1/26. Ophthalmic manifestation of congenital protein c deficiency.Under normal conditions activated protein C is a natural anticoagulant that cleaves 2 activated coagulation factors, factor va and factor viiia, thereby inhibiting the conversion of factor X to factor xa and of prothrombin to thrombin. Additionally, activated protein C enhances tissue-plasminogen activator-mediated fibrinolysis by inhibition of plasminogen activator inhibitor-1. This results in an increase in circulatory plasminogen activator levels. protein c deficiency, a genetic or acquired thrombophilic abnormality, has been demonstrated to predispose to episodes of potentially blinding and lethal thromboembolic events. Heterozygous-deficient subjects usually remain asymptomatic until adolescence or adulthood. In homozygous-deficient patients, protein C activity is usually less than 1% (reference range, 70%-140%), resulting in thromboembolism as early as in the neonatal period. The major clinical symptoms in affected newborn infants have been purpura fulminans, vitreous hemorrhage, and central nervous system thrombosis. The age of onset of the first symptoms has ranged from a few hours to 2 weeks after birth, usually after an uncomplicated full-term pregnancy and delivery. In contrast to the genetic form, acquired neonatal protein c deficiency occurs particularly in ill preterm babies. Typical complications of prematurity such as respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis may also be present. In the medical literature, there are only a few reports of homozygous protein c deficiency in neonates. We present 2 cases of homozygous protein c deficiency with ocular and extraocular manifestation.- - - - - - - - - - ranking = 1keywords = thromboembolism (Clic here for more details about this article) |
2/26. Transthoracic echocardiographic demonstration of massive pulmonary thrombus caused by protein c deficiency.Few cases of pulmonary embolism detected by transthoracic echocardiography (TTE) have been reported. We present a case of a patient affected by pulmonary embolism caused by protein c deficiency. Transthoracic echocardiography showed a thrombus in transit (ie, visualization of a thrombus within the pulmonary artery). A hypercoagulable state caused by deficiency of protein C is a rare cause of pulmonary thromboembolism. Our experience demonstrates a massive pulmonary thrombus resulting from such a deficiency. Transthoracic echocardiography should be considered as the first diagnostic method for patients with suspected pulmonary embolism.- - - - - - - - - - ranking = 1keywords = thromboembolism (Clic here for more details about this article) |
3/26. Multiple aortic thrombi associated with protein C and S deficiency.We describe a woman with an unusual case of thromboembolism of the mesenteric artery in whom multiple thrombi were subsequently found in the aorta and right heart chambers on transesophageal echocardiography. Further evaluation revealed a deficiency of protein C and S plasma proteins, inhibitors of the clotting system. The patient was treated successfully with systemic anticoagulation. Aortic thrombus is common in the setting of underlying atherosclerosis. However, the association of aortic thrombus with a deficiency of protein C and S is rare. To our knowledge, this is the first reported case of mural thrombus of the thoracic aorta associated with combined protein C and S deficiency. Our report underscores the important role of transesophageal echocardiography in the evaluation of patients with arterial thromboembolism.- - - - - - - - - - ranking = 2keywords = thromboembolism (Clic here for more details about this article) |
4/26. protein c deficiency manifesting as an acute myocardial infarction and ischaemic stroke.protein c deficiency is a disorder in the coagulation cascade that results in predominantly venous thromboembolism. However, recent studies have implicated this disorder as a possible contributor to arterial thrombosis, especially myocardial infarction. There are six reported cases of myocardial infarction secondary to protein c deficiency in the literature. This is the first report of myocardial infarction and ischaemic stroke in the same patient as a manifestation of protein c deficiency. The investigation of hypercoagulable state is an essential component of the investigation of young patients with myocardial infarction.- - - - - - - - - - ranking = 2.1819654463209keywords = venous thromboembolism, thromboembolism (Clic here for more details about this article) |
5/26. Combined protein C and protein s deficiency in a family with repetitive thromboembolism and segregated gene mutations.A young man with repetitive deep venous thrombosis of the legs and the inferior vena cava, and his family were eventually diagnosed by means of molecular genetic analysis as having both hereditary protein C and protein s deficiency. There have been a few reports of families with combined protein C and protein s deficiency and only one report of such a family characterized at the dna level. This was the first reported family in japan with combined deficiency of protein C and protein S accompanied by segregation of gene lesions.- - - - - - - - - - ranking = 4keywords = thromboembolism (Clic here for more details about this article) |
6/26. protein c deficiency and thromboembolism: recurrent mutation at Arg 306 in the protein C gene.A CGA TGA transition in the protein C gene, resulting in an Arg306 Term substitution, was detected in a Swedish kindred with thrombotic disease whose members exhibit plasma protein C activity/antigen levels consistent with type I protein c deficiency. Although an identical lesion has been reported previously in several Dutch families, RFLP typing indicated that the Dutch and Swedish mutations were unlikely to be identical by descent and probably arose by recurrent mutation.- - - - - - - - - - ranking = 4keywords = thromboembolism (Clic here for more details about this article) |
7/26. Homozygous protein c deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C.We analyzed the promoter region and all the coding exons and exon-intron boundaries of the protein C gene in a Japanese patient with recurrent thromboembolism and complete protein c deficiency. By sequencing these fragments we identified a previously undescribed mutation. A guanine residue was replaced by an adenine residue converting Gly-292 (GGC) to Ser (AGC) in the last exon coding for the catalytic domain. Substitution of this key amino acid, invariably conserved in the serine protease superfamily to which protein C belongs, probably leads to destabilization of the tertiary structure. In a transient expression assay with COS 7 cells, the protein C level was extremely low in the culture medium of the cells transfected with the mutated protein C expression vector, as compared with the normal vector. In contrast, the cell extracts contained similar amounts of mutant and normal protein C, suggesting impaired secretion of the mutant protein C. Using mutagenic primers to introduce a new PvuII site into the mutant allele, we made a study of the family members in this patient's pedigree, revealing that the mutant allele had been inherited in the affected individuals in this pedigree.- - - - - - - - - - ranking = 1keywords = thromboembolism (Clic here for more details about this article) |
8/26. Gene analysis of heterozygous protein c deficiency in a patient with pulmonary arterial thromboembolism.A 16-yr-old male patient with heterozygous protein c deficiency developed acute pulmonary thromboembolism. The patient had low levels of plasma protein C antigen and activity (33 and 35% of normal, respectively). Analysis of the protein C gene by polymerase chain reaction (PCR) and direct sequencing revealed a nucleotide substitution (Arg169CGG Trp169 TGG) in exon VII. This mutation is identical with protein C Tochigi, and the substituted amino acid is located at the cleavage site of the activation peptide of protein C. The mutant sequence was also detected in the mRNA transcripts of protein C gene. These results suggest that the possible mechanism of plasma protein C reduction is impaired stability or susceptibility to protein degradation during intracellular processing or after secretion into plasma. As this is a third independent case of protein C Tochigi with thromboembolism, the mutation of Arg169 (CGG) to Trp169 (TGG) in the protein C gene may be a "hot spot" and a common type of genetic lesion in congenital protein c deficiency with thromboembolic complications.- - - - - - - - - - ranking = 6keywords = thromboembolism (Clic here for more details about this article) |
9/26. Failure of thromboprophylaxis in pregnancy caused by dual deficiencies of protein S and protein C.Protein S and protein C deficiencies are commonly identified biochemical abnormalities associated with a hypercoagulable state; they result in an increased incidence of venous thromboembolism. We report the case of a pregnant woman with dual deficiencies of protein S and protein C, who encountered a venous thromboembolism 7 days postpartum despite of the use of danaparoid.- - - - - - - - - - ranking = 4.3639308926419keywords = venous thromboembolism, thromboembolism (Clic here for more details about this article) |
10/26. Protein C Sapporo (protein C Glu 25 --> Lys): a heterozygous missense mutation in the Gla domain provides new insight into the interaction between protein C and endothelial protein C receptor.Interaction of the gamma-carboxyglutamic acid (Gla) domain of protein C with endothelial protein C receptor (EPCR) is a critical step for efficient activation of protein C, though interactions by mutants in the Gla domain of protein C with EPCR have been rarely evaluated. We identified a 44-year-old Japanese woman with a history of recurrent thromboembolism as an inherited missense mutation, the first such case reported in japan, which involved a protein C Gla 25 mutation. Total protein C antigen and Gla protein C antigen levels in the proband were normal. Protein C activity measured with an anticoagulant assay was reduced, whereas that measured with an amidolytic assay was normal. She was therefore phenotypically diagnosed as type IIb protein c deficiency. Direct sequencing of the PCR fragments revealed a heterozygous G to A transition at nucleotide position 1462 in exon 3, which predicted an amino acid substitution of Glu 25 by Lys. Her mother and one son were also heterozygous for this mutation. A molecular dynamics simulation of Gla 25-->Lys/EPCR complex in water suggested that the affinity between the molecules was decreased compared to the wild type Gla domain/EPCR complex. Since Gla 25 has been shown to play an important role in protein C function, not only in membrane phospholipid binding but also in binding to EPCR, our findings provide new insight into the mechanism by which the Glu 25-->Lys mutation induces type IIb protein c deficiency in individuals.- - - - - - - - - - ranking = 1keywords = thromboembolism (Clic here for more details about this article) |
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