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)

Resistance to activated protein C (RAPC) is a newly recognized hypercoagulable state that was first described in 1993. It has become apparent that RAPC is even more common than deficiencies in protein C, protein S, or antithrombin III (AT-III) and affects an estimated 5% of the general population. The majority of patients with RAPC have an abnormality in factor V (Arg506Gln), which renders factor Va resistant to degradation by activated protein C. Studies in 75 patients referred to the Hematology Laboratory at Walter Reed Army Institute of Research (WRAIR) over a 14-month period for evaluation of venous thromboembolism were reviewed to determine the percentage of those with RAPC. Of the 75 patients in the study, one was deficient in protein S, one was deficient in protein C, and none was deficient in AT-III. In contrast, 27 (36%) patients tested positive for RAPC. Blood was available for DNA analysis in 15 patients with RAPC. Of these 15 patients, nine (60%) tested positive for the Arg506Gln mutation in factor V. Six other patients with RAPC did not have the factor V mutation. Additional risk factors for thrombosis were immobility, obesity, use of oral contraceptives, and pregnancy. The majority of patients had deep venous thrombosis of the lower extremities; 71% had a recurrence if not placed on chronic anticoagulation therapy. Thus RAPC is a significant risk factor for venous thrombosis. Evaluation for inherited hypercoagulable states should include testing for this newly described condition.
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PMID:Resistance to activated protein C: a common inherited cause of venous thrombosis. 873 70

Hereditary protein S deficiency (HSPD) is a predisposing factor to recurrent venous thrombosis but is not currently associated with stroke. We report two cases of HSPD revealed by stroke in young adults. The first one was a 36-year-old patient whith a pure motor hemiplegia, who gradually recovered without sequelae. Total and free protein S was decreased (55 and 10%). One of his brothers died from pulmonary embolism at 20 years and a sister had low protein S level without clinical signs. The second case was a 26-year-old patient who had a right hemiplegia with aphasia due to an infarction in middle cerebral artery area. He partially recovered, but the course of the illness was complicated by deep venous thrombosis of the lower limbs and pulmonary embolism. Total and free serum protein S level was severely decreased (25 and 0%). The patient's mother and one of his sisters also had low protein S but never had clinical complications. In both case, dupplex scanning, transcranial doppler, echocardiography, serum antithrombin III and protein C were normal. Cigarette smoking was the only risk factor for arterial disease. These two cases suggest that HSPD must be investigated in young patients with stroke, even in cases of lacunar stroke.
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PMID:[Cerebrovascular complications and hereditary protein S deficiency: 2 cases]. 876 59

The diagnosis of thromboembolic diseases is still difficult to establish before the occurrence of the pathological event, although it is now known that they are the result of a progressive alteration of the cardiovascular system. Introduction of new diagnostic tools for the evaluation of the thromboresistance capacity of the body or for the measurement of molecular markers allows the testing of the body defenses against thrombosis which is becoming a routine clinical diagnosis. Antithrombin III (AT III), protein C, protein S, and parameters of fibrinolysis have been recognized to be very important anticoagulant proteins and regulators of thrombin formation and thrombus extension. Furthermore, a normal factor V is necessary for the normal function of the protein C pathway. The presence of a factor V mutation leads to the activated protein C resistance syndrome. However, the major incidence of thrombotic events concerns the overall population. It has been epidemiologically related to the existence of risk factors producing blood activation, which progressively saturates the body's thromboresistance. This period is clinically silent for a long time. The new molecular markers recently introduced can show the existence of a preclinical state of blood activation at the plasma level (fibrinopeptide A, thrombin-antithrombin complexes, modified antithrombin III, fragments 1 + 2 of prothrombin, D-dimer) or at the platelet level (B-thromboglobulin, platelet factor 4, and thrombospondin), and promising developments concern the endothelial level (soluble thrombomodulin). The most universally used blood activation test is the D-dimer assay. This analyte has become very popular in past years for its high sensitivity, its long half-life, and its easy detection directly on citrated plasma. Its negative predictive value (in deep venous thrombosis or pulmonary embolism) as well as its use for monitoring of thrombotic risk in the post-operative period have been well documented clinically. New investigations are initiated to find analytes reflecting endothelial damage, an early platelet activation, or the involvement of blood cells (mainly monocytes and neutrophils) in abnormal processes. It also becomes possible to evaluate directly pathological causes inducing blood activation, such as the presence of antiphospholipid antibodies or other autoimmune antibodies.
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PMID:Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis. 880 28

The effect of oral contraceptive therapy was studied in five patients with homozygous activated protein C resistance. Patients with this congenital abnormality, in contrast to those with antithrombin, protein C or protein S deficiencies, showed only a mild thrombotic tendency. In fact, only two of six observations (one patient took the pill on two separate occasions many years apart) showed deep vein thrombosis. No patient had pulmonary embolism. Two additional patients had a superficial vein thrombosis of the legs. In two instances, a superficial vein thrombosis and a deep vein thrombosis, concomitant risk factors were present (immobilization and surgery for an ovarian cyst, respectively). However, compared with heterozygous for the same abnormality, the symptomatic homozygous patients with APC resistance appeared to develop thrombosis after a shorter period of oral contraception.
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PMID:Homozygous patients with APC resistance may remain paucisymptomatic or asymptomatic during oral contraception. 889 47

In a 6-month, randomized, double-blind study the effects of two combined oral contraceptives containing 150 micrograms desogestrel and either 20 or 30 micrograms ethinylestradiol on hemostatic parameters were investigated in 1633 healthy women. Compared with baseline, the 30 micrograms ethinylestradiol formulation increased prothrombin fragment 1 + 2 (+72.2%), D-dimer (+42.4%) and protein C activity (+6.1%), whereas antithrombin-III activity (-6.3%) and protein S activity (-19.7%) were decreased. The use of the 20 micrograms ethinylestradiol formulation was associated with the same pattern of changes, but with lower magnitude (F1+2 + 61.1%, D-dimer +36.0%, antithrombin III -5.3%, protein C +4.6% and protein S-16.0%). The changes from baseline were significantly smaller in the 20 micrograms ethinylestradiol group for D-dimer, antithrombin III and protein S than in the 30 micrograms ethinylestradiol group (p = 0.019, p = 0.038 and p = 0.001, respectively). One woman with a combined deficiency of proteins C and S developed deep venous thrombosis while using the 20 micrograms ethinylestradiol formulation. Use of both formulations was associated with a shift of the coagulation-fibrinolysis balance to an enhanced fibrin-generating and fibrin-degradating activity. The less-pronounced effect on hemostasis with the 20 micrograms ethinylestradiol preparation is reassuring with regard to thromboembolic risk in general. However, women with coagulation inhibitor deficiency should be advised not to use oral contraceptives.
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PMID:Ethinylestradiol 20 versus 30 micrograms combined with 150 micrograms desogestrel: a large comparative study of the effects of two low-dose oral contraceptives on the hemostatic system. 890 27

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

Pregnancy is a risk factor for deep and superficial venous thrombosis because of hemodynamic changes and modifications of the coagulation and fibrinolitic systems. In case of a patient suffering from a congenital or acquired thrombophilia, risk of severe and recurrent thrombosis becomes much higher, with the possibility of a life threatening complication as pulmonary embolism. Recently a number of congenital thombophilic syndromes have been described, in particular congenital hereditary deficit of coagulation inhibitors. Among the acquired pathologies, the antiphospholipid syndrome has been recently object of studies. Diagnostic and therapeutic options are still controversial. The authors present a case of recurrent deep vein thrombosis in pregnancy treated with positioning of a caval filter for the prophylaxis of pulmonary embolism. Diagnostic difficulties are discussed, as the patient presented with low levels of the coagulation inhibitor protein S, and also circulating antibodies anticardiolipin.
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PMID:[Deep venous thrombosis in pregnancy: diagnostic difficulties and therapeutic indications. Discussion of a clinical case]. 892 85

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10%). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84% of cases and a recurrent thrombotic episode occurred in 50% of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.
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PMID:Diagnosis and clinical characteristics of inherited activated protein C resistance. 897 37

In the UK, the Committee for Safety of Medicines (CSM) issued a warning in October 1995 about the possible increased risk of nonfatal deep venous thrombosis (DVT) among users of oral contraceptives (OCs) containing the third generation progestogens, desogestrel and gestodene. Subsequent media coverage increased the number of consultations and enquiries about these OCs. CSM had concluded that, overall, the third generation OCs are safe. CSM recommended their continued use. Nevertheless, many women stopped using them and induced abortions increased by 11%. In April 1996, the Committee for Proprietary Medicinal Products issued a more cautious statement about the OCs and called for further evaluation. Chance, confounding, and bias may account for the increased risk observed in the studies in question. Yet, it is possible that these OCs may increase the risk of DVT. The increased risk may be offset by a reduced risk of acute myocardial infarction. Physicians need to conduct careful and thorough counseling and to allow the patient to be involved and to take responsibility in making a decision about OC use. They should document all counseling with a note that the patient understands and accepts the increased risk of DVT. They should not prescribe the third generation OCs to women with any of the absolute contraindications to OC use (ischemic heart disease, hypertension, atherogenic lipid disorders, focal or crescendo migraine, cigarette smoking, transient ischemic attacks, past cerebral/subarachnoid hemorrhage, history of vascular thrombosis, prothrombotic abnormalities [e.g., Factor V Leiden], conditions predisposing to thrombosis [e.g., systemic lupus erythematosus], and obesity. Women who are intolerant of second generation OCs may prefer third generation OCs. Physicians should selectively screen women with a family history of a first-degree relative younger than 45 with thromboembolism for Factor V Leiden. They should also screen for protein C, protein S, and antithrombin III deficiency and for acquired antiphospholipid antibodies.
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PMID:Oral contraceptives and the risk of DVT. 898 64

One hundred and thirty unrelated patients with recurrent deep venous thrombosis were studied over a period of 4 years (1986-1990) in order to determine the possible etiology. Protein C levels were estimated in plasma both by chromogenic substrate assay and by immunoassay. Protein S levels in plasma was determined by immunoassay using antisera to human protein S. Antithrombin III (AT-III) was assayed using monospecific rabbit antiserum to human AT-III. Fifteen patients were found to have hereditary protein C deficiency (11.52%). Family studies revealed autosomal recessive inheritance in one patient and a dominant pattern in the remaining 14 patients. Protein S deficiency was found in eight cases (6.1%), AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect in 33 cases (25.4%). Thrombosis of visceral and cerebral vessels and a positive family history were more frequently found among patients who had hereditary deficiency of one or the other antithrombotic factor. Thrombophlebitis of superficial veins was found to be very common in patients with protein C and protein S deficiency and virtually absent in AT-III deficiency. The high frequency of protein C and protein S deficiency in this ethnic group is attributed to the high frequency of consanguinity.
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PMID:Thrombophilia in ethnic Arabs in Kuwait. 900 58


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