Activated protein C resistance due to factor V Leiden, elevated coagulation factor VIII and postoperative deep vein thrombosis in late breast reconstruction with a free TRAM flap: a report of two cases

AbstractThrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A), Prothrombin (G20210A), and MTHFR (C677T) mutations in Saudi women with Deep Vein Thrombosis (DVT) and women with recurrent pregnancy loss (RPL). Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6%) had a significant association for DVT χ2 (OR = 5.1, P = 0.03). In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05). In conclusion, we recommend expanding on these data to provide larger-scale studies.

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Uncertain thrombophilia markers

Thrombosis and Haemostasis ◽

10.1160/th15-06-0478 ◽

2016 ◽

Vol 115 (01) ◽

pp. 25-30 ◽

Cited By ~ 17

Author(s):

Massimo Franchini ◽

Ida Martinelli ◽

Pier Mannuccio Mannucci

Keyword(s):

Protein C ◽

Factor V Leiden ◽

Coagulation Factor ◽

High Plasma ◽

Prothrombin G20210a ◽

Factor V ◽

Dna Testing ◽

Vein Thrombosis ◽

Thrombophilia Screening ◽

Deep Vein

SummaryThe development of venous thromboembolism (VTE), which includes deep-vein thrombosis and pulmonary embolism, may be associated with inherited or acquired risk factors that can be measured in plasma or DNA testing. The main inherited thrombophilias include the plasma deficiencies of the natural anticoagulants antithrombin, protein C and S; the gain-of-function mutations factor V Leiden and prothrombin G20210A; some dysfibrinogenaemias and high plasma levels of coagulation factor VIII. Besides these established biomarkers, which usually represent the first-level laboratory tests for thrombophilia screening, a number of additional abnormalities have been less consistently associated with an increased VTE risk. These uncertain causes of thrombophilias will be discussed in this narrative review, focusing on their clinical impact and the underlying pathogenetic mechanisms. Currently, there is insufficient ground to recommend their inclusion within the framework of conventional thrombophilia testing.

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The HR2 Haplotype of Factor V: Effects on Factor V Levels, Normalized Activated Protein C Sensitivity Ratios and the Risk of Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613866 ◽

2000 ◽

Vol 83 (04) ◽

pp. 577-582 ◽

Cited By ~ 48

Author(s):

Joan Guasch ◽

Pieter Kamphuisen ◽

Hans Vos ◽

Frits Rosendaal ◽

Rogier Bertina ◽

...

Keyword(s):

Venous Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Compound Heterozygous ◽

Factor V ◽

Vein Thrombosis ◽

Increased Risk ◽

V Antigen ◽

Deep Vein

SummaryWe studied the HR2 haplotype of the factor V gene in a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched healthy controls (Leiden Thrombophilia Study, LETS). We investigated both the original His1299Arg (A4070G) polymorphism and the Met385Thr (T1328C) polymorphism. This latter polymorphism, located in exon 8 (heavy chain), is always present in the HR2 haplotype, but also occurs on its own in a His1299 (wt) background. The HR2 haplotype was not associated with an increased risk of venous thrombosis (OR = 1.2, 95% confidence interval: 0.8-2.0). We did not find an association between the HR2 haplotype and a reduced sensitivity for activated protein C (APC) in non-carriers of factor V Leiden (FVL). However, in compound heterozygous FVL/HR2 carriers the sensitivity for APC was reduced. The HR2 haplotype was also associated with reduced factor V antigen levels in both patients and controls. Sequence analysis of the promoter region of factor V in HR2 homozygotes did not reveal any sequence variations that could explain the reduced FV levels. Our results show that the HR2 haplotype is not associated with an increased risk of venous thrombosis or with a reduced sensitivity for APC in non-FVL carriers. However, the HR2 haplotype is associated with a reduced sensitivity for APC in carriers of FVL and with reduced factor V antigen levels.

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