Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe two families with heterozygous plasminogen deficiency. In the first the patient was a 27 year-old female who suffered an acute episode of ischemic cerebrovascular disease affecting the left temporal lobe documented by arteriographic, gammagraphic and CAT studies. She had no family history of thrombotic conditions. In the other family the propositus was a 31 year-old man with spontaneous deep venous thrombosis in the left leg. His father was also symptomatic, with a history of recurrent thrombotic complications after predisposing factors, that included multiple venous thrombosis and a pulmonary embolism. Laboratory data showed normal hemostasis test results. Antigenic and functional levels of protein C, protein S and antithrombin III were within normal limits. The only abnormality found was decreased plasminogen activity in plasma; antigenic and functional levels were reduced to about half-normal levels. In both cases crossed immunoelectrophoresis revealed a normal migration pattern of plasminogen. Thus, we conclude that our patients were carriers of congenital hypoplasminogenemia or familial type I plasminogen deficiency, due to decreased synthesis. We also reported on fibrinolytic response to infusion of DDAVP, a synthetic analogue of the antidiuretic hormone. Fibrinolytic activity was normal in basal conditions as well as in response to DDAVP infusion.
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PMID:[Plasminogen deficiencies in 2 Spanish families. Response to the administration of DDAVP]. 236 94

The observation of protein S deficiency in a family six members of which had recurrent cerebral strokes prompted a prospective study so far including 33 patients (23 women, 10 men) with cerebral arterial thrombosis at the age of 19 to 57 years (mean 31 years) admitted to the neurological departments of several hospitals. Diseases associated with cerebral arterial occlusions, such as arterial embolism or hematological, infectious and immunological disorders were not found. The following parameters were tested: antithrombin III, protein C, plasminogen, fibrinolytic capacity after infusion of DDAVP, and free and total protein S. Prothrombin times of all patients were within normal ranges; no woman had taken oral contraceptives for at least 3 months before examination. In 9 patients (8 women, 1 man) a decrease of free and total protein S was found; in 4 additional patients (2 women, 2 men) only the free protein S was reduced. Protein S deficiency was confirmed as an inherited defect in 5 cases by family studies, but excluded in one (both parents normal). Protein S deficiency was combined with protein C deficiency in 3 cases, plasminogen deficiency in 2 cases and reduced fibrinolytic capacity in two. Venous thromboembolism occurred only in one of the 13 patients with protein S deficiency and cerebral arterial thrombosis. Protein S deficiency may be found-mainly as a familial trait-in a substantial percentage of younger patients with "idiopathic" cerebral arterial thrombosis.
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PMID:[Protein-S deficiency in young patients with thrombotic brain infarction]. 252 95

The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p less than 0.005, ECLT p less than 0.0125, by Student's t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p less than 0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p less than 0.005) than control at all stages of operation and a significant shortening (5 sec p less than 0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage.
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PMID:The influence of DDAVP infusion on the coagulation and fibrinolytic response to surgery. 308 64

We studied a Spanish family in which one of the female members presented recurrent thrombophlebitis in both legs after three different deliveries. Biological and antigenic activity of protein C was decreased (35% and 42% respectively). Reduced protein C levels were also observed in 6 other family members. Administration of danazol (600 mg/day) in two patients with protein C deficiency elevated this protein and discontinuation of the drug resulted in a reduction of protein C to pretreatment values. The proposita showed a normal fibrinolytic activity and infusion of DDAVP produced a similar response of FVIII/VWF and plasminogen activator to those observed in healthy subjects.
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PMID:Protein C deficiency--response to danazol and DDAVP. 384 Feb 87

The effect of desmopressin (DDAVP) on protein C (PC) and PC inhibitors was investigated in 7 uremic predialysis patients, 7 hemodialysis patients and 7 controls. Significant decrease in PC activity was observed in all groups after DDAVP administration. Desmopressin did not influence PC antigen and two well-known PC inhibitors, plasminogen activator inhibitor-3 and alpha 1-antitrypsin. Thus, it is suggested that DDAVP-induced decrease in PC activity is not related to the changes in PC inhibitors; further studies are needed to clarify the precise mechanisms of the effect of DDAVP on PC in uremia.
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PMID:Effect of desmopressin (DDAVP) on protein C and protein C inhibitors in uremia. 832 56

A prothrombotic and hemorrhagic state can separately manifest in one patient and can potentially cause several diagnostic problems. We report an intriguing case as an example of a potential hemostasis-based diagnostic dilemma. A 29-year-old female patient presented with a personal history of menorrhagia and other mucosal bleeding and renal ovarian thrombosis. Previous investigations had uncovered several diagnostic anomalies, including von Willebrand disease (VWD), factor V Leiden (FVL), antiphospholipid syndrome, and thrombocytopaenia. Previous therapy in this patient included heparin and warfarin for the thrombosis and desmopressin acetate (DDAVP) and antifibrinolytic therapy for surgical management. Subsequent laboratory testing with fresh samples consistently confirmed an equivocal (borderline normal/abnormal) level of von Willebrand factor (VWF) and FVL with activated protein C resistance (APCR). A patient sample, differentially labeled according to the tests being performed, was later distributed for blind testing to participants within several modules of the RCPA Quality Assurance Program (QAP). Most participants reported a low level of VWF consistent with possible mild Type 1 VWD, and most (but not all) reported a positive finding for APCR. All participants correctly reported the sample as heterozygous for the FVL mutation, negative for the Prothrombin gene mutation G20210A, and heterozygous for the methylenetetrahydrofolate reductase (MTHFR) mutation C677T. Interestingly, a significant number of laboratories performing Protein S testing using clot-based procedures also identified a false Protein S deficiency. In conclusion, this exercise showed how, either depending on the clinical review and specific laboratory investigation and tests performed, a pro-bleeding diagnosis (of either VWD or thrombocytopenia) or pro-thrombophilia risk (Antiphospholipid Syndrome or FVL/APCR or false Protein S deficiency) could potentially and differentially arise in the one patient.
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PMID:The diagnostic dilemma: dual presentations of clinical mucosal bleeding and venous thrombosis associated with the presence of thrombophilia markers and mild reduction in von Willebrand factor. 1819 44

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.
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PMID:[Proteins influencing the blood coagulation]. 2204 25