Inherited thrombophilia due to factor V Leiden mutation*

1998 ◽  
Vol 3 (1) ◽  
pp. 55-62 ◽  
Author(s):  
J MATTSON ◽  
D CRISAN
Keyword(s):  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia

scholarly journals Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Maria Khan ◽  
Chaudhry Altaf ◽  
Hamid Saeed Malik ◽  
Muhammad Abdul Naeem ◽  
Aamna Latif
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia ◽  
At Deficiency ◽  
Prothrombin Gene

Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

A Heparin Cofactor II Mutation (HCII Rimini) Combined with Factor V Leiden or Type I Protein C Deficiency in Two Unrelated Thrombophilic Subjects

1996 ◽  
Vol 76 (04) ◽  
pp. 505-509 ◽  
Author(s):  
F Bernardi ◽  
C Legnani ◽  
F Micheletti ◽  
B Lunghi ◽  
P Ferraresi ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Type I ◽  
Factor V ◽  
Protein C Deficiency ◽  
Heparin Cofactor Ii ◽  
Factor V Leiden Mutation ◽  
Heterozygous Condition ◽  
Inherited Thrombophilia

Summary305 patients with juvenile thromboembolic episodes were screened for the presence of heparin cofactor II deficiency. The heterozygous deletion of two bases was found in the exon 5 of the heparin cofactor II gene in two unrelated patients, very likely due to a founder effect. This molecular lesion, causing a frameshift and elongated translation, affects the core of the molecule and should cause the complete unfolding of the protein, which is in accordance with the observed type I deficiency. The corresponding region of antithrombin III gene is affected by a cluster of frameshift mutations suggesting that heparin cofactor II and antithrombin III could share similar mutational patterns.The heparin cofactor II gene alteration was associated with, in one patient, the factor V Leiden mutation and, in the other, type I protein C deficiency. The tracing of the single defects in several family members indicated that the mutations became clinically manifest only when present in the doubly heterozygous condition. This study provides two examples, based on molecular findings, of the interplay of risk factors which is potentially useful to define a role for heparin cofactor II deficiency in inherited thrombophilia.

Prophylactic Therapy with Enoxaparin in Children with Acute Lymphoblastic Leukemia and Inherited Thrombophilia During L-Asparaginase Treatment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4120-4120
Author(s):  
Dan Harlev ◽  
Irina Zaidman ◽  
Galit Sarig ◽  
Myriam Ben Arush ◽  
Benjamin Brenner ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia ◽  
G20210a Mutation ◽  
Number Of Patients ◽  
Prothrombin Mutation

Abstract Abstract 4120 Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL) receiving L-asparaginase in combination with vincristine, prednisone and anthracyclines. They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) is widely used for the prevention of thrombosis in a variety of diseases. Its advantages are prolonged half-life and the low rate of induced thrombocytopenia. To date, there is a debate as to whether or not to give prophylactic treatment for TE using low-dose warfarin or LMWH in children with ALL receiving a combination of L-asparaginase and steroids. In a previous study done by us LMWH was given to all children with ALL during L-asparaginase treatment. In the current study presented herein it was decided to give prophylactic LMWH during L-asparaginase treatment only to patients with ALL and genetic thrombophilia. Eighty-seven consecutive children with acute onset of ALL treated at Rambam Medical Center between the years 1999 and 2008 were included. Eighty patients were above the age of 1 year and were treated according to the Israeli version of the BFM protocols 1998 and 2002, while seven patients with infant leukemia were treated according to the Interfant-99 protocol. Median age at diagnosis was 4.9 years (range: 0.1-16 years). There were 56 boys and 31 girls. Forty-five patients were Arabic (including Druze), 41 were Jewish and one was Bahai. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1 mg/kg starting with the first dose of L-asparaginase (day 12 during induction, day 8 during consolidation) until one week after the last dose (day 40 during induction, day 25 during consolidation) to patients with inherited thrombophilia; either factor V Leiden or prothrombin mutation. Twenty (22.9%) patients were found to have a genetic predisposition for TE. Six (6.9%) patients were heterozygous for prothrombin G20210A mutation, while 14 (16%) patients were heterozygous for factor V Leiden mutation. Seven of the 87 (8%) patients developed eight thromboembolic events. Three of these seven were heterozygous for prothrombin mutation and received prophylactic LMWH. The other 4 patients had no genetic thrombophilia and did not receive LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH (Table 1). No bleeding occurred during treatment with LMWH. It is suggested that prophylactic use of LMWH for prevention of TE events during L-asparaginase treatment is more beneficial to patients harboring factor V Leiden mutation than for those who have prothrombin mutation. A randomized trial of LMWH should be performed in children with ALL during L-asparaginase and steroids treatment, in order to properly asses its safety and efficacy in preventing TE. Table 1 Number of patients (%) LMWH treatment TE episodes Total number of patients ➞ 7 patients No genetic thrombophilia 67 (77) no 4 Genetic thrombophilia 20 (23) Factor II G20210A 6 Yes 3     Homozygous     Heterozygous 0 Factor V Leiden     Homozygous 14 Yes (in 12 patients) 0     Heterozygous 0 14 Disclosures: Brenner: sanopi-aventis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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.

Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

1998 ◽  
Vol 80 (08) ◽  
pp. 344-345 ◽  
Author(s):  
Pasra Arnutti ◽  
Motofumi Hiyoshi ◽  
Wichai Prayoonwiwat ◽  
Oytip Nathalang ◽  
Chamaiporn Suwanasophon ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Coagulation Factor V

Low Prevalence of the Factor V Leiden Mutation Among “Severe” Hemophiliacs with a “Milder” Bleeding Diathesis

1995 ◽  
Vol 74 (05) ◽  
pp. 1255-1258 ◽  
Author(s):  
Arnaldo A Arbini ◽  
Pier Mannuccio Mannucci ◽  
Kenneth A Bauer
Keyword(s):  
Hemophilia A ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor Ix ◽  
Hemophilia B ◽  
Factor V ◽  
Bleeding Diathesis ◽  
Mutation Site ◽  
Spontaneous Bleeding ◽  
Factor V Leiden Mutation

SummaryPatients with hemophilia A and B and factor levels less than 1 percent of normal bleed frequently with an average number of spontaneous bleeding episodes of 20–30 or more. However there are patients with equally low levels of factor VIII or factor IX who bleed once or twice per year or not at all. To examine whether the presence of a hereditary defect predisposing to hypercoagulability might play a role in amelio rating the hemorrhagic tendency in these so-called “mild severe” hemophiliacs, we determined the prevalence of prothrombotic defects in 17 patients with hemophilia A and four patients with hemophilia B selected from 295 and 76 individuals with these disorders, respectively, followed at a large Italian hemophilia center. We tested for the presence of the Factor V Leiden mutation by PCR-amplifying a fragment of the factor V gene which contains the mutation site and then digesting the product with the restriction enzyme Mnll. None of the patients with hemophilia A and only one patient with hemophilia B was heterozygous for Factor V Leiden. None of the 21 patients had hereditary deficiencies of antithrombin III, protein C, or protein S. Our results indicate that the milder bleeding diathesis that is occasionally seen among Italian hemophiliacs with factor levels that are less than 1 percent cannot be explained by the concomitant expression of a known prothrombotic defect.

Detection of the Factor V Leiden Mutation Using Whole Blood PCR

1996 ◽  
Vol 75 (03) ◽  
pp. 520-521 ◽  
Author(s):  
D C Rees ◽  
M Cox ◽  
J B Clegg
Keyword(s):  
Whole Blood ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation

“Pseudo Homozygous” Activated Protein C Resistance due to Double Heterozygous Factor V Defects (Factor V Leiden Mutation and Type I Quantitative Factor V Defect) Associated with Thrombosis: Report of Two Cases Belonging to Two Unrelated Kindreds

1996 ◽  
Vol 75 (03) ◽  
pp. 422-426 ◽  
Author(s):  
Paolo Simioni ◽  
Alberta Scudeller ◽  
Paolo Radossi ◽  
Sabrina Gavasso ◽  
Bruno Girolami ◽  
...  
Keyword(s):  
Protein C ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Type I ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Apc Resistance ◽  
Quantitative Factor

SummaryTwo unrelated patients belonging to two Italian kindreds with a history of thrombotic manifestations were found to have a double heterozygous defect of factor V (F. V), namely type I quantitative F. V defect and F. V Leiden mutation. Although DNA analysis confirmed the presence of a heterozygous F. V Leiden mutation, the measurement of the responsiveness of patients plasma to addition of activated protein C (APC) gave results similar to those found in homozygous defects. It has been recently reported in a preliminary form that the coinheritance of heterozygous F. V Leiden mutation and type I quantitative F. V deficiency in three individuals belonging to the same family resulted in the so-called pseudo homozygous APC resistance with APC sensitivity ratio (APC-SR) typical of homozygous F. V Leiden mutation. In this study we report two new cases of pseudo homozygous APC resistance. Both patients experienced thrombotic manifestations. It is likely that the absence of normal F. V, instead of protecting from thrombotic risk due to heterozygous F. V Leiden mutation, increased the predisposition to thrombosis since the patients became, in fact, pseudo-homozygotes for APC resistance. DNA-analysis is the only way to genotype a patient and is strongly recommended to confirm a diagnosis of homozygous F. V Leiden mutation also in patients with the lowest values of APC-SR. It is to be hoped that no patient gets a diagnosis of homozygous F. V Leiden mutation based on the APC-resi-stance test, especially when the basal clotting tests, i.e., PT and aPTT; are borderline or slightly prolonged.

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