Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe deep venous thrombosis and a circulating anticoagulant in a male adolescent with systemic lupus erythematosus (SLE). The association of deep vein thrombosis with SLE in a pediatric patient has not, to our knowledge, been previously reported. The circulating anticoagulant was characterized as a lupus-type inhibitor. This was demonstrated by an abnormal partial thromboplastin time (PTT), the failure of the PTT to correct with the addition of an equal amount of normal plasma, and a positive tissue thromboplastin inhibitor test. Physicians should be aware that a circulating anticoagulant can be associated with SLE and that there may be a paradoxically increased incidence of thromboembolic phenomena in patients with this abnormality.
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PMID:Deep venous thrombosis and a circulating anticoagulant in systemic lupus erythematosus. 721 77

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
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PMID:Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). 749 71

Safety and efficacy of the thrombolytic agent pro-urokinase (pro-UK) in the treatment of deep vein thrombosis of the lower limbs (DVT) have been investigated in an open, uncontrolled, pilot study. Fifteen patients were infused with 800.000 IU (5 mg)/h of pro-UK over 24 h (120 mg), together with unfractionated heparin adjusted to maintain the activated partial thromboplastin time between 1.5 and 2.5 times the basal value. Efficacy was assessed comparing venographic changes in the 11 evaluable limbs before and after pro-UK infusion. The Marder score decreased from a median pre-thrombolysis value of 28 (range 4-40) to 16 (3-38) (p < 0.05). One major hemorrhagic event (retroperitoneal bleeding 4 days after the end of the pro-UK infusion) occurred. Fibrinogen, alpha 2-antiplasmin and plasminogen significantly decreased from baseline values after 12 and 24 h, fibrin(ogen) degradation products significantly increased. Changes in hemostasis parameters were unrelated to thrombolytic efficacy. The results of this pilot study indicate that pro-UK is thrombolytic in DVT and that it can be administered simultaneously with conventional heparin treatment.
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PMID:A pilot study of pro-urokinase in the treatment of deep vein thrombosis. 753 76

Deep vein thrombosis of the right leg occurred in a 77-year-old woman after percutaneous cardiac catheterization via the right femoral vein, performed to assess mitral valve disease with atrial fibrillation. She thereupon received intravenous heparin (1,000 IU/h; partial thromboplastin time 60-70s). 13 days later she developed a transient incomplete right brachiofacial hemiparesis with motor aphasia. Transthoracic echocardiography revealed a fresh left atrial thrombus. Platelet count fell from initially normal levels to 20 x 10(9)/l. Because type II heparin-associated thrombocytopenia was suspected heparin administration was discontinued and phenprocoumon administered. Heparin-dependent antibodies were demonstrated with the heparin-induced platelet activation test. Cross reactions occurred in vitro against all low-molecular heparins and heparinoid ORG 10172. The platelet count had become normal 17 days later, the leg veins had recanalized and the intraatrial thrombus had become much smaller. The patient declined cardiac surgery and was discharged on the 41st hospital day in satisfactory general condition on maintenance anticoagulant dosage.
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PMID:[Intracardial thrombus formation in heparin-associated thrombocytopenia type II]. 753 53

A point mutation in coagulation factor V which causes resistance to cleavage of factor Va by activated protein C (APC), was recently found to underlie thrombotic events. We examined 20 consecutive patients, under the age of 40, who suffered from idiopathic venous or arterial thrombosis. In 8 (40%) there was resistance to APC manifested by absence of the expected prolongation of activated partial thromboplastin time (aPTT). In 3, the addition of normal plasma corrected the anomaly in the patient's plasma, although the addition of factor V- deficient plasma caused no change. In a family of a 17-year-old boy with idiopathic deep venous thrombosis we found a mutation in factor V which was responsible for APC resistance. The patient and 4 family members showed a single G to A transition in position 1691 in their cDNA, resulting in substitution of arginine (506) for glutamine. The mutation in this area, which is the cleavage site for APC, is associated with thrombotic episodes and is frequently observed in patients with familial thrombophilia.
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PMID:[Resistance to activated protein C--a novel cause of thrombophilia]. 755 99

To determine the adequacy of initial anticoagulation by intravenous heparin for patients who have deep venous thrombosis (DVT), and the factors that influence delayed anticoagulation, independent, duplicate chart review of 63 consecutive patients who had venography-proven DVT was conducted. Adequate heparinization (AH) was defined as an activated partial thromboplastin time (PTT) of more than 1.5 times the normal laboratory control. The proportions of patients achieving AH within 24 hours and 48 hours of initial heparin bolus were 46% and 62%, respectively. Patients who weighed more were less likely to achieve AH (p < 0.05), while patients receiving care from the thromboembolism service were more likely to achieve AH (p < 0.05). Low initial infusion rate was strongly but not significantly predictive of inadequate anticoagulation (p = 0.06). The mean heparin bolus and initial infusion rates were significantly lower than those suggested in the literature (p < 0.01). The AH rates were comparable to historical controls but suboptimal compared with the rates of 66% at 24 hours and 81% at 48 hours reported in association with heparin nomogram use (p < 0.05). A heparin nomogram is likely to achieve consistently higher rates of adequate heparinization.
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PMID:Inadequacy of intravenous heparin therapy in the initial management of venous thromboembolism. 756 29

Management of thromboembolic disease involves administration of anticoagulants, thrombolytics or antiplatelet agents to lyse or prevent thrombus extension. Despite widespread use and decades of experience with some of these agents, much is unknown about the effects of dose and plasma concentration on patient response. Unfractionated heparin (UFH) improves outcome in many thromboembolic disorders when administered to a target activated partial thromboplastin time (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with absorption from subcutaneous sites and elimination. Doses based on bodyweight or estimated blood volume attain therapeutic aPTTs faster than fixed or standard doses. Low molecular weight heparins (LMWHs) were developed to increase the anti-factor Xa:anti-factor IIa activities. Several different LMWHs are as effective as UFH in treating deep venous thrombosis. Evidence fails to support a relationship between anti-factor Xa activity and either thrombosis evolution or bleeding. No comparisons have been made between bodyweight-based and anti-factor Xa activity-based doses. The dose of orally administered warfarin is adjusted to achieve a target International Normalised Ratio (INR). Maintenance doses are estimated on the basis of the patient's INR during the first 3 days of therapy: the dose required to achieve an optimal INR decreases with age > 50 years. The thrombolytic agents are administered in standard doses to achieve rapid thrombolysis with minimal alteration in systemic haemostasis. Accelerated intravenous alteplase may result in the highest rate of coronary artery reperfusion. Nevertheless, standard doses of streptokinase, anisoylated plasminogen streptokinase complex and alteplase result in similar 1-month mortality rates. The minimal advantage seen with alteplase is offset by higher rates of stroke. Future trials will focus on administration strategies achieving rapid thrombolysis, while minimising the risk of serious bleeding. With the antiplatelet agents, unpredictability in the pharmacokinetic parameters of different products has confounded interpretation of published reports. Optimal aspirin (acetylsalicylic acid) administration would include administration of an initial dose of 160 to 325mg after an acute vascular event, followed by maintenance dosages of approximately 75 mg/day for prophylaxis or treatment. Ticlopidine does not exhibit a relationship between either plasma concentration or dose and adverse effects, while pharmacodynamic effects may be dose-, but not plasma concentration-, dependent. The correlation between the concentration of dipyridamole and some of its antiplatelet effects may be the strongest amongst all the antiplatelet agents. However, unfortunately all clinical trials used standard doses and the current consensus is that dipyridamole alone is not an effective antiplatelet agent.
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PMID:Pharmacokinetic optimisation of the treatment of embolic disorders. 771 62

Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin, administered subcutaneously (s.c.) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i.e. an Internation Normalised Ratio, of 2.0-3.0). A second venogram was obtained after Fragmin or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.
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PMID:Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. 783 49

The aim of this study was to evaluate over one year the minimal etiologic screening carried out on each patient hospitalized in Internal Medicine for a deep venous thrombosis (DVT) and to search for clinical features possibly relating thrombosis to neoplasia. 53 patients (27 male and 26 female; mean age 63.6 years, range: 18-19) with DVT of the lower limbs were included in the study. The initial etiologic screening consisted of a complete clinical examination, a biological assessment (blood cell and platelet count, Activated Partial Thromboplastin Time, inflammation and liver investigations), a radiography of the thorax and abdomino-pelvic ultrasonography. This etiologic screening was evaluated one year after the thrombotic event. The initial assessment was positive in 44 cases (83% of the patients), 9 thrombosis remained unexplained. Neoplasia was identified in 8 cases (15% of the patients), the diagnosis being often evoked at the time of interrogation or during the clinical examination; the systematic biological assessment only revealed an etiology in one case: this was a primary thrombocythemia discovered by platelet count. On evaluation one year later, amount the 9 DVT unexplained by the initial screening, 8 remained totally unexplained. On the other hand, a cancer of the colon revealed by proctorrhagia during oral anticoagulant treatment, had been undiscovered. No significant difference was found between the two groups (cancers and noncancerous etiologies) as concerns age, sex, thrombus topography, the side affected or the embolic events. However, the occurrence of subsequent thrombosis under well controlled anticoagulant treatment clearly characterises thrombosis associated with neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Deep venous thrombosis and cancer. A one year evaluation of etiologic screening of patients hospitalized in Internal Medicine]. 785 70

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well-known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre-B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients.
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PMID:Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: leukemic cell procoagulant activity is not responsible for the hypercoagulable state. 796 91


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