Thromb Haemost 2009; 101(02): 305-311
DOI: 10.1160/TH08-05-0330
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia

Attila Molvarec
1   Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
,
János Rigó Jr
1   Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
,
Tamás Bõze
1   Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
,
Zoltán Derzsy
1   Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
,
László Cervenak
2   Research Group of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary
,
Veronika Makó
3   Department of Internal Medicine and Szentágothai Knowledge Center, Semmelweis University, Budapest, Hungary
,
Tímea Gombos
3   Department of Internal Medicine and Szentágothai Knowledge Center, Semmelweis University, Budapest, Hungary
,
Miklós László Udvardy
4   Clinical Research Center, University of Debrecen, Debrecen, Hungary
,
Jolán Hársfalvi
4   Clinical Research Center, University of Debrecen, Debrecen, Hungary
,
Zoltán Prohászka
2   Research Group of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Budapest, Hungary
3   Department of Internal Medicine and Szentágothai Knowledge Center, Semmelweis University, Budapest, Hungary
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 28. Mai 2008

Accepted after major revision: 16. Januar 2008

Publikationsdatum:
23. November 2017 (online)

Summary

The activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease is low in several conditions, including HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. As HELLP syndrome develops in most cases on the basis of preeclampsia, our aim was to determine whether plasma ADAMTS13 activity is decreased in preeclampsia. Sixty-seven preeclamptic patients, 70 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Plasma ADAMTS13 activity was determined with the FRETS-VWF73 assay, while VWF antigen (VWF:Ag) levels with an enzyme-linked immunosorbent assay. The multimeric pattern of VWF was analyzed by SDS-agarose gel electrophoresis. There was no significant difference in plasma ADAMTS13 activity between the preeclamptic and the healthy pregnant and non-pregnant groups (median [25–75 percentile]: 98.8 [76.5–112.8] %, 96.3 [85.6–116.2] % and 91.6 [78.5–104.4] %, respectively; p>0.05). However, plasma VWF:Ag levels were significantly higher in preeclamptic patients than in healthy pregnant and non-pregnant women (187.1 [145.6–243.1] % versus 129.3 [105.1–182.8] % and 70.0 [60.2–87.3] %, respectively; p<0.001). The multimeric pattern of VWF was normal in each group. Primiparas had lower plasma ADAMTS13 activity than multi-paras (92.6 [75.8–110.6] % versus 104.2 [92.1–120.8] %; p=0.011). No other relationship was found between clinical characteristics, laboratory parameters and plasma ADAMTS13 activity in either study group. In conclusion, plasma ADAMTS13 activity is normal in preeclampsia despite the increased VWF:Ag levels. However, further studies are needed to determine whether a decrease in plasma ADAMTS13 activity could predis-pose preeclamptic patients to develop HELLP syndrome.

 
  • References

  • 1 Duckitt K, Harrington D. Risk factors for preeclampsia at antenatal booking: systematic review of controlled studies. Br Med J 2005; 330: 565.
  • 2 Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999; 180: 499-506.
  • 3 Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension 2005; 46: 1243-1249.
  • 4 Dong JF, Moake JL, Bernardo A. et al. ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem 2003; 278: 29633-29639.
  • 5 Dong JF. Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions. J Thromb Haemost 2005; 3: 1710-1716.
  • 6 Zhou W, Inada M, Lee TP. et al. ADAMTS13 is expressed in hepatic stellate cells. Lab Invest 2005; 85: 780-788.
  • 7 Turner N, Nolasco L, Tao Z. et al. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost 2006; 4: 1396-1404.
  • 8 Suzuki M, Murata M, Matsubara Y. et al. Detection of von Willebrand factor-cleaving protease (ADAMTS-13) in human platelets. Biochem Biophys Res Commun 2004; 313: 212-216.
  • 9 Peyvandi F, Ferrari S, Lavoretano S. et al. von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol 2004; 127: 433-439.
  • 10 Mannucci PM, Peyvandi F. TTP and ADAMTS13: When Is Testing Appropriate?. Hematology Am Soc Hematol Educ Program 2007; 2007: 121-126.
  • 11 Remuzzi G, Galbusera M, Noris M. et al. von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Blood 2002; 100: 778-785.
  • 12 Mannucci PM, Canciani MT, Forza I. et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98: 2730-2735.
  • 13 Sanchez-Luceros A, Farias CE, Amaral MM. et al. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women. Thromb Haemost 2004; 92: 1320-1326.
  • 14 Mannucci PM, Vanoli M, Forza I. et al. Von Wille-brand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue diseases (systemic lupus erythematosus and systemic sclerosis). Haematologica 2003; 88: 914-918.
  • 15 Mannucci PM, Karimi M, Mosalaei A. et al. Patients with localized and disseminated tumors have reduced but measurable levels of ADAMTS-13 (von Willebrand factor cleaving protease). Haematologica 2003; 88: 454-458.
  • 16 Feys HB, Canciani MT, Peyvandi F. et al. ADAMTS13 activity to antigen ratio in physiological and pathological conditions associated with an increased risk of thrombosis. Br J Haematol 2007; 138: 534-540.
  • 17 Mannucci PM, Parolari A, Canciani MT. et al. Opposite changes of ADAMTS-13 and von Willebrand factor after cardiac surgery. J Thromb Haemost 2005; 3: 397-399.
  • 18 Claus RA, Bockmeyer CL, Sossdorf M. et al. Physical stress as a model to study variations in ADAMTS-13 activity, von Willebrand factor level and platelet activation. J Thromb Haemost 2006; 4: 902-905.
  • 19 Bockmeyer CL, Claus RA, Budde U. et al. Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor. Haematologica 2008; 93: 137-140.
  • 20 Moore JC, Hayward CP, Warkentin TE. et al. Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders. Blood 2001; 98: 1842-1846.
  • 21 Loof AH, van Vliet HH, Kappers-Klunne MC. Low activity of von Willebrand factor-cleaving protease is not restricted to patients suffering from thrombotic thrombocytopenic purpura. Br J Haematol 2001; 112: 1087-1088.
  • 22 Bianchi V, Robles R, Alberio L. et al. Von Wille-brand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood 2002; 100: 710-713.
  • 23 Lattuada A, Rossi E, Calzarossa C. et al. Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica 2003; 88: 1029-1034.
  • 24 Hulstein JJ, van Runnard Heimel PJ, Franx A. et al. Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. J Thromb Haemost 2006; 4: 2569-2575.
  • 25 Joubert K. Standards of the body mass and body length of birth in Hungary on the basis of the 1990–1996 nation-wide liveborn data. Magy Noorv L 2000; 63: 155-163.
  • 26 Kokame K, Nobe Y, Kokubo Y. et al. FRETSVWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 2005; 129: 93-100.
  • 27 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.
  • 28 John Bowen D, Bowley SJ. Improved visualisation of high-molecular-weight von Willebrand factor multimers. Thromb Haemost 2007; 97: 1051-1052.
  • 29 Budde U, Schneppenheim R, Eikenboom J. et al. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD). J Thromb Haemost 2008; 6: 762-771.
  • 30 Reiter RA, Varadi K, Turecek PL. et al. Changes in ADAMTS13 (von-Willebrand-factor-cleaving pro-tease) activity after induced release of von Willebrand factor during acute systemic inflammation. Thromb Haemost 2005; 93: 554-558.
  • 31 Coppola R, Mari D, Lattuada A. et al. Von Wille-brand factor in Italian centenarians. Haematologica 2003; 88: 39-43.
  • 32 Oleksowicz L, Bhagwati N, DeLeon-Fernandez M. Deficient activity of von Willebrand’s factor-cleaving protease in patients with disseminated malignancies. Cancer Res 1999; 59: 2244-2250.
  • 33 Mannucci PM, Capoferri C, Canciani MT. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease. Br J Haematol 2004; 126: 213-218.
  • 34 Dong JF, Moake JL, Nolasco L. et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Wille-brand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100: 4033-4039.
  • 35 Lopez JA, Dong JF. Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells. Semin Hematol 2004; 41: 15-23.
  • 36 Nadar SK, Al Yemeni E, Blann AD. et al. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension. Thromb Res 2004; 113: 123-128.
  • 37 Molvarec A, Prohaszka Z, Nagy B. et al. Association of increased serum heat shock protein 70 and C-reactive protein concentrations and decreased serum alpha(2)-HS glycoprotein concentration with the syndrome of hemolysis, elevated liver enzymes, and low platelet count. J Reprod Immunol 2007; 73: 172-179.
  • 38 Paternoster DM, Stella A, Simioni P. et al. Coagulation and plasma fibronectin parameters in HELLP syndrome. Int J Gynaecol Obstet 1995; 50: 263-268.