Novel Biomarkers Associated with Deep Venous Thrombosis: A Comprehensive Review

Primary and recurrent venous thromboembolic disease (VTE, deep venous thrombosis and pulmonary embolism) remain a significant source of morbidity and mortality in the hospitalized patient. Non-specific subjective complaints and lack of specific objective findings related to acute deep venous thrombosis (DVT) and pulmonary embolism (PE) complicate the diagnosis. There remains no single serum marker available to exclusively confirm the diagnosis of VTE. While D-dimer is highly sensitive and useful for diagnostic exclusion, it lacks the specificity necessary for diagnostic confirmation resulting in the need for a variety of additional studies (i.e.: duplex ultrasound, venography, V/Q scanning, helical thoracic and pelvic CT scans and pulmoary angiography). There is evolving research supporting the utility of various plasma markers as novel “biomarkers” for VTE including selectins, microparticles, interleukin-10 and other cytokines. This review attempts to examine recent literature assessing the utility of P-selectin, microparticles, D-dimer, E-selectin, thrombin, interleukins and fibrin monomers in the diagnosis and guidance of therapy for VTE

Clinical Application of Sonographic Elasticity Imaging for Aging of Deep Venous Thrombosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135197/1/jum2003225443.pd

“Bull's-eye” sign on gadolinium-enhanced magnetic resonance venography determines thrombus presence and age: A preliminary study

AbstractPurpose: Venous thrombosis is associated with a significant inflammatory response, which can be visualized by gadolinium magnetic resonance venography (MRV). Gadolinium extravasates into tissue during inflammation, producing perithrombus enhancement on magnetic resonance scanning. This study determines (1) whether gadolinium enhancement occurs during deep venous thrombosis (DVT); and (2) whether this enhancement changes with time and can therefore establish the age of thrombus.Methods: Patients with a diagnosis of iliofemoral DVT by duplex ultrasound who were referred for MRV to document central thrombus extent were studied. T1 weighted images were obtained before and after gadolinium injection (0.1 mmol/kg); repeat scans were obtained up to 3 months thereafter. At the level of maximum thrombus, measurements of signal intensity were made at the periphery (rim), and the center of the thrombosed vein, as well as the contralateral normal vein, on images after gadolinium enhancement. Rim-center vein signal intensity ratios were then calculated and followed.Results: A total of 39 scans were obtained in 14 patients (eight men, six women). The thrombosed veins were enlarged, with a peripheral rim of enhancement (“bull's-eye” sign). The rim-center ratio for thrombosed veins (2.16 ± 0.18) was different from that of normal veins (0.66 ± 0.10; n = 39; p < 0.001). For all acute studies (≤14 days) the rim-center ratio was 2.38 ± 0.17 (n = 31), whereas for all chronic studies (>14 days) the rim-center ratio was 1.29 ± 0.44 (n = 8; p = 0.001). Among patients who underwent both early and late studies, the rim-center ratio dropped significantly, from 2.33 ± 0.20 acutely to 1.29 ± 0.44 in chronic studies (n = 8; p = 0.03). One patient with active malignancy had a paradoxic increase in rim-center ratio over time and a clinical recurrence of symptoms, suggesting active thrombosis.Conclusions: We conclude that (1) a pattern of peripheral gadolinium enhancement (bull's-eye sign) is seen around acutely thrombosed veins on gadolinium-enhanced MRV, facilitating DVT diagnosis; and (2) the ratio of signal intensity at the rim versus the center of the thrombosed vein may be a good discriminator of acute compared with chronic DVT, which may help direct therapy. (J Vasc Surg 1997;26:809-16.

Increased prostacyclin and adverse hemodynamic responses to protamine sulfate in an experimental canine model

Prostanoid activity was correlated with the hemodynamic effects of protamine sulfate reversal of heparin in 24 dogs undergoing three different pretreatment regimens: Group I (n = 8) received saline, Group II (n = 8) received the thromboxane synthetase inhibitor U63,557A (30 mg/kg), and Group III (n = 8) received indomethacin (10 mg/kg). Pretreatment substances were administered as 5-min intravenous infusions 20 min before anticoagulation with intravenous heparin (150 IU/kg). Protamine sulfate (1.5 mg/kg) was subsequently given as a 10-sec intravenous infusion 30 min after heparin had been administered. Hemodynamic data, as well as prostacyclin (PGI2) and thromboxane (TxA2) activity in aortic, venous, and pulmonary artery blood samples, were assessed over a 30-min time period following protamine administration. Group III indomethacin pretreatment provided the most protection from declines in blood pressure, heart rate, cardiac output, venous oxygen saturation, oxygen consumption, and elevations in pulmonary pressures and was accompanied with actual declines in PGI2. Group II U63,557A pretreatment was associated with the most severe hemodynamic changes and the greatest increase in PGI2 (+576%). Elevated PGI2 correlated with hypotension at 1 and 3 min (P 2 changes did not correlate with hemodynamic changes. Protamine's adverse hemodynamic responses were attenuated with cyclooxygenase blockade by indomethacin, but were worsened with selective TxA2 blockade with U63,557A. Excess arachadonic acid precursors in the latter setting may increase PGI2 production. This study, for the first time, raises the possibility that PGI2 contributes to the adverse effects accompanying protamine reversal of heparin anticoagulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29365/1/0000434.pd

Time-related anticoagulation after regional and systemic administration of heparin in patients undergoing aortoiliac surgery

Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood. The objective of this investigation was to assess the effectiveness of three methods of heparin administration. Heparin sulfate (75 IU/kg) administered to patients undergoing aortoiliac surgery was randomised to one of three methods: Group I (n = 9) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping; Group II (n = 9) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping; and Group III (n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping. Blood samples were analysed for anticoagulant activity from both the upper and lower extremities at 5, 15, 30, 60, and 120 minutes after heparin administration. Anticoagulation, as measured by aPTT, antifactor Xa levels, and ACT, was achieved in all three groups by 5 minutes, but initially with lower heparin activity (measured as antifactor Xa) in the upper extremity (Group II) and lower extremity (Group III), respectively. These differences were also evident in ACT and aPTT determinations. Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation (anti-factor Xa ~ 1 U/ml) in both upper and lower extremities after 5 minutes. With regional administration, rapid heparin redistribution occurs, but it takes longer to achieve the same level of anticoagulation distant from the site of administration. Nevertheless, from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31338/1/0000248.pd

Animal Models for the Study of Lower Extremity Chronic Venous Disease: Lessons Learned and Future Needs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42432/1/10016-12-5-487_12n5p487.pd

Carotid Embolectomy in the Treatment of a Paradoxical Embolus

Development of a paradoxical embolus to the carotid circulation through a patent foramen ovale is uncommon but well documented. Previous surgical experience with this entity is limited. Treatment for this condition typically involves anticoagulation or the use of an inferior vena cava filter with concurrent closure of the patent foramen itself. We report successful surgical treatment of a woman with a paradoxical embolus lodged in her left carotid artery. In addition, we provide a brief review of this rare topic and treatment rationale.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41366/1/10016_2003_Article_13.pd