Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin has a short half-life (8 to 12 hours) and therefore must be administered by continuous infusion or by intermittent subcutaneous injection. Intermittent subcutaneous injection may lead to fluctuation in the levels of anticoagulation attained. In correcting this deficiency, the programmable automated subcutaneous infusion pump in conjunction with weekly home nursing visits has been used. Eight pregnant women with documented deep venous thrombosis or embolic events before pregnancy who received such therapy were studied. Eight similar subjects who received intermittent subcutaneous injection, matched for age, parity, site of deep venous thrombosis, and days on a regimen of heparin therapy, served as the control group. The mean daily dose of heparin by subcutaneous infusion pump was higher (29,445 vs 13,822 U), resulting in smoother, more therapeutic heparinization (mean partial thromboplastin time, 20.6 vs 10.4 seconds above control) when compared with the intermittent subcutaneous injection group (p less than 0.05, p less than 0.007). There were two complications (hematoma, site infection) in the intermittent subcutaneous injection group while none occurred in the subcutaneous infusion pump group. When used in concert with weekly home visits, the subcutaneous infusion pump method of administration allowed more even control of anticoagulation, appeared to result in fewer complications (although not statistically significant), and subjectively was better received by patients than the intermittent subcutaneous injection technique.
...
PMID:Administration of heparin by subcutaneous infusion with a programmable pump. 147 20

Standard unfractionated heparin is a mixture of mucopolysaccharide chains of various length that may vary from 5000 to 30,000 daltons. Heparin is only effective as an anticoagulant in the presence of a plasma protein termed antithrombin III, with which it forms a complex. High- and low-affinity heparin are 2 types that readily bind or do not bind, respectively, to antithrombin III. The pharmacokinetics of unfractionated heparin are compatible with a model based on the combination of a saturable and a linear mechanism. The primary indication for intravenous infusion of conventional heparin is to prevent extension of an established arterial, venous or intracardiac thrombus. The average requirement is 400 U/kg/24h. Subcutaneous administration of 5000U of concentrated unfractionated heparin, administered every 8 or 12 hours, is effective and safe in the prevention of postoperative venous thrombosis and pulmonary embolism in patients at medium thrombotic risk. Adequate prophylaxis is also obtained in patients at high thrombotic risk if 5000U of heparin combined with 0.5mg dihydroergotamine is given subcutaneously 3 times daily, or by monitoring the 3 subcutaneous doses of heparin in order to maintain an adjusted activated partial thromboplastin time (APTT) of around 50 to 70 seconds. Low molecular weight heparins have been produced by a variety of techniques and their molecular weights range from 3000 to 9000 daltons. These preparations have a ratio of anti-factor Xa activity to anti-factor IIa activity of about 4, while the ratio for unfractionated heparin is 1. After intravenous administration of low molecular weight heparin, the half-life of the anti-factor Xa activity is considerably longer than for unfractionated heparin, while the anti-factor IIa half-lives are similar. In contrast to unfractionated heparin, low molecular weight heparin is completely absorbed after subcutaneous administration and its biological half-life is almost twice as long. In spite of certain differences with regard to the ratio between factor Xa and IIa inhibition, the various low molecular weight preparations show a rather similar absorption pattern. The bioavailability of all low molecular weight heparin fractions is substantially higher than that of unfractionated heparin, which renders their use more simple. Low molecular weight heparins less readily enhance platelet aggregation although there is no evidence that low molecular weight heparins are less antigenic or that they do not interact with platelet IgGFc receptor. A lower bleeding incidence for equivalent antithrombotic efficacy of fractionated heparins when compared to unfractionated heparins has yet to be established in humans.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Pharmacotherapeutic aspects of unfractionated and low molecular weight heparins. 196 34

Heparin fractions and fragments are useful tools in the elucidation of the mechanism of action of heparin and similar substances. The identification of portions with low or high affinity for antithrombin III and of a 'core' pentasaccharide responsible for anti-factor Xa activity has been possible thanks to heparin fractionation and fragmentation procedures. The development of low molecular weight heparins led to the production of substances with a molecular weight around 5,000, considerably variable in chemical structure, anti-factor Xa and anti-factor IIa activities, and experimental antithrombotic effects. The original rationale according to which fragments with high anti-factor Xa activity and anti-factor Xa/anti-factor IIa ratio would retain optimal antithrombotic activity with greatly reduced prohemorrhagic actions, turned out to be an oversimplification of the problem. In fact, neither is the anti-factor Xa activity the only determinant of the antithrombotic effect, nor is the anti-factor IIa activity a good predictor of hemorrhage. Despite disaggregation of the original rationale, low molecular weight heparins have already proved to be at least as effective and safe, and more conveniently and practically administered, as unfractionated heparin in the prophylaxis of deep-vein thrombosis.
...
PMID:Low molecular weight heparins: an introduction. 196 66

Kinetic analyses of antithrombin III (AT-III)-thrombin or heparin cofactor II (HC-II)-thrombin or AT-III-factor Xa interactions were carried out in the absence or in the presence of one of the sulfated xylans or unfractionated heparin or low molecular weight (LMW) heparin utilizing chromogenic substrates. These studies demonstrated that under pseudo first order conditions the inhibitions were proportional to the AT-III or HC-II concentrations used and the apparent second order rate constants determined from the slopes of the pseudo first order plots of log of thrombin or Xa remaining as a function of time were significantly elevated in presence of the sulfated compounds. On a molar basis oat spelts xylan sulfate was the most effective compound in accelerating the rate of thrombin-AT-III interaction followed by commercial heparin while the latter was most effective in accelerating the rate of thrombin-HC-II interaction. Heparin and LMW heparin were more effective in that order in accelerating the rate of Xa-AT-III interaction while oat spelts xylan sulfate, corn cob xylan sulfate, SP-54 were less effective than the heparins in that order. Studies were also conducted on the concentrations of the sulfated compounds required to inhibit by 50% the thrombin activity by AT-III or HC-II or that required to inhibit by 50% the factor Xa activity by AT-III. The results showed an inverse relationship between the increase in the rate of acceleration by the sulfated compound with the decrease in the amount required for 50% inhibition. SDS-polyacrylamide gel study of the reaction mixture containing thrombin, AT-III or HC-II along with heparin or oat spelts xylan sulfate showed that like heparin, oat spelts xylan sulfate potentiated the formation of thrombin-AT-III or thrombin-HC-II complexes which were stable in presence of denaturing or reducing agents. Chemical modification of arginine or lysine of AT-III significantly lowered its potentiation of thrombin or Xa inhibition by oat spelts xylan sulfate.
...
PMID:Mechanism of potentiation of antithrombin III and heparin cofactor II inhibition by sulfated xylans. 197 2

To evaluate the feasibility of long-term extracorporeal membrane oxygenation (ECMO) without heparin, we placed six lambs on standard venoarterial ECMO for 71 to 96 hours. Group 1 (3 animals) was given doses of heparin to maintain activated clotting times (ACT) greater than 400 seconds. No form of anticoagulant was used for the three animals in group 2. Blood flow was maintained at 60 mL/kg/min. No histological evidence of thrombosis was noted at necropsy. ACT, prothrombin time, and partial thromboplastin time were higher in group 1, and much lower, although still above normal in group 2. Fibrinogen was significantly lower in group 2 (75 +/- 35 v 219 +/- 64 mg/dL group 1), and, although the platelet count was lower in group 2 (142 +/- 76 x 10(3)/mm3 v 225 +/- 167 x 10(3)/mm3), it was clinically acceptable. These results encouraged us to discontinue heparin when faced with severe hemorrhage in four patients on ECMO, rather than withdraw support at a time when there was little chance of survival. Heparin was discontinued for 10.5 +/- 6 hours. The mean ACT was reduced from 220 +/- 23 seconds to 144 +/- 22 seconds. One patient, who required repair of gastric necrosis while on ECMO following repair of a congenital diaphragmatic hernia, survived and had a decrease in blood loss from 2 to 0 mL/kg/h after the heparin was discontinued. One of the three patients who died had an autopsy with no evidence of thrombosis. We conclude that it may be reasonable to discontinue heparin in the face of life-threatening hemorrhage while on ECMO.
...
PMID:ECMO without heparin: laboratory and clinical experience. 203 Apr 79

An in vivo thromboplastin (TP)-induced venous stasis thrombosis model in rabbits was used to compare the efficacy of standard heparin with the selective factor Xa inhibitors, recombinant tick anticoagulant peptide (rTAP) and recombinant antistasin (rATS), in prophylactic prevention of thrombus formation. Heparin significantly reduced TP-induced clot formation at doses of 55 and 100 U kg-1h-1 yielding clot weights of 9 +/- 4 and 6 +/- 2%, respectively. Clot formation was significantly decreased by i.v. infusions of rTAP at doses of 21, 37 and 64 micrograms kg-1 min-1 resulting in normalized clot weights of 13 +/- 3, 8 +/- 2 and 2 +/- 1%, respectively. rATS was approximately 10-fold more potent than rTAP, reducing normalized clot weights to 16 +/- 5, 2 +/- 1 and 1 +/- 0.8% at rATS doses of 1.25, 2.5 and 5.0 micrograms kg-1 min-1, respectively. These data suggest that factor Xa-mediated inhibition of coagulation with rTAP and rATS is as effective as conventional anticoagulant treatment with heparin in preventing venous thrombosis.
...
PMID:Comparison of the in vivo anticoagulant properties of standard heparin and the highly selective factor Xa inhibitors antistasin and tick anticoagulant peptide (TAP) in a rabbit model of venous thrombosis. 204 51

A method for the prevention of thrombotic complications with heparin was developed during examination of 30 elderly and old-aged patients who underwent operation for gastric carcinoma. It was established that the therapeutic activity of heparin in plasma is maintained for 6 hours after a single subcutaneous injection of 5,000 u. Four injections of this dose of heparin ensures its continuous therapeutic activity for 24 hours in elderly oncological patients. Heparin prevention in a daily dose of 20,000 u is safe from the standpoint of hemorrhagic complications. Under clinical conditions, control of plasma heparin activity may be accomplished by means of activated partial thromboplastin time.
...
PMID:[Use of heparin in the prevention of thrombotic complications in aged oncologic patients]. 206 46

Heparin, after subcutaneous administration, has been found to be able to bind to endothelial receptors both in rabbits and in humans. N-sulphonate 35S-heparin remains bound in rabbits for at least 24 h and is able to enhance the inactivation process of thrombin and factor Xa. Heparin subcutaneously (200 U/kg) injected for 2 weeks resulted in an enhanced inactivation of thrombin and factor Xa by the endothelium. The antithrombin-enhancing activity persists longer than the anti-Xa activity. In man, daily subcutaneous administration of heparin (12,500 U/day) for 2 weeks significantly reduces the increased fibrinopeptide A plasma levels and normalizes the increased 125I-fibrinogen turnover. The present work indicates that heparin administration at a low dose represents a treatment able to remarkably enhance the antithrombotic properties of the vessel wall, independently of the presence of detectable heparin levels in the circulating blood.
...
PMID:Low-dose heparin as an antithrombotic agent. 208 64

A 55-year-old woman was transferred to our institution from another hospital. The history of her present illness began 17 days earlier with a right-sided cerebral vascular accident (CVA). Three days later she had a superior mesenteric artery (SMA) embolus with infarcted bowel. Her small bowel was resected leaving about 20-25 centimeters of small bowel. A cardiac echo on hospital day 6 documented the presence of a left ventricular embolus, which was considered to be the cause of her CVA and SMA embolus. The cardiologists recommended lifelong anticoagulation, preferably with warfarin when technically feasible. After one month of warfarin therapy, with doses as high as 25 mg/d, the patient's prothrombin times (PTs) were not changed from baseline; however, this was probably due to concomitant therapy with vitamin K. Heparin was incorporated into her total parenteral nutrition (TPN) in preparation for her discharge. Because the TPN was cycled, she required subcutaneous heparin twice daily while off TPN. This patient's clinical course while she was maintained on heparin therapy was complicated by bleeding episodes and extensive thigh and abdominal hematomas, which led to erratic heparin absorption and widely fluctuating partial thromboplastin times. Ten months after the initiation of anticoagulation the patient was again tried on an oral warfarin regimen. She was successfully titrated to achieve the desired PT ratio. This case led to a review of the literature of patients with short-bowel syndrome requiring anticoagulation.
...
PMID:Oral anticoagulation in patients with short-bowel syndrome. 211 45

The protein C activity assay of Francis and Patch (Thromb Res 1983; 32: 605-613) is based on the prolongation of the activated partial thromboplastin time in the presence of activated protein C isolated from the test samples. The assay was modified and standardized by Rapaport et al. (Am J Clin Pathol 1987; 87: 491-497), but could still only be used in patients on heparin therapy after chromatographic removal of the heparin. In this study we attempted to eliminate the heparin separation step without losing the advantages of the modified (Rapaport) method. Heparin was added to the isolated protein C to obtain a rapid and complete antithrombin effect after the thrombin activation step and polybrene was subsequently used to neutralize the excess heparin. Using this modified assay protein C activity ranged from 67 to 133% in the normal population, and from 9 to 25% in coumarin-treated patients. Precision of the modified method was acceptable in both normal and pathological PC ranges: within- and between-batch variations were 5.6 and 3.6%, and 8 and 14%, respectively. The assay correlated well (r = 0.84) with the ELISA technique in both healthy donors and non-coumarin-treated patients.
...
PMID:The use of polybrene for heparin neutralization in protein C activity assay. 213 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---