Michael J. Rohrer

Extended indications for placement of an inferior vena cava filter

To study the morbidity and mortality rates after placement of an inferior vena cava filter and to define the appropriate indications for interruption of the inferior vena cava, the records of all patients who underwent insertion of a Greenfield filter during the decade January 1978 to December 1987 were reviewed. Patients were designated as having either a traditional or extended indication for placement of an inferior vena cava filter. Two hundred sixty inferior vena cava filters were placed in 264 attempts, with no deaths related to insertion of the filter. An extended indication was the primary reason for placement of the Greenfield filter in 66 (25%) of the patients. In patients with extended indications there were no cases of air embolism or filter misplacement and only three wound complications (4.5%). Pulmonary embolism after insertion of the inferior vena cava filter occurred in three patients (4.5%), with one fatality (1.5%). Inferior vena cava occlusion was documented in three cases (4.5%), and manifestations of the postphlebitic syndrome in early follow-up were present in two patients (3.0%). As the procedures to prevent fatal pulmonary embolism have become safer, more efficacious, and less morbid, the number of patients in whom the potential benefits of insertion of an inferior vena cava filter outweigh the risks has become larger. Our results support the liberalized use of Greenfield filters in those patients who do not necessarily have one of the traditional indications for placement of an inferior vena cava filter but are at a high risk of having a fatal pulmonary embolus.

Ultrasound-guided compression of iatrogenic femoral pseudoaneurysm failure, recurrence, and long-term results

PURPOSE Iatrogenic femoral pseudoaneurysms (IFP) have traditionally been treated surgically. Recently, this common problem has been successfully treated without operation by use of ultrasound-guided compression (UGC) to induce thrombosis of the false aneurysm cavity, but the risk factors for failure and the long-term outcome have not been defined. METHODS All patients referred to the vascular laboratory from June 1992 to November 1994 whose femoral pseudoaneurysms were treated by UGC were included in the study. Data were collected prospectively during the last 18 months of the study. Data regarding the location and morphologic characteristics of the pseudoaneurysms and anticoagulation status were documented. Patients who had successful UGC underwent follow-up duplex scanning and ankle-brachial arterial pressure evaluations. RESULTS Fifty-seven patients with IFP were treated with UGC over a 30-month period; the last 34 were evaluated prospectively. UGC was successful at obliterating the false aneurysm cavity with the initial attempt in 47 (83%). Thrombosis of seven additional pseudoaneurysms was achieved on subsequent UGC attempts for an overall success rate of 95%. Recurrent false aneurysms were noted in two patients 2 and 10 days after initially successful UGC. Both were treated successfully with repeat UGC. Multivariate analysis of 14 variables revealed heparin anticoagulation (chi-square 9.025, p = 0.001) as the only significant risk factor for failure of UGC. There were no episodes of arterial thrombosis, embolization, or femoral nerve injury associated with UGC. Temporary occlusion of femoral artery during UGC and compression intervals of 20 minutes were well tolerated. Long-term follow-up from 30 to 400 days after UGC was available in 36 patients. There was no late recurrence or significant change in ankle-brachial pressures (p > 0.05). CONCLUSION UGC is a safe and effective treatment for most catheter-induced femoral pseudoaneurysms with a low complication rate and excellent long-term results at a cost substantially lower than operative treatment. Because the natural history of IFP is unpredictable, UGC appears to be the preferred treatment for all IFPs persisting after cessation of heparin anticoagulation.

Axillary artery compression and thrombosis in throwing athletes.

A 28-year-old major league baseball pitcher sustained an axillary artery thrombosis which was successfully treated with intraarterial urokinase. Subsequent angiography and duplex scanning with the arm elevated in the pitching position demonstrated inducible compression of the axillary artery by the humeral head as well as compression at the thoracic outlet. To determine the incidence of axillary and subclavian artery compression and to investigate the mechanism of injury, brachial artery blood pressures and duplex scans of the subclavian and axillary arteries were performed in both the neutral position and the throwing position in the 92 extremities of 19 major league baseball pitchers, 16 non-pitching major league players, and 11 nonathlete controls. A drop in blood pressure of greater than 20 mm Hg was noted in the position in 56% of extremities tested, with a loss of a detectable blood pressure in 13%. Compression of the axillary artery by the humeral head was documented in 83% of extremities, but in only 7.6% was a greater than 50% stenosis inducible. No statistical difference was found in the incidence of arterial compression between the three groups tested or between their dominant and nondominant extremities. Dissection of the axillary artery in two cadavers documented that abduction and external rotation of the arm causes compression of the axillary artery by the humeral head, which acts as a fulcrum. We conclude that the repetitive mechanical trauma of the throwing motion can cause intermittent compression and contusion of the axillary artery by the humeral head and predisposes the athlete who throws to thrombosis of the axillary artery.

Clinical management of the symptomatic but unruptured abdominal aortic aneurysm

Pain or tenderness of an abdominal aortic aneurysm is widely believed to signify acute expansion and imminent rupture. To assess the potential benefit of emergency operation for the group of patients with an acutely expanding aneurysm, the clinical course of 19 patients with a symptomatic but unruptured expanding abdominal aortic aneurysm was compared with 117 patients undergoing elective abdominal aortic aneurysm resection, and 69 patients having operation for a ruptured abdominal aortic aneurysm. Postoperative morbidity was high in the patients with an expanding abdominal aortic aneurysm, and included a 21% incidence of myocardial infarction, a 10% incidence of stroke, a 37% risk of ventilatory failure, and a 31% incidence of acute renal failure, which was not statistically different from the results in patients having ruptured abdominal aortic aneurysm resection. Patients undergoing elective abdominal aortic aneurysm resection had only an 8% risk of myocardial infarction, and only a 2% risk of stroke, ventilatory failure, or renal failure. The mortality rate for expanding abdominal aortic aneurysm resection was 26% compared to 35% for ruptured abdominal aortic aneurysm (p = 0.31). Both emergency operations had a mortality rate more than five times greater than the 5.1% after elective procedures (p = 0.008). Our findings emphasize the need for early and aggressive treatment of abdominal aortic aneurysm in the elective setting, even in the patient at high risk, and suggest that the preoperative assessment and modification of risk factors is important to prevent the cardiac, cerebrovascular, pulmonary, and renal complications seen accompanying an emergency operation of this magnitude.

Human neutrophil cathepsin G is a potent platelet activator

PURPOSE Neutrophil activation has been implicated in the pathophysiologic condition of ischemia-reperfusion injury, the formation of arterial aneurysms, the progression of myocardial ischemia, and the initiation of deep venous thrombosis. Activated neutrophils release cathepsin G, a serine protease, from their granules, which may cause platelet activation that leads to intravascular thrombosis, tissue infarction, and systemic release of the thrombogenic products of platelet granules. This study used flow cytometry to quantify the extent of cathepsin G-induced platelet activation and degranulation through changes in the expression of platelet surface glycoproteins. METHODS Increasing concentrations of human neutrophil-derived cathepsin G were incubated with washed platelets or whole blood from healthy human donors. The platelet surface expression of glycoproteins, including P-selectin, a platelet membrane glycoprotein only expressed after platelet alpha granule release, were determined by quantifying the platelet binding of a panel of fluorescently labeled monoclonal antibodies. Results were compared with the effect of a maximal dose of thrombin, the most potent known platelet activator. RESULTS In a washed platelet system, cathepsin G increased platelet surface expression of P-selectin (an activation-dependent neutrophil binding site), the glycoprotein IIb/IIIa complex (fibrinogen receptor), and glycoprotein IV (thrombospondin receptor), and decreased surface expression of glycoprotein Ib (von Willebrand factor receptor) to an extent comparable to maximal thrombin. However, these effects were not observed in a whole blood system. Further experiments revealed that preexposure to plasma completely inhibited cathepsin G-induced washed platelet activation and degranulation. Prostacyclin treatment of washed platelets markedly inhibited cathepsin G-induced platelet activation. CONCLUSIONS Cathepsin G is a very potent platelet agonist and degranulator, comparable to maximal thrombin, which alters platelet surface glycoprotein expression for enhanced neutrophil binding and effective platelet aggregation. This study helps to elucidate a possible pathway through which neutrophils may directly activate platelets, leading to intravascular thrombosis, irreversible ischemia, and tissue death in cardiovascular disease states. Patients with diseased endothelium that is deficient in prostacyclin production may be particularly prone to the detrimental effects of neutrophil-derived cathepsin G platelet activation.

Is coronary angiography necessary for vascular surgery patients who have positive results of dipyridamole thallium scans

PURPOSE Because dipyridamole thallium (DT) scanning is a useful predictor of perioperative cardiac events, a positive results of a DT scan is frequently the basis for performing more invasive cardiac evaluation and for consideration for performing coronary revascularization procedures before performing peripheral vascular surgery. The rationale for this approach has been that the treatment of anatomically significant coronary artery disease would lower the risk of performing a subsequent vascular operation. However, the benefit of performing aggressive diagnostic and therapeutic cardiac procedures in such patients remains unproved. To examine this issue, data from patients who underwent coronary angiography because of thallium redistribution were compared with data from matched control subjects who underwent peripheral vascular operations without further cardiac evaluation. METHODS The medical records of 70 consecutive patients who underwent coronary angiography because of the presence of two or more segments of redistribution on DT scan were reviewed and compared with 70 other patients matched with respect to age, gender, peripheral vascular operation, and number of segments of redistribution on DT scan who did not undergo additional cardiac evaluation. RESULTS DT scans were performed on 934 preoperative peripheral vascular surgery patients to help in the assessment of operative risk. Ischemic responses, defined as two or more segments of redistribution, were observed in 297. Of these, 70 underwent cardiac catheterization and 25 underwent coronary revascularization procedures. Adverse outcomes affected 46% of the coronary angiography group and 44% of the control group (p = NS). Patients who underwent coronary angiography and were considered for myocardial revascularization had fewer cardiac events with a subsequent vascular operation than did the control subjects. However, any possible benefit from invasive cardiac evaluation was offset by the three deaths and two myocardial infarctions (MIs) that complicated the cardiac evaluation. There was no significant difference between the angiography group and the matched control subjects with respect to perioperative nonfatal MI (13% vs 9%), fatal MI (4% vs 3%), late nonfatal MI (16% vs 19%), or late cardiac death (10% vs 13%). In long-term follow-up, MIs occurred later in patients who underwent coronary angiography than the control subjects (p = 0.049), but this difference was not associated with an improvement in the overall survival rate. CONCLUSIONS The risks of extended cardiac evaluation and treatment did not produce any improvement in either the perioperative or the long-term survival rate. For most vascular surgery patients who have a positive result of a DT scan, coronary angiography does not provide any additional useful information.

A prospective study of the incidence of deep venous thrombosis in hospitalized children

PURPOSE It is commonly believed that the incidence of deep venous thrombosis (DVT) in hospitalized children is less than in adults. However, it is possible that the disease is significantly underdiagnosed in children because the index of suspicion of pediatric practitioners is low, a substantial number of patients may have no symptoms, and DVT screening is not routinely performed. We therefore undertook a prospective study to define the incidence of DVT in hospitalized children with no symptoms. METHODS Patients included in the study were those younger than 18 years of age who were hospitalized for more than 72 hours and were identified to have two or more risk factors for the development of DVT and had at least one screening duplex scan. Risk factors for the development of DVT considered were a history of DVT or pulmonary embolism, recent operation, immobilization, trauma, stroke or acute neurologic deficit, the presence of cancer, sepsis, greater than 150% ideal body weight, a hypercoagulable state, and the presence of a femoral venous catheter. RESULTS Over the 9-month period ending December 1994, 1997 patients 17 years of age and younger were admitted to the hospital, and 59 patients including 19 girls and 40 boys were enrolled in the study. The one patient with DVT was a 17-year-old boy hospitalized after a motor vehicle accident with blunt head trauma and a neurologic deficit who underwent multiple orthopedic and neurosurgical procedures. CONCLUSIONS The development of acute DVT in children is unusual. As a result, DVT prophylaxis and screening is unnecessary in young children with only two risk factors for the development of the disease. Young age appears to be an important protective risk factor for the prevention of DVT.

The effects of aspirin and hypothermia on platelet function in vivo

Patients undergoing hypothermic cardiopulmonary bypass are often receiving aspirin therapy. Hypothermia, aspirin and cardiopulmonary bypass can each induce a platelet function defect, but it is not known if the effects of aspirin and hypothermia are additive in this regard. To address this question in humans in vivo, the forearm skin temperature of healthy volunteers was equilibrated and maintained at either normothermia (32°C) or hypothermia (28°C or 22°C) before and 16 h after the ingestion of 650 mg aspirin. A standardized template bleeding time was performed on the forearm and the shed blood emerging from the wound was assayed for platelet surface P‐selectin expression by whole blood flow cytometry (reflecting α granule secretion) and thromboxane B2 (the stable metabolite of thromboxane A2) by radioimmunoassay. Hypothermia resulted in marked prolongation of the bleeding time. Aspirin resulted in prolongation of the bleeding time under normothermic conditions, but only minimally augmented the hypothermia‐induced prolongation of the bleeding time. Platelet surface P‐selectin up‐regulation in shed blood was abolished by hypothermia. Aspirin had no effect on maximal platelet surface P‐selectin expression under normothermic or hypothermic conditions. Both hypothermia and aspirin resulted in markedly reduced shed blood thromboxane B2. Although aspirin slightly augmented the hypothermia‐induced reduction in shed blood thromboxane B2, the concentration of thromboxane generated in shed blood under hypothermic conditions in the absence of aspirin had no effect on platelet surface P‐selectin or platelet aggregation in whole blood. In conclusion, as determined by three independent parameters of the shed blood emerging from a standardized bleeding time wound (bleeding time, platelet surface P‐selectin, and thromboxane B2), aspirin did not significantly augment hypothermia‐induced platelet dysfunction in vivo.

Chronic venous insufficiency is associated with increased platelet and monocyte activation and aggregation

PURPOSE This study assessed whether the increased numbers of platelet-monocyte aggregates observed in patients with venous stasis ulceration (VSU) represent a response to dermal ulceration or if it is a condition associated with underlying chronic venous insufficiency (CVI). We also analyzed the expression of CD11b in patients with CVI to determine whether leukocyte activation, known to occur in VSU, is a precursor of or a response to ulceration. METHODS Patients with varying classes of CVI (n = 24) and healthy control subjects (n = 15), whose status was documented by means of duplex scanning, stood upright and stationary for 10 minutes. Two aliquots of blood, drawn from a distal leg vein and an antecubital fossa vein, were incubated with either buffer or one of three platelet agonists. After fixation, these samples were further incubated with fluorescent-labeled monoclonal antibodies (f-MoAb) specific for CD14 (monocytes) and CD61 (platelets). The activated leukocyte assay was performed by incubating another aliquot of the blood samples with f-MoAb specific for CD11b and CD14. All samples were evaluated by means of flow cytometry. RESULTS We observed significantly more platelet-monocyte aggregates throughout the circulation in patients with CVI than in control subjects (29% vs. 8%; P <.0002). Furthermore, patients with CVI formed significantly more of these aggregates in response to all platelet agonists than did control subjects. There were no significant differences between baseline numbers of aggregates or response to agonists in patients who had CVI with (n = 10) or without (n = 14) ulceration. Patients with CVI had more circulating platelet-neutrophil aggregates than control subjects (7.2% vs. 3.6%; P =.05). The addition of platelet agonists to the blood of patients with CVI resulted in more platelet-neutrophil aggregates than in control subjects. Monocyte CD11b expression was higher in patients with CVI than in control subjects (7.5 vs. 3.7; P <.01), with no differences noted in CD11b expression between patients with or without ulceration. Neutrophil CD11b expression was low and similar in control subjects and patients with CVI. CONCLUSION All classes of CVI are associated with significantly increased percentages of platelet-monocyte aggregates and increased percentages of platelet-neutrophil aggregates throughout the circulation. The presence of more of these aggregates and the increased propensity to form aggregates in the presence of platelet agonists in all classes of CVI suggests an underlying state of platelet activation and increased reactivity that is independent of the presence of ulceration. The increased expression of monocyte CD11b throughout the circulation in all classes of CVI suggests that although systemic monocyte activation occurs in CVI, its presence is independent of VSU as well.

Precoating expanded polytetrafluoroethylene grafts alters production of endothelial cell-derived thrombomodulators.

Although the use of extracellular matrix proteins to precoat small-caliber vascular grafts before endothelial cell seeding has been shown to improve cell attachment, proliferation, and adherence, the effect of precoating on the thrombomodulatory properties of the seeded cells is unknown. The use of vascular prostheses lined with confluent endothelial cell monolayers expressing optimal thromboresistant properties may enhance patency rates. In this study human saphenous vein endothelial cells were seeded onto expanded polytetrafluoroethylene (ePTFE) graft material, both unmodified and precoated with fibronectin, type I collagen, or fibronectin and type I collagen (fibronectin/type I collagen). After 3 days of in vitro cultivation, endothelial cell production of prostacyclin, tissue plasminogen activator, and plasminogen activator inhibitor was evaluated under basal conditions and after stimulation with arachidonate or thrombin. Production of tissue plasminogen activator by endothelial cells cultured on fibronectin-ePTFE was significantly greater compared with production by endothelial cells grown on noncoated or fibronectin/type I collagen-ePTFE under basal conditions (p values less than 0.01 and less than 0.05, respectively) and in response to thrombin (p values less than 0.002 and less than 0.003, respectively). Plasminogen activator inhibitor-1 production was not detected in any of the four experimental groups. Endothelial cells cultured on fibronectin-ePTFE also synthesized significantly more prostacyclin than endothelial cells grown on type I collagen- or fibronectin/type I collagen-ePTFE, under basal conditions (p values less than 0.02 and less than 0.01, respectively) and in response to arachidonate (p values less than 0.03 and less than 0.002, respectively) and thrombin (p values less than 0.003 and less than 0.002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)