Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

von Willebrand disease (VWD) is a most common inherited bleeding disorder. von Willebrand factor (VWF) exists as an extracellular adaptor molecule and generally involves in the hemostasis mechanism through binding with GP (Glycoprotein) Ib-IX-V platelet receptor. Clinical phenotype of bleeding disorders modulated to a decrease in bleeding symptoms by thrombogenic mutations. We made an attempt to investigate the impact of thrombogenic mutations/polymorphisms on the clinical phenotype of 114 different types of patients with VWD, and 120 healthy controls were screened for methylenetetrahydrofolate reductase (MTHFR) 677C/T, factor V (FV) Leiden (1691G/A), beta(3) integrin (HPA-I) (Human platelets antigen-I) gene (1565T/C), and prothrombin 20210G/A mutations. Genotypic analysis was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism. Forty-five patients (39.5%) were found to be positive for at least one of the prothrombotic risk factors screened. Prothrombin 20210G/A was not found in any patient with VWD as well as healthy control. Eight patients with VWD were carrying the defective alleles of different thrombogenic markers, showing milder phenotypes than expected. A high prevalence was observed for MTHFR 677C/T (677C/C 73.6%, 677C/T 24.6%, 677T/T 1.8%) and PLA1/A2 (1565T/T 88.6%, 1565T/C 10.5%, 1565C/C 0.87%) polymorphism followed by FV Leiden (1691G/G 97.4%, 1691G/ A 2.6%, 1691A/A 0.00%) in patients with VWD with allelic frequencies 11.4% (677T), 5% (1565C), and 1.3% (1691A). Hence, we concluded that thrombophilic markers were seen to be influencing the clinical phenotypes of patients with VWD.
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PMID:Impact of thrombogenic mutations on clinical phenotypes of von Willebrand disease. 1995 86