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)

Mild hyperhomocysteinaemia is an established risk factor for deep vein thrombosis (DVT); few data concerning its potential interaction with thrombophilic genotypes are available at the present time. We investigated 121 thrombosis-free individuals and 111 patients with at least one objectively confirmed episode of DVT. A thrombophilic condition (deficiency in antithrombin, protein C and S, factor V Leiden, prothrombin G20210A) was detected in 25.2% of the patients; mutant factor V or prothrombin genotypes were present in 6.6% of the controls. Hyperhomocysteinaemia was found in 14.4% of patients and 3. 3% of the controls, with a 3.7-fold increase in risk for DVT (95% CI 1.1-12.3). Adoption of different cut-off levels for definition of hyperhomocysteinaemia did not substantially change the magnitude of the risk. Carriership of both hyperhomocysteinaemia and factor V Leiden or prothrombin G20210A was detected in 2.7% of patients for each combination and in none of the controls. An approximate estimate of 30-fold increased risk in carriers of both hyperhomocysteinaemia and factor V Leiden and 50-fold increased risk in carriers of both hyperhomocysteinaemia and prothrombin G20210A was calculated, suggesting a synergistic interaction between hyperhomocysteinaemia and such thrombophilic genotypes. Yet statistical analysis is highly unstable due to the small number of individuals with combined defects. Further investigations on large series of patients are needed.
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PMID:Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease. 1046 Jun 23

Hemostatic abnormalities were examined in 40 patients with deep vein thrombosis (DVT), 40 patients treated with warfarin, and 30 healthy volunteers. Plasma D-dimer levels were measured by an enzyme linked fluorescent assay (ELFA; Vidas-D-dimer) and an enzyme immunosorbent assay (ELISA; D-dimer-ELISA). Plasma levels of D-dimer, thrombin-antithrombin complex (TAT), soluble fibrin monomer (SFM) were significantly higher in patients with DVT than in the other groups. Both the sensitivity and specificity of D-dimer for diagnosis of DVT were the highest among hemostatic molecular markers examined. The most adequate cut off value of Vidas-D-dimer was 0.6 microgram/ml. Plasma levels of Vidas-D-dimer were well correlated with D-dimer ELISA, SFM and TAT. As the time of measurement for Vidas-D-dimer is less than one hour, the measurement of D-dimer using a EFLA might be useful for the diagnosis of DVT in bed side.
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PMID:[Plasma D-dimer levels in patients with deep vein thrombosis]. 1051 28

Inherited thrombophilic states are associated with an increased risk for deep vein thrombosis (DVT), but whether they are also risk factors for superficial vein thrombosis (SVT) is uncertain. We assessed the risk conferred by inherited thrombophilic states in patients with a first episode of SVT in whom the coexistence of DVT had been ruled out by ultrasonography. Sixty-three patients with SVT, after exclusion of patients with varicose veins, malignant or autoimmune disease, and 537 healthy individuals were investigated. The G1691A mutation in the factor V gene, the G20210A mutation in the prothrombin gene, and deficiencies of the naturally occurring inhibitors of coagulation (antithrombin, protein C, protein S) were searched. The prevalence of each thrombophilic state was higher in patients than in controls. The odds ratios for SVT were 6.1 (95% confidence interval [CI], 2.6 to 14.2) in patients with the G1691A factor V mutation, 4.3 (95% CI, 1.5 to 12.6) in those with the G20210A prothrombin mutation, and 12.9 (95% CI, 3.6 to 46.2) in those with deficiencies of the naturally occurring inhibitors of coagulation taken together. Risks did not substantially change when the analysis was restricted to 43 patients who had SVT as their only thrombotic manifestation, being 4.3 (95% CI, 1.5 to 12.3) in patients with factor V mutation, and 3.6 (95% CI, 1.0 to 13.1) in those with the prothrombin mutation. Among the circumstantial risk factors investigated (surgery, trauma, prolonged immobilization, oral contraceptives and pregnancy or puerperium), pregnancy or puerperium was the most frequently associated with SVT, being present in 38% of women. Our findings indicate that inherited thrombophilic states are associated with an increased risk for SVT. Hence, a laboratory search of these alterations is recommended in patients with SVT, because it allows the identification of patients at high risk of DVT in whom antithrombotic prophylaxis is particularly warranted.
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PMID:Genetic risk factors for superficial vein thrombosis. 1054

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46 v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.
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PMID:Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). 1055 90

Various pathogenic factors have been proposed to explain the abnormal hemostasis observed in AL amyloidosis. Since imbalance between clotting factors and inhibitors could play a pathogenic role in both hemorrhagic and thrombotic manifestations, we investigated the thrombin-antithrombin pathway in 35 patients with AL amyloidosis. Ten patients suffered from bleeding while 3 patients experienced deep venous thrombosis. Thrombin time was prolonged in 29 subjects, the mean values of antithrombin III activity (ATIII Act) were significantly lower than those of antithrombin III antigen (ATIII Ag) with loss of relationship between these two different techniques of ATIII detection, normally observed in healthy controls. In 19 patients increased levels of thrombin-antithrombin (TAT) complexes were present. Crossed immunoelectrophoresis of ATIII, performed in presence of heparin, evidenced ATIII forms with reduced binding capacity to heparin and TAT complexes of various electrophoretic mobilities. In conclusion, the impairment of the thrombin-antithrombin pathway, in association with the low ATIII biological activity, might play a pathogenic role in the hypercoagulable state reported in AL amyloidosis, despite the higher frequency of bleeding manifestations.
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PMID:Abnormalities in thrombin-antithrombin pathway in AL amyloidosis. 1061 48

During and following significant surgical intervention, deep venous thrombosis prophylaxis by application of anticoagulants is routinely used. However, patients with malignant disorders are subject to an especially high risk of deep venous thrombosis progressing in severe cases to subsequent pulmonary embolism. The present study focuses on appraising modern markers of deep vein thrombosis in 34 patients undergoing major maxillofacial surgery, with some malignant disorders. No significant differences between the two patient groups were noted using the markers of the kallikrein-kinin-system. From the first postoperative day plasma levels of the coagulation indicator thrombin-antithrombin-III complexes were significantly higher in the group of tumour patients. Markers of fibrinolysis indicated corresponding results: on the first postoperative day tissue-plasminogen activator values rose to 18.9 +/- 3.2 micrograms/l in the group of malignant patients, but only to 7.4 +/- 1.1 micrograms/l (P < 0.05) in the control group. Also postoperative D-dimer concentrations in the malignancy group were significantly above those of the control group. In the present study it could be demonstrated that patients with malignant neoplasia undergoing major maxillofacial surgery are exposed postoperatively to a particularly high risk of developing thromboembolic complications. All in all, the status of anti-thrombotic therapy requires reappraisal with respect to the current treatment approach adopted in tumour patients.
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PMID:Evaluation of markers of deep vein thrombosis in patients undergoing surgery for maxillofacial malignancies. 1062 61

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.
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PMID:Antithrombin agents: the new class of anticoagulant and antithrombotic drugs. 1072 36

A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW. The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk). Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy.
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PMID:Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis. 1076 96

We examined various nonSTAT commercially available coagulation activation markers in an attempt to help diagnose or exclude the often subtle clinical presentations of proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Fifty-five patients presenting to the Emergency Department were completely assessed. Eleven patients were diagnosed with PDVT, six patients were diagnosed with PE, and three patients were diagnosed with both PDVT and PE. Thrombus precursor protein (TpP) excluded the diagnosis in 19 of the 35 patients negative for PDVT and/or PE, D-Dimer in 15 patients, prothrombin fragment 1.2 in 17 patients, and thrombin-antithrombin (TAT) in 14 patients. Both the TpP and TAT enzyme-linked immunosorbent assay (ELISA) tests had 100% sensitivity and negative predictive value for evaluating PDVT and/or PE. The TpP ELISA had the highest specificity (54%) of all four markers studied.
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PMID:The use of thrombus precursor protein, D-dimer, prothrombin fragment 1.2, and thrombin antithrombin in the exclusion of proximal deep vein thrombosis and pulmonary embolism. 1084 25

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.
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PMID:Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states. 1093 61


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