Patrick DePippo

Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population

PURPOSE Although much attention has been focused on lower extremity deep venous thrombosis (LEDVT), there is a relative paucity of data regarding the impact of upper extremity deep venous thrombosis (UEDVT) on morbidity and mortality rates. To increase our knowledge with the latter disease, we have reviewed our experience at our institution with 170 patients who had brachial, axillary, and subclavian vein thromboses. METHODS Over the past 5 years, UEDVT was diagnosed in 170 patients by duplex scanning. The indications for duplex examination were either upper extremity swelling (95%) or as part of the workup for pulmonary embolism (5%). There were 103 women (61%) and 67 men (39%), with ages ranging from 9 to 101 years (mean, 68 +/- 17 years). The diagnosis was made in 152 patients (89%) while they were admitted to the hospital and in 18 patients (11%) in the outpatient clinic. Risk factors included presence of a central venous catheter or pacemaker in 110 patients (65%), malignancy in 63 patients (37%), concomitant LEDVT in 19 patients (11%), and history of LEDVT in 18 patients (11%). Fifty-six patients (33%) had multiple risk factors, whereas 36 patients (21%) had no obvious risk factor. RESULTS The 1-month and 3-month mortality rates for the entire study group were 16% and 34%, respectively. Patients who had concomitant LEDVT, were 75 years of age or older, and were not treated with anticoagulation medication had a significantly higher 1-month mortality rate. Patients whose diagnoses were made in the outpatient setting were statistically younger and had a lower 3-month mortality rate when compared with the patients whose diagnoses were made as inpatients. Pulmonary embolism was documented by ventilation/perfusion scan in 12 patients (7%). Although no patient in the group in which UEDVT was diagnosed on an outpatient basis was documented to have a pulmonary embolism and 12 patients (8%) in the inpatient group had pulmonary emboli, this difference was not statistically significant. Anticoagulation medication did not totally prevent pulmonary embolism in this review. All patients were followed-up for between 0 to 49 months (mean, 13 +/- 1 months). No swelling of the affected arm was observed in 145 patients (94%); four patients complained of mild intermittent swelling (2%), and seven patients reported significant swelling (4%). CONCLUSIONS Contrary to previous reports, these data suggest that UEDVT is associated with a low incidence of postthrombotic upper extremity swelling, but a significant incidence of pulmonary embolism and rate of mortality. This review suggests that UEDVT is at least as serious a disease entity as LEDVT and should be managed as aggressively as LEDVT.

Upper extremity versus lower extremity deep venous thrombosis

BACKGROUND In contrast to lower extremity deep venous thrombosis (LEDVT), it is widely believed that upper extremity deep venous thrombosis (UEDVT) is associated with minimal morbidity or mortality. METHODS In an attempt to compare the two disease processes with respect to pulmonary embolism and mortality, we have reviewed records and performed interviews of 430 patients with LEDVT and 52 patients with UEDVT presenting to our institution between January 1994 and June 1995. RESULTS Pulmonary embolism was documented by ventilation/perfusion lung scan in 9 of 52 patients (17%) with UEDVT and 33 of 430 patients (8%) with LEDVT (P <0.05). Twenty-five of the UEDVT patients (48%) died within 6 months of the diagnosis of UEDVT. Conversely, 14 patients (13%) in the LEDVT group died within 6 months of the diagnosis of LEDVT (P <0.0002). CONCLUSION Contrary to previous reports, this study suggests that UEDVT is associated with a higher morbidity and mortality as compared with LEDVT. These data show that UEDVT has been an underrecognized predictor of morbidity and mortality.

Saphenous vein thrombophlebitis (SVT): A deceptively benign disease

PURPOSE The association between deep vein thrombosis (DVT) and the hypercoagulable state is a well-established entity. However, the association between saphenous vein thrombophlebitis and coagulation abnormalities has not been investigated. Although thrombosis of varicose veins typically runs a benign course, phlebitis of the saphenous system may propagate to the deep system or saphenofemoral junction that requires more aggressive therapy. Given the potential similarity in clinical outcome between saphenous vein thrombophlebitis (SVT) and DVT, we have investigated the coagulation profile of patients presenting with isolated SVT. METHODS Seventeen consecutive patients who presented to our vascular laboratory with isolated SVT had a coagulation profile performed that included antithrombin III (AT III), protein C (PC), protein S (PS) antigen and activity levels, activated protein C (APC) resistance, factor V DNA mutation, and coagulation factors II and X. All patients had duplex scans performed on both the superficial and deep venous systems. Patients with SVT only were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as outpatients, whereas those patients found to have DVT or a clot at the saphenofemoral junction were fully anticoagulated with heparin and coumadin therapy. All 17 patients had at least one repeat coagulation profile performed up to 5 months after their SVT occurrence to ensure that the results of hypercoagulability were not transient. RESULTS Ten (59%) of the 17 patients with SVT had abnormal coagulation profiles on initial presentation. All 10 patients who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four patients who had abnormal results converted to normal values. Seven patients with normal coagulation profiles on initial presentation had repeat tests and all remained normal. CONCLUSION The incidence of the hypercoagulable state in patients with SVT is high. Thirty-five percent of patients with isolated SVT had consistently abnormal coagulation profiles. Patients with SVT may be prone to the development of DVT or saphenofemoral junction thrombophlebitis and should be closely followed after the initial diagnosis of hypercoagulability.

The effect of tumor necrosis factor binding protein and interleukin-1 receptor antagonist on the development of abdominal aortic aneurysms in a rat model ☆ ☆☆ ★ ★★

PURPOSE Tumor necrosis factor (TNF), interleukin 1 (IL-1), and matrix metalloproteases have been noted to be elevated in human abdominal aortic aneurysms (AAAs) as compared with normal and occlusive aortic disease. Because TNF and IL-1 have been shown to cause release of proteases that weaken the aortic matrix, it has been suggested that these cytokines may play a central role in the aortic dilatation process. To substantiate this hypothesis, we investigated the effects of TNF and IL-1 antagonists, tumor necrosis factor binding protein (TNF-BP) and interleukin-1 receptor antagonist (IL-1RA), on the development of AAAs in a well-described rat model. METHODS Isolated segments of infrarenal aorta of 16 rats were perfused with porcine elastase. In the treated group, eight rats were given intravenous TNF-BP prior to elastase perfusion, at 48 hours and at 96 hours. In the control group, eight rats were given only intravenous vehicle at the same time intervals. Isolated segments of infrarenal aorta of an additional 16 rats were perfused with porcine elastase in a similar fashion. In the treated group, eight rats were given intraperitoneal IL-1RA prior to celiotomy and every eight hours. In the control group, eight rats were given only intraperitoneal vehicle at the same time intervals. On the sixth postoperative day, all rats underwent celiotomy and measurement of the infrarenal aortic diameter with a micrometer while the animal was alive. Aortic specimens were collected on day six for hematoxylin and eosin staining, trichrome staining, and gel polyacrylamide gel electrophoresis (PAGE) zymography. RESULTS TNF-BP was completely able to block post elastase dilation, whereas IL-1Ra seemed to have no effect. Hematoxylin and eosin staining and trichrome staining revealed that animals treated with TNF-BP had less of an inflammatory response and preservation of the elastin and smooth muscles in the media of the aortic wall as compared with animals treated with IL-1RA or vehicle. Zymography was not able to detect significant protease activity in the aortic wall of any of the rats at six days. CONCLUSION TNF-BP, but not IL-1RA, may inhibit the development of AAAs in this model.

The value and limitations of magnetic resonance angiography of the circle of Willis in patients undergoing carotid endarterectomy.

Magnetic resonance angiography is a useful technique to determine the patency of the circle of Willis when compared with conventional four-vessel angiography. The purpose of this study is to determine whether the integrity of the circle of Willis, assessed by magnetic resonance angiography, provides adequate collateral cerebral circulation during carotid endarterectomy and correlates with internal carotid artery back pressure. Over a recent 20-month period, 35 patients were studied preoperatively with magnetic resonance angiography of the carotid bifurcations of the circle of Willis and the vertebrobasilar system. All patients underwent standard carotid endarterectomy with intraoperative measurement of internal carotid artery back pressure. Patients with an internal carotid artery back pressure < 50 mmHg had an intraluminal shunt placed. Deficiencies in branches of the circle of Willis, the carotid bifurcation and the vertebrobasilar system determined by magnetic resonance angiography were correlated with internal carotid artery back pressure using Fishers exact test. Only one patient had a completely intact circle of Willis. Eleven of 16 patients (69%) who had an internal carotid artery back pressure < 50 mmHg had an occluded A1 segment of the anterior cerebral artery combined with an occluded posterior communicating artery, whereas only five of 19 patients (26%) who had an internal carotid artery back pressure > 50 mmHg had similar findings (P < 0.03). Severity of occlusive disease of the contralateral internal carotid artery and the basilar artery did not independently predict internal carotid artery back pressure. An occluded anterior branch of the circle of Willis in combination with an occluded posterior branch of the circle of Willis is associated with an internal carotid artery back pressure < 50 mmHg. Although magnetic resonance angiography of the circle of Willis may provide valuable anatomic information, it is not sufficiently accurate to predict the need for carotid shunting and therefore its use cannot be justified on a routine basis.

Does repeat duplex ultrasound for lower extremity deep vein thrombosis influence patient management

The clinical significance of lower extremity deep vein thrombus (DVT) propagation in the setting of anticoagulation therapy remains unclear. The purpose of this study is to compare results of thrombus outcome found with repeat duplex ultrasonography to the incidence of pulmonary embolism and mortality. During a recent 18-month period, 457 patients were diagnosed with lower extremity DVT with duplex ultrasonography and their data were retrospectively analyzed. Repeat examinations were available for review in 118 patients (51 men, 67 women). Results of repeat duplex exams were divided into 4 groups: resolved, improved, unchanged, or extended proximally. All patients received heparin and warfarin therapy. Ventilation-perfusion (V./Q.) scans were obtained only for signs and symptoms of pulmonary embolism (n=30). Mortality, the prevalence of high-probability V./Q. scans, frequency of intracaval-filter insertion, gender, mean age, mean prothrombin time (PT), mean partial thromboplastin time (PTT), mean number of repeat ultrasounds per patient, and mean time over which the repeat ultrasounds took place were compared among the 4 groups. Patients who had proximal extension of DVT (19%) on repeat duplex ultrasound had an increased prevalence of pulmonary embolism (p<0.05). Also, patients whose DVT resolved were younger (p<0.05). There was no difference among the 4 groups in mortality, placement of Greenfield filters, mean PT, mean PTT, mean number of ultrasound exams per patient, or mean follow-up time over which the exams took place. Proximal extension of DVT documented by repeat duplex ultrasound is a significant risk factor for pulmonary embolism. Repeat duplex ultrasound can identify a group of patients who may benefit from insertion of an intracaval filter device.