Elevated plasma factor VIII levels in patients with venous thrombosis – Constitutional risk factor or secondary epiphenomenon?

2012 ◽  
Vol 129 (2) ◽  
pp. 105-106 ◽  
Author(s):  
Kevin Ryan ◽  
James S. O'Donnell
1983 ◽  
Vol 74 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Nancy W. Stead ◽  
Kenneth A. Bauer ◽  
Thomas R. Kinney ◽  
James G. Lewis ◽  
Elizabeth E. Campbell ◽  
...  

1980 ◽  
Vol 8 (4) ◽  
pp. 435-437 ◽  
Author(s):  
Kenneth S. Kosik ◽  
Bruce Furie

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 478-478 ◽  
Author(s):  
Neil Zakai ◽  
Pamela Lutsey ◽  
Aaron Folsom ◽  
Mary Cushman

Abstract Abstract 478 Black-White Differences in Venous Thrombosis Risk: The Longitudinal Investigation of Thromboembolism Etiology (LITE). Neil A. Zakai, Pamela L. Lutsey, Aaron R. Folsom, Mary Cushman. Introduction: Venous thrombosis (VT) is more common in blacks than whites. The reasons for this difference and whether it is explained by racial differences in VT risk factors is not known. Methods: VT was ascertained by physician review of medical records in the Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective observational study of 21,680 men and women age 45–100 years participating in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) cohorts. VT was classified as provoked if preceded within 90 days by major surgery, trauma, immobility, or associated with active cancer or chemotherapy. We used age- and sex-adjusted Cox models to evaluate whether certain VT risk factors explained the increased risk of VT in blacks vs whites. We also tested if the impact of VT risk factors differed by race using interaction terms. Most risk factors were assessed in both ARIC and CHS cohorts (body mass index (BMI), diabetes, hypertension, chronic kidney disease (CKD), factor VIII, and education) except the activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), and protein C were measured in ARIC only and C-reactive protein was measured in CHS only. Results: With up to 15 years of follow up, among 20,964 participants (5,054 blacks) without VT at baseline, 648 developed new VT (200 blacks). The age- and sex-standardized incidence of VT per 1000 person-years was higher in blacks than whites for all VT (3.18 vs 1.96), whether the VT was provoked (2.11 vs. 1.24) or unprovoked (1.12 vs. 0.74), all p <0.01. Blacks and whites had a similar incidence of pulmonary embolism (PE) (0.83 vs. 0.76, p = 0.56). Blacks had more adverse levels of many VT risk factors except CKD and a lower aPTT: BMI (29.3 vs. 26.8 kg/m2), diabetes (21 vs 11%), hypertension (59 vs 38%), CKD (5 vs. 12%), high school graduation (58 vs 80%), factor VIII (146 vs 124%), vWF (134 vs 113%), CRP (2.4 vs 1.8 mg/L) protein C (3.13 vs. 3.18 mg/L), all p <0.01. In age- and sex-adjusted Cox models, the relative risk of total VT for blacks vs. whites was 1.67 (95% CI 1.41, 1.97). When risk factors were added to age-, sex- and race-adjusted Cox models, BMI explained 36% of the excess risk of VT in blacks, factor VIII 58%, and vWF 54%. The other risk factors had a minimal impact on the HR for race. When all risk factors measured in both cohorts were considered in the same model, the association of black race with VT was attenuated (HR 1.15; 95% CI 0.94, 1.42). Of the risk factors evaluated, there were significant interactions between race and hypertension, CKD, and aPTT below the median (29s). The table lists the HR for each of these risk factors stratified by race; hypertension and CKD were stronger risk factors for VT in blacks while an aPTT less than the median was a stronger risk factor for VT in whites. Conclusions: Blacks have a higher incidence of VT than whites, whether provoked or unprovoked. The increased risk in blacks was largely explained by a greater prevalence of VT risk factors among blacks, particularly obesity, higher factor VIII and higher vWF. Further, CKD and hypertension were stronger risk factors for VT in blacks, while a shorter aPTT was a weaker risk factor for VT in blacks. Larger studies of VT in blacks addressing environmental and genetic risk factors and health-care disparities are needed to fully understand reasons for these ethnic differences in VT incidence. Disclosure: No relevant conflicts of interest to declare.


2004 ◽  
Vol 91 (02) ◽  
pp. 267-275 ◽  
Author(s):  
Martine Hollestelle ◽  
Hendrika Geertzen ◽  
Irene Straatsburg ◽  
Thomas van Gulik ◽  
Jan van Mourik

SummaryLiver disease is associated with markedly elevated plasma factor VIII (FVIII) levels, whereas the synthesis of many other coagulation factors and proteins is reduced. In order to define the mechanism of FVIII increase, we have determined the expression levels of FVIII, both at mRNA and protein level, in patients with liver disease who underwent partial liver resection. In addition, the expression of von Willebrand factor (VWF) and low density lipoprotein receptor-related protein (LRP), proteins known for their ability to modulate FVIII plasma levels, were examined. Tissue samples for RNA extraction were obtained from 4 patients with cirrhosis, 9 patients with liver failure without cirrhosis and 6 patients with liver metastasis of a colon or rectum carcinoma (control group). In patients with liver cirrhosis hepatic FVIII and LRP mRNA levels were significantly lower than controls (p ≤ 0.010), while VWF mRNA was significantly higher (p ≤ 0.050). Immunohistochemical analysis revealed that cellular VWF protein distribution was also increased in cirrhotic livers compared to liver tissue from patients with non-cirrhotic liver disease. In cirrhotic tissue enlarged portal veins appeared to overgrow FVIII producing sinusoidal endothelial cells. Similarly, the number of LRP-producing cells appeared to be lower in cirrhotic tissue than in controls. The plasma concentration of both FVIII and VWF was significantly higher in patients with cirrhosis than control subjects (p = 0.038 and 0.010 respectively). These results demonstrate that elevated plasma FVIII levels in liver cirrhosis are associated with increased hepatic biosynthesis of VWF and decreased expression of LRP, rather than increased FVIII synthesis.


2019 ◽  
Vol 10 ◽  
pp. 204062071988668 ◽  
Author(s):  
Farjah Hassan Algahtani ◽  
Ruth Stuckey

Thrombotic disorders are one of the most common causes of morbidity and mortality in developing and developed countries. Several well-known genetic traits underlie predisposition to venous thrombosis. In particular, high factor VIII levels are a risk factor for venous thrombosis and coronary artery disease (CAD). However, similar insight into the genetic component of arterial thrombosis predisposition has not materialized fully, despite considerable effort. The authors present an illustrative case of a 32-year-old Saudi Arabian patient with peripheral arterial thrombosis whose only identifiable risk factor were high factor VIII levels. We also provide a comprehensive review of the current state of knowledge concerning the role of high factor VIII levels in determining the risk of arterial thrombosis or ischemic heart disease (IHD). We conclude that high factor VIII levels are a risk factor for thrombosis, with a greater impact on venous than on arterial thrombosis. However, due to a lack of international consensus on methods for the laboratory testing of factor VIII levels in plasma, we would not currently recommend the measurement of factor VIII levels as part of routine thrombophilia screening.


2004 ◽  
Vol 351 (11) ◽  
pp. 1081-1088 ◽  
Author(s):  
Neil A. Goldenberg ◽  
R. Knapp-Clevenger ◽  
Marilyn J. Manco-Johnson

Sign in / Sign up

Export Citation Format

Share Document