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)

An assay measuring the thrombin inactivating effect of human plasma in the presence of dermatan sulfate (DS) is described. Test plasma, diluted 1/50, is incubated with human thrombin in the presence of DS. Remaining thrombin is determined with chromogenic substrate 2AcOH . H-D-CHG-Ala-Arg-pNA. Three dilutions of reference plasma suffice and the standard curve is linear. Antithrombin III (AT) exerts a small (3-8%) effect in the assay. When test plasma contains heparin above 0.05 U/ml, this unspecific effect of AT increases, but it may be abolished by antibodies against AT. In a normal material (n = 50), the SD of DS cofactor activity was greater (15%) than that of AT (8.7%). DS cofactor was normal in hereditary AT deficiency and in 15 patients with deep venous thrombosis. In liver cirrhosis and in DIC, both inhibitors were markedly depressed, to similar degrees (r = 0.84).
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PMID:Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. 654 86

A point mutation in coagulation factor V which causes resistance to cleavage of factor Va by activated protein C (APC), was recently found to underlie thrombotic events. We examined 20 consecutive patients, under the age of 40, who suffered from idiopathic venous or arterial thrombosis. In 8 (40%) there was resistance to APC manifested by absence of the expected prolongation of activated partial thromboplastin time (aPTT). In 3, the addition of normal plasma corrected the anomaly in the patient's plasma, although the addition of factor V- deficient plasma caused no change. In a family of a 17-year-old boy with idiopathic deep venous thrombosis we found a mutation in factor V which was responsible for APC resistance. The patient and 4 family members showed a single G to A transition in position 1691 in their cDNA, resulting in substitution of arginine (506) for glutamine. The mutation in this area, which is the cleavage site for APC, is associated with thrombotic episodes and is frequently observed in patients with familial thrombophilia.
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PMID:[Resistance to activated protein C--a novel cause of thrombophilia]. 755 99

This paper reports the case of an adult patient with severe protein C(PC) deficiency. She had the first deep vein thrombosis when she was 14 years old and developed skin necrosis when oral anticoagulant treatment was started. The same sequence of thrombotic complications recurred several times. Analysis of the PC gene coding sequences allowed two mutations (Arg-1 to His and Arg 178 to Gln) to be identified in this compound heterozygote. Oral anticoagulant treatment during PC concentrate infusion and low-molecular-weight heparin administration was successful and uncomplicated.
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PMID:Protein C infusion in a patient with inherited protein C deficiency caused by two missense mutations: Arg 178 to Gln and Arg-1 to His. 779 52

A dysfunctional protein C (PC) molecule (Protein C Padua 2) was found in a 40-year-old man presenting with recurrent deep vein thrombosis/pulmonary embolism and a family history of thrombotic disease. The patient exhibited a normal PC antigen level, normal chromogenic activity (using Protac as PC activator) but markedly reduced coagulometric activity. After adsorption of patient plasma onto Al(OH)3, between 30% and 45% PC antigen/chromogenic activity but no coagulometric activity was detectable in the supernatant. The dysfunctional molecule exhibited reduced affinity for a Ca++ dependent anti-protein C monoclonal antibody as detected by specific ELISA assay. Immunoblotting experiments showed that PC Padua 2 had an increased MW (95 kD v 65 kD for normal PC). The lesion responsible was determined by PCR/direct sequencing to be a heterozygous CGT/TGT transition in exon 3 of the protein C gene resulting in the substitution of Arg by Cys at residue--1 in the pro-peptide leader sequence. The presence of a high MW PC was consistent with the fact that (part of) the propeptide (at least Cys-1) still was attached to the protein C molecule. This finding could also explain the strongly reduced affinity of PC Padua 2 for the Ca++ dependent anti-protein C monoclonals.
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PMID:A novel dysfunctional protein C (protein C Padua 2) associated with a thrombotic tendency: substitution of Cys for Arg-1 results in a strongly reduced affinity for binding of Ca++. 813 74

A patient with recurrent deep vein thrombosis and heterozygous type II deficiency, characterized by reduced protein C activity in both amidolytic and clotting functional assays, was investigated by direct sequencing of PCR fragments derived from the coding portion of the protein C gene. AG (8856) to A transition was noted in the patient which was not present in healthy controls. This mutation is predicted to cause the substitution of Ser for Gly 381, an evolutionari'y conserved residue in the substrate binding pocket of serine-proteases (Gly 216, chymotrypsin numbering). A computer model of the structure of the serine-protease domain indicates that the properties of the altered protein C molecule can be explained on the basis of steric hindrance between the substituted serine and the substrate arginine side chains.
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PMID:Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket. 839 32

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.
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PMID:[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. 852 25

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20% to 30% of patients with a history of deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5 to 10 fold in heterozygotes, and 50- to 100- fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis or in the occurrence of myocardial infarction.
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PMID:[Activated protein C resistance: role in venous and arterial thrombosis]. 876 Jun 61

Resistance to activated protein C (APC resistance) was measured in 284 individuals (169 females, 115 males) with a history of objectively confirmed venous thrombosis and/or pulmonary embolism. A decreased APC resistance ratio was found in 75 patients (26%), 47 were females, 28 males. Factor V Leiden was investigated in 60 of 75 patients with APC resistance, of whom 46 were heterozygous, 4 homozygous. In 10 APC resistant patients the Arg 506 Glu mutation was not identified. The median age of the first thromboembolic event in patients with APC resistance was 42 years (range 15-82 years). Most patients had a history of deep vein thrombosis (83%), 28% had experienced pulmonary embolism. More unusual sites of thrombosis were the deep arm veins (7%) and mesenteric veins (one patient, 1.3%). 53% of patients developed the first thromboembolic event spontaneously. Precipitating conditions for thromboembolism were surgery in 9.3% and trauma in 8%. In one third of female patients the first thromboembolic event occurred in conjunction with pregnancy and delivery (14.8%) or oral contraceptives (19%). At the time of investigation 40% of patients with APC resistance had experienced recurrent thromboembolic events. The family history was positive in 60% of patients. We conclude that the clinical feature of APC resistance is similar to the feature of a deficiency of antithrombin, protein C and protein S. Pregnancy, delivery and oral contraceptives seem to be a relevant additional risk factors for thrombosis in females with APC resistance.
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PMID:Thrombotic tendency in 75 symptomatic, unrelated patients with APC resistance. 892 76

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20 to 30% of patients with a deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5- to 10-fold in heterozygotes, and 50- to 100-fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis and in the occurrence of myocardial infarction.
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PMID:Resistance to activated protein C: role in venous and arterial thrombosis. 895 64

Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.
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PMID:Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise. 895 94


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