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 identified 100 patients (51 males and 49 females) as having the lupus anticoagulant. The following diagnoses were found in the patient population: human immunodeficiency virus positivity, 20%; systemic lupus erythematosus, 10%; prolonged preoperative activated partial thromboplastin time (APTT), 10%; procainamide hydrochloride-induced inhibitor, 9%; deep vein thrombosis, 6%; seizure disorders/epilepsy, 5%; and miscellaneous conditions, 40%. Identification was based on a prolonged APTT (> 40 seconds) that normalized with increased phospholipid concentrations and/or a prolonged Russell viper venom clotting time patient-control ratio of 1.20 or greater. In 68 cases (group 1), patient plasma prolonged the APTT of normal plasma in a 1:1 mixing study. However, in 32 cases (group 2), no such prolongation was observed. There was a significant difference between presenting APTTs in patients from group 1 (mean +/- SD, 58.29 +/- 13.30 seconds) compared with that in group 2 (mean +/- SD, 47.93 +/- 5.09 seconds). Furthermore, 66% of group 1 patients had elevated anticardiolipin antibody titers compared with only 41% in group 2. Of the 32 patients in group 2, 16 (50%) were positive for human immunodeficiency virus. We concluded that the investigation of a lupus anticoagulant should not be abandoned because patient plasma does not prolong the APTT of normal plasma in a mixing study, especially in a human immunodeficiency virus-positive population.
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PMID:The lupus anticoagulant. High incidence of 'negative' mixing studies in a human immunodeficiency virus-positive population. 850 27

The objective was to retrospectively study the initiation of anticoagulant therapy in inpatients of the two major teaching hospitals in Tasmania, Australia. The medical records of a random sample of patients with an admission diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) during the period February 1992 to June 1994 were studied, to examine therapeutic issues including (i) the time taken after commencing heparin to achieve a therapeutic activated partial thromboplastin time (APTT), (ii) when warfarin was commenced, (iii) the time taken after commencing warfarin to achieve a therapeutic International Normalized Ratio (INR), and (iv) the degree of anticoagulant control at the time of discharge from hospital. The medical records of 99 patients (median age: 65 years and range: 16-93 years; 52 females) were studied. Heparin was generally commenced within 4 h of admission to hospital. The median duration of heparin therapy was 5 days (range: 2-26 days). The median number of APTTs performed per patient was 6 (range: 1-24), with most results (60%) being below the optimum range. Warfarin was commenced from day 1 of hospitalization in only 34% of patients. The INR was within the therapeutic range in only 29% of cases when heparin was ceased. The median time taken to achieve a therapeutic INR after starting warfarin was 3 days (range: 1-15 days).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of the initiation of anticoagulant therapy. 855 86

The potential value of measurements of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer for the assessment of antithrombotic efficacy of heparin in acute deep venous thrombosis (DVT) was prospectively investigated. These variables were determined at presentation and subsequently once daily during a course of seven days heparin therapy. Heparin doses were adjusted according to the activated partial thromboplastin time (APTT). Compression ultrasonography was performed at presentation and on day 7 to determine the extent of thrombosis according to a predefined score. Out of a total of 50 patients accrued to the study 44 patients had reduced or unchanged extent of thrombosis, whereas in six patients an extension was documented. Although thrombin generation was significantly inhibited after initiation of heparin therapy as reflected by a decrease in F1 + 2 and TAT levels, these markers were not useful for the detection of patients with DVT extension. In contrast, anti-factor-Xa activities but not APTT measurements were significantly lower in the group of patients with propagation of DVT (median: 0.22 U/ml versus 0.38 U/ml, interquartile range: 0.1-0.33 U/ml versus 0.19-0.55 U/ml; P = 0.001). D-dimer decreased within the first days of heparin therapy but failed to indicate DVT progression. These data suggest that plasma anti-factor-Xa activity correlates better with the antithrombotic efficacy of heparin than APTT measurements and markers of coagulation or fibrinolysis activation.
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PMID:Markers of coagulation activation for evaluation of the antithrombotic efficacy of heparin: a prospective study in acute deep venous thrombosis. 856 38

Adjusted-dose subcutaneous unfractionated heparin (SC heparin) was used in the initial management of deep venous thrombosis (DVT) to allow shortened hospital stay. Of 78 patients screened, 41% were eligible and 18 (23%) were enrolled. Follow-up venous ultrasound examination was performed 6 weeks after discharge. Of enrolled patients, 16 (89%) completed the protocol. Hospital length of stay was 2 days in protocol patients compared with 5 days for patients receiving conventional inpatient heparin with a continuous intravenous infusion (p = 0.0009). Very high heparin doses (mean 42,000 to 62,000 U daily, given in three divided doses every 8 hours) and a median time of 21 hours were required initially to achieve a target activated partial thromboplastin time (aPTT) > 55 seconds. Subsequently many patients had supratherapeutic levels, yet there were no bleeding complications. Four patients (25%) did not show improvement at follow-up ultrasound in spite of aPTTs > 55 seconds after the second injection. Clot regression was evident in remaining patients. Hospital cost savings were offset partially by the need for time- and labor-intensive outpatient monitoring after hospital discharge.
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PMID:Shortened hospitalization by means of adjusted-dose subcutaneous heparin for deep venous thrombosis. 857 21

Low molecular weight heparin (LMWH) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin (UFH). Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin (Fragmin) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve. Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection than after 8 a.m. injection (p < 0.05) while no chrono-pharmacological variation of anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection. A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.
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PMID:Chrono-pharmacological study of once daily curative dose of a low molecular weight heparin (200 IU antiXa/kg of Dalteparin) in ten healthy volunteers. 858 3

The cornerstone of therapy of deep venous thrombosis (DVT) of the lower extremities is anticoagulation. Surgical thrombectomy and thrombolytic treatment are restricted to a small number of selected patients. Anticoagulation is started either with unfractionated heparin (continuous intravenous infusion or subcutaneous injection b.i.d.) with dose adjustments according to the partial thromboplastin time (PTT), or with subcutaneous injections of low-molecular-weight heparin (LMWH) in one or two daily injections without laboratory monitoring. This initial treatment is rapidly followed and replaced by oral anticoagulants at an intensity corresponding to an International Normalized Ratio (I.N.R.) of 2-3 and for a duration of about 3 months after a first episode of proximal DVT. This duration should be modulated on an individual basis according to the risks of recurrent thromboembolism and hemorrhage.
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PMID:[Drug therapy of deep venous thrombosis]. 865 49

1. Low molecular weight heparins (LMWHs) are produced by different depolymerization processes and may therefore differ with respect to their pharmacokinetic properties. 2. We designed a single dose, randomized cross-over study in 10 healthy volunteers to compare the 24 h pharmacokinetics of two LMWHs, reviparin and enoxaparin, which have been previously shown to be clinically equivalent in terms of post-operative deep vein thrombosis prevention, despite significant differences in their in vivo biological activity. The two LMWHs were subcutaneously administered at the same dosages that are used in clinical studies: 4250 anti-Xa iu for reviparin and 40 mg for enoxaparin which have similar in vitro anti-Xa activities. 3. The overall 24 h profiles of the plasma anti-Xa and anti-thrombin activities were similar for reviparin and enoxaparin. The Amax and the AUC(0, 24h) of plasma anti-Xa activity after reviparin administration were both slightly but significantly lower than those observed after enoxaparin administration (difference between treatments of 0.03 95% CI[0.01-0.05] iu ml-1 h and 0.56 95% CI[0.22-0.90] iu ml-1 for Amax and AUC(0, 24h) respectively). After adjustment for in vitro anti-Xa activity, the statistical difference between the two LMWHs persisted for the AUC(0, 24h) but not for the Amax of plasma anti-Xa activity. The tmax and the MRT values for plasma anti-Xa activity did not significantly differ between the two drugs. The t1/2 for reviparin did not significantly differ from that of enoxaparin (2.7 +/- 0.7 h vs 3.5 +/- 0.9 h respectively, NS). The Amax of the plasma anti-thrombin activity after reviparin administration was also slightly but significantly lower than that observed after enoxaparin administration, (difference between treatments of 0.018 95% CI[0.01-0.025] iu ml-1) whereas the AUC(0, 24h) of anti-thrombin activity vs time was not. A slight but significant increase of the activated partial thromboplastin time of a similar magnitude was observed after both reviparin and enoxaparin injections. 4. The calculated surface under the thrombin generation curve vs time (or thrombin potential) at peak was significantly higher after reviparin than after enoxaparin (367 +/- 53 UA vs 305 +/- 48 UA respectively, P < 0.05). Four hours after injection, thrombin potential was significantly correlated to plasma anti-Xa activity after reviparin but not after enoxaparin injection (r = 0.65, n = 10, P = 0.05 and r = -0.38, n = 10, P = 0.25 respectively). 5. After a single-dose injection in healthy subjects, two LMWHs with comparable in vitro activities differed slightly kinetically. Such minor differences are probably of little importance in the prevention of post-operative deep vein thrombosis, since these two LMWHs were previously shown to be comparable in this setting.
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PMID:Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers. 870 65

Dermatan sulfate is an antithrombotic glycosaminoglycan which has been shown to be effective in preventing deep venous thrombosis in general surgery patients when present at concentrations less than 1 microgram/ml. It has also been found to circulate physiologically in similar concentrations in pregnant women at term and in cord blood. We investigated the ability of dermatan sulfate added to plasma at 0.2, 0.5 and 1.0 microgram/ml to inhibit thrombin generation initiated by low concentrations of recombinant human tissue factor in defibrinated plasma. A dose dependent decrease in thrombin potential was demonstrated at therapeutically relevant concentrations of dermatan sulfate (0.5 and 1.0 microgram/ml) but there was no induction of a lag phase in thrombin generation. We were unable to demonstrate a significant effect on thrombin potential of dermatan sulfate at a concentration similar to that found in pregnancy plasma (0.2 microgram/ml). This indicates that either the dermatan sulfate concentration found in pregnancy plasma is not physiologically relevant or that our experimental system (which lacks platelets and fibrin) does not accurately reflect physiologic conditions. The effect on the thrombin potential was somewhat greater at the lowest concentration of tissue factor and amounted to a maximum inhibition of approximately 50% at 1 microgram/ml dermatan sulfate. A dose dependent increase in formation of thrombin-heparin cofactor II complexes and a decrease in thrombin-antithrombin complex formation with increasing dermatan sulfate concentration were observed at all dermatan sulfate concentrations. Prothrombin consumption was not changed by any dose of dermatan sulfate. We conclude that dermatan sulfate, at the concentrations tested, catalyses inhibition of free thrombin by heparin cofactor II but not efficiently enough to inhibit prothrombinase formation.
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PMID:The effects of dermatan sulfate at submicrogram/ml concentrations on in vitro thrombin generation. 872 17

A retrospective study of the management of patients with suspected acute deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) in a general and maternity hospital was conducted over a two month period in 1992. Ninety six patients with suspected DVT/PTE were identified, of whom only two were pregnant. Forty four patients had suspected DVT and confirmatory investigations were performed in 84%. The most common risk factor for DVT was intra-venous drug (IVD) use. Unfractionated heparin was prescribed to all patients except one with acute DVT at an average daily dose of 25,000 iu. In patients receiving heparin, 68% had measurements of the activated partial thromboplastin time (APTT) ratio and on 38% of occasions the result was subtherapeutic. Complications of heparin therapy were infrequent. Fifty two patients had suspected PTE and 50 underwent ventilation/perfusion (V/Q) scanning. No patient underwent pulmonary angiography. The management of patients with normal, low and high probability V/Q scans was in keeping with the guidelines, but only 8% [corrected] of patients with an intermediate V/Q scan result had further investigations and 33% received heparin. This study revealed suboptimal anticoagulation of patients with acute DVT and scope for improvement in the management of patients with an intermediate V/Q scan result.
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PMID:Management of suspected acute venous thromboembolism in a general and maternity hospital. 873 3

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.
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PMID:A fixed-dose combination of low molecular weight heparin with dihydroergotamine versus adjusted-dose unfractionated heparin in the prevention of deep-vein thrombosis after total hip replacement. 881 69


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