Abstract
Severe ADAMTS13 deficiency (activity < 10%) is pathognomonic of thrombotic thrombocytopenic purpura. ADAMTS13 testing is time-consuming and unavailable in many hospitals. Recently, a seven-variables score named PLASMIC score, has been developed to stratify acute patients, based on their risk of having a severe ADAMTS13 deficiency. We present the application of this score in a cohort of patients referred to our Center. From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of “Casa Sollievo della Sofferenza” Hospital/Research Institute for ADAMTS13 testing. For all patients, relevant medical and laboratory information were collected. To obtain the statistical measure of the discriminatory power of PLASMIC scoring system, the Area Under the Curve Receiver Operating Characteristic (AUC ROC) was calculated. We were able to calculate the PLASMIC score in 27 out of 42 patients; we found a good discrimination performance of the score with a resulting AUC value of 0.86 (95% CI 0.71–1.0; p = 0.015). All patients but one with a high risk PLASMIC score (6–7) showed a severe deficiency. Among patients belonging to the intermediate risk (PLASMIC score 5) group, 2 showed normal ADAMTS13 activity and 2 levels below 10%. In none of the patients in the low risk group (PLASMIC score 0–4), a severe ADAMTS13 deficiency was found. Present results confirm and extend previous data regarding the predictive value of the PLASMIC score. Indeed, it shows a good diagnostic performance and can be useful for decision makers to properly and promptly define the better therapeutic approach.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dong JF, Moake JL, Nolasco L, Bernardo A, Arceneaux W, Shrimpton CN et al (2002) ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface underflowing conditions. Blood 100:4033–4039
Dong JF, Moake JL, Bernardo A, Fujikawa K, Ball C, Nolasco L et al (2003) ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem 278:29633–29639
Dong JF (2005) Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions. J Thromb Haemost 3:1710–1716
Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD (1986) Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 78:1456–1461
Tsai HM (1996) Physiologic cleavage of von Willebrandfactor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 87:4235–4244
Moake JL (2002) Thrombotic microangiopathies. N Engl J Med 347:589–600
Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J et al (1982) Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 307:1432–1435
Hassan S, Westwood JP, Ellis D, Laing C, Mc Guckin S, Benjamin S et al (2015) The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry. Br J Haematol 171:830–835
Starke R, Machin S, Scully M, Purdy G, Mackie I (2007) The clinical utility of ADAMTS13 activity, antigen and autoantibody assays in thrombotic thrombocytopenic purpura. Br J Haematol 136:649–655
Tripodi A, Peyvandi F, Chantarangkul V, Palla R, Afrasiabi A, Canciani MT et al (2008) Second international collaborative study evaluating performance characteristics of methods measuring the von Willebrand factor cleaving protease (ADAMTS-13). J Thromb Haemost 6:1534–1541
Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J et al (2017) Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 15:312–322
Zheng XL, Kaufman RM, Goodnough LT, Sadler JE (2004) Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 103:4043–4049
Scully M, Yarranton H, Liesner R, Cavenagh J, Hunt B, Benjamin S et al (2008) Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol 142:819–826
Bendapudi PK, Hurwitz S, Fry A, Marques MB, Waldo SW, Li A et al (2017) Derivation and external validation of the PLASMIC score forrapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol 4:e157–e164
Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN (2010) Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 115:1500–1511
Li A, Khalighi PR, Wu Q, Garcia DA (2018) External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment. J Thromb Haemost 16:164–169
Jajosky R, Floyd M, Thompson T, Shikle J (2017) Validation of the PLASMIC score at a University Medical Center. Transfus Apher Sci 56:591–594
Li A, Makar RS, Hurwitz S, Uhl L, Kaufman RM, Stowell CP et al (2016) Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score-matched study. Transfusion 56:2069–2077
Zuber J, Fakhouri F, Roumenina LT, Loirat C, Frémeaux-Bacchi V, French Study Group for aHUS/C3G (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657
Legendre CM, Licht C, Muus P et al (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181
Greenbaum LA, Fila M, Ardissino G et al (2016) Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 89:701–711
Author information
Authors and Affiliations
Contributions
GLT, AO and EG contributed to study conception and design; GLT, AO, EG prepare the manuscript draft; AO, NC, PS, CB, AA, FA, CB, MB, BDP, GG, BI, SP, LT, and EG selected and enrolled the patients; GLT, AO, EG analysed and interpreted data; FC, GDA, PR performed biochemical assays; EG makes critical revision of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The corresponding author states that there are no potential conflicts of interest to disclose.
Ethical approval
This research study has been performed according to the general principles of the Declaration of Helsinki (General Assembly, Helsinki, Finland, June 1964), on ethical principles for medical research involving human subjects.
Informed consent
Informed consent to use their medical information was obtained by all patients included in the study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Tiscia, G.L., Ostuni, A., Cascavilla, N. et al. Validation of PLASMIC score and follow-up data in a cohort of patients with suspected microangiopathies from Southern Italy. J Thromb Thrombolysis 46, 174–179 (2018). https://doi.org/10.1007/s11239-018-1674-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11239-018-1674-6