Pregnancy-related thrombosis risk in patients with protein C deficiency and comparison with pregnant women with heterozygous factor V Leiden mutation

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.

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#710 Priapism as a presentation of protein C deficiency and the factor V leiden mutation

Journal of Pediatric Hematology/Oncology ◽

10.1097/00043426-199807000-00147 ◽

1998 ◽

Vol 20 (4) ◽

pp. 414

Author(s):

J. Zimbelman ◽

T. Hays ◽

R. Nuss

Keyword(s):

Protein C ◽

Factor V Leiden ◽

Factor V ◽

Protein C Deficiency ◽

Factor V Leiden Mutation

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The G20210A Prothrombin Polymorphism Is not Associated with Increased Thromboembolic Risk in a Large Protein C Deficient Kindred

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613822 ◽

2000 ◽

Vol 83 (03) ◽

pp. 366-370 ◽

Cited By ~ 11

Author(s):

Sandra Hasstedt ◽

Peter Callas ◽

Julia Valliere ◽

Bruce Scott ◽

Kenneth Bauer ◽

...

Keyword(s):

Protein C ◽

Factor V Leiden ◽

Complex Nature ◽

Type I ◽

Factor V ◽

Protein C Deficiency ◽

Additional Increase ◽

Factor V Leiden Mutation ◽

Increased Risk ◽

Risk For Thrombosis

SummaryLikelihood analysis was used to test the effect of the G20210A prothrombin mutation and the His107Pro protein C mutation (resulting from a C insertion) on thrombosis status and prothrombin level in a large kindred of French Canadian descent with type I protein C deficiency. Genotypes were available on 279 pedigree members or their spouses. Of this total, 36 pedigree members were heterozygous for the G20210A variant and one pedigree member was homozygous for G20210A, while 64 were heterozygous for the His107Pro protein C mutation. The factor V Leiden mutation (Arg506Gln) was observed in only one of 181 tested family members. Objectively verified thrombosis was present in 26 of the 279 pedigree members. Thrombosis was suspected in an additional 19 pedigree members. The transmission disequilibrium test of Spielman, 1996, as extended to pedigrees, was used to test for excess transmission of G20210A or His107Pro to thrombosis cases, with transmission of 0.5 specifying no effect. Although the His107Pro mutation was over transmitted (0.837 ± 0.075 p <0.001) to thrombosis cases in this pedigree, the G20210A variant was not (0.491 ± 0.130 NS).Measured genotype analysis was used to examine a total of 184 individuals for the relationship between prothrombin level and both the G20210A variant and thrombosis. The G20210A variant increased prothrombin level from 97 ± 2% to 124 ± 4% (p <0.0001), but thrombosis status was not associated with any additional increase in prothrombin level. Thus, in a large thrombophilic, protein C deficient kindred, with the G20210A variant present in a proportion (13%) far higher than the general Caucasian population (∼2%), neither the presence of the variant nor the plasma concentration of prothrombin were associated with increased risk for thrombosis. These findings contrast with those of others who have established the G20210A variant as a thrombophilic risk factor; and emphasize the complex nature of the multigenic pathogenesis of thrombophilia.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650612 ◽

1996 ◽

Vol 76 (04) ◽

pp. 505-509 ◽

Cited By ~ 11

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.

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Postpartum cerebral venous thrombosis, congenital protein C deficiency, and activated protein C resistance due to heterozygous factor V Leiden mutation

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.65.5.801 ◽

1998 ◽

Vol 65 (5) ◽

pp. 801-802 ◽

Cited By ~ 2

Author(s):

L. DEREX ◽

F. PHILIPPEAU ◽

N. NIGHOGHOSSIAN ◽

P. TROUILLAS ◽

M. BERRUYER

Keyword(s):

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Factor V ◽

Activated Protein C Resistance ◽

Protein C Deficiency ◽

Factor V Leiden Mutation ◽

Congenital Protein C Deficiency

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Thrombogenesis in Thrombophilic Pregnancy: Evaluation of Low-Molecular-Weight Heparin Prophylaxis

Acta Haematologica ◽

10.1159/000467385 ◽

2017 ◽

Vol 137 (4) ◽

pp. 201-206 ◽

Cited By ~ 2

Author(s):

Roberto Simeone ◽

Roberta Giacomello ◽

Germano Bruno ◽

Sergio Parco ◽

Natalia Maximova ◽

...

Keyword(s):

Molecular Weight ◽

Pregnant Women ◽

Low Molecular Weight Heparin ◽

Factor V Leiden ◽

Control Group ◽

Low Molecular Weight ◽

Factor V ◽

Protein C Deficiency ◽

Factor V Leiden Mutation ◽

Heparin Prophylaxis

The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women.

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615201 ◽

1998 ◽

Vol 80 (08) ◽

pp. 344-345 ◽

Cited By ~ 2

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

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“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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650290 ◽

1996 ◽

Vol 75 (03) ◽

pp. 422-426 ◽

Cited By ~ 53

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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A Hemi-nested, Allele Specific, Whole Blood PCR Assay for the Detection of the Factor V Leiden Mutation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656129 ◽

1997 ◽

Vol 77 (06) ◽

pp. 1154-1155 ◽

Cited By ~ 4

Author(s):

Gary D Sinclair ◽

Sandra Low ◽

Man-Chiu Poon

Keyword(s):

Whole Blood ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Restriction Enzyme Digestion ◽

Factor V ◽

Pcr Assay ◽

Specific Primers ◽

Factor V Leiden Mutation ◽

Allele Specific

SummaryWe describe a novel hemi-nested, allele specific whole blood PCR assay for detection of the factor V Leiden mutation associated with the plasma defect, activated protein C resistance. This assay utilizes 5 μl of whole blood without prior DNA extraction. The hemi-nested design, employing an outer primer pair in combination with nested, allele specific primers obviates the need for restriction enzyme digestion. PCR reactions are analysed directly on agarose or polyacrylamide minigels. The assay confirmed the genotypes of 50 individuals previously categorized by PCR and Mnll digestion, and has been subsequently utilized in the genotyping of 445 individuals referred for thrombosis studies.

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