Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis Michelle A.H. Sonneveld, Moniek P.M. de Maat, Frank W.G. Leebeek PII: DOI: Reference:
S0268-960X(14)00034-4 doi: 10.1016/j.blre.2014.04.003 YBLRE 341
To appear in:
Blood Reviews
Received date: Accepted date:
28 February 2014 14 April 2014
Please cite this article as: Sonneveld Michelle A.H., de Maat Moniek P.M., Leebeek Frank W.G., Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis, Blood Reviews (2014), doi: 10.1016/j.blre.2014.04.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Von Willebrand factor and ADAMTS13 in arterial
T
thrombosis: a systematic review and meta-analysis
IP
Michelle AH Sonneveld1, MD; Moniek PM de Maat1, PhD; Frank WG Leebeek1, MD,
SC R
PhD
1
NU
Department of Hematology, Erasmus University Medical Center, Rotterdam, The
MA
Netherlands
D
Correspondence:
TE
Professor Frank W.G. Leebeek, MD, PhD Erasmus University Medical Center
Room Na-820
CE P
Department of Hematology
P.O. Box 2040, 3000 CA Rotterdam
AC
The Netherlands
Tel: +31 10 703 16 72 Fax: +31 10 703 58 14 E-mail: [email protected]
1
ACCEPTED MANUSCRIPT Abstract Von Willebrand Factor (VWF) plays an important role in hemostasis by mediating platelet adhesion and aggregation. Ultralarge VWF multimers are cleaved by ADAMTS13 in smaller,
IP
T
less procoagulant forms. An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been
SC R
observed between low ADAMTS13 levels and arterial thrombosis. We reviewed the current literature and performed meta-analyses on the relationship between both VWF and
NU
ADAMTS13 with arterial thrombosis. Most studies showed an association between high VWF levels and arterial thrombosis. It remains unclear whether ADAMTS13 is a causal
MA
independent risk factor because the association between low ADAMTS13 and arterial thrombosis is so far only shown in case-control studies. Prospective studies are awaited. A causal role for ADAMTS13 is supported by mice studies of cerebral infarction where the
TE
D
infusion of recombinant human ADAMTS13 reduced the infarct size.
CE P
Keywords: Von Willebrand Factor, ADAMTS13, myocardial infarction, coronary heart
AC
disease, ischemic stroke.
2
ACCEPTED MANUSCRIPT 1. Introduction Arterial thrombosis, specifically coronary heart disease and ischemic stroke, is associated with a high mortality and morbidity in the Western World. Multiple risk factors for arterial
IP
T
thrombosis are known, including the classical risk factors hypertension, diabetes and obesity. Many studies have shown that the variation in coagulation factors may also confer a higher
SC R
risk of arterial thrombosis (1-4). Previous studies have suggested a role for Von Willebrand Factor (VWF) in the pathogenesis of arterial thrombosis. VWF, a large multimeric
NU
glycoprotein, has an important function in primary hemostasis. It facilitates platelet adhesion and aggregation by interacting with the GPIb receptor on platelets and it is a carrier protein of
MA
factor VIII, thereby protecting factor VIII from proteolytic degradation (5). ADAMTS13, A Disintegrin and Metalloprotease with TrompoSpondin motif repeats 13, cleaves ultralarge very active VWF multimers into smaller, less procoagulant forms (6, 7). Hypothetically, lower
TE
D
levels of ADAMTS13 are associated with increased VWF activity and can thereby contribute to arterial thrombosis. Many studies have focused on the role of VWF in the pathogenesis of
CE P
arterial thrombosis, both on the occurrence of the first event and on recurrence. A limited number have been published on the role of ADAMTS13 in arterial thrombosis yet. In this review we summarize the current literature on VWF and ADAMTS13 in arterial thrombosis.
AC
We additionally present meta-analyses of the published studies on this research topic.
3
ACCEPTED MANUSCRIPT 2. Methods 2.1 Search strategy and selection criteria Medline and Embase were used to search literature till October 1st 2013. The following
IP
T
search was used:
('von Willebrand Factor'/de OR 'Von Willebrand Factor cleaving proteinase'/de OR
SC R
('Willebrand Factor' OR ADAMTS13 OR 'ADAMTS 13'):ab,ti) AND ('Brain ischemia'/exp OR (stroke* OR CVA OR ((brain OR cerebr* OR neural) NEAR/4 (ischem* OR ischaem* OR
NU
accident* OR circulat* OR flow*))):ab,ti OR 'Ischemic heart disease'/exp OR (((myocardial OR heart OR cardia* OR cardio*) NEAR/4 (ischem* OR ischaem* OR infarct*)) OR (coronary
MA
NEAR/4 (syndrome* OR disease* OR obstruct* OR occlusi* OR stenos* OR thromb* OR atherosclero*)) OR angina):ab,ti).
The search strategy was restricted to published data and the English language. In total, 2656
TE
D
citations were found of which titles and abstracts were screened. Potentially suitable studies were read in full text. Studies were selected when the following criteria were met: 1)
CE P
prospective cohort studies or case-control studies; 2) association between VWF or ADAMTS13 and myocardial infarction, coronary heart disease, (unstable) angina pectoris or
AC
ischemic stroke.
2.2 Statistical analysis Odds ratios were presented in the forest plots using random effects models. The overall effects were determined using the Z-test. P-values
S0268-960X(14)00034-4 doi: 10.1016/j.blre.2014.04.003 YBLRE 341
To appear in:
Blood Reviews
Received date: Accepted date:
28 February 2014 14 April 2014
Please cite this article as: Sonneveld Michelle A.H., de Maat Moniek P.M., Leebeek Frank W.G., Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis, Blood Reviews (2014), doi: 10.1016/j.blre.2014.04.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Von Willebrand factor and ADAMTS13 in arterial
T
thrombosis: a systematic review and meta-analysis
IP
Michelle AH Sonneveld1, MD; Moniek PM de Maat1, PhD; Frank WG Leebeek1, MD,
SC R
PhD
1
NU
Department of Hematology, Erasmus University Medical Center, Rotterdam, The
MA
Netherlands
D
Correspondence:
TE
Professor Frank W.G. Leebeek, MD, PhD Erasmus University Medical Center
Room Na-820
CE P
Department of Hematology
P.O. Box 2040, 3000 CA Rotterdam
AC
The Netherlands
Tel: +31 10 703 16 72 Fax: +31 10 703 58 14 E-mail: [email protected]
1
ACCEPTED MANUSCRIPT Abstract Von Willebrand Factor (VWF) plays an important role in hemostasis by mediating platelet adhesion and aggregation. Ultralarge VWF multimers are cleaved by ADAMTS13 in smaller,
IP
T
less procoagulant forms. An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been
SC R
observed between low ADAMTS13 levels and arterial thrombosis. We reviewed the current literature and performed meta-analyses on the relationship between both VWF and
NU
ADAMTS13 with arterial thrombosis. Most studies showed an association between high VWF levels and arterial thrombosis. It remains unclear whether ADAMTS13 is a causal
MA
independent risk factor because the association between low ADAMTS13 and arterial thrombosis is so far only shown in case-control studies. Prospective studies are awaited. A causal role for ADAMTS13 is supported by mice studies of cerebral infarction where the
TE
D
infusion of recombinant human ADAMTS13 reduced the infarct size.
CE P
Keywords: Von Willebrand Factor, ADAMTS13, myocardial infarction, coronary heart
AC
disease, ischemic stroke.
2
ACCEPTED MANUSCRIPT 1. Introduction Arterial thrombosis, specifically coronary heart disease and ischemic stroke, is associated with a high mortality and morbidity in the Western World. Multiple risk factors for arterial
IP
T
thrombosis are known, including the classical risk factors hypertension, diabetes and obesity. Many studies have shown that the variation in coagulation factors may also confer a higher
SC R
risk of arterial thrombosis (1-4). Previous studies have suggested a role for Von Willebrand Factor (VWF) in the pathogenesis of arterial thrombosis. VWF, a large multimeric
NU
glycoprotein, has an important function in primary hemostasis. It facilitates platelet adhesion and aggregation by interacting with the GPIb receptor on platelets and it is a carrier protein of
MA
factor VIII, thereby protecting factor VIII from proteolytic degradation (5). ADAMTS13, A Disintegrin and Metalloprotease with TrompoSpondin motif repeats 13, cleaves ultralarge very active VWF multimers into smaller, less procoagulant forms (6, 7). Hypothetically, lower
TE
D
levels of ADAMTS13 are associated with increased VWF activity and can thereby contribute to arterial thrombosis. Many studies have focused on the role of VWF in the pathogenesis of
CE P
arterial thrombosis, both on the occurrence of the first event and on recurrence. A limited number have been published on the role of ADAMTS13 in arterial thrombosis yet. In this review we summarize the current literature on VWF and ADAMTS13 in arterial thrombosis.
AC
We additionally present meta-analyses of the published studies on this research topic.
3
ACCEPTED MANUSCRIPT 2. Methods 2.1 Search strategy and selection criteria Medline and Embase were used to search literature till October 1st 2013. The following
IP
T
search was used:
('von Willebrand Factor'/de OR 'Von Willebrand Factor cleaving proteinase'/de OR
SC R
('Willebrand Factor' OR ADAMTS13 OR 'ADAMTS 13'):ab,ti) AND ('Brain ischemia'/exp OR (stroke* OR CVA OR ((brain OR cerebr* OR neural) NEAR/4 (ischem* OR ischaem* OR
NU
accident* OR circulat* OR flow*))):ab,ti OR 'Ischemic heart disease'/exp OR (((myocardial OR heart OR cardia* OR cardio*) NEAR/4 (ischem* OR ischaem* OR infarct*)) OR (coronary
MA
NEAR/4 (syndrome* OR disease* OR obstruct* OR occlusi* OR stenos* OR thromb* OR atherosclero*)) OR angina):ab,ti).
The search strategy was restricted to published data and the English language. In total, 2656
TE
D
citations were found of which titles and abstracts were screened. Potentially suitable studies were read in full text. Studies were selected when the following criteria were met: 1)
CE P
prospective cohort studies or case-control studies; 2) association between VWF or ADAMTS13 and myocardial infarction, coronary heart disease, (unstable) angina pectoris or
AC
ischemic stroke.
2.2 Statistical analysis Odds ratios were presented in the forest plots using random effects models. The overall effects were determined using the Z-test. P-values
