The study of the thrombin generation mechanism and the effect of low molecular weight heparin as thromboprophylaxis in patients undergoing total knee and hip replacement.

INTRODUCTION: The recommended duration of post-operative Low-Molecular-Weight-Heparins (LMWHs) thromboprophylaxis in Total-Hip-Replacement (THR) and Total-Knee-Replacement (TKR) surgery is controversial. Our aim is to study the thrombin generation (TG) modifications induced by surgery and to evaluate the effect of LMWH on TG during and after the recommended duration. PATIENTS/METHODS: Thirty-one patients received 4000IU anti-Xa/day of enoxaparin, 8-hours post-operatively (15 THR for 30-days and 16 TKR for 15-days). TG assay sensitive to enoxaparin was performed, pre-operatively (D0), 7-hours post-surgery (D1), 8-days post-surgery (D8), and 2-days after thromboprophylaxis withdrawal (D32 and D17), evaluating: lag-time, endogenous thrombin potential (ETP), peak amount of generated thrombin (Peak), time-to-Peak (tt-Peak), and the Mean-Rate-Index [MRI=Peak/(tt-Peak-lag-time)]. RESULTS: TKR surgery decreased lag-time and tt-Peak and increased MRI on D1 vs D0 (p<0.05). In contrast, THR did not significantly modify TG. Enoxaparin effectively reduced thrombin generation in both groups. Thromboprophylaxis withdrawal resulted in rebound increase of TG in the TKR patients (ETP, Peak & MRI significantly increased on D17 vs D0; p<0.05, and vs. D1; p<0.05) but not in THR patients. Variability in the response to enoxaparin was observed among patients of the same group. CONCLUSIONS: TKR surgery is more thrombogenic than THR surgery. In THR patients TG was efficiently inhibited by 30-day thromboprophylaxis, whereas, in TKR patients treated for 15-days TG was not effectively inhibited. Individual variability of the response to enoxaparin was observed in both groups revealing some form of biological resistance to enoxaparin. TG assay may represent the breakthrough step to efficient antithrombotic strategy in clinical settings with high thrombotic risk.

Effects of isoflurane anesthesia on aortic compliance and systemic hemodynamics in compliant and noncompliant aortas.

OBJECTIVES: To investigate the effect of general anesthesia on aortic compliance and other cardiovascular hemodynamics in chronically instrumented pigs with compliant and noncompliant (stiff) aortas. DESIGN: Experimental study. SETTING: University animal laboratory. PARTICIPANTS: Twelve adult Yucatan miniature pigs. INTERVENTIONS: Chronic instrumentation of a compliant (control; n = 7) and noncompliant (n = 5) group to measure pressure and flow in the ascending aorta. A Teflon prosthesis was wrapped around the aorta (noncompliant group) to limit wall compliance. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded on the 15th postoperative day, both awake and after general anesthesia. Banding the aorta caused a significant decrease in arterial compliance (-49%, p<0.001) and increases in systolic blood pressure (SBP: +38%, p = 0.001) and pulse pressure (+107%, p< 0.01). Induction of anesthesia in the control group produced a 15% increase in arterial compliance (p<0.05), resulting in a subtle decrease in SBP (-12%), diastolic blood pressure (DBP; -13%) and mean blood pressure (MBP; -12%). Induction of anesthesia in the noncompliant group also caused a significant increase in arterial compliance (17%, p<0.001), but caused significant decreases in SBP (21%, p<0.01), DBP (23%, p<0.01) and MBP (22%, p<0.01) as compared with controls. CONCLUSIONS: Induction of general anesthesia caused a similar increase in total arterial compliance and was associated with a decrease in SBP that was more pronounced in animals with noncompliant aortas. These results indicated that anesthesia caused a greater hemodynamic effect on noncompliant (stiff) aortas and may explain the extensive hemodynamic fluctuation and instability often observed in atherosclerotic, elderly patients with stiff aortas.

Spinal cord ischemia after endovascular embolization of a type II endoleak following endovascular aneurysm repair.

BACKGROUND: We report a rare case of severe spinal cord ischemia with neurological consequences in a patient who presented after endovascular treatment of a type II endoleak following endovascular aneurysm repair. METHODS AND RESULTS: An enlarging abdominal aortic aneurysm post-endovascular aneurysm repair was detected owing to a persistent type II endoleak caused by a communication between the iliolumbar and L4 lumbar artery for which the patient underwent supraselective embolization with particles and coils. Immediately after the procedure, the patient experienced an acute onset of neurological symptoms in the right lower limb while limb arterial perfusion remained unaffected. Magnetic resonance imaging-magnetic resonance angiography revealed an acute ischemic process at the L2-L4 level. Further follow-up revealed persistence of the endoleak, and the patient was referred to our institution for open surgical treatment. CONCLUSIONS: To the best of our knowledge, this is the first report of severe spinal cord ischemia after transcatheter embolization of the feeding iliolumbar branches of a type II endoleak. Care must be taken during embolization of the feeding artery of type II endoleaks, which may also supply the spinal cord, to minimize the risk of possible spinal cord ischemia.

Computational evaluation of aortic aneurysm rupture risk: what have we learned so far?

In current clinical practice, aneurysm diameter is one of the primary criteria used to decide when to treat a patient with an abdominal aortic aneurysm (AAA). It has been shown that simple association of aneurysm diameter with the probability of rupture is not sufficient, and other parameters may also play a role in causing or predisposing to AAA rupture. Peak wall stress (PWS), intraluminal thrombus (ILT), and AAA wall mechanics are the factors most implicated with rupture risk and have been studied by computational risk evaluation techniques. The objective of this review is to examine these factors that have been found to influence AAA rupture. The prediction rate of rupture among computational models depends on the level of model complexity and the predictive value of the biomechanical parameters used to assess risk, such as PWS, distribution of ILT, wall strength, and the site of rupture. There is a need for simpler geometric analogues, including geometric parameters (e.g., lumen tortuosity and neck length and angulation) that correlate well with PWS, conjugated with clinical risk factors for constructing rupture risk predictive models. Such models should be supported by novel imaging techniques to provide the required patient-specific data and validated through large, prospective clinical trials.

Chronic venous disease progression and modification of predisposing factors.

AIM: This study evaluated long-term characteristics of chronic venous disease (CVD) progression and its correlation with the modification of specific risk factors. METHODS: The contralateral limb of 73 patients (95% women; mean age, 48 +/- 12 years) undergoing varicose vein surgery was prospectively evaluated using physical and color duplex examination and classified by CEAP. After 5 years of follow-up, development of new sites of reflux among the contralateral, preoperatively asymptomatic limbs and modification of predisposing factors, including prolonged orthostatism, obesity, estrogen therapy (ET), multiparity, and elastic stockings use (ESU), were assessed. Data were analyzed with Pearson chi(2), t test, binary logistic regression, and Spearman rho. RESULTS: Forty-eight new sites of reflux (superficial system, 37; perforators, 5; deep veins, 6) were revealed in 38 limbs (52%). CEAP scores significantly deteriorated: clinical, 2.2 +/- 0.5 from 0.1 +/- 0.03 (P < .01); anatomic, 3.8 +/- 1.2 from 2.6 +/- 2.5 (P < .05); disability, 1.9 +/- 0.7 from 0 (P < .01); and severity, 7.9 +/- 2.4 from 2.7 +/- 2.2 (P < .01). Patient compliance to predisposing factor modification was low; no change was observed during follow-up (orthostatism, P = .9; obesity, P = 0.7; ET, P = .9; multiparity, P = .4; ESU, P = .3). CVD progression was significantly lower in patients who controlled orthostatism vs those who maintained orthostatism or initiated it (P < .001) and in patients who controlled preoperative obesity vs those who became obese or maintained obesity (P < .001). Non-ESU patients had a significantly higher incidence of CVD progression vs those who started ESU or continued during the study (P < .001). By binary logistic regression analysis, orthostatism (P = .002; B coefficient value [BCV] = 1.745), obesity (P = .009; BCV = 1.602), and ESU (P = .037; BCV = 0.947) were independent predictive factors for CVD progression, whereas multiparity (P = .174) and ET (P = .429) were not. CONCLUSIONS: In about half of patients with unilateral varicosities, CVD developed in the contralateral initially asymptomatic limb in 5 years. CVD progression consisted of reflux development and clinical deterioration of the affected limbs. Obesity, orthostatism, and noncompliance with ESU were independent risk factors for CVD progression, but ET and multiparity were not. Maintenance of a normal body weight, limitation of prolonged orthostatism, and systematic ESU may be recommended in patients with CVD to limit future disease progression.

Left ventricular hypertrophy induced by reduced aortic compliance.

AIM: It was the aim of this study to investigate the long- term effects of reduced aortic compliance on cardiovascular hemodynamics and cardiac remodeling. METHOD: Sixteen swine, divided into 2 groups, a control and a banding group, were instrumented for pressure and flow measurement in the ascending aorta. Teflon prosthesis was wrapped around the aortic arch in order to limit wall compliance in the banding group. Hemodynamic parameters were recorded throughout a 60-day period. After sacrifice, the mean cell surface of the left ventricle was documented. RESULTS: Banding decreased aortic compliance by 49 +/- 9, 44 +/- 16 and 42 +/- 7% on the 2nd, 30th and 60th postoperative day, respectively (p < 0.05), while systolic pressure increased by 41 +/- 11, 30 +/- 11 and 35 +/- 12% (p < 0.05), and pulse pressure by 86 +/- 27, 76 +/- 21 and 88 +/- 23%, respectively (p < 0.01). Aortic characteristic impedance increased significantly in the banding group. Diastolic pressure, cardiac output and peripheral resistance remained unaltered. The mean left ventricular cell surface area increased significantly in the banding group. CONCLUSIONS: Acute reduction in aortic compliance results in a significant increase in characteristic and input impedance, a significant decrease in systemic arterial compliance and a subsequent increase in systolic and pulse pressures leading to left ventricular hypertrophy.

Total occlusion of the common carotid artery: a modified classification and its relation to clinical status.

To investigate the hemodynamics and clinical presentation of common carotid artery occlusion (CCAO), we reviewed 6,415 patients with suspected carotid artery disease in whom a color Duplex imaging (CDI) examination was performed. According to distal vessel patency, the following CDI classification of CCAO was adopted: type I (patent both distal vessels); type II (isolated patency of external carotid artery); type III (isolated patency of internal carotid artery); and type IV (both distal vessels occluded). Thirty-five (0.5%) cases met the CDI criteria for CCAO. Twenty-nine of those (83%) had at least one patent distal vessel. Ten patients (29%) presented with stroke, 20 (57%) with transient ischemic attacks (TIAs) and five (14%) were asymptomatic. The incidence of stroke was higher in type IV (50%) vs. type II (30%) and in type II vs. type I (10%) lesions. Similarly, TIAs presented more often in type II (67%) and IV (50%) vs. in type I (40%) lesions (p = 0.002). Retrograde flow in the ophthalmic artery and concomitant severe contralateral carotid artery stenosis were more often related with type II and IV lesions (p = 0.02 and 0.04, respectively). CCAO is usually accompanied by patent distal vessel(s). The proposed CCAO classification correlates well with the patients' clinical status and may help to better clarify the outcome of this rare entity. Among the main arteries of the developed collateral circulation, only the flow direction in the ophthalmic artery may be of clinical value.

The appropriate length of great saphenous vein stripping should be based on the extent of reflux and not on the intent to avoid saphenous nerve injury.

OBJECTIVE: To investigate the effect of stripping the below knee great saphenous vein (GSV) segment on varicose vein recurrence as well as any disability induced after saphenous nerve injury (SNI) during a 5-year period. METHODS: One hundred and six limbs (86 patients, 64 female, mean age 46 years), that underwent GSV stripping, to the knee or ankle level, were prospectively followed up at 1 month and 5 years postoperatively with clinical examination and color duplex imaging (CDI), in order to evaluate SNI and the development of recurrence. The extent of GSV stripping complied with preoperative CDI in 84 limbs (79%) that were subjected to GSV stripping to the ankle and full abolishment of duplex-confirmed reflux. Furthermore, 19 limbs (18%) underwent stripping restricted to the below knee level since the distal GSV was competent. On the contrary, in three limbs (3%), the extent of stripping did not comply with preoperative CDI due to the absence of varicosities in the tibia, and stripping was restricted to the knee level, although they had reflux along the whole GSV length. RESULTS: Overall recurrence was found in 24 out of 106 operated limbs (23%) after 5 years. Recurrence was found to be 20% (17/84) in the limbs with total GSV stripping and 32% (7/22) in the limbs with restricted GSV stripping (P > .05). However, the recurrence rate in the tibial area was significantly lower in limbs subjected to GSV stripping, which was in compliance with the preoperative CDI (9/103, 9%) compared with those that had undergone GSV stripping that was not in agreement with the preoperative CDI (3/3, 100%; P < .005). Neurological examination at 1 month postoperatively, revealed SNI in 17 limbs (16%). However, at the 5-year neurological reassessment, we found that seven out of these limbs (40%) were alleviated from SNI adverse symptoms presenting only deficits in sensation. In addition, no significance was found concerning SNI between limbs subjected to total and restricted GSV stripping (16/84 vs 1/22; P > .05). CONCLUSIONS: Though SNI may occur after both restricted and total GSV stripping, this does not influence limb disability since any related symptoms seem to regress in almost half of the limbs 5 years postoperatively. Additionally, it seems that recurrence could be reduced in the tibial area if the level of GSV stripping complies with the extent of the ultrosonographically proven GSV reflux. Therefore, the extent of GSV stripping should not be guided by the intent of avoiding SNI.

Acute lower limb ischemia as the initial symptom of acute myeloid leukemia.

Although coagulatory system disorders are well recognized in patients with acute leukemia, these usually present with either hemorrhagic complications or thrombosis of small vessels. Large vessel thrombosis is a very rare clinical presentation. We present a patient with previously undiagnosed acute myeloid leukemia (M5), who was referred to our hospital with symptoms of acute ischemia of his right lower limb. Occlusion of the right external iliac artery due to a combination of leucostasis and coagulation disorders was noted and successfully treated with urgent leukapheresis, immediate chemotherapy and surgical thromboembolectomy.

A decoupled fluid structure approach for estimating wall stress in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a localized dilatation of the aortic wall. The lack of an accurate AAA rupture risk index remains an important problem in the clinical management of the disease. To accurately estimate AAA rupture risk, detailed information on patient-specific wall stress distribution and aortic wall tissue yield stress is required. A complete fluid structure interaction (FSI) study is currently impractical and thus of limited clinical value. On the other hand, isolated static structural stress analysis based on a uniform wall loading is a widely used approach for AAA rupture risk estimation that, however, neglects the flow-induced wall stress variation. The aim of this study was to assess the merit of a decoupled fluid structure analysis of AAA wall stress. Anatomically correct, patient specific AAA wall models were created by 3D reconstruction of computed tomography images. Flow simulations were carried out with inflow and outflow boundary conditions obtained from patient extracted data. Static structural stress analysis was performed applying both a uniform pressure wall loading and a flow induced non-uniform pressure distribution obtained during early systolic deceleration. For the structural analysis, a hyperelastic arterial wall model and an elastic intraluminal thrombus model were assumed. The results of this study demonstrate that although the isolated static structural stress analysis approach captures the gross features of the stress distribution it underestimates the magnitude of the peak wall stress by as much as 12.5% compared to the proposed decoupled fluid structure approach. Furthermore, the decoupled approach provides potentially useful information on the nature of the aneurysmal sac flow.

Flow dynamics in expansions characterizing abdominal aorta aneurysms.

Our purpose was to identify and quantify hemodynamic factors contributing to the generation, proliferation, and rupturing of abdominal aorta aneurysms (AAAs) using a computational investigation of steady laminar and turbulent flow in AAA models. Steady laminar and turbulent flows were computed using the incompressible Navier-Stokes equations. Flow fields in symmetric shapes of different extents and degrees of expansion are presented first. Two representative cases of asymmetric AAAs are considered next: an aneurysm with an elliptic cross section and an aneurysm with preferential expansion in one direction. For symmetric aneurysms, parametric studies are presented. For asymmetric aneurysms, flow fields are computed only for high flow rates representative of systolic flow. For all cases, a recirculating flow region was found in the expanded part of the AAA. Recirculation is accompanied by a minor increase in pressure but a significant increase in wall shear stress. For cases where turbulent flow was considered, it was found that the recirculation zone diminishes but the computed wall shear stress reaches levels higher than laminar flow. The levels of wall shear stress reached in turbulent flow may cause lesions of the aneurysmal wall. The minor variation of pressure within the aneurysms with smooth expansions indicates that the structural properties of the arterial wall tissue may play a significant role for the generation and subsequent proliferation of the aneurysm. However, the high values of the wall shear stress in AAAs appear to be an important hemodynamic factor that may contribute to wall degeneration and eventual rupturing. The recirculating flow in AAAs may explain the generation of intraluminal thrombi. Furthermore, the asymmetry and complexity of the flow in asymmetric AAAs may explain the frequently observed asymmetric thrombi distribution.

Peripheral arterial embolism due to a left ventricular diverticulum in a young adult.

A 32-year-old man was admitted to the emergency department of our hospital after experiencing a peripheral arterial embolism. Investigation of the possible embolic sources in an otherwise asymptomatic patient revealed the existence of a left ventricular diverticulum. The left ventricular diverticulum is a rare congenital anomaly, either isolated or as a part of a syndrome including other congenital malformations. The treatment of choice, especially in symptomatic patients, is surgical resection, while in asymptomatic patients anticoagulation therapy is indicated.

Potential benefits from heating the high-dose rtPA boluses used in catheter-directed thrombolysis for acute/subacute lower limb ischemia.

PURPOSE: To explore the potential benefits from heating recombinant tissue plasminogen activator (rtPA) before catheter-directed thrombolysis in patients with lower-limb ischemia of <30 days' duration. METHODS: Over a 2-year period, 34 patients (26 men; mean age 63.5 years, range 39-80) with 10 iliac and 24 infrainguinal arterial occlusions (5 embolic and 29 thrombotic) were treated with two 5-mg boluses of rtPA injected into the proximal clot, followed by 2 additional 5-mg boluses of rtPA. In the first 18 patients (group A), room temperature rtPA was administered, whereas in the last 16 patients (group B), the rtPA boluses were heated to 38 degrees C for 30 minutes before injection. Residual thrombus was treated with a continuous infusion of 2.5 mg/h of rtPA for 4 hours then at a reduced dose (1 mg/h). RESULTS: Successful thrombolysis was achieved in 28 (82%) arteries. Unmasked lesions were treated with balloon angioplasty/stenting in 17 cases and with surgery in 4. One fatal retroperitoneal hematoma occurred in group A. Heating the rtPA did not significantly alter the outcome of thrombolysis. However, a statistically significant reduction in the total rtPA dose was observed in group B (24.28 mg versus 27.9 mg in group A, p=0.05), as well as quicker lysis (2 hours, 42 minutes versus 6 hours, 12 minutes in group A, p=0.001). There was no statistical difference in the amputation-free survival at 30 days between the groups. CONCLUSIONS: In patients with acute or subacute lower limb ischemia treated with catheter-directed thrombolysis, heating the rtPA results in faster lysis with a considerable reduction in the total dose of the lytic agent.

Suspected acute deep vein thrombosis of the lower limb in outpatients: considerations for optimal diagnostic approach.

The objective of this study was to review our diagnostic approach using color duplex scanning (CDS) in the management of symptomatic outpatients with suspected lower limb deep venous thrombosis (DVT). CDS was carried out in 315 consecutive outpatients with unilateral symptoms consistent with DVT. Both limbs were assessed in 205 patients. Other pathology was routinely sought when the symptomatic limb was free of thrombosis. Acute DVT was present in 25% (76/315) of the symptomatic limbs, and in only 8% it was confined to calf veins. Other pathology was detected in 90 limbs (28%). Swelling with or without pain was associated with DVT in 44% and 10%, respectively. The time elapsed between the onset of symptoms and CDS was 3 days (range 1-6 days). DVT in the contralateral asymptomatic limb was present in 5 (9%) of the 56 patients with DVT in the symptomatic limb. In the absence of DVT in the symptomatic limb, the contralateral asymptomatic limb was free of thrombosis. Clinical diagnosis of DVT in outpatients was unreliable. CDS revealed that only one-fourth of the symptomatic limbs had DVT, and other pathology mimicking DVT was present in 28%. CDS is a useful tool that offers a prompt, efficient diagnosis. Investigation of the contralateral asymptomatic limb seems to be necessary only when DVT is found in the symptomatic limb.

Use of the Trellis Peripheral Infusion System for enhancement of rt-PA thrombolysis in acute lower limb ischemia.

The Trellis Peripheral Infusion System is an over-the-wire 0.035" guidewire compatible device, designed to isolate a region of the peripheral vasculature to allow for lytic drug infusion and dispersion. We used it successfully through a percutaneous approach in two cases of acute thrombosis of a native lower limb artery. The total amount of rt-PA used was 12 and 9 mg, respectively and was delivered through bolus injections obviating the need for a supplementary continuous infusion of the agent. The time for dissolution of thrombus was 45 and 35 minutes, respectively. No complications were observed.

Vibrational angioplasty in the treatment of chronic infrapopliteal arterial occlusions: preliminary experience.

PURPOSE: To evaluate the safety and efficacy of vibrational angioplasty in chronic infrapopliteal arterial occlusions. METHODS: Twelve patients (9 men, aged 54 to 90 years) with 13 below-knee arterial chronic total occlusions were treated percutaneously using vibrational angioplasty. The occlusions were located in the anterior tibial artery (n=5), the tibioperoneal trunk (n=4), the peroneal artery (n=1), the posterior tibial artery (n=1), and in both the tibioperoneal trunk and peroneal artery (n=2). The length of the lesions ranged from 5 to 14 cm. RESULTS: Recanalization was successful in 12 (92.3%) lesions. In 1 case, the wire perforated the arterial wall; the procedure was abandoned without clinical sequelae. The time to cross the occlusions with the wire ranged from 6 to 19 minutes. No other complications were observed. Clinical follow-up ranged to 18 months. Ten patients with ulceration or gangrene demonstrated good wound healing, and pain was alleviated in all successfully treated patients. CONCLUSIONS: Vibrational angioplasty appears feasible as a means of safely recanalizing chronic total occlusions of the infrapopliteal arteries. Further experience should be acquired to assess its short- and long-term effects on this vascular territory.