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)

Lipodermatosclerosis of the lower extremity, with or without ulceration, is a common manifestation of severe venous disease and the result of sustained venous hypertension. The latter is generally a sequela of deep vein thrombosis. Factors that enhance clot formation or impair fibrinolysis contribute to the pathogenesis of venous disease. It is already established that faulty fibrinolysis may play a pathogenic role in patients with venous disease. We examined the possibility that patients with venous disease have abnormally low plasma levels of proteins C and S, two proteins whose deficiencies have been reported to cause an increased frequency of thromboembolic disease. Using immunologic and functional assays for plasma proteins C and S, we found that 4 (21%) of 19 patients with lipodermatosclerosis and leg ulcers had abnormally low levels of protein C or protein S. One of 7 patients with lipodermatosclerosis without ulceration had a profoundly depressed level of protein C and a history of cerebral stroke at a young age. Plasma levels of protein C were normal in five patients with arterial insufficiency severe enough to cause leg ulceration. We conclude that abnormally low plasma levels of proteins C and S may be found in patients with lipodermatosclerosis and venous ulceration. As with the abnormally low fibrinolytic activity in these patients, our findings indicate a possible propensity for increased thrombotic disease.
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PMID:Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration. 203 43

Inherited deficiencies of protein S, an inhibitor of the coagulation system, are now recognized as occurring at least twice as frequently as antithrombin III deficiency in patients with venous thrombosis. Protein S is present in plasma in a complexed form, which is inactive, and in a free or functional form. Free protein S combines with activated protein C to inhibit factors V and VIII. This report describes the evaluation of a family with recurrent deep venous thrombosis and superficial thrombophlebitis. Levels of antithrombin III and protein C as well as plasminogen were normal. The levels of total protein S, which includes the value for the free and complexed forms of protein S, were also normal. However, the free protein S levels were greatly reduced in all symptomatic members who were studied. This report illustrates the importance of obtaining measurement of free protein S levels in patients who are suspected of having inherited venous thrombotic disorders.
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PMID:Free protein S deficiency in a family with venous thrombosis. 214 6

Subjects with congenital deficiency of protein S, a natural anticoagulant which serves as a co-factor for the antithrombotic activity of activated protein C, are at risk of thrombosis. We describe a family in which deep vein thrombosis-occurring during pregnancy in three members with abnormally low protein S activity - was the only manifestation of congenital heterozygous protein S deficiency. Early diagnosis and active treatment of protein S deficiency should be pursued in any woman with a family history of thrombosis, who is planning pregnancy.
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PMID:Familial protein S deficiency presenting as deep vein thrombosis occurring during pregnancy. 214 88

The protein C inhibitor (PCI) concentration and other parameters of the protein C pathway were studied in 19 patients with symptomatic acute deep vein thrombosis before and during the first 5 days of heparin treatment. The mean levels of PCI antigen and activity decreased rapidly and significantly during the first day of heparin therapy from 83 and 84% to 60 and 59% of the pooled normal human plasma (p less than 0.01), respectively, and to 56 and 54% after 5 days of treatment (p less than 0.01). In contrast, antithrombin III decreased progressively 25% during 5 days of heparin treatment. Protein C antigen and activity and total protein S remained unchanged during heparin treatment. Free protein S was decreased before heparin treatment (83%, p less than 0.05) and increased to normal values after 5 days of treatment. C4b-binding protein was significantly increased before and during heparin treatment (p less than 0.01). Activated protein C (APC) complexed to its two major plasma inhibitors, PCI and alpha 1-antitrypsin (alpha 1AT) were measured by specific ELISA's. Before treatment, 18 of the 19 patients studied had increased levels of APC:alpha 1AT complexes with a mean value of 27 +/- 22 ng/ml (range, 6-86 ng/ml) compared to normal values (8 +/- 2 ng/ml) and 12 of the patients also had detectable APC:PCI complex levels with a mean value of 11 +/- 17 ng/ml (range, 5-68 ng/ml). Both APC:inhibitor complexes decreased significantly during heparin treatment.
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PMID:Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment. 216 56

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

Broad spectrum assays which measure a range of fibrinogen/fibrin derivatives (FDPs) in serum have become an established means of identifying activation of blood coagulation and/or fibrinolysis, such as occurs in disseminated intravascular coagulation (DIC). There is considerable interest in the application of these assays to the diagnosis of other hypercoagulable states, such as recurrent deep venous thrombosis and myocardial infarction. In recent years, more sensitive and specific FDP assays (e.g. for fragment E, fragment E neoantigen, D-dimer, fragment D neoantigen, fibrinopeptide A and fibrin fragment beta 15-42) have been devised, some of which allow measurement in plasma of FDPs without interference from fibrinogen or certain of its derivatives. It was predicted that these assays would both avoid the possibility of artifacts introduced as a consequence of serum preparation and improve detection of hypercoagulable states. In the light of these expectations we have reviewed data published on the use of assays to detect clinical hypercoagulability, giving prominence to assays of crosslinked fibrin derivatives and nothing particularly certain studies that have compared the performance of different assays on the same samples. The accumulating evidence indicates that all of the assays are adequate for detection of DIC. The same cannot be said for other hypercoagulable states. Here much variation is evident between different studies of similar patients in the ability of a particular marker to discriminate between a normal control group and patients determined to be hypercoagulable by an independent method. This variability would seem to be a function of patient group heterogeneity and selection, as assays that detect different antigenic determinants produce results on the same plasma samples that are well correlated. It appears that the precise antigenic determinant does not critically affect detection of hypercoagulability. Additionally, some studies have indicated that use of serum need not introduce artifacts. Despite there being no other obvious advantage, the convenience of some of the plasma assays may well encourage their widespread use. Assays have also been developed for measuring activation fragments of coagulation proteins (e.g. prothrombin fragment F1 + 2 and protein C activation peptide) and for proteinase inhibitor complexes (e.g. thrombin-antithrombin complex) generated during activation of coagulation. The latter assays have been useful in providing a biochemical definition of a 'prethrombotic state'.
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PMID:Assessment of hypercoagulable states by measurement of activation fragments and peptides. 218 46

The study was carried out of 53 patients with acute myocardial infarction receiving no anticoagulant treatment. Changes were traced in certain indices of the blood clotting system and fibrinolysis in plasma in the first 14 days of the disease, with particular attention given to patients in whom during the hospitalization signs of deep vein thrombosis in the lower extremities appeared or a positive result was obtained of the test with 125I-fibrinogen. In a group of 9 patients with deep vein thrombosis developing during the observation, on the first day of myocardial infarction shortening of the kaolin-cephalin clotting time and considerable rise of the level of fibrinogen-fibrin (FDP) degradation products were noted in serum, and on the 14th day raised fibrinogen level and reduced exogenous fibrinolytic activity of the plasma were noted. Increased level of fibrinogen and FDP and exogenous and endogenous plasma fibrinolytic activity observed on the 7th day of the disease were not related to the development of thrombotic complications. The thrombin clotting time, platelet count, factor X level, protein C concentration and antithrombin III activity in the plasma were not significantly changed during myocardial infarction. The obtained results suggest a limited usefulness of the basic tests of the clotting and fibrinolytic systems for early diagnosis of deep vein thrombosis in acute myocardial infarction.
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PMID:[Assessment of hemostasis in patients with myocardial infarction complicated by deep venous thrombosis]. 227 86

A congenital deficiency of protein C (PC) is reported in a 42-year-old male, suffering from his first spontaneous episode of deep venous thrombosis in the left lower limb. The only defect found in laboratory assays for hemostasis and hepatic function was half normal level of PC, measured by both immunological and functional assays. To confirm congenital PC deficiency, the functional activity levels of PC were compared with those of other vitamin K-dependent factors during stabilized anticoagulant therapy under stable conditions. Although the patient's father had a history of a cerebral vascular accident, his PC level was found to be within normal levels. The patient's mother, free from thromboembolic events, also had a normal PC level. So the patient seemed to be a sporadic case. However, the patient's 14-year-old son, who has been asymptomatic to this time, has the same PC deficiency state.
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PMID:[A sporadic case of protein C deficiency]. 228 72

The pre-surgery identification of patients at risk for the development of post-operative venous thromboembolism has not yet been achieved. It is a well recognized fact that major surgery without prophylaxis encompasses a high risk for thrombosis, in particular orthopaedic operations (hip/knee surgery approximately 50%) and abdominal surgery (approximately 20%). Other well-defined risk factors, though rarely occurring, are deficiencies of the major inhibitors of blood coagulation (i.e. protein C, protein S and antithrombin III). Less well-defined risk factors are a history of previous thrombosis, obesity, varicosis, cancer etc. In an attempt to identify patients at risk for thrombosis prior to surgery, several investigators have developed complicated risk predictors, i.e. formulae comprising combinations of coagulation test results and physical characteristics such as body weight. However, the clinical usefulness has only been demonstrated in two small studies evaluating gynaecological surgery patients. These prognostic indices have not, however, found general acceptance and are not used routinely. The importance of all these risk factors for patient management with regard to thrombosis prevention is relatively small. Irrespective of the absence or presence of identified risk factors, currently the majority of patients will receive some formal thrombosis prophylaxis. The major problem at present is the development of proximal vein thrombosis despite the best possible thrombosis prophylaxis (approximately 10% after hip surgery). Identification of these patients pre-operatively or in an early stage in the post-operative phase by single screening tests should be a major research issue. Furthermore, the development of a prophylactic regimen which eliminates proximal deep vein thrombosis is still desperately needed.
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PMID:Pre-surgical identification of the patient at risk for developing venous thromboembolism post-operatively. 228 76

Protein C and antithrombin III represent main inhibitors of the plasmatic coagulation system. Due to the lack of practicable assays the clinical importance of protein C was only established during the last six years. In familial protein C deficiency 77% of patients present with recurrent venous thromboses, half of them below the age of 30. In addition to recurrent superficial thrombophlebitis more serious manifestations like deep vein thrombosis and pulmonary embolism have been described. Mesenteric vein thrombosis has been reported in only 5 cases all of which could be controlled by conservative treatment. In our patient protein C deficiency was discovered 10 years after the angiographic diagnosis of portal and mesenteric vein thrombosis. Thereafter, the patient complained of recurrent abdominal discomfort. Intestinal ischaemia due to mesenteric vein thrombosis required segmental resection twice. Postoperatively the patient was heparinized. After excluding a secondary protein C deficiency due to a lack in vitamin K, hepatic disease, or disseminated intravascular coagulation, long-term anticoagulation by dicumarol was implemented as therapy of first choice.
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PMID:[Protein C deficiency with recurrent infarct of the small intestine]. 231 54


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