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Thromb Haemost 2017; 117(04): 691-699
DOI: 10.1160/TH16-11-0834
Coagulation and Fibrinolysis
Schattauer GmbH

Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid haemorrhage

Monisha Kumar   *
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
Wenjing Cao   *
2   Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Jenny K. McDaniel
2   Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Huy P. Pham
2   Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Dheeraj Raju
3   Department of Acute, Chronic, and Continuing Care, The University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Kelsey Nawalinski
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
Suzanne Frangos
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
David Kung
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
Eric E. Zager
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
Scott E. Kasner
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
Joshua M. Levine
1   Departments of Neurology, Neurosurgery, & Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
,
X. Long Zheng
2   Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
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Publikationsverlauf

Received: 09. November 2016

Accepted after major revision: 15. Januar 2016

Publikationsdatum:
28. November 2017 (online)

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Summary

Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). It was our objective to determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Forty consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Mean age of SAH patients was 52.4 years (26–84 years) and 30 (75 %) were women. 12/40 (30 %) had a high Hunt and Hess grade (IV-V) and 25 (62.5 %) were treated with coil embolisation. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. In conclusion, the relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome.

Keywords

Subarachnoid haemorrhage - delayed cerebral ischaemia - von Willebrand factor - ADAMTS13 - platelet hypercoagulability - microvascular thrombosis - and brain aneurysm

* Contributed equally to this work.


 

  • References

  • 1 Ruggeri ZM, Ware J. The structure and function of von Willebrand factor. Thromb Haemost 1992; 67: 594-599
    Thieme ConnectPubMedSuche in Google Scholar
  • 2 Sonneveld MA, de Maat MP, Leebeek FW. Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis. Blood Rev 2014; 28: 167-178
    CrossrefPubMedSuche in Google Scholar
  • 3 Horii M, Uemura S, Uemura M. et al. Acute myocardial infarction as a systemic prothrombotic condition evidenced by increased von Willebrand factor protein over ADAMTS13 activity in coronary and systemic circulation. Heart Vessels 2008; 23: 301-307
    CrossrefPubMedSuche in Google Scholar
  • 4 Wieberdink RG, van Schie MC, Koudstaal PJ. et al. High von Willebrand factor levels increase the risk of stroke: the Rotterdam study. Stroke 2010; 41: 2151-2156
    CrossrefPubMedSuche in Google Scholar
  • 5 Andersson HM, Siegerink B, Luken BM. et al. High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischaemic stroke and myocardial infarction in young women. Blood 2012; 119: 1555-1560
    CrossrefPubMedSuche in Google Scholar
  • 6 Bongers TN, de Maat MP, van Goor ML. et al. High von Willebrand factor levels increase the risk of first ischaemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke 2006; 37: 2672-2677
    CrossrefPubMedSuche in Google Scholar
  • 7 Zheng XL. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura. Annu Rev Med 2015; 66: 211-225
    CrossrefPubMedSuche in Google Scholar
  • 8 Bernardo A, Ball C, Nolasco L. et al. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 2004; 104: 100-106
    CrossrefPubMedSuche in Google Scholar
  • 9 Sporn LA, Marder VJ, Wagner DD. von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood 1987; 69: 1531-1534
    CrossrefPubMedSuche in Google Scholar
  • 10 Arya M, Anvari B, Romo GM. et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood 2002; 99: 3971-3977
    CrossrefPubMedSuche in Google Scholar
  • 11 Dong JF, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039
    CrossrefPubMedSuche in Google Scholar
  • 12 Moake JL. Thrombotic thrombocytopenic purpura: the systemic clumping „plague“. Annu Rev Med 2002; 53: 75-88
    CrossrefPubMedSuche in Google Scholar
  • 13 Zheng X, Majerus EM, Sadler JE. ADAMTS13 and TTP. Curr Opin Hematol 2002; 9: 389-394
    CrossrefPubMedSuche in Google Scholar
  • 14 Roger VL, Go AS, Lloyd-Jones DM. et al. Heart Disease and Stroke Statistics--2011 Update: A Report From the American Heart Association. Circulation 2011; 123: e18-e209
    CrossrefPubMedSuche in Google Scholar
  • 15 Peltonen S, Juvela S, Kaste M. et al. Haemostasis and fibrinolysis activation after subarachnoid haemorrhage. J Neurosurg 1997; 87: 207-214
    CrossrefPubMedSuche in Google Scholar
  • 16 Nina P, Schisano G, Chiappetta F. et al. A study of blood coagulation and fibrinolytic system in spontaneous subarachnoid haemorrhage. Correlation with hunt-hess grade and outcome. Surg Neurol 2001; 55: 197-203
    CrossrefPubMedSuche in Google Scholar
  • 17 Rabinstein AA, Friedman JA, Weigand SD. et al. Predictors of cerebral infarction in aneurysmal subarachnoid haemorrhage. Stroke 2004; 35: 1862-1866
    CrossrefPubMedSuche in Google Scholar
  • 18 Vergouwen MD, Vermeulen M, Coert BA. et al. Microthrombosis after aneurysmal subarachnoid haemorrhage: an additional explanation for delayed cerebral ischaemia. J Cereb Blood Flow Metab 2008; 28: 1761-1770
    CrossrefPubMedSuche in Google Scholar
  • 19 Bell JD, Thomas TC, Lass E. et al. Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid haemorrhage. J Neurosurg 2014; 121: 1424-1431
    CrossrefPubMedSuche in Google Scholar
  • 20 Juvela S, Ohman J, Servo A. et al. Angiographic vasospasm and release of platelet thromboxane after subarachnoid haemorrhage. Stroke 1991; 22: 451-455
    CrossrefPubMedSuche in Google Scholar
  • 21 Raya AK, Diringer MN. Treatment of subarachnoid haemorrhage. Crit Care Clin 2014; 30: 719-733
    CrossrefPubMedSuche in Google Scholar
  • 22 Jin SY, Skipwith CG, Shang D. et al. von Willebrand factor cleaved from endothelial cells by ADAMTS13 remains ultralarge in size. J Thromb Haemost 2009; 7: 1749-1752
    CrossrefPubMedSuche in Google Scholar
  • 23 Gerritsen HE, Turecek PL, Schwarz HP. et al. Assay of von Willebrand factor (vWF)-cleaving protease based on decreased collagen binding affinity of degraded vWF: a tool for the diagnosis of thrombotic thrombocytopenic purpura (TTP). Thromb Haemost 1999; 82: 1386-1389
    Thieme ConnectPubMedSuche in Google Scholar
  • 24 Zhang L, Lawson HL, Harish VC. et al. Creation of a recombinant peptide substrate for fluorescence resonance energy transfer-based protease assays. Anal Biochem 2006; 358: 298-300
    CrossrefPubMedSuche in Google Scholar
  • 25 Yoav B, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach To Multiple Testing. J Roy Stat Soc 2005; 57: 289-300
    PubMedSuche in Google Scholar
  • 26 Sullivan GM, Feinn R. Using Effect Size-or Why the P Value Is Not Enough. J Grad Med Educ 2012; 4: 279-282
    CrossrefPubMedSuche in Google Scholar
  • 27 Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ, Lawrence Erlbaum Associates, Inc.; 1988
    PubMed
  • 28 Benjamini Y, Yekutieli D. Quantitative trait Loci analysis using the false discovery rate. Genetics 2005; 171: 783-790
    CrossrefPubMedSuche in Google Scholar
  • 29 Armitage P, Colton T. Encyclopedia of Biostatistics 2nd ed. Hoboken, NJ, Wiley Interscience 2005
    PubMed
  • 30 Kelley K. Confidence Intervals for standardized effect sizes: THeory, application, and implementation. J Stat Soft 2007; 20: 1-24
    PubMedSuche in Google Scholar
  • 31 Gordon Ad. Null models in cluster validation. Springer; 1996
    PubMed
  • 32 De Meyer SF, Schwarz T, Deckmyn H. et al. Binding of von Willebrand factor to collagen and glycoprotein Ibalpha, but not to glycoprotein IIb/IIIa, contributes to ischaemic stroke in mice--brief report. Arterioscler Thromb Vasc Biol 2010; 30: 1949-1951
    CrossrefPubMedSuche in Google Scholar
  • 33 Kleinschnitz C, De Meyer SF, Schwarz T. et al. Deficiency of von Willebrand factor protects mice from ischaemic stroke. Blood 2009; 113: 3600-3603
    CrossrefPubMedSuche in Google Scholar
  • 34 De Meyer SF, Stoll G, Wagner DD. et al. von Willebrand factor: an emerging target in stroke therapy. Stroke 2012; 43: 599-606
    CrossrefPubMedSuche in Google Scholar
  • 35 Dopheide SM, Maxwell MJ, Jackson SP. Shear-dependent tether formation during platelet translocation on von Willebrand factor. Blood 2002; 99: 159-167
    CrossrefPubMedSuche in Google Scholar
  • 36 Zheng XL. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura. Annu Rev Med 2015; 66: 211-225
    CrossrefPubMedSuche in Google Scholar
  • 37 Sonneveld MA, de Maat MP, Portegies ML. et al. Low ADAMTS13 activity is associated with an increased risk of ischaemic stroke. Blood 2015; 126: 2739-2746
    CrossrefPubMedSuche in Google Scholar
  • 38 Fujioka M, Hayakawa K, Mishima K. et al. ADAMTS13 gene deletion aggravates ischaemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischaemic hypoperfusion. Blood 2010; 115: 1650-1653
    CrossrefPubMedSuche in Google Scholar
  • 39 Parra A, McGirt MJ, Sheng H. et al. Mouse model of subarachnoid haemorrhage associated cerebral vasospasm: methodological analysis. Neurol Res 2002; 24: 510-516
    CrossrefPubMedSuche in Google Scholar
  • 40 Findlay JM, Weir BK, Kanamaru K. et al. Arterial wall changes in cerebral vasospasm. Neurosurgery 1989; 25: 736-745
    CrossrefPubMedSuche in Google Scholar
  • 41 Suzuki S, Kimura M, Souma M. et al. Cerebral microthrombosis in symptomatic cerebral vasospasm--a quantitative histological study in autopsy cases. Neurol Med Chir (Tokyo) 1990; 30: 309-316
    CrossrefPubMedSuche in Google Scholar
  • 42 Iuliano BA, Pluta RM, Jung C. et al. Endothelial dysfunction in a primate model of cerebral vasospasm. J Neurosurg 2004; 100: 287-294
    CrossrefPubMedSuche in Google Scholar
  • 43 Hirashima Y, Nakamura S, Endo S. et al. Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid haemorrhage. Neurochem Res 1997; 22: 1249-1255
    CrossrefPubMedSuche in Google Scholar
  • 44 Zhao BQ, Chauhan AK, Canault M. et al. von Willebrand factor-cleaving protease ADAMTS13 reduces ischaemic brain injury in experimental stroke. Blood 2009; 114: 3329-3334
    CrossrefPubMedSuche in Google Scholar
  • 45 Vergouwen MD, Knaup VL, Roelofs JJ. et al. Effect of recombinant ADAMTS-13 on microthrombosis and brain injury after experimental subarachnoid haemorrhage. J Thromb Haemost 2014; 12: 943-947
    CrossrefPubMedSuche in Google Scholar