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) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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PMID:[Familial thrombophilia due to resistance to activated protein C]. 798 58

An abnormal anticoagulant response in vitro to activated protein C (aPC) has been proposed as an aetiological factor in familial thrombophilia. It is postulated that this phenomenon is due to an inherited molecular defect of factor V resulting in poor inactivation by aPC. We conducted a family study when the proband presented in her second pregnancy with superficial phlebitis, a history of deep venous thrombosis and a family history of venous thromboembolic disease. No abnormality of antithrombin activity, protein C activity or deficiency of protein S were demonstrated in the family members tested. The proband had aPC ratios below the laboratory range on three consecutive occasions. In addition, her mother, who had a history of recurrent DVTs and a pulmonary embolus, and also an asymptomatic nulliparous sister, both had aPC resistance ratios below the laboratory range on consecutive samples. Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated.
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PMID:Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy? 798 34

Several parameters of fibrinolytic and protein C pathways were evaluated in three groups of patients with high (HR), moderate (MR) and low (LR) postoperative thrombotic risk undergoing major gynaecological surgery. The HR and MR groups were subjected to low molecular weight heparin (LMW) prophylaxis. A significant increase in plasminogen activator inhibitor type 1 (PAI-1) antigen and activity levels was observed in the HR patient group in comparison with the MR and LR groups in the preoperative and early postoperative period. In all the groups studied, the maximum increase in the levels of PAI-1 was seen on day 1 after surgery. However, the D-dimeric levels reached the highest level on day 7. A significant increase in activated protein C:alpha 1 antitrypsin (APC:alpha 1AT) complex levels was observed in the HR group in comparison with the LR group, and a strong decrease in protein C inhibitor in the early postoperative period was detected in all the groups. In spite of heparin prophylaxis, 2 HR patients were diagnosed as deep vein thrombosis (DVT) during the postoperative period. Both patients showed pre-operative levels of PAI-1 antigen or activity and APC:alpha 1AT complexes above the mean + 1 SD of the pre-operative levels in the HR group. In conclusion, in HR patients a hypofibrinolytic and hypercoagulable state was detected in the pre-operative and early postoperative periods. The prophylactic LMW heparin dose used in the present report (20 mg/day x 7) was insufficient to prevent DVT in the HR group. At present our HR patients are given higher doses of LMW heparin (40 mg/day x 7).
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PMID:Alterations in fibrinolytic and protein C pathways in gynaecological surgery: low molecular weight heparin prophylaxis. 798 53

A 13-year-old male presented with new onset seizures, sagittal sinus thrombosis with cerebral hemorrhage, and extensive venous thrombosis of the lower limbs. Laboratory investigation demonstrated combined deficiency of protein C, protein S, and antithrombin III. He and his 17-year-old sister had a mental retardation-multiple anomaly syndrome associated with microcephaly, unusual facies, and lax connective tissue. Their dysmorphology included elongated faces with narrow forehead, arched eyebrows, large mouth with down-turned corners, malformed teeth, and furrowed tongue. Both had Marfanoid habitus with lax joints, pectus excavatum, kyphoscoliosis, and flat narrow feet. The most likely diagnosis for these siblings is the autosomal recessive Cohen syndrome of mental retardation, congenital hypotonia with Marfanoid habitus, microcephaly, pleasant affect, micrognathia, and open mouth with prominent incisors. The sagittal sinus thrombosis, left frontal intracranial hemorrhage, carotid aneurysm, tortuous descending aorta, and deep venous thrombosis suffered by the male sibling adds the Cohen syndrome to genetic vasculopathies that may be associated with stroke.
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PMID:Multiple coagulation defects and the Cohen syndrome. 806 42

Phlegmasia cerulea dolens is a rare form of deep vein thrombosis. A patient with recurrent episodes of such thrombosis caused by protein C deficiency who developed phlegmasia cerulea dolens is reported. Limb perfusion with urokinase successfully restored venous outflow after unsuccessful attempts at thrombectomy.
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PMID:Thrombectomy and isolated limb perfusion with urokinase in the treatment of phlegmasia cerulea dolens. 807 98

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

Activated protein C (APC) is a serine protease with potent anticoagulant properties, which is formed in blood on the endothelium from an inactive precursor. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa (ref. 2). To do this efficiently the enzyme needs a nonenzymatic cofactor, protein S (ref. 3). Recently it was found that the anticoagulant response to APC (APC resistance) was very weak in the plasma of 21% of unselected consecutive patients with thrombosis and about 50% of selected patients with a personal or family history of thrombosis; moreover, 5% of healthy individuals show APC resistance, which is associated with a sevenfold increase in the risk for deep vein thrombosis. Here we demonstrate that the phenotype of APC resistance is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC. The allelic frequency of the mutation in the Dutch population is approximately 2% and is at least tenfold higher than that of all other known genetic risk factors for thrombosis (protein C (ref. 8), protein S (ref. 9), antithrombin10 deficiency) together.
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PMID:Mutation in blood coagulation factor V associated with resistance to activated protein C. 816 30

The first generation high-dose ( 80 mcg estrogen) oral contraceptives (OCs) were associated with an increased risk of deep venous thrombosis (DVT). So manufacturers removed the high-dose OCs and first replaced them with OCs with 50 mcg estrogen, resulting in a lower incidence of thromboembolic events (40 vs. 20/100,000 users). When they introduced an even lower dose OC (30 mcg estrogen), the incidence fell further (about 8/100,000 users). Yet, women using the lowest-dose OCs still have DVT more often than do control women. Life-style, age, and smoking may be confounding factors, however. It is not clear whether loss of endogenous ovarian steroid production or the effects of the orally administered contraceptive steroids cause significant changes in hemostatic factors (antithrombin III, protein S, protein C, plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor 1, histidine-rich glycoprotein, and VII, VIII, X, XII coagulation factors) during OC use. These changes tend to be within normal ranges. There is some doubt that these changes have any clinical significance. In nonsmokers, increased activity of anticoagulant factors and fibrinolytic factors counteract the effects on coagulation factors. Progestin-only OCs appear to affect hemostasis but have not increased the risk of thrombosis. There are considerable differences between people in pharmacokinetics and pharmacodynamics of contraceptive steroids. These differences may account for the increased risk of thromboembolic events in some people. Further research should identify methods of individualizing the dose of contraceptive steroids for a single patient. It should also explore the close interrelationship between hemostasis and lipid metabolism, carbohydrate metabolism, and hypertension in the development of cardiovascular disease in OC users. Providers should discourage women with a past history of DVT from using hormonal contraception.
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PMID:Coagulation and anticoagulation effects of contraceptive steroids. 817 1

We present a 57-year-old man with end-stage renal failure due to chronic glomerulonephritis, who had been on hemodialysis for 13.5 years and had suffered from recurrent painful swelling of the left leg for 4.7 years. A diagnosis of deep venous thrombosis was made by the phlebography. Coagulation studies showed decreased protein C activity despite a normal protein C antigen level. None of his relatives had decreased protein C activity, and the levels of the other coagulation factors synthesized by the liver were all normal. Accordingly, the patient was diagnosed as having acquired type II protein C deficiency.
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PMID:Acquired type II protein C deficiency in a long-term hemodialysis patient. 819 Jan 90

The case of an adult patient with moderately severe protein C deficiency (antigen 16%, activity 12%) is reported. Both parents had protein C levels compatible with heterozygous deficiency. Unlike other reported cases of severe protein C deficiency in adults, the onset of thrombotic symptoms occurred at 1 month of age; however, a symptom-free period until age 17 followed. Replacement therapy with a monoclonal antibody purified protein C concentrate was carried out during the initiation of oral anticoagulation after a course of i.v. heparin for deep vein thrombosis. The administration of the concentrate allowed maintenance of protein C above 50% until a stable therapeutic anticoagulation level could be obtained. This was reached within a short time, thus allowing safe administration of a loading dose of warfarin. We conclude that this approach to the prevention of skin necrosis seems more rapid and safer than previous schedules of oral anticoagulation in protein C-deficient patients.
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PMID:Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency. 823 28


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