Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-five patients with ischemic cerebrovascular disease (ICD) and 44 with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) have been investigated in a non-active state of the disease with VIIIR:Ag, plasminogen activator before and after stasis, antiplasmin, antithrombin (activity, antigen, activity/antigen ratio) and spontaneous platelet aggregation. Control groups of 20 respectively 80 healthy females and males were used in the study. VIIR:Ag was elevated in the group with deep venous thromboembolic disease compared with the ICD group and a control group. VIIIR:Ag in the ICD group was elevated compared with the control group. Plasminogen activator determined before and after stasis was lowered in the two diseased groups. There was no statistically significant difference in any of the blood coagulation variables between patients on or off coumarol treatment. The patients on courmarol were, however, not reinvestigated when this medication had been withdrawn. Antithrombin levels below the reference interval of the control group of 80 blood donors were found in 11.4% of the patients with DVT/PE, whiel no patient in the ICD group had low antithrombin values.
 ...
PMID:Blood coagulation studies in 45 patients with ischemic cerebrovascular disease and 44 patients with venous thromboembolic disease. 677 May 84

Antithrombin 3 (AT 3) is the most potent physiologic inactivator of thrombin and other serine proteases in the blood clotting mechanism. Hereditary deficiency of this protein is associated with recurrent deep vein thrombosis that begins in late adolescence. Untreated, this disease may lead to early death from recurrent and massive pulmonary emboli. Attempts to identify groups of patients most likely to develop thromboembolic disease because of an acquired deficiency of AT 3 have been frustrated by the lack of standardization of the assays and the inability to compare results of different AT 3 assays. The functional assays and immunoelectrophoretic determinations do not measure the same component. In order to compare the ability of current AT 3 procedures to determine levels of AT 3 in various disease states, we used immunoelectrophoretic, chromogenic, and clottable assays to measure AT 3 in patients with congenital AT 3 deficiency and with possible acquired AT 3 deficiency.
 ...
PMID:A comparison of antithrombin III procedures. 688 70

Fibrinogen is an independent risk factor for cardiovascular disease and both D-Dimer and Thrombin-Antithrombin complexes may be suitable as laboratory markers of deep venous thrombosis and are becoming more widespread in clinical practice. The aim of our study was to evaluate their normal range and to examine their correlation with various cardiovascular risk factors. Fibrinogen, D-Dimer and Thrombin-Antithrombin complexes were assessed in 516 normal subjects randomly selected from the National Health Service register of Trieste (Italy). In our community the mean value of fibrinogen was 283 +/- 71 mg/dl. Fibrinogen increases with age in males and was significantly higher in male smokers. In non-smokers, females had significantly higher fibrinogen values than males. The mean value of D-Dimer was 306 +/- 130 ng/ml. In females it is significantly higher. The fibrinogen and D-Dimer correlation coefficient was 0.20 (p < 0.001). The mean level of Thrombin-Antithrombin complexes was 6.25 +/- 6.8 ng/ml with a distribution markedly skewed towards the left; males had lower concentration than females (p = 0.047). Multiple regression analysis for fibrinogen as a dependent variable showed that D-Dimer, LDL-cholesterol, Body-Mass Index and Thrombin-Antithrombin complexes were poor predictors for fibrinogen plasma levels (R2 = 0.23) and that fibrinogen, ApoA1 and age can explain only about 10% of the observed variability in D-Dimer.
 ...
PMID:Fibrinogen, D-dimer and thrombin-antithrombin complexes in a random population sample: relationships with other cardiovascular risk factors. 809 84

Deep venous thrombosis (DVT) is associated with a genetic risk factor in about half of all cases. Antithrombin, protein C or protein S deficiencies account for 5 to 10 per cent of hereditary thrombophilia whereas the Arg 506 Gln factor V mutation is found in 20 to 30 per cent of DVTs and the G20210A factor II gene mutation in 5 to 10 per cent of them. The risk for DVT is increased three- to fourfold in women using oral contraceptives (OC); it is also increased during menopause hormonotherapy. Oestrogens modify the haemostatic balance, inferring a role in the thrombotic risk. The only thrombophilic factor which in association with OC was demonstrated to multiply the risk is the factor V Arg 506 Gln mutation, with a relative risk around 30. This observation reinforces the hypothesis that venous thrombosis is a multifactorial disease.
 ...
PMID:[Interaction of estrogens and genetic risk factors for thrombosis]. 1050 Apr 51

Antithrombin drugs represent a wide group of natural agents, recombinant agents equivalent to some of the naturally occurring proteins, and synthetic agents. This group of drugs is characterized by marked structural and functional heterogeneity. Several of these drugs are currently in various phases of development. Argatroban represents the first clinically approved antithrombin agent, which was made available in Japan several years ago. Two recombinant hirudin preparations, Revasc (Novartis) and Refludan (Aventis), are available for postsurgical DVT prophylaxis and alternate anticoagulant use in patients with heparin-induced thrombocytopenia. A synthetic antithrombin agent based on the combined structures of hirudin and antithrombin peptides, hirulog (Bivalirudin), is undergoing clinical trials in cardiovascular indications. Additional studies on the hirudins are being carried out to test their efficacy as surgical and interventional anticoagulants as replacements for heparin. However, the need for a proper antagonist is one of the limiting factors for the optimal development of hirudin in this indication. Several of the synthetic thrombin inhibitors are also being developed for oral use for the prophylaxis of DVT in surgical patients. Since the therapeutic index of thrombin inhibitors is narrower than that of heparin, this route may not be an optimal approach for the development of these agents. Despite several unresolved developmental issues, the thrombin inhibitors provide a useful alternative to heparin anticoagulation and may prove to be useful in validated clinical use.
 ...
PMID:Antithrombin agents: the new class of anticoagulant and antithrombotic drugs. 1072 36

Since the first patient with antithrombin deficiency was reported, various hereditary thrombophilia have been discovered. However, we experienced a family line of multiple thrombosis in which known hereditary thrombophilia were all refuted. Case 1 died of inferior vena cava thrombosis at the age of 56 days. Case 2, the elder sister of Case 1, developed deep vein thrombosis of the left leg at age 2. She was started on warfarin but contracted deep vein thrombosis of the right leg at the age of 7. In the family of these cases there have been another five cases of thrombosis, spanning three generations, giving a total of seven cases. Six of the cases developed at an early age, below 50 years. Antithrombin, protein C, protein S, heparin cofactor II, soluble thrombomodulin, plasminogen, alpha 2 plasminogen inhibitor, and tissue factor pathway inhibitor were measured but there were no abnormalities, nor was there any resistance to activated protein C. The onset of thrombosis in this family is becoming younger with the passing of generations, and clinical symptoms have been showing a worsening tendency.
 ...
PMID:[A family with multiple thrombosis including infancy occurrence]. 1157 53

Antithrombin is one of the main endogenous anticoagulants and its deficiency is associated with deep venous thrombosis. The aim of the present study was to evaluate the prevalence of antithrombin deficiency in patients with chronic lower extremity ulcers. Forty-eight patients with chronic lower limb ulcers for longer than 10 years, evaluated during 1997, were studied: 40 were female (83.3%) and eight were male (16.6%), with ages ranging from 43 to 73 years (mean, 55.2 years). Antithrombin was dosed by the coagulometric method, with evaluation of the functional activity. Measurement was repeated in those cases where deficiency was found to be present. The highest prevalence rate for antithrombin deficiency in the general population was one in every 2000 cases. Data analysis was performed by utilizing the odds ratio with a confidence interval of 95% and P < 0.05. Deficiency in antithrombin levels was recorded in two (4.1%) of the patients with chronic ulcer. These results indicate a higher prevalence rate of antithrombin deficiency in those patients with chronic leg ulcers, suggesting that an association may be present. Further studies with a larger number of patients are required to confirm this hypothesis.
 ...
PMID:Prevalence of antithrombin deficiency in patients with chronic leg ulcer. 1168 49

As a result of advanced technology, dramatic developments in the area of new anticoagulant and antithrombotic drugs appear to have made a profound impact on the use of LMWHs. Furthermore, because porcine mucosal heparin is used for the preparation of these agents, it is likely that alternative drugs with comparable pharmacologic and clinical efficacy are sought. Antithrombin drugs such as argatroban and hirudin are already approved for alternative management of heparin-compromised patients. Their efficacy in other indications is less superior. The development of specific anti-Xa drugs is slow. Although these agents may inhibit factor Xa and thrombin generation, none of them are capable of mimicking the polytherapeutic effects of LMWHs and thus can only be given in drug combinations. Synthetic and recombinant protein-derived anti-tissue factor agents have also been developed. These drugs only inhibit the tissue factor-mediated process and are limited in their therapeutic spectrum. Plasma-derived and recombinant serine protease inhibitors (serpins) are also available for the management of thrombotic and inflammatory disorders, but these agents cannot be given subcutaneously. Furthermore, because they are proteins, antibodies to these agents are generated. Nucleic acid derivatives (natural and synthetic aptomers) are developed for intravenous administration, but they are relatively weak antithrombotic agents. Dermatans, heparans, and chondroitin sulfates represent nonheparin GAGs, and, in mono-compositional and polycompositional form, these drugs are mainly used for the intravenous management of DVT prophylaxis. They can be given to patients who are heparin compromised. Synthetic heparinomimetics include heparin consensus-binding oligosaccharides and synthetic oligosaccharides with non-serpin affinity. In addition, binding oligosaccharides are conjugated with antithrombin agents to mimic the anti-Xa/anti-IIa activities of heparin. Biotechnology using bacterial and yeast cultures, aqua cultures for marine products, and plant carbohydrates have been the focus of developing heparin analogues. Development of these agents is in the early phase; however, it is likely that this approach may provide a reasonable alternative to LMWHs. Despite these developments, it is unlikely that any of these drugs will have a profound impact on the use of LMWHs in the near future. Unfractionated heparin and LMWHs collectively represent an important group of polypharmacologic drugs without which the management of thrombosis and vascular disorders would not be possible. The continual development of LMWHs in expanded indications did not comprise the use of unfractionated heparin in surgical and interventional cardiovascular indications. Ever since their introduction in the 1980s, the use of LMWHs has continually increased. This is primarily because of expanded indications and growing awareness among the clinicians. It is likely that once an antidote is developed and additional information is available on the mechanism of action of LMWHs, these drugs may gradualty be used for surgery patients. Despite these developments, it is likely that unfractionated heparin will continue to be used for specific indications. Drug combinations with heparins may necessitate dose adjustments, but it is unclear whether unilateral reduction of heparins will be optimal. The coming years will provide useful clinical and applied data on the improved use of unfractionated heparin. LMWHs, and pentasaccharide in the management of thrombotic and cardiovascular disorders. In addition, use of these drugs will be extended to many conditions, including cancer, inflammation, sepsis, and autoimmune diseases. Polytherapeutic approaches emphasizing LMWHs as primary and secondary drugs will also have an impact on the management of thrombotic and nonthrombotic disorders. Ultra-LMWHs and synthetic heparinomimetics, such as fondaparinux, that exhibit a narrow pharmacologic spectrum will only be useful in specific indications and in combination with other drugs.
 ...
PMID:Heparin, low-molecular-weight heparins, and heparin pentasaccharide: basic and clinical differentiation. 1262 73

During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.
 ...
PMID:Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations. 1832 12

Antithrombin is a potent inhibitor of the coagulation cascade exerting its primary effects on activated factors X, IX and II. It is the mechanism by which heparin and low-molecular weight heparin cause anti-coagulation. Deficiency of antithrombin presents as a hypercoagulable state, and may result in unexplained deep venous thrombosis, arterial thrombosis and systemic embolization.
 ...
PMID:Acute mesenteric and aortic thrombosis associated with antithrombin deficiency: a rare occurrence. 1993 50


1 2 Next >>