Blood Res.  2018 Jun;53(2):130-137. 10.5045/br.2018.53.2.130.

Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia

• Yap YY
• Sathar J
• Law KB
• Zulkurnain PAB
• Edmund SC
• Chang KM
• Baker R

• KMID: 2451031
• DOI: http://doi.org/10.5045/br.2018.53.2.130

Abstract

BACKGROUND
Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia.
METHODS
This was a retrospective epidemiological study involving all cases of TMA from 2012-2016.
RESULTS
We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methylprednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclophosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment.
CONCLUSION
This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.

Keyword

Thrombotic microangiopathy; TTP; ADAMTS13 activity; Overall survival; Secondary TMA

MeSH Terms

Asian Continental Ancestry Group
Atypical Hemolytic Uremic Syndrome
Azathioprine
Bortezomib
Cyclophosphamide
Cyclosporine
Epidemiologic Studies
Female
Humans
Immunoglobulins
Lupus Erythematosus, Systemic
Malaysia*
Methylprednisolone
Mortality
Plasma Exchange
Pregnancy
Purpura, Thrombotic Thrombocytopenic
Retrospective Studies
Rituximab
Tacrolimus
Thrombospondins
Thrombotic Microangiopathies*
Vincristine
Azathioprine
Bortezomib
Cyclophosphamide
Cyclosporine
Immunoglobulins
Methylprednisolone
Rituximab
Tacrolimus
Thrombospondins
Vincristine

Figure

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  Fig. 1 Flow chart for the methods.

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  Fig. 2 Overall survival according to the types of TMA. Overall survival according to ADAMTS-13 activity for (A) cut-off=5% and (B) cut-off=10%.

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  Fig. 3 Overall survival according to secondary causes of TMA.

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  Fig. 4 Overall survival according to secondary causes of TMA. Overall survival according to ADAMTS-13 activity for (A) cut-off=5% and (B) cut-off=10%.

Reference

1. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014; 164:759–766. PMID: 24387053.

2. Jokiranta TS. HUS and atypical HUS. Blood. 2017; 129:2847–2856. PMID: 28416508.

3. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015; 125:3860–3867. PMID: 25784681.

4. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017; 129:2836–2846. PMID: 28416507.

5. Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017; 129:2857–2863. PMID: 28416509.

6. Bendapudi PK, Makar RS. An algorithmic approach to the diagnosis and management of the thrombotic microangiopathies. Am J Clin Pathol. 2016; 145:152–154. PMID: 26864515.

7. Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006; 108:1267–1279. PMID: 16621965.

8. Sadler JE. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2015; 2015:631–636. PMID: 26637781.

9. Alwan F, Vendramin C, Vanhoorelbeke K, et al. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2017; 130:466–471. PMID: 28576877.

10. Green D. Predicting mortality in thrombotic thrombocytopenic purpura. Waltham, MA: NEJM Journal Watch;2017. Accessed July 5, 2017. at http://www.jwatch.org/na44328/2017/06/09/predicting-mortality-thrombotic-thrombocytopenic-purpura.

11. Bendapudi PK, Li A, Hamdan A, et al. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. Br J Haematol. 2015; 171:836–844. PMID: 26314936.

12. Bendapudi PK, Li A, Hamdan A, et al. Derivation and prospective validation of a predictive score for the rapid diagnosis of thrombotic thrombocytopenic purpura: the plasmic score. Blood (ASH Annual Meeting Abstracts). 2014; 124(Suppl):abst 231.

13. Jodele S, Laskin BL, Dandoy CE, et al. A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015; 29:191–204. PMID: 25483393.

14. Matevosyan K, Sarode R. Thrombosis, microangiopathies, and inflammation. Semin Thromb Hemost. 2015; 41:556–562. PMID: 26276936.

15. Fuchs TA, Kremer Hovinga JA, Schatzberg D, Wagner DD, Lämmle B. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood. 2012; 120:1157–1164. PMID: 22611154.

16. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016; 31:15–39. PMID: 25859752.

17. Coppo P. French Reference Center for Thrombotic Microangiopathies. Treatment of autoimmune thrombotic thrombocytopenic purpura in the more severe forms. Transfus Apher Sci. 2017; 56:52–56. PMID: 28110841.

18. Scully M, McDonald V, Cavenagh J, et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011; 118:1746–1753. PMID: 21636861.

19. Froissart A, Buffet M, Veyradier A, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012; 40:104–111. PMID: 21926591.

20. Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2016; 127:3092–3094. PMID: 27060171.

21. Patriquin CJ, Thomas MR, Dutt T, et al. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haematol. 2016; 173:779–785. PMID: 27009919.

22. Lapponi MJ, Carestia A, Landoni VI, et al. Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs. J Pharmacol Exp Ther. 2013; 345:430–437. PMID: 23536315.