Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of unexpected cardiac arrest occurring in a 17-year-old male patient is reported. The patient had been admitted after sustaining hand trauma. A first emergency surgical procedure was carried out, followed about three weeks later by another one. No incidents occurred during or after either of these two operations. A third procedure was required about two months after the accident (free toe graft to the thumb of the left hand). The twelve-hour operation was carried out under general anaesthesia and axillary block. The patient was given intravenous heparin (800 IU.h-1) during the procedure on the arm. The patient recovered quickly, and was extubated before his transfer to the recovery room. Fifteen minutes later, the patient's heart rate decreased to 40 b.min-1, followed by a transient cardiorespiratory arrest. The suspicion of pulmonary embolism was confirmed by pulmonary scintigraphy. Thrombolysis was carried out with 2,000 IU.kg-1.h-1 of urokinase for a 72 h period, combined with continuous heparin administration (16 to 36 x 10(3) IU.day-1). The patient recovered after one week. No thrombophlebitis was found for origin of the emboli. Biological investigations carried out both before and after 10 minutes of anoxia revealed a normal fibrinolytic system, but a deficit in protein C (62% antigen, 64% activity). Two years after the episode of pulmonary embolism, the patient, still taking acenocoumarol, remained free from any sequela. Current perioperative management of patients with a known protein C deficit is discussed.
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PMID:[Disclosure of protein C deficiency with pulmonary embolism followed by cardiac arrest during the recovery period]. 144 21

The use of thrombolytic agents in the treatment of postoperative pulmonary embolism presents a dilemma to the surgeon. On one hand, postoperative pulmonary embolism usually occurs within 2 weeks of surgery. On the other hand, recent surgery is considered a contraindication for the use of thrombolytics. We developed a protocol for treating pulmonary embolism patients who have recently undergone surgery. Urokinase, at a dose of 2,200 U/kg wt, is injected directly into the clot via a catheter positioned in the pulmonary artery. This is followed by continuous infusions of urokinase at 2,200 U/kg wt/hr until the clot is lysed (up to 24 hrs). Simultaneously, heparin is administered peripherally at 500 U/hr. The level of serum fibrinogen is monitored every 6 hours and maintained at no less than 0.2 g/dL to prevent bleeding. Thirteen patients were treated for angiographically proven pulmonary embolism within 14 days of surgery. Complete lysis of every embolus was achieved, and no deaths or bleeding complications occurred. Two patients received inferior vena cava filters, and nine patients no longer needed chronic anticoagulants within 3 months after the embolic event.
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PMID:Thrombolytic therapy for postoperative pulmonary embolism. 155 78

Heparin-induced thrombocytopenia with thrombotic complications is a serious clinical problem. The diagnosis is confirmed by a positive heparin-induced platelet aggregation test and/or detection of white clots upon pathological exam after a presumptive diagnosis based on these criteria: (1) Development of thrombocytopenia of less than 100,000 mm3 while receiving heparin therapy; (2) Normalization of the platelet count after an interruption in heparin therapy; (3) The presence of thrombotic complications; and (4) Exclusion of other causes of thrombocytopenia. Eight patients with heparin-induced thrombocytopenia were encountered at the Charleston Area Medical Center, Memorial Division, in a recent 20-month period. Various types of heparin, routes of administration, and indications were implicated. The mean platelet nadir was 25,750 mm3 and the mean time to onset of of heparin-induced thrombocytopenia was 4.9 days. Thrombotic complications included seven patients with arterial occlusions of the legs, six with deep-vein thrombosis of the legs (three had pulmonary embolism), and five with combined arterial and venous thrombosis. Treatment strategies included discontinuation of heparin in all patients; intravenous infusion of dextran in five patients, followed by arterial thrombectomy in three patients; urokinase therapy in two patients for arterial thrombotic complications; and insertion of Greenfield filters in four patients for venous thrombotic complications. All surviving patients were given warfarin. The mortality rate was 25 percent and the morbidity rate was 38 percent. In conclusion, an initial platelet count should be obtained on all patients prior to receiving heparin, followed by repeat platelet counts every two to three days. Once thrombocytopenia or thrombosis is diagnosed, heparin should be discontinued and other therapeutic modalities considered.
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PMID:Heparin-induced thrombocytopenia with thrombotic complications. 157 77

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.
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PMID:Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. 160 32

This study describes our experience with 12 patients with white clot syndrome encountered during a recent 36-month period. The diagnosis was based on the following criteria: (1) development of thrombocytopenia of less than 100,000/mm3 during administration of heparin therapy, (2) normalization of the platelet count after an interruption in heparin therapy, (3) exclusion of other causes of thrombocytopenia, (4) a positive heparin-induced platelet aggregation test, (5) detection of white clots on pathologic examination, and (6) the presence of thrombotic complications. Of 2,500 patients who received heparin therapy, 12 (0.48%) developed white clot syndrome. Various indications, routes of administration, and types of heparin were implicated. The mean platelet nadir was 26,900/mm3, and the mean time to onset of heparin-induced thrombocytopenia was 5 days. Thrombotic complications included arterial occlusions of the legs in 11 patients, deep vein thrombosis of the legs in 9 patients (4 had pulmonary embolism), and combined arterial and venous thrombosis in 8 patients. Treatment strategies included discontinuation of heparin in all patients and intravenous infusion of dextran, followed by arterial thrombectomy in four patients, urokinase therapy in two patients for arterial complications, and insertion of Greenfield filters in six patients. All patients were given warfarin. The mortality rate was 25% and the morbidity rate was 50%. An initial platelet count should be obtained on all patients prior to receiving heparin, followed by repeat platelet counts every 2 to 3 days. Once thrombocytopenia or thrombosis is diagnosed, heparin should be discontinued and other methods of therapy considered.
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PMID:Diagnostic and therapeutic strategies of white clot syndrome. 171 45

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h. At 2 h, total pulmonary resistance decreased by 18 +/- 22% in the urokinase group and by 36 +/- 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h. After 12 h, the decrease in total pulmonary resistance was 53 +/- 19% in the urokinase group compared with 48 +/- 17% in the alteplase group and the reduction in the angiographic severity score was 30 +/- 25% compared with 24 +/- 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinase-treated patients experienced hematomas at puncture sites.
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PMID:Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. The European Cooperative Study Group for Pulmonary Embolism. 173 48

For the treatment of massive pulmonary embolism thrombolytic therapy is efficient in reducing late mortality and complications from chronic pulmonary hypertension. Best results are achieved if treatment is started as soon as possible. Even after days or weeks after pulmonary thromboembolism, however, thrombolytic therapy is beneficial. In life threatening conditions due to right heart failure an initial bolus of 2,000,000 U urokinase should be administered. The number of contraindications can be markedly reduced due to the well controlled thrombolysis with urokinase.
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PMID:Thrombolytic therapy in fulminant pulmonary thromboembolism. 178 41

A hybrid hybridoma (FU1-74), secreting a bispecific monoclonal antibody (bs mAb), was obtained by fusion of a murine hybridoma secreting a monoclonal antibody (mAb) specific for human fibrin with a murine hybridoma secreting a mAb against urokinase-type plasminogen activator (u-PA). The bs mAb (MA-FU1-74), purified to homogeneity from mouse ascitic fluid, migrated as a single band with apparent Mr 150,000 on nonreduced SDS-PAGE and had an affinity for both human fibrin (Ka = 2 x 10(7) M-1) and for u-PA (Ka = 10(8) M-1) comparable to that of the mAbs obtained from the respective parental hybridomas. MA-FU1-74 did not influence the enzymatic activity of two-chain u-PA (tcu-PA) towards plasminogen or towards a chromogenic substrate. The complex of MA-FU1-74 with recombinant single chain u-PA (rscu-PA) or with tcu-PA (urokinase) enhanced the fibrinolytic potency of the plasminogen activator towards clotted human plasma 20-fold and 5-fold, respectively. In a hamster pulmonary embolism model, the rscu-PA/MA-FU1-74 complex had a 13- to 17-fold increased thrombolytic potency (percent lysis per mg/kg u-PA administered) relative to that of rscu-PA. The specific thrombolytic activity (percent lysis per microgram/ml steady state plasma level of u-PA antigen) of the complex was, however, not significantly different from that of rscu-PA. The complex of rscu-PA with the parental anti-u-PA mAb (MA-UK1-3) had only a 2-fold enhanced thrombolytic potency relative to that of rscu-PA and had a 5-fold decreased specific thrombolytic activity. The plasma clearance rates of the complexes of rscu-PA with both MA-FU1-74 and MA-UK1-3 were about 10-fold lower than that of rscu-PA. In a rabbit jugular vein thrombosis model, the rscu-PA/MA-FU1-74 complex had a 4-fold enhanced thrombolytic potency, an unchanged specific thrombolytic activity and 20-fold reduced plasma clearance. In both animal models, the rscu-PA/MA-FU1-74 complex did not cause more extensive systemic activation of the fibrinolytic system than rscu-PA. It is concluded that the bispecific anti-fibrin/anti-u-PA mAb MA-FU1-74 targets u-PA to the fibrin clot, resulting in a significantly enhanced thrombolytic potency of the plasminogen activator.
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PMID:Enhancement of clot lysis in vitro and in vivo with a bispecific monoclonal antibody directed against human fibrin and against urokinase-type plasminogen activator. 179 14

170 patients were treated with continuous infusion of epirubicin, mitoxantrone, carboplatin or 5-fluorouracil through an implanted venous access port with a portable infusion pump. A total of 440 cycles were given on an outpatient basis. The patients were instructed how to dissolve their drugs and to change the syringes. The complication rate was low. 10 patients developed a thrombosis of the subclavian vein, resulting in cessation of therapy in 5. Pulmonary embolism occurred twice, in 1 patient during a period of subclavian vein thrombosis. Needle dislocation occurred 6 times and catheter occlusion 20 times. Patency was restored with saline or urokinase. Local infection occurred 3 times and systemic infection only once. This technique is suitable for continuous infusion of different cytostatic drugs on an outpatient basis. Patients were able to prepare their drugs at home and the system can remain in situ for 3 weeks without increasing the complication rate.
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PMID:Continuous infusion of chemotherapy on an outpatient basis via a totally implanted venous access port. 182 78

The murine monoclonal antiplatelet antibodies MA-TSPI-1 (directed against human thrombospondin) and MA-PMI-2, MA-PMI-1, and MA-LIBS-1 (directed against ligand-induced binding sites [LIBS] on human platelet glycoprotein IIb/IIIa) were conjugated with recombinant single-chain urokinase-type plasminogen activator (rscu-PA) using the cross-linking reagent N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The conjugates (rscu-PA/MA-TSPI-1, rscu-PA/MA-PMI-2, rscu-PA/MA-PMI-1, and rscu-PA/MA-LIBS-1), purified by immunoadsorption and gel filtration, were obtained with recoveries of 34% to 45%, with an average stoichiometry of 1.6 to 1.8 IgG molecules per rscu-PA molecule, and with unaltered specific activities and affinities. Preincubation of human platelet-rich plasma with rscu-PA/MA-PMI-2, rscu-PA/MA-PMI-1, or unconjugated rscu-PA resulted in partial inhibition of ADP-induced aggregation; 25% inhibition was obtained with 63 micrograms/mL rscu-PA and with 6 micrograms u-PA/mL rscu-PA/MA-PMI-2 or 1.2 micrograms u-PA/mL rscu-PA/MA-PMI-1. In an in vitro system composed of a 125I-fibrin-labeled platelet-rich human plasma clot immersed in normal human plasma, the conjugates had threefold to greater than 15-fold less fibrinolytic potency than unconjugated rscu-PA. The thrombolytic potency of rscu-PA/MA-PMI-1 and rscu-PA/MA-LIBS-1 was compared with that of rscu-PA and that of a control conjugate rscu-PA/MA-1C8 in a pulmonary embolism model in the hamster, using clots prepared from platelet-poor or platelet-rich human plasma. Lysis was measured 30 minutes after the end of a 60-minute intravenous infusion of the thrombolytic agents. rscu-PA, rscu-PA/MA-PMI-1, rscu-PA/MA-LIBS-1, as well as rscu-PA/MA-1C8 had comparable thrombolytic potencies (percent lysis per dose administered) towards platelet-poor human plasma clots. In contrast, the thrombolytic potency of rscu-PA/MA-PMI-1 and of rscu-PA/MA-LIBS-1 towards platelet-rich clots was 2.3- to 3-fold higher than that of rscu-PA (P less than .005) and fivefold to sevenfold higher than that of the control conjugate (P less than .01).
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PMID:Effect of chemical conjugation of recombinant single-chain urokinase-type plasminogen activator with monoclonal antiplatelet antibodies on platelet aggregation and on plasma clot lysis in vitro and in vivo. 183 Oct 57


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