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Arterial Thrombosis in Factor V Leiden or Activated Protein C Resistance. Clinical and Experimental Studies.

Sampram, Ellis LU (2012) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2012:79.
Abstract
Abstract

The last two decades has seen an avalanche of studies establishing Activated protein C (APC) resistance due to Factor V Leiden mutation as the most prevalent genetic risk factor, yet known, for venous thromboembolism. This has been documented in 20-60% of patients with deep vein thrombosis (DVT). Whether such propensity also exists in arterial circulation is still controversial. The general aim of the present thesis is to clearify some of the controversies that cloud the impact of APC resistance or Factor V leiden mutation on arterial thrombosis.

Paper I showed a significantly high prevalence of APC resistance or factor V Leiden mutation in peripheral vascular patients compared to the control group (22.7% vs... (More)
Abstract

The last two decades has seen an avalanche of studies establishing Activated protein C (APC) resistance due to Factor V Leiden mutation as the most prevalent genetic risk factor, yet known, for venous thromboembolism. This has been documented in 20-60% of patients with deep vein thrombosis (DVT). Whether such propensity also exists in arterial circulation is still controversial. The general aim of the present thesis is to clearify some of the controversies that cloud the impact of APC resistance or Factor V leiden mutation on arterial thrombosis.

Paper I showed a significantly high prevalence of APC resistance or factor V Leiden mutation in peripheral vascular patients compared to the control group (22.7% vs 12.2%).

In Paper II, association between early occlusions of vascular reconstructions and Factor V Leiden mutation was shown. At one month, there was a two-fold risk of occlusion of vascular reconstructions compared to non-carriers (14% vs 7%, p=0.02). At one year, the same tendency was noted although not significant (22% vs 12%).

Paper III, an experimental arterial thrombosis study with factor V Leiden mice, revealed increased thrombogenicity in mice with Factor V Leiden mutation and arterial injury. There was a significant relationship between time to occlusion (TTO) and genotype (p=0.002). TTO was highest in the wild type mice (TTO: homozygote <heterozygote <wild type; p <0.001).

Paper IV analyzing the mortality, amputation rate and inflammatory mediators in critical limb ischemia (CLI) patients with Factor V Leiden did not find any significant difference in inflammatory mediators between critical limb ischemia patients with Factor V Leiden and non-carriers. There was neither a significant difference in the rate of amputation at one year nor mortality up to 10 years between CLI patients with FVL mutation and non-carriers.

Conlusions: Resistance to activated protein C or Factor V Leiden mutation is more prevalent in patients with peripheral vascular diseases than the general population, the risk for early occlusions of vascular reconstructions increases two-folds in FVL patients compared to non-carriers and FVL enhances arterial thrombosis development after vessel wall injury in experimental FVL mice. However, no difference in long-term (10 years) mortality or one-year amputation rate is seen between critical limb ischemia patients with FVL mutation and non-carriers. (Less)
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author
supervisor
opponent
  • Professor Lindahl, Tomas, Linköping University Medical School
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Activated protein c resistance, Factor V Leiden mutation, thrombophilia, hypercoagulable state, Factor V Leiden mice, arterial thrombosis, venous thromboembolism, peripheral vascular reconstructions, peripheral vascular reconstruction occlusion
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2012:79
pages
58 pages
publisher
Clinical Coagulation Research Unit, Clinical Science, Malmö.
defense location
Waldenströmssalen, Jan Waldenströmsgatan 14, Skanes University Hospital, Malmö. Sweden
defense date
2012-11-24 09:00
ISSN
1652-8220
ISBN
978-91-87189-42-5
language
English
LU publication?
yes
id
3b5cf931-3499-4a8e-ba2d-8c78c28548cd (old id 3164139)
date added to LUP
2012-11-06 12:09:06
date last changed
2016-09-19 08:44:47
@phdthesis{3b5cf931-3499-4a8e-ba2d-8c78c28548cd,
  abstract     = {Abstract<br/><br>
The last two decades has seen an avalanche of studies establishing Activated protein C (APC) resistance due to Factor V Leiden mutation as the most prevalent genetic risk factor, yet known, for venous thromboembolism. This has been documented in 20-60% of patients with deep vein thrombosis (DVT). Whether such propensity also exists in arterial circulation is still controversial. The general aim of the present thesis is to clearify some of the controversies that cloud the impact of APC resistance or Factor V leiden mutation on arterial thrombosis. <br/><br>
Paper I showed a significantly high prevalence of APC resistance or factor V Leiden mutation in peripheral vascular patients compared to the control group (22.7% vs 12.2%).<br/><br>
In Paper II, association between early occlusions of vascular reconstructions and Factor V Leiden mutation was shown. At one month, there was a two-fold risk of occlusion of vascular reconstructions compared to non-carriers (14% vs 7%, p=0.02). At one year, the same tendency was noted although not significant (22% vs 12%).<br/><br>
Paper III, an experimental arterial thrombosis study with factor V Leiden mice, revealed increased thrombogenicity in mice with Factor V Leiden mutation and arterial injury. There was a significant relationship between time to occlusion (TTO) and genotype (p=0.002). TTO was highest in the wild type mice (TTO: homozygote &lt;heterozygote &lt;wild type; p &lt;0.001).<br/><br>
Paper IV analyzing the mortality, amputation rate and inflammatory mediators in critical limb ischemia (CLI) patients with Factor V Leiden did not find any significant difference in inflammatory mediators between critical limb ischemia patients with Factor V Leiden and non-carriers. There was neither a significant difference in the rate of amputation at one year nor mortality up to 10 years between CLI patients with FVL mutation and non-carriers.<br/><br>
Conlusions: Resistance to activated protein C or Factor V Leiden mutation is more prevalent in patients with peripheral vascular diseases than the general population, the risk for early occlusions of vascular reconstructions increases two-folds in FVL patients compared to non-carriers and FVL enhances arterial thrombosis development after vessel wall injury in experimental FVL mice. However, no difference in long-term (10 years) mortality or one-year amputation rate is seen between critical limb ischemia patients with FVL mutation and non-carriers.},
  author       = {Sampram, Ellis},
  isbn         = {978-91-87189-42-5},
  issn         = {1652-8220},
  keyword      = {Activated protein c resistance,Factor V Leiden mutation,thrombophilia,hypercoagulable state,Factor V Leiden mice,arterial thrombosis,venous thromboembolism,peripheral vascular reconstructions,peripheral vascular reconstruction occlusion},
  language     = {eng},
  pages        = {58},
  publisher    = {Clinical Coagulation Research Unit, Clinical Science, Malmö.},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Arterial Thrombosis in Factor V Leiden or Activated Protein C Resistance. Clinical and Experimental Studies.},
  volume       = {2012:79},
  year         = {2012},
}