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)

Dermatan sulphate (MF 701) is a natural glycosaminoglycan that catalyses thrombin inhibition by heparin cofactor II. The aim of the study was to evaluate the efficacy and safety of MF 701 for prevention of deep vein thrombosis (DVT) in patients with hip fracture. A randomised, double-blind, placebo-controlled design was used to assess two dose regimens of MF 701 in two consecutive study phases. Treatment was started within 48 h from the trauma and continued for 14 days for non-operated patients or until the 10th postoperative day. Bilateral mandatory venography was used to assess the end-point. Eighty patients were included in the first phase (40 MF 701, 40 placebo). MF 701, 100 mg IM b.i.d., did not reduce incidence of DVT from that on placebo and did not induce any bleeding. In the second phase 126 patients were included, with a randomisation ratio of 2:1 (84 MF 701, 300 mg IM b.i.d., 42 placebo). Bilateral venography was obtained for 110 patients. The incidence of DVT was 64% (23/36) in the placebo group and 38% (28/74) in the MF 701 group (p = 0.01; odds ratio [OR] = 0.34, 95% confidence limits [CL] = 0.15-0.80p; proximal DVTs were 42% (15/36) and 20% (15/74), respectively (p = 0.02; OR = 0.36, CL = 0.15-0.89). No significant differences were found in haemorrhagic complications (2.4% in each group), blood loss from drains, blood transfusions, haemoglobin and haematocrit values. This study is the first demonstration that dermatan sulphate is a clinically effective antithrombotic agent without bleeding effects. It also provides evidence of the biological role of heparin cofactor II.
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PMID:A randomised, double-blind, placebo-controlled trial of dermatan sulphate for prevention of deep vein thrombosis in hip fracture. 162 Dec 39

In human plasma, heparin cofactor II (HCII) is a thrombin inhibitor which displays similarities with antithrombin III (ATIII). As previously reported for hereditary ATIII deficiency, cases of recurrent thrombosis were reported in patients with hereditary HCII deficiency. Here, plasma HCII activity was studied in 372 patients with a history of thrombosis, classified according to their anticoagulant therapy. The mean plasma HCII level was significantly higher in patients with acute deep vein thrombosis (DVT) under heparin therapy than in patients with a history of thrombosis, who were studied more than 3 months after the acute event, and were either on, or had been on, oral anticoagulant therapy. HCII and fibrinogen were significantly correlated in all three groups of patients. These results were strengthened by those of a follow-up study in 23 patients with acute DVT. Changes in plasma HCII activity paralleled those of fibrinogen. This suggests that HCII might behave like an acute phase reactant in patients with thrombosis and that the measurement of its plasma level as a risk factor for thrombosis should be performed some time after the acute episode. In conclusion, the prevalence of HCII deficiency in patients with a history of thrombosis might have been underestimated in series which included patients with acute thrombosis.
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PMID:Heparin cofactor II: an acute phase reactant in patients with deep vein thrombosis. 171 66

6 patients with deep vein thrombosis triggered by drug therapy, that is oral contraceptives in 5 and the anticonvulsant tranexamic acid in 1, are described. These cases were among 40 symptomatic patients out of a total group of 81 with congenital coagulation inhibitor defects studied over 10 years at the Institute of Medical Semiotics, Padua, Italy. The 5 women with deep vein thrombosis ranged in age from 20-34, and had typically taken oral contraceptives containing 35 mcg ethinyl estradiol in combined or phasic preparations, for 1 to 8 cycles. One women, however, had been prescribed sequential pills containing 50 mcg mestranol. Another had taken oral contraceptives with impunity for 3 years, but developed deep vein thrombosis after taking tranexamic acid for 10 days. All recovered after heparin or oral anticoagulant therapy, except a 21 year old whose condition evolved into complete ileo-caval obstruction up to the renal veins, and was treated with urokinase. the congenital defects involved were 3 probable heterozygous true deficiencies of antithrombin III (low ATIII antigen and activity); a decreased protein C antigen to factor X antigen ratio; a heparin cofactor II deficiency; and a type I protein S deficiency (low free protein S, with normal total protein S and normal levels of C4B-bp.) While 5 of these 6 women had family histories of thromboembolic disease, the drug was prescribed without knowing that they were heterozygous for a coagulation inhibitor deficiency. The incidence of drug-induced thromboembolism was low in this series overall, where most of the events were triggered by surgery or trauma.
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PMID:The role of drugs, particularly oral contraceptives, in triggering thrombosis in congenital defects of coagulation inhibitors: a study of six patients. 178 39

A simple assay method of heparin cofactor II (HC II) activity is described. The procedure is based on the following principle: Antithrombin III (AT III) in plasma is inactivated by addition of an IgG fraction of goat serum after immunization of the animals against human AT III. Complete inactivation of AT III could be shown by absence of an anti Xa-effect of heparinized plasma treated with this antibody. Thrombin was only partially inhibited after inactivation of AT III. The characteristics of this inhibition were typical for the action of HC II. This method was applied for an assay of HC II activity. After optimizing of the method practical application in clinical routine screening was carried out. A diminution of HC II was observed in liver cirrhosis and in DIC but not in AT III deficiency. In 15 out of 269 cases of recurrent DVT there were HC II activities below 70% of normal. In 4 out of these patients activities of HC II were repeatedly between 44% and 52%. In arterial obstructive disease there was an HC II activity of less than 60% in 18 out of 583 patients and in 11 of them the HC II levels were repeatedly between 45% and 54%.
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PMID:Heparin cofactor II: a simple assay method and results of its clinical application. 342 87

Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III (AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the plasmas of cancer patients (1.56 +/- 0.09 nM) was significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5- and 2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo escapes inhibition in cancer and contributes to the high risk of DVT in malignancy.
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PMID:The hypercoagulable state in cancer patients: evidence for impaired thrombin inhibitions. 751 51

Dermatan sulphate catalyses thrombin inhibition by heparin cofactor II; it has a lower haemorrhagic to antithrombotic ratio than that of heparin in animal models. Consecutive patients aged forty years or more, electively undergoing total hip replacement under general anaesthesia, were randomly allocated to one of three dosage regimens of dermatan sulphate (MF701, Mediolanum Farmaceutici) given intramuscularly. These were 200 mg once daily (n = 50), 200 mg twice daily (n = 52) and 300 mg twice daily (n = 51), administered from twenty-four hours pre-operatively until the tenth postoperative day. The overall incidence of DVT assessed by bilateral venography was 53%, 51% and 34% respectively (Chi-square test for trend p = 0.06). The incidence of major proximal DVT was 10.6%, 8.5% and 2.1% respectively. Pulmonary embolism (PE) and bleeding were assessed in all 153 patients. There was one case of PE in each dose group. The incidence of bleeding episodes, volume of blood lost and blood transfusion requirements were low and showed no increase with increasing dose. The patients were followed up 4-8 weeks after discharge. We conclude that the two lower doses were subtherapeutic in this population, however dermatan sulphate given 300 mg twice daily, proved to be efficacious with an incidence of proximal major DVT of 2.1% and a low incidence of bleeding complications. A trial of dermatan sulphate 300 mg twice daily compared to standard prophylactic agents is needed.
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PMID:A dose ranging study to evaluate dermatan sulphate in preventing deep vein thrombosis following total hip arthroplasty. 774 Apr 43

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

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.
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PMID:New antithrombotic agents for the prevention and treatment of deep vein thrombosis. 897 41

This article addresses the issue of thromboembolic disorders associated with the prothrombin G20210A gene mutation, with heparin cofactor II (HC-II) defects and with primary (essential) thrombocythemia. The prothrombin gene mutation is of recent discovery, is inherited as an autosomal dominant disorder, and seems to be highly prevalent in the general white population. The incidence is almost as high as that known for factor V Leiden. Both venous and arterial thromboses are noted, especially deep venous thrombosis, including cerebral venous events and myocardial infarction. As with other congenital thrombophilic states, additional risk factors or multiple defects seem to precipitate the events. Although initially elevated plasma prothrombin levels were described in these patients, this is no longer valid for all patients. At this time there is no easy screening test to detect this defect, but, because of the high prevalence, prothrombin G20210A gene mutation should routinely be assayed for in thrombophilic patients. The association between HC-II defects and thromboembolism is more controversial, and reports both confirming and denying this association have been described. The congenital form of HC-II defect is autosomal dominant. HC-II can be determined by its activity and immunologically. HC-II defects very likely play a role in conjunction with other congenital or acquired defects. Acquired HC-II defects are found in association with systemic disseminated intravascular coagulation (DIC) but not with local activation of the hemostasis system. HC-II levels are also decreased in preeclamptic women, and newborns have physiologically low levels. HC-II defects in thrombophilic patients should be considered after the more common disorders have been ruled out. Primary (essential) thrombocythemia can be associated with both thromboembolic events and bleeding. Typical thrombotic manifestations are erythromelalgia and microvascular thrombosis. Also, pregnant females suffer high rates of complications, such as spontaneous abortion. A number of treatment modalities are at present available to not only decrease platelet counts but also manage thromboembolic events.
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PMID:Prothrombin G20210A gene mutation, heparin cofactor II defects, primary (essential) thrombocythemia, and thrombohemorrhagic manifestations. 1054 71

The antithrombotic activity of dermatan sulfate from avian crown with the mean molecular weight of 38000 was compared to those from bovine intestine with the mean molecular weight of 16000 in vivo and in vitro. In an in vitro test, bovine intestine dermatan sulfate exhibited stronger effects on stimulation of heparin cofactor II and activation of Glu-plasminogen by tissue plasminogen activator. In vivo, avian crown dermatan sulfate more effectively prevented the development of thrombus in a rat deep vein thrombosis model. The measurement of plasma levels of these two kinds of dermatan sulfate revealed that avian crown dermatan sulfate circulated in higher concentration and longer duration than bovine intestine dermatan sulfate after intravenous administration to rats.
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PMID:Antithrombotic activity of avian crown dermatan sulfate. 1063 69


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