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 a familial study of AT III, a type III antithrombin III variant which was identified in the propositus by gene analysis as Pro 41 Leu heterozygous mutation. None of the four members of the family who presented with defective heparin cofactor (hep-cofactor) activity, and therefore probably carried the mutation, had experienced deep venous thrombosis. The abnormal AT III was purified from the propositus' plasma, taking advantage of the difference in NaCl concentrations required to elute variant and normal AT III from heparin-Sepharose. The antithrombin and anti-Xa activities of the purified variant AT III were comparable to those observed for normal AT III, but hep-cofactor activity was strikingly reduced. The enhancement by heparin of thrombin and F Xa inhibition by normal and variant AT III was compared in the absence of NaCl and in the presence of normal NaCl concentrations. The difference between the degrees of inhibition by normal and variant AT III was maximal at physiological ionic strength (i.e. at a concentration of 0.15 M). The quantification of heparin AT III interaction with both normal and variant purified proteins in a double reciprocal plot yielded similar dissociation constants but a 9-fold decrease in the maximal pseudo-first order constant. This suggests that Pro 41 is more involved in the molecular changes induced by heparin than in the primary binding of the activator.
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PMID:Clinical and biochemical characterization of antithrombin III Franconville, a variant with Pro 41 Leu mutation. 237 10

In a longitudinal study the plasma levels of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C were followed in two groups of patients with acute myocardial infarction (AMI), one with and one without deep vein thrombosis (DVT). None of the sequentially studied periods revealed significant differences between the two groups of patients. However, small but consistently higher levels of histidine-rich glycoprotein in patients with DVT suggested the existence among patients submitted for myocardial infarction of a subgroup with increased thrombophilic potential. It was concluded that the inhibitors studied are of little value as possible indicators of the presence of DVT at early stages of the disease when clinical signs are absent and when antithrombotic prophylaxis should preferably be initiated.
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PMID:On the significance of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C in patients with acute myocardial infarction and deep vein thrombosis. 241 53

A retrospective study is presented of 23 patients with congenital antithrombin (AT) III deficiency who underwent 57 operations of various types. Thromboprophylaxis was given in 28 operations. Dextran was used in most cases, sometimes in combination with specific AT III concentrate. No patient given AT III concentrate alone or in combination with other methods had signs of thromboembolism. Deep venous thrombosis followed four of the operations with prophylaxis (3 patients). After the 29 operations without prophylaxis there were three cases of deep venous thrombosis, one with clinical signs of pulmonary embolism and another with superficial thrombophlebitis. Despite its inherent drawbacks, this retrospective study indicated that AT III concentrate can effectively prevent postoperative thromboembolism. But as the selection criteria for thromboprophylaxis are difficult to evaluate, a prospective study should be of great value.
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PMID:Surgery in patients with congenital antithrombin III deficiency. 245 83

We describe a 43-year-old male patient with congenital antithrombin III deficiency requiring haemodialysis due to extension of venous thrombus from recurrent deep vein thrombosis. During dialysis with adequate heparinization, the patient often revealed clot formation in the extracorporeal circuit resulting in unexpected discontinuation of dialysis. When either a combination of antithrombin III concentrate plus heparin or the newly developed synthetic antithrombin preparation, MD805, was infused during dialysis, he could be uneventfully dialysed with either of the two regimens. The functional antithrombin III activity with MD805 increased to the same level as that obtained with antithrombin III concentrate, and it was possible to achieve an antithrombotic effect, as measured from the APTT and thrombin-antithrombin III complex with MD805 during and after dialysis. We thus found that MD805 could be used as an anticoagulant drug when an AT III-deficient patient required anticoagulation in the extracorporeal circulation.
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PMID:Choice of anticoagulant in a congenital antithrombin III (AT III)-deficient patient with chronic renal failure undergoing regular haemodialysis. 268 3

Sixteen patients with mesenteric venous thrombosis were reviewed retrospectively during a period from 1983 to 1987. Twelve patients had progressive abdominal pain, three had gastrointestinal bleeding, and one had general malaise. Seven of these 16 patients had previous deep-vein thrombosis. After negative routine gastrointestinal and hepatobiliary evaluation, 11 patients underwent an infusion computerized tomographic scan. Of these, 10 had superior mesenteric vein thrombosis; three of these 10 patients had portal vein thrombosis. Selective arteriography was done in two patients because of gastrointestinal bleeding, and a diagnosis of mesenteric vein thrombosis was made on the venous phase of the examination. The remaining four patients developed acute abdominal symptoms requiring surgical exploration, at which time mesenteric venous thrombosis was discovered. An identifiable coagulopathy was detected in nine patients (protein C deficiency in six, protein S deficiency in two, and factor IX deficiency treated with factor IX concentrate in one). No case of congenital antithrombin-III deficiency was identified. Six of these nine patients had a past history of deep venous thrombosis. Of five patients who underwent surgical exploration, all required bowel resection. In follow-up, two patients died of intestinal necrosis and a third died of associated pancreatic cancer. Thirteen patients were discharged from the hospital. Treatment of coagulopathy was by heparin in three patients and sodium warfarin (Coumadin) in four patients. Long-term anticoagulation was not instituted because of gastrointestinal bleeding in three and cirrhosis in three patients. Mesenteric venous thrombosis can occur without gangrenous bowel. Diagnosis should be suspected when acute abdominal symptoms develop in patients with prior thrombotic episodes and a coagulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mesenteric venous thrombosis. 172 86

Numerous investigators have postulated that a hypercoagulable state exists in humans for a period of time before the development of thrombotic episodes. A clear biochemical definition of the prethrombotic state, however, has proved elusive due in part to the lack of reliable techniques for monitoring pertinent changes in blood coagulability. Based on recent advances in our knowledge of the biochemistry of the coagulation system, a series of highly sensitive and specific immunochemical tools has been developed that can quantitate the activities of various steps of the hemostatic mechanism in vivo at the subnanomolar level. We have established assays for F1+2 and the protein C activation peptide, which measure the cleavage of the prothrombin molecule by factor Xa and the scission of protein C by the thrombin-thrombomodulin complex, respectively. Nossel and coworkers had previously constructed similar assays for fibrinopeptide A (FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by thrombin and the proteolysis of fibrin I by plasmin, respectively. Substantial elevations in the levels of these markers have been found in patients with disseminated intravascular coagulation and many subjects with acute deep venous thrombosis. The F1+2 and FPA assays have been used to demonstrate that significant increments in factor Xa activity but not thrombin activity regularly occur in the blood of nonanticoagulated individuals with congenital deficiencies of antithrombin or protein C. These two disorders are known to be correlated with the subsequent development of thrombosis. Patients with protein C deficiency have also been noted to have significantly reduced plasma levels of protein C activation peptide. By using the immunoassays for FPA and B beta 1-42 in studies of postoperative patients, it has been shown that an imbalance between the procoagulant action of thrombin and the anticoagulant effect of plasmin on fibrin I polymer may induce an acquired thrombotic diathesis. Finally, we have recently demonstrated that prothrombin activation as measured by the F1+2 assay is suppressed by oral anticoagulants in the blood of patients with thrombotic diatheses. These investigations suggest that these assay techniques can be used to improve our understanding of the hypercoagulable state as well as to develop more effective treatment strategies for the prevention of thromboembolic events.
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PMID:The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. 360 75

Antithrombin-III assays are performed to assess response to heparin therapy and efficacy of antithrombin concentrate therapy and in diagnosing hereditary thrombophilia, deep venous thrombosis, pulmonary embolus, and disseminated intravascular coagulation. Synthetic substrate assays for antithrombin-III are the methods of choice; however, most existing assay systems are semiautomated. A fully automated, antithrombin-III assay using the Kabi Chromogenic Synthetic Substrate S-2238 COATEST on the MULTISTAT III has been developed. This assay was compared with the Dade Protopath fluorometric assay. The correlation (r-sq) between the two assay systems was 0.82. Additionally, a three-way assay comparison was also performed, incorporating a new fluorometric substrate for antithrombin-III. The three-way comparative assays revealed correlation as follows: MULTISTAT III fluorometric assay and the MULTISTAT III/Kabi COATEST assay r-sq = 0.90; MULTISTAT III fluorometric assay and the Dade fluorometric assay r-sq = 0.86; and the MULTISTAT III/Kabi COATEST assay and the Dade Protopath fluorometric assay r-sq = 0.95. These automated assays were extremely cost effective and were a fraction of the cost of performing other types of antithrombin-III assays.
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PMID:Fully automated antithrombin-III assays by synthetic substrate on the Multistat III. 361 51

Chromogenic substrate (CS) assay of heparin may be performed with or without addition of antithrombin (AT) to the test plasma. Both types of assay are used for monitoring of heparin therapy, reflecting either heparin activity (heparin act), or heparin concentration (heparin conc) when AT is added. In plasma samples from 43 patients treated with intravenous heparin for DVT, the ratio between heparin act and heparin conc varied from 0.36 in patients with AT plasma concentration below 0.50 U/ml, to 0.85 in patients with AT above 1.00 U/ml (mean ratio 0.61). A formula expressing heparin act as a function of AT and heparin concentration in the test plasmas of the patients was used to calculate heparin act of the total material comprising 280 patients. Mean heparin act and heparin conc were both significantly correlated to clinical outcomes (bleeding complications, pulmonary embolism and phlebography score). For monitoring heparin therapy, guidelines for plasma heparin activity or concentration ("therapeutic ranges") are requested. When using a heparin act assay, the heparin dose needed in patients with low plasma AT concentration to reach a fixed therapeutic range, may imply undue risk of bleeding. On the other hand, when a heparin conc assay indicate plasma heparin conc within therapeutic range, antithrombotic activity may still be inadequate in patients with low plasma AT concentration.
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PMID:Monitoring of heparin therapy: should heparin assays also reflect the patient's antithrombin concentration? 362 42

Seven members of a family affected by hereditary antithrombin III deficiency were identified. The disorder was associated with recurrent spontaneous episodes of phlebitis, deep venous thrombosis, and pulmonary embolism in middle age. Danazol, a 17-alkyl derivative of ethinyl testosterone, which has been used to treat other antiprotease deficiency states, was assessed in the management of two men with antithrombin deficiency. In a dose of 600 mg a day danazol appeared to correct the antithrombin deficiency. This drug may provide a useful adjunct to anticoagulant treatment, particularly before surgery.
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PMID:Effect of danazol on the biochemical abnormality of inherited antithrombin III deficiency. 406 Jan 4

Plasma antithrombin (AT) measured as heparin cofactor activity decreased 0.16 +/- 0.13 U/ml (mean +/- SD) in 198 patients who received heparin infusion during 1 wk for deep venous thrombosis (DVT). The decrease was weakly, but significantly correlated to heparin dose (r = 0.15, p = 0.02) and to heparin plasma concentration (r = 0.12, p = 0.05). In patients with subnormal AT at start of heparin treatment, AT decreased less and tended to normalize at the end of heparin infusion, suggesting increased synthetic rate. The decrease in AT was apparently unrelated to the extension or the fate of the thrombus, and also unrelated to other patient and disease characteristics apart from a significantly higher decrease in diabetics. 5 out of 9 patients with AT values below 0.60 U/ml had serious disease, and 1 died from pulmonary embolism (PE) shortly after cessation of heparin (AT 0.22 U/ml). We conclude that the main decrease in AT occurs during the initial 3 d of heparin treatment. If AT stays above 0.70 U/ml after 3 d of treatment, further AT monitoring is hardly indicated.
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PMID:Changes in plasma antithrombin (heparin cofactor activity) during intravenous heparin therapy: observations in 198 patients with deep venous thrombosis. 408 34


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