Clinical and Laboratory Management of the Prothrombin G20210A Mutation

2002 ◽  
Vol 126 (11) ◽  
pp. 1319-1325 ◽  
Author(s):  
Ronald C. McGlennen ◽  
Nigel S. Key
Keyword(s):  
Significant Risk ◽  
Factor V Leiden ◽  
Initial Assessment ◽  
Prothrombin G20210a ◽  
Factor V Leiden Mutation ◽  
Published Evidence ◽  
G20210a Mutation ◽  
Key Points ◽  
Prothrombin Mutation ◽  
History Of

Abstract Objective.—To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. Data Sources.—Review of the medical literature, primarily since 1996. Data Extraction and Synthesis.—After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. Conclusions.—Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.

The Association Between Parameters of Erythrocytes Morphology and Thrombophilia-Related Mutations

2021 ◽  
Vol 16 ◽  
Author(s):  
Ozlem Oz ◽  
Ataman Gonel
Keyword(s):  
Factor V Leiden ◽  
Mthfr C677t ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Cross Sectional ◽  
Factor V Leiden Mutation ◽  
Erythrocyte Morphology ◽  
Mthfr A1298c ◽  
G20210a Mutation ◽  
History Of

Background: Alterations in erythrocyte morphology parameters have been identified and associated with hematological disorders and other chronic and cardiovascular diseases. Erythrocytes are abundant in thrombus content. Their hemoglobin density and differences in the ratio of macrocytic and microcytic cells may be associated with hypercoagulopathy in those with a history of thrombosis. Objective: This cross-sectional study aimed to investigate the relationship between hemogram parameters and thrombophilia genetic parameters. Method: A total of 55 patients whose thrombophilia panel was reviewed due to the diagnosis of thrombosis were included in the study. %MIC, %MAC, %HPO, %HPR and all hemogram parameters were measured using Abbott Alinity HQ. Prothrombin G20210A, MTHFR C677T, MTHFR A1298C, Factor V Leiden G169A and PAI-1 4G/5G mutations were studied using Real Time-PCR. Results: The MTHFR C677T mutation was detected in 58.2% of the patients. The Factor V Leiden mutation was detected in 5.5% of the patients. The MTHFR A1298C mutation was detected in 58.2%, The PAI mutation was detected in 74.5%, and the Factor 13 mutation was detected in 29% of the patients. Prothrombin G20210A mutation was not detected in any of the patients. Red blood cell (RBC) and Hct values were higher in Factor 13 mutant group; the Hgb and Htc values were higher in the MTHFR C677T mutant group. Conclusion: The MTHFR C677T and Factor 13 mutations may be associated with high Hct and RBC, Hgb, and Htc values, respectively and coagulation tendency in patients with a history of thrombosis.

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.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity

2020 ◽  
Vol 19 ◽  
pp. 127-130
Author(s):  
Jeske J.K. van Diemen ◽  
Jeske M. Bij de Weg ◽  
Arda Arduç ◽  
Olivier Veraart ◽  
David Mager ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Relationship Of ◽  
The Relationship

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2055-2061 ◽  
Author(s):  
Elizabeth F. W. van Vlijmen ◽  
Nic J. G. M. Veeger ◽  
Saskia Middeldorp ◽  
Karly Hamulyák ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Contraceptive ◽  
Factor V Leiden ◽  
Informed Choice ◽  
Rational Approach ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractCurrent guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.

The Outcome of Pregnancy in Patients with Thrombophilia after Anticoagulation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4164-4164
Author(s):  
Qingqi Jiang ◽  
Judith Andersen
Keyword(s):  
Unfractionated Heparin ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Protein S ◽  
Severe Bleeding ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
History Of

Abstract Background: Both inherited and acquired thrombophilia predispose pregnant women to venous thromboembolism and recurrent fetal loss. The safety profile and tolerability of low molecular heparin (LWMH) has allowed us to evaluate effects of anticoagulation in the outcome of pregnancy in patients with thrombophilia. Methods: 20 patients with thrombophilia received either tinzaparin or enoxaparin combined with aspirin before and during pregnancy and the outcome of pregnancy was monitored for a period of 2 years. The median age of the patients was 28 years (25–49); 75% were Caucasians, 20% were aferican-american, 5% were others. The inherited and acquired thrombophilias include Factor V leiden mutation, prothrombin mutation in G20210A, mutation in methylenetetrahydrofolate (MTHFR), protein S deficiency, protein C deficiency, hyperhomocyteinemia, antiphospholipid syndrome, sticky platelet syndrome, etc. The majority of patients had more than 2 thrombophilia factors and had history of miscarriage. 15 of 20 patients (75%) received tinzaparin and 4 of 20 (20%) patients received enxoparin subcutaneously before they were conceived. Only one patient received unfractionated heparin. The LWMH was continued during pregnancy until 34 to 36 weeks gestation when it was changed to unfractionated heparin in order to prevent large amount of bleeding from upcoming delivery. All of the patients also received aspirin prior, during, and after the pregnancy. There were 21 live births including one triplet and one twins. Only two patients were complicated with miscarriage. There was no episode of severe bleeding or thromboembolism during pregnancy or postpartum. Conclusion: LWMH and aspirin has been effective in the prevention of fetal loss in women with thrombophilia disorders.

scholarly journals Laboratory Investigation of Thrombophilia / LABORATORIJSKO ISPITIVANJE TROMBOFILIJA

2014 ◽  
Vol 33 (1) ◽  
pp. 28-46 ◽  
Author(s):  
Sandra Margetić
Keyword(s):  
Risk Factors ◽  
Laboratory Investigation ◽  
Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Prothrombin G20210a ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Increased Risk ◽  
Assay Methods

Summary Laboratory investigation of thrombophilia is aimed at detecting the well-established hereditary and acquired causes of venous thromboembolism, including activated protein C resistance/factor V Leiden mutation, prothrombin G20210A mutation, deficiencies of the physio - logical anticoagulants antithrombin, protein C and protein S, the presence of antiphospholipid antibodies and increased plasma levels of homocysteine and coagulation factor VIII. In contrast, investigation of dysfibrinogenemia, a very rare thrombophilic risk factor, should only be considered in a patient with evidence of familial or recurrent thrombosis in the absence of all evaluated risk factors mentioned above. At this time, thrombophilia investigation is not recommended for other potential hereditary or acquired risk factors whose association with increased risk for thrombosis has not been proven sufficiently to date. In order to ensure clinical relevance of testing and to avoid any misinterpretation of results, laboratory investigation of thrombophilia should always be performed in accordance with the recommended guidelines on testing regarding the careful selection of patients, time of testing and assays and assay methods used. The aim of this review is to summarize the most important aspects on thrombophilia testing, including whom and when to test, what assays and assay methods to use and all other variables that should be considered when performing laboratory investigation of thrombophilia.

scholarly journals Homozygous Carrier of Prothrombin G20210A Mutation with Massive Pulmonary Embolism and His Family: Gender Differences of Susceptibility to Mutation

Folia Medica ◽  
2016 ◽  
Vol 58 (1) ◽  
pp. 64-66
Author(s):  
Natalia Y. Stoeva ◽  
Vessela S. Koleva
Keyword(s):  
Pulmonary Embolism ◽  
Massive Pulmonary Embolism ◽  
Male Gender ◽  
The Other ◽  
Prothrombin G20210a ◽  
Homozygous Carrier ◽  
G20210a Mutation ◽  
Prothrombin Mutation ◽  
Balkan Countries ◽  
History Of

Abstract Prothrombin 20210 G>A mutation is the second most frequent inherited factor increasing the risk for developing venous thromboembolism (VTE). The risk for VTE in homozygous carriers of this mutation is not well studied because of their rarity are rare. We report a case of a homozygous carrier of prothrombin mutation: a young man with massive pulmonary embolism, and his family - an asymptomatic homozygous sister, heterozygous parents with asymptomatic mother, and father with history of deep venous thrombosis (DVT). To our knowledge, this is the first reported case of homozygous prothrombin mutation carriers in Bulgaria and the other Balkan countries. We conclude that the homozygous prothrombin mutation creates predisposition for VTE that can manifest or not depending on additional factors, one of which could be male gender.

Thrombotic risk factors in Chinese Budd-Chiari syndrome patients

2013 ◽  
Vol 109 (05) ◽  
pp. 878-884 ◽  
Author(s):  
Chuangye He ◽  
Zhanxin Yin ◽  
Jing Niu ◽  
Ming Bai ◽  
Zhiping Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myeloproliferative Neoplasms ◽  
Factor V Leiden ◽  
Jak2 V617f ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

SummaryIn Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria, etc. However, the data regarding thrombotic risk factors in Chinese BCS patients are extremely limited. An observational study was conducted to examine this issue. A total of 246 BCS patients who were consecutively admitted to our department between July 1999 and December 2011 were invited to be examined for thrombotic risk factors. Of these, 169 patients were enrolled. Neither factor V Leiden mutation nor prothrombin G20210A mutation was found in any of 136 patients tested. JAK2 V617F mutation was positive in four of 169 patients tested. Neither MPL W515L/K mutation nor JAK2 exon 12 mutation was found in any of 135 patients tested. Overt myeloproliferative neoplasms were diagnosed in five patients (polycythemia vera, n=3; essential thrombocythemia, n=1; idiopathic myelofibrosis, n=1). Two of them had positive JAK2 V617F mutation. Both CD55 and CD59 deficiencies were found in one of 166 patients tested. This patient had a previous history of paroxysmal nocturnal haemoglobinuria before BCS. Anticardiolipin IgG antibodies were positive or weakly positive in six of 166 patients tested. Hyperhomocysteinaemia was found in 64 of 128 patients tested. 5,10-methylenetetrahydrofolate reductase C677T mutation was found in 96 of 135 patients tested. In conclusion, factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, and paroxysmal nocturnal haemoglobinuria are very rare in Chinese BCS patients, suggesting that the etiological distribution of BCS might be different between Western countries and China.

Inherited Thrombophilia

2014 ◽  
Vol 27 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Haley M. Phillippe ◽  
Lori B. Hornsby ◽  
Sarah Treadway ◽  
Emily M. Armstrong ◽  
Jessica M. Bellone
Keyword(s):  
Thrombus Formation ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Clotting Factors ◽  
Inherited Thrombophilia ◽  
G20210a Mutation ◽  
Prothrombin Mutation ◽  
Normal Hemostasis

Thrombophilia alters normal hemostasis, shifting the balance in favor of thrombus formation. Inherited conditions include factor V Leiden (FVL), prothrombin G20210A mutation, deficiencies in natural anticoagulants (antithrombin [AT], protein C, and protein S), hyperhomocysteinemia, and elevations in clotting factors (factors VIII and XI). Although FVL and prothrombin mutation are common disorders, deficiencies in the natural anticoagulants are rare. The risk of initial thrombosis conferred by inherited thrombophilia varies with the highest risk in those homozygous for either FVL or prothrombin mutation, or with AT deficiency. In the nonpregnant patient, the presence of a thrombophilia does not affect treatment of an acute event. Although vitamin B supplementation has been shown to decrease the levels of homocysteine, the treatment has failed to show a benefit in thrombus prevention and is therefore not recommended.

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