Donna Jo Mayo

Pulse-Spray Treatment of Subclavian and Jugular Venous Thrombi with Recombinant Tissue Plasminogen Activator☆

PURPOSE To evaluate the efficacy of recombinant tissue plasminogen activator (rtPA) injected by pulse-spray in lysing subclavian and jugular venous thrombi. MATERIALS AND METHODS Twelve patients with symptomatic, venogram-confirmed, occlusive thrombi of the subclavian-axillary or jugular veins were treated with one or two daily 15-minute injections of rtPA delivered directly into the clots with pulse-spray catheters. Twenty-four hours after each treatment, repeated venograms were obtained to assess venous patency. Successful thrombolysis was defined as antegrade flow through the previously occluded segments with minimal collateral venous flow. Continued patency was assessed with repeated venograms obtained after 1 and 2 months of oral anticoagulation. RESULTS The 15-minute rtPA injections successfully lysed thrombi in eight of the 12 patients. Hypofibrinogenemia developed in only one patient. The technique had a high success rate with thrombi less than 2 weeks old (seven of eight) regardless of the length of the clot, but had limited success with thrombi more than 2 weeks old (one of four). Continued patency over a 2-month interval was documented in four of the eight patients whose thrombi were successfully lysed. However, patency could be maintained in only one of the four patients who retained a venous access device in the treated vein. CONCLUSION Pulse spray rtPA is an effective, safe, and practical alternative to continuous infusions of thrombolytic agents to treat upper extremity venous thrombi.

Serologic evidence of heparin sensitization in cancer patients receiving heparin flushes of venous access devices.

Abstract Cancer patients with venous access devices (VADs) often receive daily flushes of heparin. Even this relatively small heparin exposure has been reported to induce immune-mediated thrombocytopenia. To estimate how frequently this occurs we tested for heparin-related antibodies in 49 patients receiving daily heparin flushes of their VADs. Although one-third of the patients showed evidence of heparin sensitization on at least one occasion during their surveillance, their antibody titers were generally low and typical of those found in other cohorts of patients who become sensitized to heparin but do not develop secondary thrombocytopenia. However, one patient developed a positive serotonin release assay indicative of a more significant sensitization, but without thrombocytopenia. Therefore, our observations suggest that heparin-induced thrombocytopenia (HIT) related to heparin flushes of VADs is uncommon but still an important diagnosis to entertain.

Low-dose urokinase infusions to treat fibrinous obstruction of venous access devices in cancer patients.

PURPOSE This study was undertaken to determine the role of low-dose urokinase infusions in treating fibrinous occlusions of venous access devices (VADs) in cancer patients. PATIENTS AND METHODS Forty-two patients with VAD occlusions refractory to routine urokinase instillations were documented by x-ray (cathetergram) to have fibrin sleeves at the catheter tips. They were randomized to receive infusions of either urokinase (40,000 U/h) or urokinase with heparin (320 U/h) through their catheters. After 1, 3, 6, and 12 hours of treatment, the function of the VADs was reassessed. Whenever the obstruction had been relieved, the infusion was stopped and a repeat cathetergram was performed. The status of the unoccluded catheters was followed to determine the longevity of the restored function. RESULTS Twenty-one catheters were treated with urokinase alone and 21 with the combination of urokinase and heparin. In each group, 16 VADs opened within 12 hours of treatment and five did not. By actuarial analysis, the probability was only 0.28 that a reopened catheter would reocclude within 6 months. CONCLUSION Low-dose urokinase infusions can restore function to the majority of catheters occluded by fibrin sleeves. Adding heparin to the urokinase does not enhance the efficacy of the infusions. The restored function often persists until the VADs are removed.

Fibrin sheath formation and chemotherapy extravasation: a case report

Abstract Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). PWO is a common problem encountered with VADs. Although PWO is often easily managed with small doses of thrombolytic therapy (e.g., urokinase), it could result in a more serious complication, such as chemotherapy extravasation. Careful assessment of all VADs is important to identify complications such as fibrin sheath formation, which can potentially lead to extravasation. To rule out fibrin sheath formation, catheter dye studies need to be obtained when fibrinolytic therapy has failed to restore catheter function. The purpose of this paper is to illustrate a retrospective case report demonstrating drug extravasation caused by the development of fibrin sheath formation.

Reductions in tissue plasminogen activator and thrombomodulin in blood draining veins damaged by venous access devices

A frequent complication of venous access devices (VADs) is axillary-subclavian venous thrombosis. To study this problem we have compared blood drawn through VADs with peripheral blood samples in a group of oncology patients with venographically demonstrated venous damage (N = 14) and a group with normal venograms (N = 21). The samples were assayed for a battery of proteins believed to be involved in thrombogenesis. After approximately six weeks of catheterization the venographically abnormal patients had significantly less thrombomodulin (P = 0.0055) and significantly higher PAI:tPA (P = 0.022) in catheter-drawn samples as compared with the venographically normal group. Although the data are inconclusive, it is hypothesized that these changes resulted from local endothelial injury.

Intraluminal Clots in Groshong Catheters

Abstract The Groshong™ catheter (Bard Access Systems, Salt Lake City), which has a unique three-way slit valve, requires less care than other, non-valved, catheters, because the valve is designed to prevent blood reflux into the catheter tubing. However, patients and nursing staff at our institution, the Warren Grant Magnuson Clinical Center, have frequently observed blood in these catheters even when they are not in use. To document this paradox more carefully, we examined 28 Groshong catheters immediately after they had been explanted. All 28 had clot in one or both lumens, usually adherent to the wall. Only 8 of the 28 catheters had documented malfunction prior to removal. There was no association between the size of the catheter lumen and clot appearance.

Applying for Training, Career Development, and Early-stage Research Grants

This chapter presents an overview of training, career development, and early-stage research applications and grants. This overview is followed by eight basic steps that should be followed when applying for one of these grants. Each Institute and Center (IC) at NIH has specific policies for training, career development, and early-stage research applications and grants. Not all NIH ICs offer all of the grants described in this chapter, and some offer additional types of grants. Even though each IC funds different types of training, career development, and early-stage research grants, there is one universal – each IC wants to fund the development of people who will become independent scientists conducting research pertinent to its mission. After reading this chapter, potential applicants will have a framework for understanding each IC’s specific information about training, career development, and early-stage research applications and grants.