Familial Thrombophilia: A Review Analysis

1996 ◽  
Vol 2 (4) ◽  
pp. 227-236 ◽  
Author(s):  
Angelique G. M. van den Belt ◽  
Martin H. Prins ◽  
Menno V. Huisman ◽  
Jack Hirsh
Keyword(s):  
Risk Factor ◽  
Odds Ratio ◽  
Protein C ◽  
Antithrombin Iii ◽  
Family Members ◽  
Protein S ◽  
Biochemical Abnormality ◽  
Thrombotic Disease ◽  
History Of ◽  
Deficiency Type

The correct approach to the management of the asymptomatic carrier with a recognized inherited thrombophilic disorder is uncertain because reliable in formation of the risk of spontaneous (unprovoked) throm bosis in these disorders is not available. To determine the best available estimate of the annual incidence of spon taneous thrombosis in asymptomatic carriers of disorders that have been linked to familial thrombophilia, we per formed a literature review. Using Medline search from 1965 to 1992, supplemented by manual searches, we re trieved all articles that presented data on antithrombin III, protein C, protein S, dysfibrinogenemia, plasmino gen, histidine-rich glycoprotein, heparin cofactor II, and fibrinolysis in relation to thrombosis. Publications were included in the analysis if they (1) reported one or more probands with thrombotic disease and a heterozygous biochemical abnormality of the hemostatic system, (2) assessed the presence of this abnormality in family mem bers independent of the presence or absence of a history of thrombotic disease, and (3) assessed the presence of a history of thrombotic disease in all available family mem bers. The biochemical status and clinical details of all family members reported were extracted from each eligi ble article. For each abnormality the odds ratio for throm bosis was compared in family members with and without the biochemical abnormality. If applicable, thrombosis- free survival and age-specific incidences of thrombosis were calculated. The thrombotic episodes were classified as spontaneous or secondary to a recognized risk factor, and the proportion of spontaneous episodes was calcu lated. The influence of diagnostic suspicion bias in symp tomatic patients with a family history of thrombosis was reduced by recalculating the absolute incidence of throm bosis from the odds ratio after adjusting the incidence of venous thrombosis in nonaffected family members to that observed in the general population. Statistically signifi cant associations between the presence of a biochemical abnormality and a history of venous thrombosis were found for antithrombin III deficiency types 1 and 2a and 2b, protein C deficiency type 1, and protein S deficiency type I. Dysfibronogenemia was statistically significantly associated with venous as well as arterial thrombosis. Thirty-five to 67% of the events were classified as being provoked, as they occurred following exposure to a rec ognized risk factor for thrombosis. The recalculated an nual incidence of spontaneous thrombosis was 0.6 to 1.6%/year. It is concluded that this relatively low inci dence does not warrant life-long continuous use of anti coagulant prophylaxis since the reported risk of major and fatal bleeding associated with the use of oral antico agulants is 2-3 and 0.4%/year, respectively.

Laboratory Evaluation and Clinical Characteristics of 2,132 Consecutive Unselected Patients with Venous Thromboembolism – Results of the Spanish Multicentric Study on Thrombophilia (EMET*-Study)

1997 ◽  
Vol 77 (03) ◽  
pp. 444-451 ◽  
Author(s):  
José Mateo ◽  
Artur Oliver ◽  
Montserrat Borrell ◽  
Núria Sala ◽  
Jordi Fontcuberta ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Odds Ratio ◽  
Protein C ◽  
Protein S ◽  
Laboratory Evaluation ◽  
Clinical Factors ◽  
Recurrent Thrombosis ◽  
Heparin Cofactor Ii ◽  
Crude Odds Ratio ◽  
History Of

SummaryPrevious studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2,132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinoge-nemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfib-rinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% Cl 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and in 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% Cl 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% Cl 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78,95% Cl 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.

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.

Protein S, Protein C, and Antithrombin III in Thrombotic Disease.

1990 ◽  
Vol 612 (1 Sixth Cooley') ◽  
pp. 549-552 ◽  
Author(s):  
S. Leonardi ◽  
G. Arcidiacono ◽  
R. Colianni ◽  
L. Gregorio ◽  
S. Musumeci
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
S Protein ◽  
Thrombotic Disease

Two Cases of Inherited Triple Deficiency in a Large Kindred with Thrombotic Diathesis and Deficiencies of Antithrombin III, Heparin Cofactor II, Protein C and Protein S

1991 ◽  
Vol 66 (03) ◽  
pp. 295-299 ◽  
Author(s):  
F Jobin ◽  
L Vu ◽  
M Lessard
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Large Family ◽  
Protein S ◽  
Type I ◽  
Heparin Cofactor Ii ◽  
First Case ◽  
Cofactor Activity ◽  
Deficiency Type

SummaryThirty-three subjects, belonging to a large family with functional antithrombin III (ATIII) deficiency (type IIa) and recurrent thromboembolism, were investigated for ATIII, heparin cofactor II (HCII), protein C (PC) and protein S (PS). We report the exceptional finding of two cases of triple deficiency: ATIII combined with HCII and PC in the first case aged 15 and ATIII combined with HCII and PS in the second case aged 27. Interestingly, both are asymptomatic thus far. Twenty-five other deficient members were found, among which seven are affected with a double deficiency. Totally, the results of our study show 38 deficiencies of four distinct antithrombotic protein: ATIII (n = 9), HCII (n = 9), PC (n = 7) or PS (n = 13). Two types of HCII deficiency were observed and type I PC deficiency was found. Functional PS deficiency was characterized by reduced levels of cofactor activity for activated PC. Our report demonstrates that combined deficiencies should be sought in a family already known to be deficient in one antithrombotic protein.

Molekularbiologische Grundlagen und Diagnostik der hereditären Defekte von Antithrombin III, Protein C und Protein S

2002 ◽  
Vol 22 (02) ◽  
pp. 57-66
Author(s):  
I. Witt
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Klinische Relevanz ◽  
At Iii

ZusammenfassungDie enormen Fortschritte in der Molekularbiologie in den letzten Jahren ermöglichten sowohl die Aufklärung der Nukleotidsequenzen der Gene für Antithrombin III (AT III), Protein C (PROC) und Protein S (PROS) als auch die Identifizierung zahlreicher Mutationen bei hereditären Defekten dieser wichtigen Inhibitoren des plasmatischen Gerinnungssystems. Da die Gene für AT III (13,8 kb) und PROC (11,2 kb) nicht groß und relativ leicht zu analysieren sind, gibt es bereits umfangreiche »databases« der Mutationen (50, 73). Für AT III sind 79 und für PROC 160 unterschiedliche Mutationen beschrieben.Sowohl beim AT-III-Mangel als auch beim Protein-C-Mangel hat die Mutationsaufklärung neue Erkenntnisse über die Struktur-Funktions-Beziehung der Proteine gebracht. Beim Protein-C-Mangel steht die klinische Relevanz der DNA-Analyse im Vordergrund, da die Diagnostik des Protein-C-Mangels auf der Proteinebene nicht immer zuverlässig möglich ist.Das Protein-S-Gen ist für die Analytik schwer zugänglich, da es groß ist (80 kb) und außerdem ein Pseudogen existiert. Es sind schon zahlreiche Mutationen bei Patienten mit Protein-S-Mangel identifiziert worden. Eine Database ist bisher nicht publiziert. Die klinische Notwendigkeit zur Mutationsaufklärung besteht ebenso wie beim Protein-C-Mangel. Es ist zu erwarten, dass zukünftig die Identifizierung von Mutationen auch beim Protein-S-Mangel beschleunigt vorangeht.

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

scholarly journals Prevalence and Predictors of Undiagnosed Hypertension in an Apparently Healthy Western Indian Population

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Anand N. Shukla ◽  
Tarun Madan ◽  
Bhavesh M. Thakkar ◽  
Meena M. Parmar ◽  
Komal H. Shah
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Odds Ratio ◽  
Indian Population ◽  
Total Population ◽  
Undiagnosed Hypertension ◽  
History Of ◽  
Major Illness ◽  
Apparently Healthy

This epidemiological study was designed to evaluate the prevalence of undetected hypertension in an apparently healthy western Indian population having no history of major illness. 3629 individuals of ≥18 years of age were included in the study. Hypertension (HTN) was defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg and prehypertension (PHTN) as SBP ≥ 120–139 mmHg or DBP ≥ 80–89 mmHg, but without HTN. The prevalence of undiagnosed HTN in the total population was 26% and was 11% and 40% in the young (≤40-year) and old (>40-year) populations, respectively. The prevalence of PHTN, 40% in the overall population, was nearly the same in the young (39%) and the old population (42%). The risk factor most strongly associated with PHTN and HTN was obesity, showing the highest odds ratio in the overall (PHTN 2.14; 95% CI 1.20–3.81; HTN 2.72; 95% CI 1.53–4.85), the young (PHTN 2.29; 95% CI 1.25–4.21; HTN 2.92; 95% CI 1.59–5.35), and the old (PHTN 1.13; 95% CI 0.65–1.96; HTN 1.38; 95% CI 0.79–2.4) populations. Hypertension is a major risk factor for cardiovascular diseases which must not be ignored, especially in the western Indian population.

Protein C, protein S and antithrombin III in children with portal vein obstruction

1997 ◽  
Vol 27 (1) ◽  
pp. 132-135 ◽  
Author(s):  
Claire Dubuisson ◽  
Catherine Boyer-Neumann ◽  
Martine Wolf ◽  
Dominique Meyer ◽  
Olivier Bernard
Keyword(s):  
Portal Vein ◽  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
C Protein ◽  
Portal Vein Obstruction

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.    

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