Abstract
To analyze the clinical characteristics of severe thrombocytopenia in patients with various connective tissue diseases (CTDs), one hundred thirty-one consecutive CTD patients with blood platelet count less than 20 × 109/L on admission, which was ascribed to the nature of diseases, during January 2011 to June 2015 in our department were enrolled and checked for their survival status in September 2015. The patients were categorized based on background diseases or therapeutic effects, and compared with clinical features, treatment strategies, and long-term outcomes among the groups. Cumulative survival rates were estimated using Kaplan-Meier analysis. Of the patients, 88.5% were female. The most frequently seen background diseases were primary Sjögren’s syndrome (pSS) (53.4%) and systemic lupus erythematosus (SLE) (40.5%). Age on admission for SLE patients (36.7 ± 14.1 years) was much younger than that for other patients (44.4 ± 15.4 years for pSS and 46 ± 16.1 years for other CTDs, p < 0.05). Ninety-six cases accompanied with various bleeding symptoms, which were more common in pSS patients than in SLE patients (80.0% vs. 64.2%, p < 0.05). Glucocorticoids and/or intravenous immunoglobulin were applied as initial therapy with an overall response rate of 36.6%. For patients failed to respond, immunosuppressive drugs were added and the other 22.8% benefited from the treatment. Compared to those ineffective to the aforementioned drugs, patients with therapeutic effects had significantly high immunoglobulin G levels. Twenty patients with refractory diseases accepted mesenchymal stem cell transplantation (MSCT) with a total effective rate of 65.0%. Eleven patients died after the follow-up for a mean time of 27.7 months, of which 7 were associated with hemorrhage. There was no difference in the survival rate among different background diseases. However, compared with those who did not gain remission, patients achieved partial or complete remission had better cumulative survival rates (p < 0.01). In conclusion, among various CTDs, severe thrombocytopenia often occurs in patients with SLE or pSS. Early response to the treatments, but not the background disease, is an important predictor of long-term prognosis. For patients with refractory thrombocytopenia, MSCT may provide an alternative therapeutic strategy.
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References
Fayyaz A, Igoe A, Kurien B et al (2015) Haematological manifestations of lupus. Lupus Sci Med 2:e000078
Sultan SM, Begum S, Isenberg DA (2003) Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Rheumatology 42:230–234
Mok CC, Lee KW, Ho CT, Lau CS, Wong RW (2000) A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population. Rheumatology 39:399–406
Ziakas PD, Giannouli S, Zintzaras E, Tzioufas AG, Voulgarelis M (2005) Lupus thrombocytopenia: clinical implications and prognostic significance. Ann Rheum Dis 64:1366–1369
Jiang B, Li T, Guo L, Shen H, Ye S, Chen S (2015) Efficacy and safety of rituximab in systemic lupus erythematosus and Sjogren syndrome patients with refractory thrombocytopenia: a retrospective study of 21 cases. J Clin Rheumatol 21:244–250
Sardesai VV, Sardesai VR, Agarwal TD (2015) Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab. Indian J Dermatol 60:106
Arnal C, Piette JC, Leone J et al (2002) Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases. J Rheumatol 29:75–83
Jung JH, Soh MS, Ahn YH, Um YJ, Jung JY, Suh CH, Kim HA (2016) Thrombocytopenia in systemic lupus erythematosus: clinical manifestations, treatment, and prognosis in 230 patients. Medicine 95:e2818
Tan EM, Cohen AS, Fries JF, Masi AT, Mcshane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725
Silman AJ (1988) The 1987 revised American Rheumatism Association criteria for rheumatoid arthritis. Br J Rheumatol 27:341–343
Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjögren's Syndrome (2002) Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61:554–558
Criteria for diagnosis of Behcet's disease (1990) International study group for Behcet’s disease. Lancet 335:1078–1080
Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347
Mosca M, Neri R, Bombardieri S (1999) Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol 17:615–620
Schuppan D, Afdhal NH (2008) Liver cirrhosis. Lancet 371:838–851
Miyakis S, Lockshin MD, Atsumi et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, Austin A, Bell A, Bloch DA, Corey PN, Decker JL, Esdaile J, Fries JF, Ginzler EM, Goldsmith CH, Hochberg MC, Jones JV, Riche NGHL, Liang MH, Lockshin MD, Muenz LR, Sackett DL, Schur PH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640
Seror R, Ravaud P, Mariette X et al (2011) EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 69:1103–1109
Koreth R, Weinert C, Weisdorf DJ, Key NS (2004) Measurement of bleeding severity: a critical review. Transfusion 44:605–617
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113:2386–2393
Klepfish A, Friedman J, Schechter Y, Schattner A (2001) Autoimmune neutropenia, thrombocytopenia and Coombs positivity in a patient with primary Sjogren’s syndrome. Rheumatology 40:948–949
Ramos-Casals M, Solans R, Rosas J, Camps MT, Gil A, del Pino-Montes J, Calvo-Alen J, Jiménez-Alonso J, Micó ML, Beltrán J, Belenguer R, Pallarés L, GEMESS Study Group (2008) Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine 87:210–219
Fernandez M, Calvo-Alen J, Bertoli AM et al (2007) Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women. J Clin Rheumatol 13:261–265
Jallouli M, Frigui M, Marzouk S, Snoussi M, Kechaou M, Kaddour N, Masmoudi H, Elloumi M, Bahloul Z (2012) Clinical implications and prognostic significance of thrombocytopenia in Tunisian patients with systemic lupus erythematosus. Lupus 21:682–687
Chugh S, Darvish-Kazem S, Lim W, Crowther MA, Ghanima W, Wang G, Heddle NM, Kelton JG, Arnold DM (2015) Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol 2:e75–e81
Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, Ding G, Gao R, Zhang C, Ding Y, Bromberg JS, Chen W, Sun L, Wang S (2012) Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood 120:3142–3151
Wang D, Huang S, Yuan X, Liang J, Xu R, Yao G, Feng X, Sun L (2017) The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Cell Mol Immunol 14:423–431
Feng X, Che N, Liu Y, Chen H, Wang D, Li X, Chen W, Ma X, Hua B, Gao X, Tsao BP, Sun L (2014) Restored immunosuppressive effect of mesenchymal stem cells on B cells after olfactory 1/early B cell factor-associated zinc-finger protein down-regulation in patients with systemic lupus erythematosus. Arthritis Rheumatol 66:3413–3423
Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, Hua B, Liu B, Lu L, Gilkeson GS, Silver RM, Chen W, Shi S, Sun L (2013) Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant 22:2267–2277
Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S (2010) Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62:2467–2475
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This work is financially supported by the National Natural Science Foundation of China (81771745), Jiangsu Provincial Medical Talent Program (ZDRCA2016059), and Jiangsu Provincial Special Program of Medical Science (BE2015602).
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Zhang, W., Wang, F., Wang, H. et al. Severe thrombocytopenia in connective tissue diseases: a single-center review of 131 cases. Clin Rheumatol 37, 3337–3344 (2018). https://doi.org/10.1007/s10067-018-4312-y
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DOI: https://doi.org/10.1007/s10067-018-4312-y