Thromb Haemostasis
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Case Reports
Novel fibrinogen truncation with deletion of Bbeta chain residues 440-461 causes hypofibrinogenaemia.
A 24-year-old male with hepatitis C was initially diagnosed with hypofibrinogenaemia during investigations prior to a liver biopsy. He had a low functional and gravimetric fibrinogen concentration of 1.0 mg/mL and DNA sequencing of all exons, exon-intron boundaries and promoter regions of the fibrinogen Aalpha, Bbeta, and gamma genes revealed a single heterozygous g-->a mutation at nucleotide 8035 of the Bbeta gene. This creates a premature stop at the Trp 440 codon and results in a 22-residue truncation of the Bbeta chain. ⋯ The principal structural feature of the independently folding betaD domain is its five-stranded anti-parallel beta sheet. The deletion here of residues 440 to 461 removes the second strand from this sheet structure and appears to impact on the viability of the nascent chain and its ability to be incorporated into mature fibrinogen molecules. The mutation does not however provoke the formation of hepatic inclusion bodies.
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Comparative Study
A performance evaluation of commercial fibrinogen reference preparations and assays for Clauss and PT-derived fibrinogen.
The wide availability of fibrinogen estimations based on the prothrombin time (PT-Fg) has caused concern about the variability and clinical utility of fibrinogen assays. In a multi-centre study, we investigated fibrinogen assays using various reagents and analysers. Clauss assays generally gave good agreement, although one reagent gave 15-30% higher values in DIC and thrombolysis. ⋯ ELISA and immunonephelometric assays correlated well, but with a high degree of scatter. Antigen levels were higher than Clauss, but slightly lower than PT-Fg assays, which appeared to be influenced by degraded fibrinogen. Clauss assays are generally reproducible between centres, analysers and reagents, but PT-Fg assays are not reliable in clinical settings.
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The ability of abciximab to prevent fibrinogen binding to activated platelets indicates it may also promote dissolution of platelet-rich thrombi. The present study examined the capacity of abciximab to reverse platelet aggregation in vitro. ⋯ These data indicate that abciximab facilitates the dispersal of newly formed platelet aggregates in vitro, by partially displacing fibrinogen from activated GPIIb/IIIa receptors. In vivo, abciximab may destabilize coronary thrombi by preventing aggregate formation and dispersing mural thrombi.
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Multicenter Study Comparative Study
Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium.
Venous thromboembolism is a rare but threatening complication of pregnancy. Little conclusive information is available on the actual risk of venous thromboembolism during pregnancy or puerperium in women with inherited thrombophilia, particularly in carriers of factor V Leiden and of the G20210A prothrombin gene mutation. To determine the pregnancy-related and puerperium-related risk of venous thromboembolism in women with inherited thrombophilia, we performed a case-control study on 119 women who had a first episode of deep vein thrombosis and/or pulmonary embolism during pregnancy or puerperium and 232 healthy women who had at least one pregnancy without thrombosis. ⋯ In conclusion, women with inherited thrombophilia have an increased risk of venous thromboembolism during pregnancy. Among thrombophilic abnormalities, the prothrombin mutation was the weakest risk factor. Thrombosis occurred more frequently in puerperium than in pregnancy, whether or not thrombophilia was diagnosed.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase.
Deep vein thrombosis (DVT) in children occurs primarily in the upper body venous system. This prospective diagnostic study compared bilateral venography and ultrasound for detection of DVT in the upper venous system in 66 children with acute lymphoblastic leukemia. Results were interpreted by central blinded adjudication. ⋯ Three of 4 DVT detected by ultrasound but not by venography were in the jugular vein. We conclude that ultrasound is insensitive for DVT in the central upper venous system but may be more sensitive than venography in the jugular veins. A combination of both venography and ultrasound is required for screening for DVT in the upper venous system.