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)

To evaluate the effects of the short-term, high-dose sodium heparin therapy on biochemical markers of bone metabolism, we studied 20 patients (11 males and 9 females) with pulmonary embolism, treated with sodium heparin (daily dose range: 40,000-45,000 I.U. by continuous i.v. infusion). Heparin therapy lasted 5-7 days, after which patients received warfarin over 12 months. Eleven patients (6 males and 5 females) with ischaemic stroke, treated with i.v. glycerol and pentoxifilline, were used as controls. Before and after therapy serum and urinary markers of bone metabolism were evaluated; in 12 heparin-treated pts., the parameters were also evaluated 4 months after discontinuation of warfarin therapy. After heparin therapy a significant reduction vs. basal value was observed in levels of serum osteocalcin (ng/ml;mean + SEM): 3.32 & 0.19 vs. 2.05 + 0.21; p < 0.001. In the 12 patients evaluated 4 months after discontinuation of warfarin therapy, serum osteocalcin levels returned to basal value: 3.41 + 0.12 ng/ml (p:n.s.). No significant changes of the examined parameters were observed in controls. In conclusion, our data seem to indicate an effect of i.v. short-term heparin therapy on bone metabolism. This effect seems to be characterized by an inhibition of osteoblast function as suggested by the reduction of serum osteocalcin levels.
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PMID:Effects of short-term, high dose, heparin therapy on biochemical markers of bone metabolism. 860 85

The low molecular weight heparin (LMWH) dalteparin sodium is notable for its improved pharmacokinetic characteristics (chiefly increased bioavailability and plasma elimination half-life) compared with unfractionated heparin (UFH). These properties enable the drug to be given subcutaneously as a single daily dose, compared with the 8- to 12-hourly regimens necessary with UFH. Dalteparin sodium also appears to exert a greater inhibitory effect than UFH on plasma activity of coagulation factor Xa relative to its effects on clotting times [usually expressed as activated partial thromboplastin time (APTT)] and activity of factor IIa. It is not associated with any clinically significant effects on the fibrinolytic system and may have less lipolytic activity than UFH. Extensive clinical studies have been conducted to compare the antithrombotic efficacy of dalteparin sodium with that of UFH in surgical thromboprophylaxis, treatment of established deep vein thrombosis (DVT) and the anticoagulation of patients undergoing haemodialysis and haemofiltration. The majority of trails of patients receiving thromboprophylactic heparin perioperatively have shown similar efficacy of dalteparin sodium and UFH in the prevention of DVT and pulmonary embolism (PE), although 2 groups of investigators reported superior antithrombotic potency for dalteparin sodium. The two types of heparin appear similarly effective in the management of established DVT and the maintenance of the extracorporeal circulation in haemodialysis circuits. Dalteparin sodium has also shown clinical benefit in the management of patients with unstable angina or non-Q-wave myocardial infarction. The overall incidence of haemorrhagic complications observed with daltparin sodium therapy is no greater than that associated with UFH, and data suggest that perioperative transfusion requirements and frequency of bleeding are lower after dalteparin sodium. The antithrombotic efficacy of dalteparin sodium is at least equivalent to that of UFH, although further clinical comparisons with other LMWHs are required. Further studies are also needed to clearly define any advantages of dalteparin sodium over UFH (and other antithrombotics) with regard to the incidence of haemorrhagic complications. The drug has also shown clinical efficacy in the prevention of myocardial infarction and death in patients with unstable coronary artery disease. In addition, there may be cost advantages attached to the once-daily subcutaneous regimen of dalteparin sodium, but this requires further examination. Thus, dalteparin sodium is an effective antithrombotic agent for perioperative thromboprophylaxis, the management of established DVT, and the anticoagulation of patients undergoing haemodialysis.
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PMID:Dalteparin sodium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. 884 43

Although venous thromboembolism has occasionally been reported after hospital discharge in patients who have undergone total hip replacement (THR), this risk has not been fully quantified and the usefulness of a prophylactic treatment has not been evaluated. We conducted a single-centre prospective randomised double-blind clinical trial in 2 parallel groups of patients who had undergone THR and were free of deep venous thrombosis (DVT) at discharge, as assessed by bilateral ascending venography. During hospitalisation, all patients received a low molecular weight heparin, enoxaparin (enoxaparin sodium), as a prophylactic treatment for venous thromboembolism. Just before hospital discharge (15 +/- 1 days from surgery) 179 consecutive patients were randomly assigned to receive subcutaneous enoxaparin 40mg (n = 90) or placebo (n = 89) once daily for 21 +/- 2 days. The primary efficacy outcome was defined as the occurrence of DVT and/or documented pulmonary embolism (PE). DVT was assessed by ascending bilateral venography performed 21 +/- 2 days after randomisation or earlier if necessary. Secondary efficacy outcomes were the occurrence of proximal and distal DVT. Safety outcomes were defined as the occurrence of major and minor haemorrhage, other adverse events and changes in laboratory parameters. All patients underwent a 3-month follow-up. There were no deaths or cases of clinical PE during the study and the follow-up periods. In 173 patients with evaluable venograms, analysis of efficacy on an intention-to-treat basis showed that the incidence of DVT at day 21 was significantly lower in the enoxaparin group (6 of 85; 7.1%) than in the placebo group (17 of 88; 19.3%; p = 0.018), a risk reduction of 63%. Distal DVT was less frequent in the enoxaparin group than in the placebo group (1.2 vs 11.4%; p = 0.006) but there was no significant difference between groups in the incidence of proximal DVT. A 'per-protocol' analysis of efficacy in 155 patients confirmed the results for total and distal DVT, but also showed a trend in efficacy in favour of enoxaparin with regard to the incidence of proximal DVT (p = 0.064). Enoxaparin was safe in comparison with placebo: only 2 minor bleedings occurred in the enoxaparin group and there was no difference in the incidence of other adverse events between the 2 groups. In patients undergoing THR, the risk of late-occurring DVT remained high during the 21 days after hospital discharge in the placebo group. Prophylactic treatment with enoxaparin reduced the risk and was well tolerated in this context.
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PMID:Efficacy and safety of postdischarge administration of enoxaparin in the prevention of deep venous thrombosis after total hip replacement. A prospective randomised double-blind placebo-controlled trial. 904 60

A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.
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PMID:A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke. 923 47

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common life threatening complications of acute myelopathy. Prophylaxis with low dose unfractionated heparin (LDUH) has been the standard of care. Studies suggest that low molecular weight heparin (LMWH) has superior efficacy, but advantages may be offset by higher expense. Since LMWH (enoxaparin sodium) became available, standard practice at our institution has been to treat all inpatients with myelopathy with LMWH. To examine the impact of this practice, all inpatients diagnosed with myelopathy and treated with LMWH were sequentially matched by diagnosis and compared in a retrospective review with inpatients treated with LDUH. In each group, 11 patients had traumatic injury, four had transverse myelitis, four had neoplasms and five had spinal stenosis. Characteristics of the LMWH/LDUH groups were: mean age--48.5/50.4; spinal level--cervical 13/7, thoracic 9/12, lumbar 2/5; American Spinal Injury Association impairment scale-A, 8/9; B, 2/2; C, 8/5; D, 6/8. There were five DVTs and two PEs in five patients taking LDUH; there were no cases of DVT or of PE in the LMWH group (p = 0.04, two-tailed chi-square test). Isolated DVTs occurred in two patients with traumatic injuries and in one patient with transverse myelitis; PE + DVT occurred in one patient with a primary and one patient with a metastatic tumor. All developed within 3.5 months of the onset of spinal dysfunction. One patient with a traumatic injury on ibuprofen and dexamethasone had a gastrointestinal hemorrhage while receiving LMWH. The cost of administration of LMWH was $24,499 compared with $5,700 for LDUH. The LDUH group spent a total of 57 days in an acute care facility, costing $57,000.00 and patients treated with LMWH spent nine days, costing $9,000.00. We conclude that treatment with LMWH was associated with a significant decrease in incidence of DVT/PE and an overall decline in health care costs of approximately $30,000 or approximately $1,250 per patient.
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PMID:A comparison of low molecular weight heparin and low dose unfractionated heparin prophylaxis in subacute myelopathy. 936 Feb 20

Intravenous heparin followed by oral warfarin sodium is effective for preventing recurrent thromboembolism in patients who have pulmonary embolism or proximal vein thrombosis. The effectiveness of intravenous heparin depends on obtaining an adequate anticoagulant response early during therapy. A validated heparin protocol should be used to ensure that an adequate anticoagulant response is obtained as soon as possible. Low molecular weight heparin has the practical advantage that it does not require monitoring and dose finding. If thrombolytic therapy is indicated, it is safer for many patients to base management on the noninvasive diagnosis rather than performing pulmonary angiography. In patients suspected to have pulmonary embolism who have nondiagnostic lung scan and adequate cardiorespiratory reserve, serial noninvasive leg testing is a practical approach that avoids pulmonary angiography, identifies patients who have proximal vein thrombosis requiring treatment, and avoids the risks of anticoagulant treatment in the majority of patients.
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PMID:Anticoagulants and thrombolysis in the treatment of pulmonary embolism. 936 67

A prospective, randomised, controlled clinical trial was carried out in order to elucidate the incidence of venous thromboembolism in selected patients undergoing laparoscopic cholecystectomy and other types of minimally invasive surgery, as well as to show safety and efficacy of a low-molecular-weight heparin (LMWH) in the prevention of post-operative venous thromboembolism. Seven hundred and eighteen patients were randomly allocated to one of two groups: One group received physical measures for prevention of deep-vein thrombosis, i.e. graduated elastic stockings (n = 359). The second group also received graduated elastic stockings and, additionally, a LMWH (reviparin sodium, Clivarin) s.c. once daily (n = 359). For safety reasons, with respect to the untreated control group, patients with three or more risk factors for venous thromboembolism were not included into the trial. Diagnosis for DVT was systematically done by duplex scan. In this, rather artificial low-risk selection the overall incidence of thromboembolic events was surprisingly low: five cases of suspected pulmonary embolism, confirmed by scintigraphy in one case only, and one patient with phlebographically confirmed calf vein thrombosis. The use of reviparin for prevention of venous thromboembolism was safe and convenient--the rate of post-operative bleeding complications was 2.3% in the LMWH group, even lower than in the control group (3.2%). The real incidence of venous thromboembolism in patients undergoing laparoscopic cholecystectomy remains unclear. Further trials with unselected patients are needed.
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PMID:[Prevention of thromboembolism in minimal invasive interventions and brief inpatient treatment. Results of a multicenter, prospective, randomized, controlled study with a low molecular weight heparin]. 948 55

A 51-year-old woman with a large uterine myoma suffered from acute pulmonary thromboembolism. Venography revealed thrombosis in the right common iliac vein and almost complete obstruction of the left common iliac vein. The ascending lumbar vein showed collateral drainage. Treatment was initiated with continuous intravenous heparin sodium, and a Greenfield filter was inserted to prevent the extension of the pulmonary embolism during and after hysterectomy. After a total hysterectomy, venography revealed restoration of patency in the bilateral common iliac veins, and no flow was seen in the ascending lumbar vein. Thorough clinical examinations failed to identify any other prothrombotic conditions. These results suggest that a large uterine myoma compressed veins in the pelvis, and the resulting impaired blood flow caused deep venous thrombosis and pulmonary thromboembolism.
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PMID:Deep venous thrombosis and pulmonary thromboembolism associated with a huge uterine myoma--a case report. 1070 25

Hysteroscopical myomectomy has recently become popular in Japan. We present two patients who developed water intoxication and air embolism during surgery. [Case 1] Hysteroscopical myomectomy was performed under general anesthesia in a 37-yr-old woman (ASA I). Three hours after the start of the surgery, the patient's serum sodium concentration dropped to 118 mEq.l-1. She was treated with furosemide and recovered without sequelae. [Case 2] A 39-yr-old woman (ASA I) was scheduled to have hysteroscopical myomectomy under spinal and epidural anesthesia. Forty-five minutes after the start of the surgery, the patient complained of severe back pain, her blood pressure decreasing to 40 mmHg, SpO2 decreased to 80%, and ECG showed atrial fibrillation. After administration of ephedrine 5 mg, she recovered within 20 min. No abnormality was observed in echocardiogram, although some negative spots were detectable in a lung scintigraphy. She was discharged without sequelae. The hysteroscopical procedure is considered a non-invasive surgery, but the cases presented here emphasize the necessity for close attention to complications, especially pulmonary embolism.
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PMID:[Complications of hysteroscopical myomectomy: a report of two cases]. 1102 64

Tinzaparin, a sodium salt of a low-molecular-weight heparin (LMWH) produced via heparinase digestion, is used for the treatment of deep vein thrombosis (DVT) and pulmonary embolism in conjunction with warfarin for the prevention of DVT in patients undergoing hip or knee replacement surgery, and as an anticoagulant in hemodialysis circuits. Its average molecular weight ranges between 5500 and 7500 daltons (Da); the percentage of chains with molecular weight lower than 2000 Da is not more than 10% in the marketed tinzaparin formulation. While this fraction is generally considered pharmacologically inactive, this has never been evaluated in vivo. The importance of the < 2000 Da fraction on the anticoagulant pharmacodynamics of tinzaparin assessed by anti-Xa and anti-IIa activity was studied in a two-way crossover trial. In this trial, 30 healthy volunteers received a single 175 IU/kg subcutaneous administration of tinzaparin containing approximately 3.5% of the < 2000 Da fraction and a tinzaparin-like LMWH containing 18.3% of the < 2000 Da fraction. The anti-Xa/anti-IIa ratios of the drug substances were comparable at 1.5 and 1.7 for tinzaparin and the tinzaparin-like LMWH, respectively. Both formulations were safe and well tolerated. Mean maximum plasma anti-Xa activity (A(max)) was approximately 0.818 IU/ml at 4 h following tinzaparin injection. Mean maximum plasma anti-IIa activity was 0.308 IU/ml at 5 h postdose. Intersubject variation was lower (< 18% for both anti-Xa and anti-IIa metrics) than in previous fixed-dose administration studies. There was no correlation between anti-Xa or anti-IIa AUC or A(max) and bodyweight in the present study supporting the weight-adjusted dosing regimen. Individual anti-Xa and anti-IIa profiles following the single 175 IU/kg subcutaneous administration of the tinzaparin-like LMWH were similar to that obtained with tinzaparin. Based on average equivalence criteria, the two LMWH preparations were determined to be bioequivalent using either anti-Xa or anti-IIa activity as biomarkers. The calculated intrasubject variabilities were low (< 14% for anti-Xa activity and < 18% for anti-IIa activity) yielding little evidence for a significant Subject x Formulation interaction. In summary, anti-Xa and anti-IIa activity following a single subcutaneous administration of tinzaparin 175 IU/kg to healthy volunteers yielded activity consistent with targeted therapeutic levels derived from previous trials in adult DVT patients. Weight-based dosing for the treatment of DVT appears rational based on the reduction in anti-Xa and anti-IIa variability consistent with the recommendation derived from earlier fixed-dose pharmacokinetic studies. Furthermore, differences in the percentage of molecules in the < 2000 Da molecular weight fraction of tinzaparin do not translate into differences in anti-Xa and anti-IIa activity in vivo.
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PMID:Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous administration to healthy volunteers. 1124 85


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