Orally administered unfractionated heparin with carrier agent is therapeutic for deep venous thrombosis.

BACKGROUND: Orally administered heparin (OHEP) is unreliable because of poor absorption. Sodium N-(8[2-hydroxybenzoyl]amino) caprylate (SNAC) is an amido acid that facilitates the gastrointestinal absorption of heparin. We evaluated the effectiveness of OHEP combined with SNAC (OHEP/SNAC) in the treatment of deep-vein thrombosis (DVT). METHODS AND RESULTS: An internal jugular DVT was produced in 54 male Sprague-Dawley rats. Animals were assigned to 6 different groups for 7 days of treatment: untreated control, subcutaneous heparin (SC HEP) (300 U/kg SC TID), SNAC only (300 mg/kg PO TID), OHEP only (30 mg/kg PO TID), low-molecular-weight heparin (LMWH) (enoxaparin 5 mg/kg SC QD), and OHEP/SNAC (30 mg/kg:300 mg/kg PO TID). The activated partial thromboplastin time (aPTT) and anti-factor X (anti-Xa) levels were measured. The incidence of residual DVT after 1 week of treatment was 100% (9 of 9) in the control group versus 10% (1 of 10) in the OHEP/SNAC and 10% (1 of 10) in the LMWH groups (P<0.001). There was also a significant reduction in clot weights between these groups. Compared with controls, there were no significant differences in the residual DVT in the SNAC-only (6 of 6), OHEP-only (9 of 9), or SC HEP (8 of 10) groups. Combination OHEP/SNAC was as effective in the resolution of the clot and reducing clot weight as LMWH. The aPTT levels in the OHEP/SNAC group peaked at 30 minutes and were significantly higher than in all other groups (P<0.01). Anti-Xa levels were elevated at 15 minutes after dosing in the OHEP/SNAC group and remained significantly elevated at 4 hours (P<0.001). CONCLUSIONS: OHEP combined with a novel carrier agent (SNAC) successfully treated DVT in this rat model.

Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis.

OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.

Complications associated with percutaneous closure devices.

BACKGROUND: In an effort to reduce time to hemostasis after angiography, several closure devices have been marketed. We report some of their complications. METHODS: A retrospective review was conducted. RESULTS: Over an 8-month study period, 2,181 diagnostic and interventional procedures were performed. Closure devices were used in 408 (19%) of these patients. The Angio-Seal closure device is composed of a collagen sponge and an absorbable polymer anchor that compresses the hole in the arteriotomy. The ProstarXL sealing device consists of a rotating barrel that deploys 4 needles through the arteriotomy, and then individual knots are extracorporeally tied. The Duett device consists of a balloon occluding catheter and injectable collagen and thrombin. Ten of the patients developed a complication from the closure device (2.5%). Four of these were subcutaneous abscesses. Two of these patients had expanding pseudaneurysms, 2 had lower extremity ischemia, and 1 patient had an acute bleed. These complications were all managed surgically. Another patient developed a retroperitoneal bleed that was managed nonoperatively. CONCLUSIONS: As the use of these devices increase, these complications will become more common.

Oral low-molecular weight heparin and delivery agent prevents jugular venous thrombosis in the rat.

PURPOSE: Sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD) is a novel carrier that allows the gastrointestinal absorption of low-molecular weight heparin (LMWH). The purpose of this experiment was to evaluate oral LMWH with SNAD for the prevention of deep venous thrombosis. METHODS: Sixty Sprague-Dawley rats were equally assigned to five experimental groups: group 1 (control), oral saline solution; group 2, oral LMWH (15 mg/kg); group 3, oral SNAD (300 mg/kg); group 4, subcutaneous LMWH (5 mg/kg); and group 5, oral LMWH (15 mg/kg) and SNAD (300 mg/kg). After treatment, the jugular vein was isolated, occluded, and bathed in an ethanol and formalin solution for 2 minutes. Two hours later, the vessel was examined for patency, presence of thrombus, and thrombus weight. Serum measurement of anti-factor Xa activity was performed in a separate set of 30 rats, which were placed into the following four groups: group A, LMWH (5 mg/kg); group B, oral LMWH (15 mg/kg) and SNAD (300 mg/kg); group C, oral LMWH (15 mg/kg); and group D, SNAD (300 mg/kg). RESULTS: The animals that underwent oral LMWH/SNAD therapy had a statistically significant decrease in visible thrombi. The thrombus weight of the oral LMWH/SNAD group was significantly less than the weights of all other groups, except the subcutaneous LMWH group. Anti-factor Xa levels were significantly elevated in the LMWH/SNAD group. There was no statistically significant difference between the data for the oral LMWH/SNAD group and the subcutaneous LMWH group. CONCLUSION: The combination of oral LMWH and SNAD prevented deep venous thrombosis. The oral LMWH and SNAD therapy effected an increase in levels of anti-factor Xa.

Carotid endarterectomy in patients with significant renal dysfunction.

PURPOSE: Recent reports suggest that carotid endarterectomy (CEA) should not be performed in patients with end-stage renal disease (ESRD) because of an unacceptable rate of perioperative stroke and other morbidity. Because these conclusions were based on a small number of patients, we reviewed the perioperative and long-term outcome of patients with ESRD and chronic renal insufficiency (CRI) who underwent CEA at our institution. METHODS: The 1081 patients who had a CEA between 1990 and 1997 were cross-referenced with those patients in whom renal insufficiency had been diagnosed. These charts were reviewed for patient demographics and perioperative and long-term outcome. Patients undergoing CEA during a 1-year period (1993) served as controls. RESULTS: Fifty-one CEAs were performed in 44 patients with CRI (32 in 27 patients) and ESRD (19 in 17 patients). In the CRI+ESRD group, 66.7% were symptomatic, and 70.7% of the control group were symptomatic. Six operations (11.8%) in the CRI+ESRD group were redo endarterectomies. There were no perioperative strokes in the CRI+ESRD group, but one patient died 29 days postoperatively because of a myocardial infarction, for a combined stroke-mortality rate of 2.0%. The control group had a 2.6% combined stroke-mortality rate. Long-term survival analysis revealed a 4-year survival rate of 12% for patients with ESRD and 54% for patients with CRI, compared with 72% for controls (P <.05). CONCLUSION: CEA can be performed safely in patients with ESRD or CRI, with perioperative stroke and death rates equivalent to that of patients without renal dysfunction. However, the benefit of long-term stroke prevention in the asymptomatic patient with ESRD is in question because of the high 4-year mortality rate of this patient population.

Orally administered heparin for preventing deep venous thrombosis.

BACKGROUND: Sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) is an acetylated amino acid molecule that facilitates the gastrointestinal absorption of heparin. This study was undertaken to evaluate the efficacy of orally administered combination SNAC:heparin in preventing deep venous thrombosis in a standard rat model. METHODS: Forty-four adult male Sprague-Dawley rats were randomly divided into five groups: group I control, group II SNAC, group III oral heparin, group IV combination SNAC:heparin, and group V intravenous heparin. Thirty minutes after drug administration, the internal jugular vein was bathed in a sclerosant mixture for 2 minutes and reexplored at 120 minutes. Activated partial thromboplastin times (aPTT) were measured in 30 rats equally divided into three groups: group I SNAC, group II oral heparin, and group III combination SNAC:heparin. Forty-five minutes posttreatment, blood was obtained for aPTT levels. RESULTS: The incidence of deep venous thrombosis in the control group was 89% (8 of 9) versus 25% (2 of 8) in the combination SNAC:heparin group (p < 0.01). There was also a significant reduction in clot weight among groups. Combination SNAC:heparin significantly increased aPTT levels compared with SNAC or oral heparin alone. CONCLUSION: In a rat model of venous thrombosis, combination of orally administered heparin:SNAC elevated aPTT levels and significantly reduced the formation of deep venous thrombosis.

Abdominal and thoracoabdominal aortic aneurysm.

Most abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms (TAAA) are asymptomatic and are found on physical exam or incidentally during radiological studies for other indications. These aneurysms are repaired primarily because their risk of rupture increases geometrically as the size exceeds 5 cm. The potential morbidity of intraoperative visceral and spinal ischemia involved with TAAA repair may be reduced with various adjunctive maneuvers.

Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia.

No serum marker has consistently proved helpful in diagnosing early acute mesenteric ischemia. D(-)-lactate is a product of bacterial metabolism and was found to be elevated in peripheral blood in a rat model of intestinal ischemia. We conducted a prospective study to evaluate preoperative D(-)-lactate levels in 31 patients undergoing laparotomy for acute abdominal emergencies, including suspected acute mesenteric ischemia. The serum was deproteinated and D(-)-lactate concentration was determined by a spectrophotometric assay. A control group was composed of patients with a benign abdominal examination who were operated on for central venous line placement. We found significant elevations in D(-)-lactate levels in patients with mesenteric ischemia compared with controls (P < 0.00005), as well as in patients with other forms of abdominal catastrophes (P < 0.00005) and with bowel obstruction (P < 0.0005). Sensitivity and specificity were 90% and 87%, respectively. The negative predictive value was 96%, and the positive predictive value was 70%. We have found that D(-)-lactate serum levels can aid in diagnosing acute mesenteric ischemia.

Blunt vascular injury associated with closed mid-shaft femur fracture: a plea for concern.

During a period of six years, 765 consecutive patients were treated by the trauma service at Allegheny General Hospital for closed mid-shaft femur fractures that were a component of their injury complex. Thirty-one patients underwent angiography of the involved extremity for indications including loss of pulses in eleven and large hematomas or deformities of the thigh in the remainder. Ten patients (1.3%) were found to have acute vascular injuries. In nine patients there was an intimal flap of the superficial femoral artery (SFA), and in one, a pseudoaneurysm. Two patients had injuries of the femoral nerve. Three patients had no other associated major injuries (Injury Severity Score range, 10-19). Twelve months after the initial injury, one patient developed an arteriovenous fistula of the SFA. Detailed, repeated physical examinations, early utilization of angiography, and intensive follow-up by the trauma surgeon or orthopedic surgeon of patients with closed mid-shaft femur fractures should lead to early recognition of this potentially serious association.