4g/5g Prevalence in 223 Patients with Thrombosis and in 162 Healthy Controls, from the Centre Region of Portugal.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4057-4057
Author(s):  
Rosa Maia ◽  
Emilia Cortesao ◽  
Catarina Geraldes ◽  
Luis Simoes ◽  
Carla Simoes ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Insertion Polymorphism ◽  
Factor V ◽  
Centre Region ◽  
History Of ◽  
Pai 1

Abstract A deletion/insertion polymorphism (4G or 5G) in the promoter of the PAI-1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression, and therefore related with thrombosis. In the present work we studied the prevalence of 4G/5G polymorphism in 223 unrelated patients with history of objectively confirmed thromboembolism, and in 162 healthy unrelated controls, both groups natural from all centre regions of Portugal. In this normal cohort, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in the affected population is, respectively, 47%, 21.5% and 30%, which means that 4G/4G is twice more frequent in the patients with thrombosis. When we relate the age of the first thrombosis episodes in the three groups, we find no significative difference, as the respective media is 36.8; 38.6 and 35.5 years in the 4G/4G, 4G/5G and 5G/5G group, respectively. This data suggest that this polymorphism by itself, even in homozygosity, is not associated with earlier thrombosis. In our patients, we studied the presence of Lupus Anticoagulant, Factor V Leiden, Factor IIG20210A, MTHFR C677T, and also Antithrombin III, Protein S and Protein C levels. We analyse the prevalence of the three mutations in patients with DVP, PTE, ischemic and venous CVA and we only find a significative difference in the 4G/4G group: 46.2% patients with DVP and 48.2% patients with PTE (23% in normal cohort). In conclusion, in the centre region of Portugal, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in our cohort of unrelated patients the only significative difference is in the 4G/4G group (47%); this variation maintain in the DVP and PTE group. We did not find difference at the age of the first thrombotic episode, in the three groups.

scholarly journals Primary Thrombophilia in Mexico: A Single Tertiary Referral Hospital Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4717-4717
Author(s):  
Dennis Lacayo-Leñero ◽  
Angel Gabriel Vargas-Ruiz ◽  
Olga Barrales-Benítez ◽  
Darinel Hernández-Hernández ◽  
Andrés Valencia-Martínez
Keyword(s):  
Protein C ◽  
Age At Onset ◽  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Factor V ◽  
Tertiary Referral Hospital ◽  
Unusual Site ◽  
Mthfr C677t Polymorphism ◽  
History Of

Abstract Background: Thrombophilia is a complex hypercoagulable state that predisposes to thrombosis. Several thrombophilia reports have been conducted in Mexicans with lack of statistical significance. The objective of this study was to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. Material and methods: Retrospective study of patients referred for primary thrombophilia between January 2011 and May 2015.. Thrombophilia study included: MTHFR C677T, anti-phopholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, APCR, JAK2 V617F, homocysteine. We used descriptive statistics according to the distribution of the variables. We used measures of central tendency and dispersion: average, median. All analyses were performed using the SPSS for Windows 20.0® Results: We identified 224 patients referred for thrombophilia testing in a 4 year period. At the time of statistical analysis 129 patients were excluded for lacking data.Ninety five patients were included.Median age at onset was 36 years. (Table 1) Nine of 60 (15%) female patients reported previous use of contraceptives and 13/60 (21.6%) reported previous obstetric morbidity. (Table 2). We identified at least one anomaly related with thrombophilia in 90/95 patients (94.7%). Eighty patients (84.1%) presented the MTHFR C677T polymorphism; heterozygous 51/95 (53.6%) presenting with hyperhomocysteinemia 18/51 (35.2%) and homozygous 29/95 (30.5%) presenting with hyperhomocysteinemia 10/29 (34.4%).Factor V Leiden was found in 5/95 (5.2%) heterozygous. It co-occurred with APCR in 3/5 cases (60%).In 44 patients we found an isolated anomaly associated with thrombophilia (46.3%). In 51/95 (53.6%) we identified co-occurring anomalies associated with thrombophilia. (Table 3). The median of co-occurring anomalies was 2 (2-4). Conclusions: The MTHFR C677T polymorphism has a very high prevalence in Mexicans compared to the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation. Table 1. Demographic characteristics. Demographic characteristics No. Patients (%) -Gender Male Female Total 35 (36.8) 60 (63.1) 95 (100) -Age Median years (range) 36 (17-75) -Family history of thrombosis -Cardiovascular risk factors Arterial Hypertension Diabetes mellitus Dyslipidemia Smoking 15 (15.7) 13 (13.6) 11 (11.5) 13 (13.6) 15 (15.7) -Surgery related thrombosis 3 (3.1) -Cancer related thrombosis 3 (3.1) -Autoimmune disease SLE Other autoimmune disease 11 (11.5) 3 (3.1) 8 (8.4) SLE: Systemic Lupus Erythematosus. Table 2. Thrombosis characteristics. Thrombosis characteristics No. Patients (%) -Thrombotic events Median (range) 1 (1-4) -Affected territory Venous Arterial Mixed 80 (84.2) 14 (14.7) 1 (1) -Thrombophilia testing indication Age at onset <45 years. Family history of thrombosis Unusual site thrombosis Intra abdominal thrombosis Cerebral vein thrombosis Other unusual site thrombosis Recurrent thrombosis Obstetric morbidity More than one indication for testing 91 (95.7) 77 (81) 15 (15.7) 48 (50.5) 25/48 (52) 11/48 (22.9) 12/48 (25) 26 (27.3) 13/60 (21.6) 62 (65.2) -Treatment VKA LMWH Clopidogrel NOAC's ASA None ND 44 (46.3) 3 (3.1) 1 (1) 8 (8.4) 14 (14.7) 6 (6.3) 19 (20) VKA: Vitamin K Antagonist LMWH: Low Molecular Weight Heparin; NOAC's: New oral anticoagulants; ASA: acetylsalicylic acid. ND: Not described. Table 3. Results of thrombophilia anomalies. TROMBOPHILIA TOTAL FREQUENCY ISOLATED FREQUENCY CO-OCCURRING WITH ANOTHER THROMBOPHILIA ANOMALY. -MTHFR C677T heterozygous 51/95 (53.6%). 22/51 (43.1%) 29/51 (56.8%) -Hyperhomocysteinemia 36/95 (37.8%). 6/36 (16.6%) 30/36 (83.3%) -MTHFR C677T homoczygous 29/95 (30.5%). 14/29 (48.2%) 15/29 (51.7%) -APCR 13/95 (13.6%). 0 13/13 (100%) -F V Leiden G1691A 5/95 (5.2%) 0 5/5 (100%) -Protein C deficiency 5/95 (5.2%) 0 5/5 (100%) -Elevated FVIII levels (>150%) 4/95 (4.2%) 0 4/4 (100%) -Protein S deficiency 3/95 (3.1%) 1/3 (33.3%) 2/3 (66.6%) -APS 3/95 (3.1%) 0 3/3 (100%) -Prothrombin G20210A 2/95 (2.1%). 0 2/2 (100%) -JAK2V617F 1/95 (1.0%) 1/1 (100%) 0 -Antithrombin deficiency 0 0 0 MTHFR: methylentetrahidrofolate reductase; APCR: Activated protein C resistance; APS: Antiphospholipid syndrome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombophilia And Arterial Ischemic Stroke

2017 ◽  
pp. 45
Author(s):  
A.A. Abrishamizadeh
Keyword(s):  
Ischemic Stroke ◽  
Vitamin K ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C Protein

Ischemic stroke (IS) is a common cause of morbidity and mortality with significant socioeconomic impact especially when it affects young patients. Compared to the older adults, the incidence, risk factors, and etiology are distinctly different in younger IS. Hypercoagulable states are relatively more commonly detected in younger IS patients.Thrombophilic states are disorders of hemostatic mechanisms that result in a predisposition to thrombosis .Thrombophilia is an established cause of venous thrombosis. Therefore, it is tempting to assume that these disorders might have a similar relationship with arterial thrombosis. Despite this fact that 1-4 % of ischemic strokes are attributed to Thrombophillia, this   alone rarely causes arterial occlusions .Even in individuals with a positive thrombophilia screen and arterial thrombosis, the former might not be the primary etiological factor.Thrombophilic   disorders can be broadly divided into inherited or acquired conditions. Inherited thrombophilic states include deficiencies of natural anticoagulants such as protein C, protein S, and antithrombin III (AT III) deficiency, polymorphisms causing resistance to activated protein C(Factor V Leiden mutation), and disturbance in the clotting balance (prothrombin gene 20210G/A variant). Of all the inherited  thrombophilic disorders, Factor V Leiden mutation is perhaps the commonest cause. On the contrary, acquired thrombophilic disorders are more common and include conditions such as the antiphospholipid syndrome, associated with lupus anticoagulant and anticardiolipin antibodies.The more useful and practical approach of ordering various diagnostic tests for the uncommon thrombophilic states tests should be determined by a detailed clinical history, physical examination, imaging studies and evaluating whether an underlying hypercoagulable state appears more likely.The laboratory thrombophilia   screening should be comprehensive and avoid missing the coexisting defect and It is important that a diagnostic search protocol includes tests for both inherited and acquired thrombophilic disorders.Since the therapeutic approach (anticoagulation and thrombolytic therapy) determines the clinical outcomes, early diagnosis of the thrombophilic  disorders plays an important role. Furthermore, the timing of test performance of some of the  thrombophilic  defects (like protein C, protein S, antithrombin III and fibrinogen levels) is often critical since these proteins can behave as acute phase reactants and erroneously elevated levels of these factors may be observed in patients with acute thrombotic events. On the other hand, the plasma levels of vitamin K-dependent proteins (protein C, protein S and APC resistance) may not be reliable in patients taking vitamin K antagonists. Therefore, it is suggested that plasma-based assays for these disorders should be repeated3 to 6 months after the initial thrombotic episode to avoid false-positive results and avoid unnecessary prolonged   anticoagulation therapy. The assays for these disorders are recommended after discontinuation of oral anticoagulant treatment or heparin for at least 2 weeks.    

Fundamentals and Patient Evaluation

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
General Population ◽  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Incidence Rates ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Occult Malignancy ◽  
History Of

Thrombophilia is the term used to describe a tendency toward developing thrombosis. This tendency may be inherited, involving polymorphism in gene coding for platelet or clotting factor proteins, or acquired due to alterations in the constituents of blood and/or blood vessels. An inherited thrombophilia is likely if there is a history of repeated episodes of thrombosis or a family history of thromboembolism. One should also consider an inherited thrombophilia when there are no obvious predisposing factors for thrombosis or when clots occur in a patient under the age of 45. Repeated episodes of thromboembolism occurring in patients over the age of 45 raise suspicion for an occult malignancy. A summary of inherited thrombophilias are summarized in Table 24.1. This list continues to grow, as new genetic polymorphisms and combined mutations are being detected. The prevalence of common thrombophilias is shown in Figure 24.1. Factor V Leiden (FVL) mutation and hyperhomocysteinemia are present in nearly 5% of the general population and are often found in patients with venous thrombosis, while deficiencies of antithrombin (AT), protein C, and protein S are relatively uncommon. Elevated levels of factor VIII (FVIII) are uncovered frequently in the general population and in patients with thrombosis. This is not surprising as FVIII is an acute-phase reactant that increases rapidly after surgery or trauma; however, prospective studies have shown that FVIII elevation in some patients cannot be attributed to a stress reaction and probably represents mutations in the genes regulating FVIII synthesis or release (Kyrle et al., 2000). The same may be true for factors IX and XI. The relative risks for thrombosis among patients with inherited thrombophilias have been determined. While AT mutations are the least common, they are associated with a substantial risk of venous thrombosis; similar risk is seen with protein C and S deficiency. In contrast, the lifetime risk of having a thromboembolic event in an individual heterozygous for FVL is comparatively low (Martinelli et al., 1998). Incidence rates markedly increase with age, and are highest among those with AT deficiency, followed by protein C and protein S, and least with FVL.

Hereditary Thrombophilia as a Model for Multigenic Disease

1999 ◽  
Vol 82 (08) ◽  
pp. 662-666 ◽  
Author(s):  
Sandra J. Hasstedt ◽  
Mark F. Leppert ◽  
George L. Long ◽  
Edwin G. Bovill
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Factor V Leiden Mutation ◽  
The Past ◽  
S Deficiency

IntroductionNearly 150 years ago, Virchow postulated that thrombosis was caused by changes in the flow of blood, the vessel wall, or the composition of blood. This concept created the foundation for subsequent investigation of hereditary and acquired hypercoagulable states. This review will focus on an example of the use of modern genetic epidemiologic analysis to evaluate the multigenic pathogenesis of the syndrome of juvenile thrombophilia.Juvenile thrombophilia has been observed clinically since the time of Virchow and is characterized by venous thrombosis onset at a young age, recurrent thrombosis, and a positive family history for thrombosis. The pathogenesis of juvenile thrombophilia remained obscure until the Egeberg observation, in 1965, of a four generation family with juvenile thrombophilia associated with a heterozygous antithrombin deficiency subsequently identified as antithrombin Oslo (G to A in the triplet coding for Ala 404).1,2 The association of a hereditary deficiency of antithrombin III with thrombosis appeared to support the hypothesis, first put forward by Astrup in 1958, of a thrombohemorrhagic balance.3 He postulated that there is a carefully controlled balance between clot formation and dissolution and that changes in conditions, such as Virchow’s widely encompassing triad, could tip the balance toward thrombus formation.The importance of the thrombohemorrhagic balance in hypercoagulable states has been born out of two lines of investigation: evidence supporting the tonic activation of the hemostatic mechanism and the subsequent description of additional families with antithrombin deficiency and other genetically abnormal hemostatic proteins associated with inherited thrombophilia. Assessing the activation of the hemostatic mechanism in vivo is achieved by a variety of measures, including assays for activation peptides generated by coagulation enzyme activity. Activation peptides, such as prothrombin fragment1+2, are measurable in normal individuals, due to tonic hemostatic activity and appear elevated in certain families with juvenile thrombophilia.4 In the past 25 years since Egeberg’s description of antithrombin deficiency, a number of seemingly monogenic, autosomal dominant, variably penetrant hereditary disorders have been well established as risk factors for venous thromboembolic disease. These disorders include protein C deficiency, protein S deficiency, antithrombin III deficiency, the presence of the factor V Leiden mutation, and the recently reported G20210A prothrombin polymorphism.5,6 These hereditary thrombophilic syndromes exhibit considerable variability in the severity of their clinical manifestations. A severe, life-threatening risk for thrombosis is conferred by homozygous protein C or protein S deficiency, which if left untreated, leads to death.7,8 Homozygous antithrombin III deficiency has not been reported but is also likely to be a lethal condition. Only a moderate risk for thrombosis is conferred by the homozygous state for factor V Leiden or the G20210A polymorphism.9,10 In contrast to homozygotes, the assessment of risk in heterozygotes, with these single gene disorders, has been complicated by variable clinical expression in family members with identical genotypes.11 Consideration of environmental interactions has not elucidated the variability of clinical expression. Consequently, it has been postulated that more than one genetic risk factor may co-segregate with a consequent cumulative or synergistic effect on thrombotic risk.12 A number of co-segregating risk factors have been described in the past few years. Probably the best characterized interactions are between the common factor V Leiden mutation, present in 3% to 6% of the Caucasian population,13,14 and the less common deficiencies of protein C, protein S, and antithrombin III. The factor V Leiden mutation does not, by itself, confer increased risk of thrombosis. The high prevalence of the mutation, however, creates ample opportunity for interaction with other risk factors when present.The G20210A prothrombin polymorphism has a prevalence of 1% to 2% in the Caucasian population and, thus, may play a similar role to factor V Leiden. A number of small studies have documented an interaction of G20210A with other risk factors.15-17 A limited evaluation of individuals with antithrombin III, protein C, or protein S deficiency revealed a frequency of 7.9% for the G20210A polymorphism, as compared to a frequency of 0.7% for controls.18 The G20210A polymorphism was observed in only 1 of the 6 protein C-deficient patients.18 In the present state, the elucidation of risk factors for venous thromboembolic disease attests to the effectiveness of the analytical framework constructed from the molecular components of Virchow’s triad, analyzed in the context of the thrombohemorrhagic balance hypothesis. Two investigative strategies have been used to study thromobophilia: clinical case-control studies and genetic epidemiologic studies. The latter strategy has gained considerable utility, based on the remarkable advances in molecular biology over the past two decades. Modern techniques of genetic analysis of families offer important opportunities to identify cosegregation of risk factors with disease.19 The essence of the genetic epidemiologic strategy is the association of clinical disease with alleles of specific genes. It is achieved either by the direct sequencing of candidate genes or by demonstration of linkage to genetic markers.

Distribution of Hypercoagulation Laboratory Diagnoses among Patients with History of Thromboembolic Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3952-3952
Author(s):  
Murray M. Bern ◽  
Nancy McCarthy ◽  
Jamie Bonner
Keyword(s):  
Protein C ◽  
Elective Surgery ◽  
Factor V Leiden ◽  
Protein S ◽  
Thromboembolic Disease ◽  
Factor V ◽  
Plasminogen Activator Inhibitor 1 ◽  
Total N ◽  
Increased Risk ◽  
Pai 1

Abstract This abstract demonstrates the distribution of hypercoagulation diagnosis among patients with histories of thromboembolic disease (TED) among a group of patients detected at surgery prescreening clinic or through other referral sources. The consulting hematologists determined which laboratory tests were ordered; thus not all patients had all tests. This abstract describes the results of those clinical consultations. For this study the hospital’s computer logs were probed for patients having had measurements of protein C and factor V Leiden from 11/7/01until 8/1/07. The laboratory records of identified patients were searched for additional hypercoagulation laboratory parameters. A total of 383 patients have been identified, among whom abnormal diagnostic results were found for 231. Genomic assays were performed often for the commonly found defects (i.e., factor V Leiden and prothrombin 20210) and selectively for other situations, such 4G/5G for patients with elevated plasminogen activator inhibitor 1 (PAI-1) and unresolved venous thrombus, or methylene tetrahydrofolate (MTH) reductace for unexplained elevation of homocysteine. The table demonstrate the distribution of these laboratory diagnoses. The risk of having TED associated with these results will be stratified to emphasize the increased risk associated with the more severe abnormalities of protein C, protein S, ATIII, PAI-1, and homocysteine. These results demonstrate that laboratory explanations for TED may be found in a large proportion of patients with TED, which thereafter can be used to design prophylactic programs for at risk patients upon entry to hospital, especially elective surgery. Hypercoagulation Parameters Patients Protein C* (&lt;60%) Protein S* (&lt;60%) AT III (&lt;80%) Homocysteine (&gt;12 um/L) Lupus anticoagulant Anti-phospholipid syndrome** * excludes patients taking warfarin; includes functional and antigen assays. ** combines anticardiolipin; anti-beta2, glycoprotein1; and anti-phosphotidyl -serine, -ethanolamine and -choline antibodies. total n 350 358 244 252 166 234 abnormal n (%) 7(2) 64(18) 29 (12) 89(35) 18 (11) 41 (18) PAI-1 (&gt;42) ng/ml) APC Resistance (&lt;2.1) VIII:c & VIII:vW (&gt;180%) Factor V Leiden Prothrombin 20210 MTH Folate Reductace 4G/5G 36 75 61 225 219 10 9 22 (61) 10 (13) 11 (18) 37 (16) 16 (7) 8 (80) 8 (90)

Retrospective Review of Hypercoagulability in Minority Populations at an Inner City Hospital’s General Hematology Clinic.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3973-3973
Author(s):  
Pritesh R. Patel ◽  
Manila Gaddh ◽  
Sunita Nathan ◽  
Griza Decebal ◽  
Rosalind Catchatourian ◽  
...  
Keyword(s):  
African American ◽  
Inner City ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Minority Populations ◽  
Factor V ◽  
History Of ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Abstract Background: Although much is known about the incidence of hypercoagulable disorders in the Caucasian population, data is lacking in many other racial groups. We therefore retrospectively analyzed charts of all patients referred to our inner city hospital’s general hematology clinic from January 2003 to December 2006 for evaluation of possible hypercoagulable state. Methods: We reviewed charts for all patients referred for investigation of thrombophilia or hypercoagulable state seen in our clinic. Data regarding history of thrombosis was recorded. In the case of venous thromboembolic disease possible precipitants were noted. Demographic data and family history were noted. A clinical diagnosis of hypercoagulability was made based on whether the patient had any of the following: age <40; strong family history of thrombosis; unusual location of thrombosis; 2 or more thrombotic events; lack of precipitant to thrombotic episode. Laboratory data was gathered on the following: factor V leiden mutation; prothrombin gene mutation; MTHFR mutation; antithrombin III levels; protein C and protein S function; antiphospholipid antibodies. Results: 59 patients were referred. Of these 12 patients were excluded from further analysis as the reason for referral was investigation of ischemic stroke or myocardial infarction. Using the above clinical criteria 33 patients were identified as having hypercoagulability. Diagnoses and demographics are noted in tables 1 and 2. Conclusions: Our study illustrates several important practical points about the investigation of hypercoagulable patients. A larger number of protein C or S deficiencies would likely have been diagnosed had these studies been performed prior to starting anticoagulation. Similarly it is likely that the proportion of patients diagnosed with antiphospholipid antibody syndrome is high as it is possible to test for this condition whilst patients are anticoagulated. It is therefore appropriate that the best time for testing be disseminated more widely to general internal medicine providers. Importantly it appears that certain diagnostic tests would have a much higher yield in minority populations. It is likely that resources would be better allocated if African American patients in particular were tested initially for the antiphospholipid antibodies and activated protein C resistance rather than prothrombin gene mutations or factor V Leiden. Further prospective studies are planned to confirm these findings. Baseline demographics Race Gender Age Male Female <40 years >40 years All patients 12 21 22 11 African American 6 12 11 7 White 3 5 5 3 Hispanic 1 3 4 0 Asian 2 1 2 1 Diagnosis by ethnic group Race Diagnosis Antiphospholipid Protein S def. ATIII def. V Leiden MTHFR Multiple Disorders Unknown No cases of Protein C deficiency or Prothrombin Gene Mutation identified All patients 12 3 3 1 (heterozygous) 1 2 15 African American 5 2 2 0 1 1 9 White 3 0 0 1 (heterozygous) 0 0 4 Hispanic 2 1 1 0 0 1 1 Asian 2 0 0 0 0 0 1

scholarly journals Compound Homozygous Factor V Leiden and Heterozygous Prothrombin Gene Mutation: The First Report in a Pregnant African with Extensive Thrombosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5056-5056
Author(s):  
Livingstone Gayus Dogara ◽  
Joseph Ogirima Ovosi ◽  
Caleb Mohammed ◽  
Bilkisu Farouk ◽  
Ziphozonke Mafika ◽  
...  
Keyword(s):  
Blood Cells ◽  
Research Funding ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
African Countries ◽  
C Protein ◽  
History Of ◽  
In Pregnancy

Abstract Background: Factor V Leiden (FVL) mutation and Protein gene G20210A mutation (PGM) are the most common inherited thrombophilias in the world. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6) Both are inherited in an autosomal recessive fashion with individuals who are homozygous having higher risk of thrombosis compared to those who are heterozygous.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) The global prevalence of FVL and PGM is variable with Caucasians carrying the highest prevalence and Africans living in Africa, Asians and Native Americans having the lowest rate of these mutations; it is zero in West and Southern African countries, 2.4%-3.9% in North African countries including Morocco, Tunisia, and Algeria. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Dziadosz M et. al, Blood Coagul Fibrinolysis. 2016 Jul;27(5):481-9) Pregnancy increases the risk of developing venous thromboembolism (VTE) by 0.05-1.8 %, (Eldor A, Thromb Haemost. 2001 12.12.2017;86(07):104-11) which is 4 to 5 fold greater than in non-pregnant female.(Croles FN et.al, BMJ. 2017;359, Greer IA, N Engl J Med. 2015 Aug 6;373(6):540-7) Inheritance of FVL and PGM increases the risk for development of VTE in pregnancy, the risk is higher with homozygous than heterozygous mutations.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) Concurrent presentation of FVL and PGM in pregnancy presenting as thrombosis is not common. Aim: The aim of this case report is to present a patient of African descent with concurrent FVL and PGM mutation who had thrombosis during pregnancy. The Case: A 32-year-old Nigerian female who was 28 weeks pregnant presented to the gynecologist with a swollen left leg. Physical examination and the Wells score were very suggestive of a deep vein thrombosis (DVT). The Duplex Doppler performed confirmed a diagnosis of bilateral lower limb DVT. The patient was referred to a physician, who together with the haematologist performed a thrombophilia screen including FVL, PGM, Protein C, Protein S and Anticardiolipin antibody tests. The D-DIMERS were raised and the viral markers including HIV, HBV, and HCV were negative. The PT, APTT and full blood counts were normal. The thrombophilia tests revealed that the patient was homozygous for FVL and also heterozygous for the PGM mutations. The rest of the thrombophilia screen including Protein C, Protein S and Antithrombin tests were all negative. She has no family history of thrombosis; no past history of hormone based contraceptives. She was counselled on the need for using anticoagulation, low molecular weight heparin (LMWH) during the rest of her pregnancy period, and therapeutic anticoagulation with a LMWH at a dose of 1mg/kg twice a day until onset of labour was started. During labour LMWH was discontinued, delivery was per vaginal and was uncomplicated. Postpartum LMWH was continued at therapeutic doses for six weeks with no bleeding or thrombotic events. After six weeks, the patient was started on lifelong warfarin. Results (See Table) Discussion: To our knowledge this is a first case of a patient born and living in Africa presenting with thrombosis and found to have homozygous FVL and heterozygous PGM during pregnancy, the one report that is similar was in a second generation South African woman of German, Dutch and French ancestry. (Wilson J et. al, Medical Technology SA. [Case Report]. December 2011;25(2):4) Most reports have shown ethnic and regional affectation. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Bavikatty NR, et.al, Am J Clin Pathol. 2000 Aug;114(2):272-5) There is no single agreed reason as to why the mutation is rare in Africa though founder effect is being studied to define how the mutation came about, it could have taken place before divergence of race. (Jadaon MM. [Thrombosis, Familiar Thrombophilia]. 2011 2011-11-28;3(1) We could not do family studies to help define the origin of this mutation whether it is denovo for Nigeria; this has to do with sentiments about genetic inheritance in Africa. Conclusion: Concurrent inheritance of both FVL and PGM is possible in Africa. This rare case has open opportunities to revisit the prevalence of thrombophilia in Nigeria and other African countries. Disclosures Mahlangu: Alnylam: Consultancy, Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Research Funding; Chugai: Consultancy; Amgen: Consultancy; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding.

Lack of Association between Inherited Thrombophilic Risk Factors and Idiopathic Sudden Sensorineural Hearing Loss in Italian Patients

2006 ◽  
Vol 115 (3) ◽  
pp. 195-200 ◽  
Author(s):  
Gabriella Cadoni ◽  
Simona Scipione ◽  
Bianca Rocca ◽  
Stefania Agostino ◽  
Carmelo La Greca ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Antithrombin Iii ◽  
Activated Protein C ◽  
Protein S ◽  
Mthfr C677t ◽  
Sudden Sensorineural Hearing Loss ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Activated Protein C Resistance

Objectives: We investigated the presence of congenital thrombophilic risk factors in a population of consecutive Italian patients affected by idiopathic sudden sensorineural hearing loss (SSNHL). Methods: We investigated 48 patients with idiopathic SSNHL for the presence of congenital thrombophilic risk factors. The factor V Leiden G1691A, the prothrombin G20210A allele, and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes were investigated. Allele frequencies and genotype distribution of all factors found in patients were compared to those of 48 healthy subjects of the same ethnic background by χ2 and odds-ratio analysis. Odds ratios and 95% confidence intervals were calculated for allele and genotype frequencies of all thrombophilia variants. Statistical significance was accepted with a p value of less than .05. We also performed the following blood tests: hemacytometric analysis including platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, erythrocyte sedimentation rate, C-reactive protein, protein S, protein C, antithrombin III, and activated protein C resistance. Results: In our series, we did not find an association between SSNHL and abnormal levels of antithrombin III, protein C, protein S, D-dimer, or fibrinogen; activated protein C resistance; or factor V G1691 A, prothrombin G20210A, or MTHFR C677T mutations. Conclusions: At present, the few studies regarding genetic polymorphisms of congenital thrombophilic factors in SSNHL are not conclusive. According to our data, factor V G1691A, prothrombin G20210A, and MTHFR C677T variants should be not considered risk factors for SSNHL. Further large prospective studies are needed to provide currently lacking information and to improve our knowledge in the field before we recommend the determination of genetic polymorphism in SSNHL as routine practice.

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