Daily catheter-directed single dosing of t-PA in treatment of acute deep venous thrombosis of the lower extremity.

The strong fibrin affinity of recombinant tissue plasminogen activator (rt-PA) theoretically obviates continuous infusion or replacement of t-PA after direct intrathrombic injection. This hypothesis led the authors to evaluate single daily catheter-directed injection of rt-PA as a thrombolytic treatment for acute deep vein thrombosis of the lower extremity. Once-daily injection of rt-PA was performed in large thrombosed veins (popliteal or larger) with use of pulse-spray catheters and in small thrombosed veins in patients' calves with use of 3-4-F coaxial catheters. Patients received only full systemic anticoagulation on his/her patient care unit. This dosing regimen has been tested in 10 patients (12 legs) with a maximum dose of 50 mg per leg per day. Extensive thrombolysis was achieved in nine patients and partial thrombolysis was achieved in one patient, at an average total dose of 106 mg of rt-PA per leg. Minor bleeding was seen in three patients and no transfusions were needed. Our technique and the rationale for this pilot study is the focus of this article.

Restricting physician-assisted death to the terminally ill.

KIE: Although physician-assisted death can be a great benefit both to those who are terminally ill and those who are not, the risks for patients in these two categories are quite different. For now it is reasonable to make the benefit available only for those near death, and to await better evidence about the risks before making it more broadly available. (HCR)^ieng

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

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.

Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases.

Three cases of heparin-induced thrombocytopenia (HIT) are reported that were provoked by daily heparin flushes of central venous access devices. Each case had confounding features that delayed recognition of the problem. A review of the literature revealed only 29 previously reported cases of HIT secondary to heparin flushes. However, the true incidence of this problem is unknown. A high index of suspicion and confirmatory laboratory tests are necessary to make the diagnosis.

Fibrin sheath formation and chemotherapy extravasation: a case report.

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.

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.

Superior vena cava thrombosis associated with a central venous access device: a case report.

A case report is presented that illustrates the signs, symptoms, and treatment of superior vena cava thrombosis (SVCT) related to a venous access device (VAD). SVCT is a rare complication associated with VADs; its symptoms can be very subtle, which makes diagnosis difficult. Knowing who is at risk, assessing these patients closely, and providing patient education will help to identify early complications. Because patients spend most of their time away from healthcare providers, education is needed to increase patients' awareness of the subtle signs and symptoms of SVCT. Patients need to know what to report to their oncology team members so that early treatment can be initiated.

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.

The effects of heparin flush on patency of the Groshong catheter: a pilot study.

PURPOSE/OBJECTIVES: To determine whether the addition or a heparinized saline flush would decrease clot formation and persistent withdrawal occlusion (PWO) in Groshong (Bard Access Systems, Salt Lake City, UT) catheters. DESIGN: A prospective, nonrandomized study using a historical control group of patients with Groshong catheters that had been flushed weekly with 5 ml normal saline compared to data from patients with Groshong catheters flushed weekly with 2.5 ml heparinized saline (100 U/ml). A retrospective chart review was performed to determine the incidence of PWO. In both groups, the presence of liquid blood and adherent or nonadherent clot in explanted catheters was recorded. SETTING: Oncology inpatient and outpatient units of a cancer research center located in a mid-Atlantic city in the United States. CONTROL GROUP: Twenty-eight 9.5 Fr. double-lumen Groshong catheters maintained with a saline flush. Experimental group: Twenty-three double-lumen Groshong catheters maintained with a heparin flush. At the time of this report, 12 of these 23 catheters had been explanted and 11 remained in place. METHODS: The frequency of PWO was measured in a retrospective chart review and determined by the number of urokinase instillations required for each catheter. All 28 catheters in the saline flush group and 8 catheters in the heparin flush group were examined immediately after removal for intraluminal liquid blood and adherent or nonadherent clot. MAIN RESEARCH VARIABLES: Urokinase usage, intra-luminal blood or clot, and PWO. FINDINGS: PWO occurred less frequently in the heparin flush group (p = 0.006) than in the saline fush group. All 28 of the saline flush catheters developed an adherent clot in one or both lumens, whereas no adherent clots were found in the heparin flush catheters (p < 0.0001). CONCLUSIONS: The addition of a heparinized saline weekly flush to maintain Groshong catheters decreased the presence of intraluminal adherent clots and improved the catheter function. IMPLICATIONS FOR NURSING PRACTICE: The safe delivery of medication and the ability to obtain blood specimens are vital for patients who depend on functioning venous access catheters. Flushing Groshong catheters with heparinized saline decreases the likelihood of intraluminal clot formation and catheter malfunction.

Discard volumes necessary for clinically useful coagulation studies from heparinized Hickman catheters.

PURPOSE/OBJECTIVES: Determine the blood volume that must be wasted to obtain a clinically useful prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration for blood drawn from a heparinized (2.5 ml of 100 units/ml), double-lumen venous catheter. DESIGN: Prospective, nonrandomized study comparing test results obtained from blood samples drawn through the catheters with those obtained via peripheral venipuncture. Patients acted as their own control. SETTING: Inpatient and outpatient units of a cancer research center located in a mid-Atlantic city in the United States. SAMPLE: Twenty double-lumen 10 Fr. Hickman catheters (Bard Access Systems, Salt Lake City, UT) were studied in 20 adult patients with cancer who had no history of coagulation disorders. METHODS: Samples were collected from the red lumen of 20 heparinized, double-lumen Hickman catheters after 5, 10, 15, 20, and 25 ml of blood first were discarded. PTs, APTTs, and fibrinogen concentrations were measured on each sample. The results were compared with those derived from a simultaneously obtained peripheral blood sample. MAIN RESEARCH VARIABLES: PT, APTT, and fibrinogen values of blood samples after 5, 10, 15, 20, and 25 ml discards and PT, APTT, and fibrinogen of peripheral blood samples. FINDINGS: The coagulation results using peripheral blood were always within the normal range except for one slightly elevated APTT. After 25 ml of discard, all of the PTs and fibrinogen concentrations and 95% of the APTTs of catheter blood were within the normal range and therefore clinically useful. CONCLUSIONS: Clinically useful PTs, APTTs, and fibrinogen concentrations often can be derived with catheter-drawn blood when the objective is to confirm normal coagulation. However, because it is very difficult to obtain heparin-free samples through heparinized, double-lumen Hickman catheters, peripheral blood should be drawn for coagulation testing when a totally heparin-free sample is needed to make a critical clinical decision. IMPLICATIONS FOR NURSING PRACTICE: These findings provide important information for practice when nurses have to decide whether to draw coagulation tests through a heparinized catheter. Further research is needed with larger samples in varied populations (e.g., pediatrics) to study catheters made of different materials and of different calibers.

Direct chiral resolution of 15-deoxyspergualin using a cellobiohydrolase liquid chromatographic column.

An LC method for the direct determination of the enantiomers of 15-deoxyspergualin was developed, optimized and validated. A commercially available LC column containing a cellulase enzyme (cellobiohydrolase I) stationary phase was used. The effect of various parameters on the separation and validation data are discussed.

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.

Chemotherapy extravasation: a consequence of fibrin sheath formation around venous access devices.

PURPOSE/OBJECTIVES: To describe, using two case studies, chemotherapy drug extravasation as a consequence of fibrin sheath formation. DATA SOURCES: Journal articles, textbooks, medical records, and personal experiences. DATA SYNTHESIS: Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). While PWO often is easily managed with small doses of thrombolytic therapy (e.g., urokinase), it may result in a more serious complication, such as chemotherapy extravasation. CONCLUSIONS: Chemotherapy should not be administered through a VAD unless a free-flowing blood return can be demonstrated. IMPLICATIONS FOR NURSING PRACTICE: Careful nursing assessment of all VADs is important to identify complications such as fibrin sheath formation. To rule out fibrin sheath formation, nurses must obtain catheter dye studies when fibrinolytic therapy fails to restore catheter function.

Determination of the enantiomer of a cholesterol-lowering drug by cyclodextrin-modified micellar electrokinetic chromatography.

The development, optimization and application of a chiral CE (capillary electrophoresis) method for the determination of the enantiomer content of a new cholesterol-lowering drug (BMS-180431-09) is discussed. The chiral CE technique, cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC), was employed with hydroxypropyl beta-cyclodextrin as the chiral selector in the run buffer. The detection limit of the unwanted enantiomer was about 0.06% w/w. The effect of various parameters on the separation, validation data and examples of the application of the chiral CE method are included.

Upper extremity impedance plethysmography in patients with venous access devices.

Central venous access devices (VADs) are often associated with thrombotic obstruction of the axillary-subclavian venous system. To explore the accuracy of impedance plethysmography (IPG) in identifying this complication we performed IPG on 35 adult cancer patients before their VADs were placed and approximately 6 weeks later. At the time of the second IPG the patients also underwent contrast venography of the axillary-subclavian system. The venograms revealed partial venous obstruction in 12 patients (34%) and complete obstruction in two (5.7%). Although the IPG results from venographically normal and abnormal patients overlapped extensively, mean measurements of venous outflow were significantly lower in the patient population with abnormal venograms (P = 0.052 for Vo; P = 0.0036 for Vo/Vc). In our hands, therefore, upper extremity IPG cannot be used to make clinical decisions about individual patients with VADs, but it can distinguish venographically normal and abnormal populations.