patients with venous stasis by these parameters.

Subendothelial layer of pseudointima of polytetrafluoroethylene graft is formed by transformation of fibroblasts migrated from extravascular space

A well organised pseudointima is formed in polytetrafluoroethylene (PTFE) grafts within 4 weeks after implantation into inferior vena cava (IVC) of rabbits. To investigate the process of the subendothelial organisation of pseudointima, an animal experiment was conducted. The outer wall of PTFE graft (30 microns fibril length, 3 mm inner diameter, 3 cm long) was coated with 10 um silicon film in the following ways to prevent cellular ingrowth from the extravascular space: non-coating; full-length coating; half-length coating; and full-length coating excluding 5 mm midportion. These grafts were implanted into rabbit IVC and were harvested 4 weeks later. All the grafts were patent but the lumen of the non-coated area was narrowed by pseudointimal hyperplasia. The degree of the hyperplasia estimated by dried tissue deposit was inversely proportional to the length of the coating. The coverage of the luminal surface with endothelial-like cells was noted at anastomotic areas and also at the surface corresponding to the non-coated area. Light microscopy and immunostaining studies on the non-coated midportion revealed the presence of fibroblasts in the interstices of PTFE and smooth muscle cells and myofibroblasts in the pseudointima. Transmission electron microscopy confirmed the presence of myofibroblasts in the midportion of the non-coated area. No transmural capillary ingrowth was observed in the midportion by histological and immunohistochemical analysis. These observations suggest that the subendothelial layer of pseudointima in PTFE grafts is formed by proliferation and transformation of fibroblasts migrating from the extravascular space and that endothelial-like cells may also be derived from such transformation.

Abdominal Aortic Grafting for Spontaneous Infrarenal Abdominal Aortic Dissection

This case report concerns a 62-year-old woman with spontaneous infrarenal abdominal aortic dissection, which developed into claudication and rest pain in the lower extremity. Multi-row detector computed tomography showed the entry site of the abdominal aortic dissection at the second lumbar artery, while the reentry site was found intraoperatively at the median sacral artery, indicating that the false lumen had progressed and compressed the true lumen. A direct approach involving grafting appears to be an effective procedure for resolving mesenteric and lower extremity hypoperfusion due to aortic dissection with a dilated false channel, even during the acute period.

Diagnostic value of plasma thrombin-antithrombin III complex and D-dimer concentration in patients with varicose veins for exclusion of deep-vein thrombosis

The aim of this study was to evaluate the usefulness of determining plasma D-dimer (DD) and thrombin-antithrombin III complex (TAT) levels in the diagnostic workup for the screening of deep-venous thrombosis (DVT) among varicose vein patients. One hundred forty consecutive patients being treated for DVT or varicose veins underwent color-flow duplex scanning, and 25 patients had DVT and the remaining 115 had primary varicose veins. When DD and TAT were analyzed statistically in combination, it was determined that the combination of either positive DD (cutoff level 1.0 microg/ml) or positive TAT (cutoff level 3.0 microg/l) had a sensitivity of 100% for DVT with a specificity, positive predictive value, and negative predictive value of 79%, 51%, and 100%, respectively. This study demonstrates plasma levels of DD (less than 1.0 microg/ml) and TAT (less than 3.0 microg/l) in combination to be useful for the exclusion of DVT among patients with varicose veins. Patients with negative hematological data may safely undergo surgical treatment for varicose veins without further evaluation such as duplex scanning or contrast venography.

Sclerotherapy for varicose veins of the lower legs in patients with dysplasminogenemia.

Sclerotherapy combined with ligation has become a widely accepted treatment for varicose veins; however, it is associated with some risk of the serous complications of deep vein thrombosis (DVT). We investigated the incidence of thrombophilia in 164 consecutive patients undergoing treatment for varicose veins and determined the activities of antithrombin-III, protein C, and plasminogen. Of the 164 patients, 10 were diagnosed as having dysplasminogenemia (DPG), showing an incidence of 6.1%, in accordance with previous reports. DVT was not found to be caused by DPG in any patient, and no difference was found between patients with and those without DPG, suggesting that DPG is not a risk factor for varicose veins. We also investigated the activation of coagulation by measuring the thrombin-antithrombin III complex (TAT). The activation of coagulation after sclerotherapy was inhibited when ligation was performed 1 month prior to sclerotherapy, whereas it was increased when sclerotherapy and ligation were performed simultaneously. Of the 10 patients with DPG, 5 were treated uneventfully, and their TAT level increased to 4.0 μg/l, which was comparable to the level after sclerotherapy and ligation. These findings indicate that sclerotherapy can be performed safely in the majority of patients with DPG, and that the temporal separation of sclerotherapy and surgery is an alternative for these patients to prevent the activation of coagulation.

Unilateral Acute Lower Extremity Ischemia with Popliteal Artery Aneurysm as a Result of Vascular Type III Entrapment in an Elderly Patient

Popliteal artery entrapment syndrome (PAES) is a rare cause of acute limb ischemia in adult patients but commonly demonstrates as claudication in young patients. The most significant, although rare, complication associated with PAES is aneurysm formation. We present the case of an elderly patient with a unilateral popliteal artery aneurysm owing to symptomatic anatomic entrapment. This report presents the oldest patient ever reported with this syndrome and highlights the advantage of multimodal treatment. As multidetector computed tomography highly contributed to the rapid diagnostic confirmation and choice of treatment in the popliteal fossa, limb salvage was achieved in this patient.

Pseudointimal hyperplasia of ridged outer wall polytetrafluoroethylene vascular prostheses

In addition to the polytetrafluoroethylene (PTFE) vascular graft (G) with its conventionally smooth surface, a unique PTFE graft with a ridged outer wall (T) is now also currently available for clinical use. Although an excellent antikinking property is provided by this unique outer structure, the possible influence of the structure on the formation of pseudointima has not yet been investigated in detail. Four kinds of T grafts (3 mm inner diameter, 3 cm long) with various fibril lengths (FL, T-15, T-30, T-60, T-90) and a G graft with 30 μm FL (G-30) were implanted into the inferior vena cava of rabbits. The patency of the grafts at 4 weeks were as follows: 6/8(T-15), 6/8(T-30), 5/8(T-60), 0/8(T-90) and 4/6 (G-30). Pseudointimal hyperplasia (PH) of the T grafts advanced as the FL increased, judging by the thickness of the pseudointima, cellular density, and maturity of fibroblasts. In addition, the maturity of endothelial-like cells on the luminal surface increased as the FL increased. The degree of pseudomintimal hyperplasia in G-30 was comparable to that of T-15, although the maturity of the endothelial-like cells was similar to that of T-60. Microscopically, there was a microheterogeneity of cellular density in T grafts probably due to the uneven outer structure. In conclusion, not only FL but also the outer structure of PTFE may thus influence the formation of the pseudointima.

Suppression of pseudointimal hyperplasia by a novel prostacyclin analogue: beraprost.

The aim of this study was to evaluate the effect of a novel prostaglandin I2 analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P<0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs.