Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5314-5322 ◽  
Author(s):  
Willem M. Lijfering ◽  
Jan-Leendert P. Brouwer ◽  
Nic J. G. M. Veeger ◽  
Ivan Bank ◽  
Michiel Coppens ◽  
...  
Keyword(s):  
Family History ◽  
Venous Thrombosis ◽  
Protein C ◽  
Positive Family History ◽  
Protein S ◽  
Factor V ◽  
Recurrence Rates ◽  
Thrombotic Risk ◽  
History Of ◽  
Fv Leiden

Abstract Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C–, and protein S–deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C–, or protein S–deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.

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.

Evidence of Increased Plasma Coagulative Capacity by CloFAL Assay among Pediatric Factor V Leiden and Prothrombin G20210A Heterozygotes with, Versus without, a First-or Second-Degree Family History of Venous Thromboembolism

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5345-5345
Author(s):  
Chris Bombardier ◽  
Linda J. Jacobson ◽  
Marilyn J. Manco-Johnson ◽  
Neil A Goldenberg
Keyword(s):  
Venous Thromboembolism ◽  
Family History ◽  
Positive Family History ◽  
Personal History ◽  
Clot Formation ◽  
Factor V ◽  
History Of ◽  
Study Population ◽  
Fv Leiden ◽  
Thrombophilia Testing

Abstract BACKGROUND: The factor V (FV) Leiden and prothrombin (PT) G20210A polymorphisms in heterozygous state are present in 5% and 1–2% of Caucasians, respectively, and confer approximately 5-fold and 2-fold increases in the risk of incident venous thromboembolism (VTE). While some families who carry these genetic thrombophilia traits exhibit a prothrombotic phenotype, others have no (or only a limited) history of VTE. The ability to discern which individuals with personal and familial carriage of these genetic thrombophilias possess a clinically meaningful increase in VTE risk remains elusive, and (particularly among children) is perhaps best informed presently by family history of VTE. OBJECTIVE AND HYPOTHESES: We sought to evaluate overall plasma coagulative capacity in FV Leiden and PT G20210A heterozygotes using the Clot Formation and Lysis (CloFAL) assay, a global turbidimetric plasma assay of tissue-factor induced fibrin clot formation and tissue-type plasminogen activator enhanced fibrinolysis. We hypothesized that children heterozygous for either thrombophilia would not uniformly demonstrate hypercoagulability, but that coagulative capacity would be increased among heterozygotes who have a family history of VTE. PATIENTS AND METHODS: Children aged birth to 18 years (inclusive) enrolled in prospective inceptional cohort study of thrombosis/thrombophilia/stroke were included in the analysis if they were found to be heterozygous for FV Leiden or PT G20210A upon comprehensive thrombophilia testing and had undergone CloFAL assay testing on a research basis. Data on personal and family history of thrombotic events, thrombophilia testing, and CloFAL assay findings were analyzed. Intergroup comparisons of continuous data were performed by Mann-Whitney U test and proportions were compared between groups using chi-square or Fisher’s exact test, as appropriate. RESULTS: Characteristics of the study population are shown in Table 1. Approximately 70% of patients were evaluated for a family history of VTE (with/without known thrombophilia) and nearly 50% had personal histories of VTE or arterial ischemic stroke (AIS)/recurrent transient ischemic attack (TIA); those evaluated for events were significantly older than those without events, and this difference was statistically significant among those with a positive family history fo VTE. Hypercoagulability was shown in 50% of patients and hypofibrinolysis in 13% using the CloFAL assay. Plasma coagulative capacity and maximal amplitude (MA) of the CloFAL waveform were significantly increased in patients with, versus without, family history of VTE (coagulation index, CI: 102% vs. 72% of the adult normal pooled plasma standard, respectively, p=0.04; MA: 0.415 vs. 0.322, p=0.02), and were not explained by age differences between groups. However, in this relatively small study population, the proportion of CloFAL CI results that exceeded the upper limit of normal values did not significantly differ between those with, versus without, family history of VTE. Pediatric FV Leiden or PT G20210A heterozygotes with positive family history of VTE were more likely to have multi-trait (>1) thrombophilia, in which case a trend toward increased plasma coagulability was demonstrated (CI: 139% [multi-trait] vs. 86% [isolated trait]; p=0.07); superimposed thrombophilias in this group most often consisted of elevated factor VIII activity and Lp(a) concentration. CONCLUSIONS: The present findings using the CloFAL global assay indicate that, while pediatric FV Leiden or PT G20210A heterozygotes do not uniformly exhibit hypercoagulability, plasma coagulative capacity is nevertheless significantly increased among heterozgyotes who have a family history of VTE, which may relate to the presence of superimposed thrombophilias. Table 1. Summary characteristics of the study population. *VTE, AIS, or recurrent TIA **Two patients were dual heterozygotes. N 32 Median age at evaluation (range) 9.5 y (1–18 y) Personal history of events* 14 y (1–18 y) No personal history of events* 8 y (2–18 y) FV Leiden heterozygote (n) 26** PT G20210A heterozygote (n) 8** Personal history of VTE (n) 11 Personal history of AIS/recurrent TIA 4 Family history (1st/2nd degree) of VTE 71% Multi-trait (>1) thrombophilia 45% Acquired thrombophilia 24% Hypercoagulability by CloFAL assay 50% Hypofibrinolysis by CloFAL assay 13%

scholarly journals Prothrombin Arg541Trp Mutation Leads to Defective PC (Protein C) Pathway Activation and Constitutes a Novel Genetic Risk Factor for Venous Thrombosis

2020 ◽  
Vol 40 (2) ◽  
pp. 483-494 ◽  
Author(s):  
Xi Wu ◽  
Jing Dai ◽  
Xiaoqian Xu ◽  
Fang Li ◽  
Lei Li ◽  
...  
Keyword(s):  
Risk Factor ◽  
Family History ◽  
Venous Thrombosis ◽  
Genetic Risk ◽  
Protein C ◽  
Positive Family History ◽  
Genetic Risk Factor ◽  
Procoagulant Activity ◽  
Factor V Leiden Mutation ◽  
History Of

Objective: Defective PC (protein C) pathway predisposes patients to venous thromboembolism (VTE) and is mostly, but not exclusively, attributed to hereditary PC or PS (protein S) deficiencies and activated PC resistance caused by factor V Leiden mutation. Approach and Results: In a patient with acute mesenteric venous thrombosis and positive family history of VTE associated with the impaired PC pathway function determined by thrombin generation test, we identified a novel heterozygous prothrombin mutation p.Arg541Trp. Two more patients with positive family history of VTE carrying the same mutation were identified in a cohort of another 373 unrelated patients, making an overall prevalence of 0.8%. Family investigation revealed 11 individuals in the 3 pedigrees harboring the heterozygous prothrombin p.Arg541Trp mutation, and 8 of them (72%) had experienced episodes of VTE. Functional studies indicated the mutation moderately decreased procoagulant activity of prothrombin and had mild impact on the inactivation of thrombin by its inhibitor antithrombin. However, the amino acid residue substitution significantly compromised PC activation by thrombin, both in the absence and presence of soluble thrombomodulin, and thus rendered prothrombin function procoagulant biased. Conclusions: In summary, the prothrombin p.Arg541Trp mutation constitutes a new genetic risk factor of VTE by impairing function of PC pathway and tilting thrombin’s procoagulant activity over anticoagulant function.

Selective Screening for the Factor V Leiden Mutation: Is it Advisable prior to the Prescription of Oral Contraceptives?

1997 ◽  
Vol 78 (06) ◽  
pp. 1480-1483 ◽  
Author(s):  
Christian M Schambeck ◽  
Stefan Schwender ◽  
Imme Haubitz ◽  
Ulrich E Geisen ◽  
Ralf E Grossmann ◽  
...  
Keyword(s):  
Family History ◽  
Oral Contraceptives ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Oral Contraception ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
History Of ◽  
Fv Leiden

SummaryThe cumulative thrombotic risk of Factor V (FV) Leiden and oral contraceptives (OC) recommends screening for the mutation. Assuming that a family history of thrombosis increases the patient’s likelihood of bearing FV Leiden, a selective rather than universal screening would be performed. We studied the utility of a family history of thrombosis for screening of FV Leiden before prescription of OC and, furthermore, the utility of screening even if oral contraception is favoured. 101 patients who had their first and single thromboembolic event while using OC were interviewed. 609 women without any history of thromboembolism recruited by gynecologists completed a standard questionnaire. 101 of these women, age-matched and currently using OC, were selected for a case-control study. Regarding patients with previous thromboembolism, a family history in a first-degree relative had a positive predictive value (PPV) of only 14% for FV Leiden. A PPV of 12% was calculated by investigating the 609 thrombosis-free women. Inherited FV Leiden (odds ratio = 4.9) and acquired risk factors (odds ratio = 10.1) were both found to be the most prominent, but independent additional risks. Nevertheless, FV Leiden carriers, both heterozygotes and homozygotes, did not suffer earlier from thromboembolism than patients without the mutation. In conclusion, family history is an unreliable criterion to detect FV Leiden carriers. Screening for factor V Leiden can be worthwhile even if the advantages of oral contraception are higher assessed than the thrombotic risk. Affected women knowing about their additional risk could contribute to the prevention of thrombosis in risk situations.

scholarly journals Clinical profile, common thrombophilia markers and risk factors in 85 young Indian patients with arterial thrombosis

2013 ◽  
Vol 131 (6) ◽  
pp. 384-388 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Ravi Kalra ◽  
Shalesh Rohatgi
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Positive Family History ◽  
Protein S ◽  
Factor V ◽  
C Protein ◽  
Indian Patients ◽  
Low Levels

CONTEXT AND OBJECTIVE: Arterial thrombosis may occur consequent to hereditary thrombophilia and increased lipoprotein(a) [Lp(a)] and fibrinogen. Our aim was to study the prevalence of common thrombophilia markers in 85 consecutive cases of arterial thrombosis. DESIGN AND SETTING: A retrospective study was conducted from 85 consecutive young patients treated as outpatients or admitted due to stroke or myocardial infarction at a tertiary care hospital. METHODS: Eighty-five Indian patients (age < 45 years) presenting ischemic stroke (n = 48) or myocardial infarction (n = 37) and 50 controls were studied for seven thrombophilia markers including antithrombin (AT), factor V, protein C, protein S, activated protein C resistance (APC-R), fibrinogen and Lp(a). Functional assays for protein C, protein S, factor V and APC-R were performed using clotting-based methods. Semi-quantitative estimation of fibrinogen was done using Clauss's method and Lp(a) using immunoturbidimetry. Statistical analysis was done using the Epi Info 6 software. RESULTS: Thirty-three samples (38.8%) tested positive for one or more thrombophilia markers. The three commonest abnormalities were elevated Lp(a) (20%), fibrinogen (17.6%) and low APC-R (14.2%). Low levels of protein C, protein S and AT were present in 4.7, 9.4 and 7% of the patients, respectively. Overall, the risk factor profile was: smoking (33%), positive family history (15.3%), hyperlipidemia (7%), hypertension, diabetes mellitus and obesity (2.3% each). CONCLUSIONS: An association was found between low levels of protein C, protein S and AT and arterial thrombosis, but only elevated fibrinogen levels, smoking, positive family history and hyperlipidemia showed statistical significance.

scholarly journals Prothrombin R541W Mutation Impairs Protein C Activation and Constitutes a New Genetic Risk Factor for Venous Thrombosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 442-442
Author(s):  
XI WU ◽  
Dai Jing ◽  
Fang Li ◽  
Qin Xu ◽  
Changming Chen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Family History ◽  
Venous Thrombosis ◽  
Genetic Risk ◽  
Protein C ◽  
Patent Application ◽  
Positive Family History ◽  
Procoagulant Activity ◽  
School Of Medicine ◽  
History Of

Defective protein C (PC) pathway predisposes patients to venous thromboembolism (VTE)and is mostly, but not exclusively, attributed tohereditary PC or protein S (PS) deficiencies and activated PC resistance caused by factor V Leiden mutation. In a patient with acute mesenteric venous thrombosis and positive family history of VTE associated with the impaired PC pathway function determined by thrombin generation test, we identified a novel heterozygous prothrombin mutation p.Arg541Trp. Two more patients with positive family history of VTE carrying the same mutation were identified in a cohort of another 373 unrelated patients, making an overall prevalence of 0.8%. Family investigation revealed 11 individuals in the three pedigrees harboring the heterozygous prothrombin p.Arg541Trp mutation, and 8 of them (72%) had experienced episodes of VTE. Functional studies indicated the mutation moderately decreased procoagulant activity of prothrombin and had mild impact on the inactivation of thrombin by its inhibitor antithrombin. However, the amino acid residue substitution significantly compromised PC activation by thrombin, both in the absence and presence of soluble thrombomodulin, and thus rendered prothrombin function procoagulant biased. In conclusion, the prothrombin p.Arg541Trp mutation constitutes a new genetic risk factor of VTE by impairing function of PC pathway and tilting thrombin's procoagulant activity over anticoagulant function. Figure Disclosures Ding: Shanghai General Hospital affiliated to Shanghai Jiao Tong University, Shanghai: Patents & Royalties: W.W, Q.D and X.W of the co-authors are named as inventors on a patent application related to this work.. Wang:Ruijin Hospital, Shanghai Jiao Tong University School of Medicine: Patents & Royalties: W.W, Q.D and X.W of the co-authors are named as inventors on a patent application related to this work.. WU:Ruijin Hospital, Shanghai Jiao Tong University School of Medicine: Patents & Royalties: W.W, Q.D and X.W of the co-authors are named as inventors on a patent application related to this work..

State-of-the-Art Review: Activated Protein C Resistance: Clinical Implications

1997 ◽  
Vol 3 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Bengt Zöller ◽  
Andreas Hillarp ◽  
Björn Dahlbäck
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Factor V ◽  
Thrombotic Risk ◽  
Western Countries ◽  
Apc Resistance ◽  
Increased Risk

The discovery of inherited resistance to activated protein C (APC) as a major risk factor for venous thrombosis has dramatically improved our understanding of the pathogenesis of venous thrombosis. In a majority of cases, APC resistance is associated with a single point mutation in the factor V gene (FV) that results in substitution of arginine, R, at position 506 by glutamine, Q. (FV:Q506). The mutation renders factor Va partially resistant to degradation by APC. A functional APC resistance test, which includes predilution of the patient plasma with factor V-deficient plasma, is found to be 100% sensitive and specific for the presence of FV:Q506 and is useful as a screening assay. Carriers of the FV:Q506 allele have increased thrombin generation, resulting in hypercoagulability and a lifelong increased risk of venous thrombosis. In Western countries, APC resistance due to the FV mutation is present in 20-60% of thrombosis patients and in 1-15% of healthy controls, whereas the mutation is virtually absent from ethnic groups other than Caucasians. This may explain the high incidence of venous thrombosis in Western countries. The thrombotic risk in APC-resistant individuals may be further increased by other genetic defects, e.g., protein C or protein S deficiency, and by exposure to circumstantial risk factors, e.g., oral contraceptives, pregnancy, immobilization, and surgery. The question is thus raised as to whether general screening for APC resistance before circumstantial risk factors occur is warranted in Western countries. Key Words: Factor V—APC resistance-Protein C-Protein S—Thrombosis—Mutation.

Inpatient Thrombophilia Workup in Patients with Acute Venous Thromboembolism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4720-4720
Author(s):  
Vivek Rashmikant Mehta ◽  
Uzma Khan ◽  
Aparna Basu ◽  
Asif Jan ◽  
Bolanie Gbadamosi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family History ◽  
Gene Mutation ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Test Results ◽  
History Of ◽  
Acute Venous Thromboembolism

Abstract Background Any inherited or acquired condition that increases the risk of developing deep venous thrombosis or pulmonary embolism is considered a thrombophilic disorder. Some examples of inherited causes of thromboembolic disorders are Factor V Leiden mutation (FVL), Prothrombin gene mutation, Protein C deficiency (low or dysfunctional), Protein S deficiency (low or dysfunctional), Anti-thrombin (AT) deficiency (low or dysfunctional). Use of these studies in clinical practice has been questioned. We attempted to identify if there are populations of patients that undergo more inpatient screening for inherited causes of venous thromboembolism (VTE). Methods Retrospective chart review of patients admitted with PE or DVT in a community teaching hospital between May 2012 and December 2014. Only patients who had DVT confirmed with ultrasound or PE confirmed with CT angiogram or had high probability of PE on V/Q scan were included in the study. Individual charts were reviewed to see if thrombophilia workup was ordered. Results A total of 704 patients with acute venous thromboembolism were identified who met our inclusion criteria for the study. Of this 111 patients (15.76%) had one or more thrombophilia screening studies ordered. Risk factors related to venous thromboembolism were evaluated for all of the 704 patients. In our patient population, patients who were smokers (31% vs 20%), had history of sleep apnea (9% vs 3%), a past medical history (PMH) of VTE (37% vs 25%) or who had a family history (FH) of VTE (11% vs 4%) were more likely to have a thrombophilia workup ordered. Table 2 shows the frequency of individual thrombophilia studies ordered among the 111 patients who had testing performed and table 3 shows distribution of positive results. Table. Test Result Abnormal Test Results ANA 1 Decreased AT III 10 Decreased Protein C 10 Decreased Protein S 7 Increased Homocysteine 6 Factor V Leiden 4 PT Gene Mutation 1 APLA 1 Conclusion The largest numbers of positive test results were noted for Protein C, Protein S and Antithrombin III and these are known to be affected by acute thrombosis and therefore could be false positives. Our study shows that those patients with PMH or FH of VTE were more likely to have thrombophilia studies. There is no consensus opinion as to whether to perform thrombophilia screenings in acute care settings. Given this and the fact that personal or family history of VTE do not usually modify future treatment decisions and that there may be significant number of false positives we do not recommend routine screening in these patient populations. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

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.

Sign in / Sign up

Export Citation Format

Share Document