Prospective Evaluation of plasma Levels of FVIII in Patients with venous Thromboembolism,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3348-3348
Author(s):  
Luis Fernando Bittar ◽  
Bruna Mazetto Fonseca ◽  
Silmara Lima Montalvão ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Erich V de Paula ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Geographic Area ◽  
First Episode ◽  
Control Group ◽  
Post Thrombotic Syndrome

Abstract Abstract 3348 Introduction: Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as risk factor for first and recurrent episodes of VTE. Some authors reported that these high levels of FVIII were still persistent after 4 years of the episode, but median follow-up in these studies are relatively short. The aim of the study was investigate if after a long-term follow-up of 4–15 years (median of 10 years), patients with high levels of FVIII after anticoagulant treatment still showed this alteration. Design and Methods: Previously, we selected 174 adult patients with a first episode of acute VTE between January 1990 and September 2004. One hundred seventy four healthy adult individuals selected from blood donors were chosen as controls, from the same geographic area of origin. Of this group of VTE patients, 68 patients with plasma FVIII: C levels above the 90th percentile were selected. FVIII levels (FVIII:C) were measured by a one-stage clotting assay with FVIII-deficient plasma in duplicate in an automated coagulometer. Levels were measured twice, in 2004 and then in 2011. C-reactive protein (CRP) levels were determined in the same samples by a nephelometric method to evaluate the influence of inflammation on FVIII levels. For individuals with CRP values higher than 1mg/dL, an additional blood sample was analyzed. High FVIII levels were only considered for further analysis when in the presence of normal CRP levels. The presence of post-thrombotic syndrome (PTS) was evaluated and classified clinically by the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification System. Results: 68 patients with VTE and high levels of FVIII (19M:49F) with a median age of 47 years (range 20–70) were included in the study. The control group consisted of 59 subjects (42M:17F) with a median age of 35 years (range 21–56 years). VTE was spontaneous in 26 (38.2%) patients and secondary to an acquired risk factor in 61.8%. In the 1st evaluation, in 2004, patients with VTE had higher plasma levels of FVIII:C (median 235.8 IU/dL vs. 127.0 IU/dL; p<0.001) compared to controls. In 2011, seven years after the first evaluation and after a median follow-up of 10 years after the first VTE episode, this difference was still present (median 144.6 IU/dL vs. 96.4 IU/dL; p<0.001). Patients with severe PTS (167 IU/dL) showed higher plasma levels of FVIII when compared with patients without PTS (median 141.4 IU/dL), mild PTS patients (median 142.8 IU/dL), and moderate PTS patients (median 143.2); p=0.04. Conclusions: Our results show that even after a median of 10 years of VTE, patients still have increased levels of FVIII. Moreover, there seems to be a relationship between severe post-thrombotic syndrome and increased plasma levels of FVIII. Disclosures: No relevant conflicts of interest to declare.

Long-term Clinical Follow-up in 265 Patients with Deep Venous Thrombosis Initially Treated with either Unfractionated Heparin or Dalteparin: A Retrospective Analysis

1999 ◽  
Vol 82 (10) ◽  
pp. 1222-1226 ◽  
Author(s):  
W. Åberg ◽  
D. Lockner ◽  
C. Paul ◽  
M. Holmström
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Malignant Disease ◽  
Duration Of Treatment ◽  
Post Thrombotic Syndrome ◽  
Recurrent Vte

SummaryThe primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

P3850Impact of sex and risk factors for venous thromboembolism on the clinical course of first acute venous thromboembolism. Insights from the PREFER in VTE

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Giustozzi ◽  
S Barco ◽  
L Valerio ◽  
F A Klok ◽  
M C Vedovati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Baseline Risk ◽  
Major Surgery ◽  
First Episode ◽  
Risk Of Recurrence ◽  
Recurrent Vte ◽  
The Impact

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%)   Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6)   Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4)   All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.

Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4284-4284
Author(s):  
J. Valentin Garcia. Gutierrez ◽  
Jesús Odriozola ◽  
Pilar Herrera ◽  
Javier Lopez ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Plasma Concentrations ◽  
Chronic Phase ◽  
Control Group ◽  
Treatment Optimisation ◽  
Number Of Patients

Abstract Abstract 4284 Introduction Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. Aims To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. Results In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. Conclusions IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed. Disclosures: No relevant conflicts of interest to declare.

Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Body Mass ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Control Group ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

Elevated Levels of IL-6 and IL-8 Are Associated with An Increased Risk of Venous Thromboembolism – a Case Control Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2975-2975
Author(s):  
Marinez F Matos ◽  
Dayse M Lourenço ◽  
Cristina M Orikaza ◽  
Maria A E Noguti ◽  
Vânia M Morelli
Keyword(s):  
Venous Thromboembolism ◽  
Prospective Studies ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Limit Of Detection ◽  
Case Control ◽  
Control Group ◽  
Case Control Studies ◽  
Increased Risk ◽  
The Impact

Abstract Abstract 2975 Poster Board II-953 Background: high levels of some cytokines have been associated with an increased risk of venous thromboembolism (VTE) in some case-control studies, but not in prospective studies. However, data regarding the impact of cytokines levels on the risk of VTE are still limited. The aim of this study was to investigate the association between the risk of VTE and plasma levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-αa and monocyte chemotactic protein (MCP)-1. Materials and Methods: we studied 122 patients (96 women, 79%), with a first objectively confirmed episode of VTE and with a median age of 39.5 years (range: 21-60). Exclusion criteria were malignancy, autoimmune diseases, antiphospholipid syndrome, chronic renal or liver disease and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Control group was comprised of 131 healthy subjects (105 women, 80%), with median age of 38 years (range: 18-66), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age and sex. Plasma levels of cytokines were measured by commercial ELISA and a highly sensitive assay was used to measure IL-1β, IL-6 and IL-10 levels. Since a high percentage of samples of IL-1β (73%), IL-10 (62%) and TNF-αa (97%) was below the lower limit of detection (LLD) of the assay, levels of these cytokines were categorized as detectable (> LLD) and not detectable (< LLD). Elevated levels of IL-6 (> 2.15pg/mL), IL-8 (> 10.11pg/mL) and MCP-1 (> 84.11pg/mL) were defined by plasma concentration of these cytokines exceeding the 90th percentile of the distribution of the control population. Results: elevated levels of IL-6 were detected in 27% of the patients with VTE in comparison with 10% (by definition) of the controls [odds ratios (OR) = 3.4, 95% Confidence Interval (CI) 1.6 - 7.6]. Elevated levels of IL-8 were detected in 21% of the patients in comparison with 10% of the controls (OR = 2.5, 95%CI 1.1 - 5.6). The risk remained significant for IL-6 (OR = 2.8, 95%CI 1.2 - 6.5) and IL-8 (OR = 2.6, 95%CI 1.1 - 6.7) after adjustment for putative confounders (sex, age, body mass index, smoking and high levels of homocysteine and C-reactive protein). On the other hand, we found no significant association between VTE and elevated levels of MCP-1 (OR = 0.8, 95%CI 0.3 - 1.9) as well as detectable levels of IL-1β (OR = 0.9, 95%CI 0.5-1.6), IL-10 (OR = 1.3, 95%CI 0.8 - 2.2) and TNF-αa (OR = 6.7, 95%CI 0.8 - 56.7). In our study, patients were included at different time intervals after the VTE episode [median: 36 months (range: 7-87)]. No correlation was found between the time since the event of VTE and levels of IL-6 (rs = 0.06, P = 0.54) and IL-8 (rs= 0.07; P = 0.48). Conclusion: this study shows a significant impact of elevated levels of IL-6 and IL-8 on the risk of VTE in a relatively young population of patients. Interestingly, no association was found between the time since the event and the level of these cytokines. Taking into account the importance of the relationship between inflammation and VTE, more epidemiological data including prospective studies are required to elucidate the role of inflammation on the risk of VTE. This study was supported by FAPESP (2005/56799-0). Disclosures: No relevant conflicts of interest to declare.

Prevalence of FACTOR IX-R338L (FACTOR IX PADUA) IN A COHORT of PATIENTS with Venous Thromboembolism and Mild Elevation of FACTOR IX LEVELS.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5057-5057
Author(s):  
Bruna de Moraes Mazetto ◽  
Fernanda A. Orsi ◽  
Lúcia Helena Siqueira ◽  
Erich Vinicius de Paula ◽  
Tayana B Mello ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Recombinant Expression ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Control Group ◽  
Increased Risk ◽  
Pcr Rflp

Abstract Abstract 5057 Introduction Elevated plasma levels of blood coagulation factor IX (FIX) have been associated with increased risk of venous thromboembolism (VTE) in humans. However, the molecular mechanisms underlying elevated FIX have not been elucidated. Recently, a mutation in the FIX gene resulting in a FIX molecule with Arginine Leucine substitution at position 338 (FIX-R338L or Factor IX Padua) has been associated with very high levels of FIX (776%) in a patient with spontaneous VTE. Recombinant expression of FIX-R338L confirmed the gain-of-function mutation. Objective Here we evaluated the levels of FIX and the prevalence of Factor IX Padua in a cohort of patients with VTE followed at our center. The prevalence of FIX Padua was evaluated by using a PCR-RFLP strategy by which PCR with specific primers was followed by digestion with the enzyme TaqI. Results The prevalence of FIX Padua was evaluated in a population of 192 patients with spontaneous VTE (69 males and 123 females; median age 36-yo). A population of 192 healthy individuals matched for age, sex and ethnicity was used as a control group for the determination of FIX levels. Median FIX levels was 128.0% (61.0-207.0%) in patients with VTE. Twenty-nine patients presented FIX levels above the 90th percentile (160.2%). Factor IX Padua was not identified in any patients or controls, even in those with elevated FIX levels. Conclusion in the present study FIX Padua was not identified in any of our patients, indicating that this mutation is not associated with mild elevations of FIX levels frequently observed in patients with VTE. Disclosures No relevant conflicts of interest to declare.

Post-Thrombotic Syndrome and Quality-of-Life after Venous Thromboembolism in Young and Middle-Aged Women

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2309-2309 ◽  
Author(s):  
Maria Ljungqvist ◽  
Margareta Holmstrom ◽  
Helle Kieler ◽  
Gerd Larfars
Keyword(s):  
Quality Of Life ◽  
Venous Thromboembolism ◽  
First Episode ◽  
Common Complication ◽  
Middle Aged ◽  
Post Thrombotic Syndrome ◽  
Increased Risk ◽  
History Of

Abstract Introduction: Post-thrombotic syndrome (PTS) is the most common complication after a venous thromboembolism (VTE). PTS is a chronic condition affecting health-related quality-of-life (QoL). In this study we aimed to determine the risk of PTS and how it affects QoL after a first episode of VTE in young and middle-aged women. Methods: We conducted a cohort study, including 1438 women with a first episode of VTE. Patients were recruited from 'Thrombo Embolism Hormonal Study' (TEHS), a Swedish nation-wide case-control study on risk factors for VTE in women 18-65 years of age. Consecutive patients with a first episode of deep vein thrombosis (DVT) in the lower leg or pulmonary embolism (PE) were included between 2002 and 2009. In 2011 all women still living in Sweden were followed up through a questionnaire. PTS was measured using self-reported Villalta score and Veins-QoL was used to measure QoL. Results: After a median follow-up time of 6 years 1049 patients accepted participation in the follow-up study. The reported prevalence of PTS was 20 % for all patients, 28 % among women with a previous episode of a proximal DVT, 19 % among women with a previous distal DVT and 12 % among women with PE. Women with a history of leg symptoms before the first VTE-event had a higher risk of PTS (OR 3.5 (95% CI 2.5 - 4.8), with a prevalence of 32% compared to 12% in women with no history of leg symptoms. Obese women were at increased risk of PTS (OR 1.9, 95% CI 1.4 - 2.7) compared to non-obese. Similar women with proximal DVT (OR 1.6, 95% CI 1.1 - 2.3) and ipsilateral recurrence (OR 3.8, 95% CI 1.9 - 7.7) had increased risk of PTS. Patients with PTS scored lower on Veins-QoL (44 vs. 52, p < 0.01). Conclusions: PTS is a common complication of VTE. Women with a history of leg-symptoms before time of VTE-diagnosis have more than 3-fold increased risk of PTS. Occurrence of PTS significantly reduces QoL. Disclosures No relevant conflicts of interest to declare.

High factor VIII and the risk of venous thromboembolism

2003 ◽  
Vol 23 (01) ◽  
pp. 41-44 ◽  
Author(s):  
Paul A. Kyrle
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Convincing Evidence ◽  
Important Risk Factor ◽  
First Episode ◽  
Phase Reaction ◽  
Therapeutic Concept

SummaryThere is now convincing evidence that a high level of coagulation factor VIII is an important risk factor for venous thromboembolism. A factor VIII plasma concentration above 1500 IU/l is associated with an almost 5-fold risk for a first episode of venous thrombosis. In thrombosis patients high factor VIII has been shown to persist over time and is not related to an acute phase reaction. High factor VIII is also an important risk factor for recurrence of venous thrombosis. In a prospective cohort study factor VIII levels exceeding the 90th percentile of the patient population confered an almost 7-fold risk of recurrent venous thrombosis. The pathomechanisms leading to venous thrombosis in patients with high factor VIII are still unclear. In many patients, however, a biochemically detectable hypercoagulable state (as represented by elevated levels of the coagulation activation marker prothrombin thrombin fragment F1.2) was demonstrated. The optimal duration of secondary thromboprophylaxis for patients with high factor VIII levels is uncertain. We currently perform an interventional trial comparing conventional to extended anticoagulation. Reduction of factor VIII by administration of a non-selective ß-receptor blocker might be a promising therapeutic concept which is currently under investigation.

Combined Factor V Leiden (R506Q) and prothrombin G20210A genotyping in young patients presenting with deep venous thrombosis

2006 ◽  
Vol 21 (1) ◽  
pp. 24-27 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Young Patients ◽  
Factor V Leiden ◽  
First Episode ◽  
Control Group ◽  
Factor V ◽  
Factor V Leiden Mutation

Objective: To evaluate the association between the Factor V Leiden (FV R506Q) and prothrombin gene (FII G20210A) mutations and deep venous thrombosis (DVT) in young people. Methods: Blood samples were drawn from 199 subjects: 100 healthy controls and 99 unselected patients, with an objectively documented first episode of DVT under 40 years old. DNA analysis was performed using the polymerase chain reaction. Results: The mean age in the patient cohort was 27 years (range 16–40) and 68 (68.7%) were women. Patient prevalences were 20.6% and 10.1% for FV R506Q and FII G20210A, respectively. In the control group, carrier frequencies were 2% and 5%, respectively. We found an increased overall relative risk of DVT with statistical significance for FV R506Q carriers (OR: 12.8; 95% CI: 2.9–56.7; P < 0.001), but not for FII G20210A mutation (OR: 2.1; 95% CI: 0.7–6.5; P = 0.19). Conclusions: Our results suggest a possible increase in DVT risk for the young G20210A allele carriers, which can be more expressed in the presence of a circumstantial risk factor. There is extremely strong evidence that the Factor V Leiden mutation is an important risk factor in the development of a first episode of DVT in young people.

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