scholarly journals Severe thrombophilia in a factor V‐deficient patient homozygous for the Ala2086Asp mutation (FV Besançon)

2021 ◽  
Vol 19 (5) ◽  
pp. 1186-1199
Author(s):  
Elisabetta Castoldi ◽  
Nathalie Hézard ◽  
Guillaume Mourey ◽  
Kanin Wichapong ◽  
Marjorie Poggi ◽  
...  
Keyword(s):  
Factor V ◽  
Deficient Patient

Gastric Bypass in a Factor V Deficient Patient

2006 ◽  
Vol 16 (8) ◽  
pp. 1104-1106 ◽  
Author(s):  
Syed Husain ◽  
Naveen Ballem ◽  
Howard Beaton
Keyword(s):  
Gastric Bypass ◽  
Factor V ◽  
Deficient Patient

scholarly journals Successful excision of a pseudotumour in a congenitally factor V deficient patient

1998 ◽  
Vol 100 (2) ◽  
pp. 380-382 ◽  
Author(s):  
Tanis ◽  
van der Meer ◽  
Bloem ◽  
Vlasveld
Keyword(s):  
Factor V ◽  
Deficient Patient

Venous thrombosis after knee arthroscopy in a factor V-deficient patient treated with virus-inactivated fresh frozen plasma

2004 ◽  
Vol 15 (8) ◽  
pp. 699-700
Author(s):  
Catherine Boinot ◽  
Laurent Macchi ◽  
Maryse Guicheteau ◽  
Louis E Gayet ◽  
Martine Aperc?? ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Knee Arthroscopy ◽  
Fresh Frozen Plasma ◽  
Factor V ◽  
Deficient Patient ◽  
Fresh Frozen ◽  
Frozen Plasma

Administration of FFP Repletes and Sustains the Megakaryocyte/Platelet-Derived Factor V Pool To Confer Hemostatic Competence in a Factor V-Deficient Individual.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1779-1779 ◽  
Author(s):  
Beth A. Bouchard ◽  
John Chapin ◽  
Nigel S. Key ◽  
Paula B. Tracy
Keyword(s):  
Gastrointestinal Bleeding ◽  
Western Blotting ◽  
Human Factor ◽  
Control Individual ◽  
Factor V ◽  
Marked Contrast ◽  
Factor Va ◽  
Activated State ◽  
Deficient Patient ◽  
Subsequent Disappearance

Abstract Recent studies by our laboratory have demonstrated unequivocally that factor V is endocytosed by megakaryocytes from plasma to form the platelet-derived factor V pool. In the current study, we have determined the time-dependent acquisition of factor V by platelets in a 67 year old factor V-deficient patient, previously shown to be completely devoid of plasma- and platelet-derived factor V. The patient now receives weekly tranfusions of two units of FFP to prevent gastrointestinal bleeding. Plasma and platelet lysate samples were prepared from fresh, whole blood drawn prior to (0 hrs), and following (2, 6, 24, 96, 168 hrs) patient transfusion. A factor V radioimmunoassay (RIA), which can detect factor V concentrations as low as 0.075 μg/mL, a standard factor V clotting-based activity assay, and/or western blotting analyses, which utilize a mixture of anti-human factor V light chain and heavy chain mAbs, were used to evaluate the appearance, and subsequent disappearance, of factor V in these two blood compartments. Prior to transfusion (t = 0 hr), the patient’s plasma-derived factor V could not be detected by any of the three factor V assays. The patient’s plasma-derived factor V level peaked immediately following transfusion (t = 2 hr) reaching a concentration of 1.3 +/− 0.08 μg/mL as measured by RIA, and declined until it reached an undetectable level at 96 hrs post transfusion. These data were confirmed by the results of both the clotting-based assays and western blotting analyses. As the patient’s platelet-derived factor V levels were below the sensitivity of both the RIA and clotting assay, they were analyzed by western blotting. Such analyses confirmed that subsequent to its endocytosis, the patient’s platelet-derived factor V is stored in a partially protelytically activated form similar to that of a control individual. Due to the partially proteolytically activated state of the platelet-derived cofactor, platelet lysates treated with thrombin to activate the factor V to factor Va were used for quantative western blotting. Interestingly, and perhaps consistent with the patient’s receipt of weekly FFP transfusions, factor V/Va could still be detected in platelets immediately prior to transfusion. Subsequent to transfusion and in marked contrast to changes in the plasma-derived cofactor pool, a significant increase in the patient’s platelet-derived factor V/Va level was not observed until 24 hrs post transfusion. These data are consistent with previous studies demonstrating that platelets do not endocytose factor V. Although the concentration of the platelet-derived factor V/Va pool decreased over the subsequent 6 days, antigen remained detectable even though the plasma-derived pool had been depleted 3 days earlier. These combined observations indicate that, subsequent to FFP administration, the patient’s megakaryocytes acquire and proteolytically process plasma-derived factor V normally. Furthermore, the consistent presence of factor V/Va within the patient’s platelets is in all likelihood preventing gastrointestinal bleeding in this individual, which supports the concept that platelet-derived factor V represents the hemostatically relevant factor V pool.

Identification and Cloning of Novel Mutations In a Compound Heterozygous Factor V Deficient Patient

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2210-2210
Author(s):  
Kimberley Talbot ◽  
Jina Song ◽  
Lily Eghdami ◽  
Jessica Tamura-Wells ◽  
Jeff Hewitt ◽  
...  
Keyword(s):  
Western Blot ◽  
Banding Pattern ◽  
Blot Analysis ◽  
Severe Bleeding ◽  
Compound Heterozygous ◽  
Factor V ◽  
Bleeding Tendency ◽  
Novel Mutations ◽  
Deficient Patient ◽  
Pre Treatment

Abstract Abstract 2210 Introduction: Congenital factor V (FV) deficiency is a rare clotting disorder associated with mild to severe hemorrhagic symptoms and a prevalence of approximately 1 per million in the general population. Patients normally present with very low or unmeasurable levels of functional and/or immunoreactive FV and are usually homozygous or compound heterozygous for mutations located in the F5 gene. Heterozygotes typically have approximately half-normal levels of FV and are asymptomatic, whilst compound heterozygotes may show mild to severe bleeding diathesis. Patient Description: A proband now aged 73, was clinically diagnosed since childhood as having severe FV deficiency (<3% FV activity by clinical lab analysis), exhibiting severe bleeding tendency with surgery or dental extraction. Other symptoms included frequent nose bleeds, bruising easily and profound menorrhagia that led to eventual hysterectomy in mid-thirties. Additional routine clinical assays for clotting factors were normal. There was no history of parental bleeding tendency. Methods: DNA was isolated from peripheral blood leucocytes. Exonic and flanking intronic sequences of F5 were amplified by PCR and subjected to automated nucleotide sequencing. To investigate the role of identified mutations in FV function and protein secretion, wildtype (WT) FV and FV variants consistent with mutations identified for the patient using the QuikChange Site-Directed Mutagenesis Kit were cloned into the pED-FV-1033 expression vector. This produced recombinant single chain FV that requires proteolytic activation to express cofactor function. Plasmids encoding WT FV, and the mutation identified in the patient were transfected into baby hamster kidney cells (BHK) using Lipofectamine and stable clones were established. Secretion of FV protein was quantified by commercial enzyme immunoassay (EIA), and FV activity was evaluated using conventional prothrombin time (PT) and activated partial thromboplastin time (APTT) clotting assays. Western blot analysis using monoclonal antibodies to both FV heavy (FVaH) and light chains (FVaL) detected FV antigen and fragmentation profiles. Results: Based on the lack of parental bleeding, compound heterozygosity was probable for this FV deficient patient because the DNA sequence analysis revealed two novel mutations; the first changed the codon for Leu1821 to Ser (L1821S), the second changed Gly2192 to Cys (G2192C). Clotting assays showed low patient plasma FV activity of 0.5±0.015% for PT and 2.0±0.10% for APTT compared to normal pooled plasma. Western blot analysis demonstrated the patient FV banding pattern was comparable to normal plasma, whilst densitometric analysis of the specific bands showed that the patient had 9% of the normal FV antigen level. Recombinant FV secretion detected by EIA from various clones ranged from 0 to 16.6ng/mL. L1821S (28%) and G2192C (25%) mutants secreted lower FV protein compared to WT. Clotting assays (n=2) showed that Leu1821S activity levels were 15% that of WT in contrast to G2192C where no FV clotting activity was detectable. Compared to WT, L1821S had 55% and G2192C had only 1.4% of the specific activity.Western blot analysis demonstrated the L1821S banding pattern was comparable to WT whilst G2192C lacked several fragments. Prolonged thrombin (FIIa) pretreatment of FV clones confirmed WT and both mutants were cleaved to FVaL (∼74k Da) and FVaH (∼105 kDa). In addition, FIIa pre-treatment enhanced clotting activity for most of the clones evaluated. Interestingly, the inactive G2192C mutant acquired modest FV function after pre-incubation with FIIa. Conclusions: Two novel FV mutations that affect both function and secretion have been identified in a FV deficient patient and have been cloned. The L1821S mutation is located close to a FV metal ion binding site that may affect function. G2192C introduces a thiol into FV, reported in the literature to have deleterious effects on protein folding, which may explain attenuated secretion and lack of clotting activity. Only after prolonged pre-treatment with FIIa, G2192C function was acquired, which may suggest that this mutation stabilizes the pro-cofactor conformation of FV. Low in vitro secretion of mutant FV compared to WT corresponds to low patient plasma FV antigen, which is compounded by profound loss of function in G2192C. Further biochemical studies are underway to understand the effect of G2192C on FV activity. Disclosures: No relevant conflicts of interest to declare.

Routine Factor V Leiden Testing Discouraged

2008 ◽  
Vol 41 (7) ◽  
pp. 26-27
Author(s):  
JANE SALODOF MACNEIL
Keyword(s):  
Factor V Leiden ◽  
Factor V

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Lea Weingarz ◽  
Marc Schindewolf ◽  
Jan Schwonberg ◽  
Carola Hecking ◽  
Zsuzsanna Wolf ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Younger Patients ◽  
Risk Of Recurrence ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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