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Thrombotic microangiopathies


Authors: J. Novotný;  M. Penka
Authors‘ workplace: Oddělení klinické hematologie FN Brno, Jihlavská 20, 625 00 Brno
Published in: Transfuze Hematol. dnes,1, 2019, No. Online only 1, p. 1-19.
Category:

Overview

Thrombotic microangiopathies are a group of heterogeneous disorders characterized by disseminated microthrombosis in arterioles and capillaries resulting in consumption of platelets and microangiopathic haemolytic anaemia with potential end organ injury. The diagnosis may be complicated because of overlapping presentations of these disorders. Thrombotic thrombocytopenic purpura (TTP) may be diagnosed on the basis of severely decreased ADAMTS 13 activity (a disintegrin and metalloprotease with thrombospondin motif 13), which is reduced below 10% with possible detection of an IgG inhibitor. The inherited form of TTP (Upshaw- Schulman syndrome) involves mutations of the ADAMTS 13 gene with no inhibitor. Severe reduction of ADAMTS 13 is activity leads to an increased concentration of ultra-large von Willebrand factor multimers with potent affinity to platelet glycoprotein Ib (GPIb) resulting in platelet aggregation. Treatment of choice of acquired TTP includes therapeutic plasma exchange with immunomodulation using corticoids and/or rituximab. The inherited form may be treated by plasma infusion only. Haemolytic-uremic syndrome is induced by shiga toxin producing Escherichia Coli mainly in young children (typical haemolytic uremic syndrome). Shiga toxins are toxic to the endothelium and activate platelets. In such cases, there is serious impairment of renal functions often necessitating haemodialysis and even renal transplantation in some cases. The manifestation of typical haemolytic uremic syndrome is preceded by haemorrhagic diarrhoea. Therapy is mainly supportive. Atypical haemolytic uremic syndromes are induced by inherited disorders of the alternative pathway of complement activation due to mutations in genes of regulatory complement proteins. Some patients have factor H inhibitors. The main therapeutic approach in these forms is the administration of the complement factor C5 inhibitor eculizumab. Secondary forms of thrombotic microangiopathies are mainly seen in association with disseminated malignancies, pregnancy, auto-aggressive disorders, cobalamin C defect (cblC), infections, following solid organ or haematopoietic stem cells transplantation of or solid organs, malignant hypertension and may also be drug induced. The main differential diagnosis involves exclusion of disseminated intravascular coagulation associated with prolongation of global coagulation tests- aPTT and PT.

Keywords:

HELLP syndrome – thrombotic microangiopathies – thrombotic thrombocytopenic purpura – haemolytic uremic syndrome – therapeutic plasma exchange – eculizumab


Sources

1. Saha M, Mc Daniel JK, Zheng XL. TTP: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Hemost 2017;15:1889–1900.

2. Caggl M, Aigner C, Sunder-Plassman G, Schmit A. Thrombotische mikroangiopathien. Med Klin Intensivmed Notfmed 2016;111:434–439.

3. Salaj P. Thrombocytopenické purpury. Vnitř Lék 2005;91:854–860.

4. Kremer Hovinga JA, Coppo P, Lämmle B, et al. TTP. Nat Rev/Dis Primers 2017;3:1–17.

5. Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undesribed disease. Proc N Y Pathol Soc 1924;24:21–24.

6. Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of TTP and other TMAs. Br J Haematol 2012;158:323–335.

7. Muia J, Gao W, Haberichter SL, et al. An optimized fluorogenic ADAMTS 13 assay with increased sensitivity for the incestigation of patients with TTP. Thromb Haemost 2013;11:1511–1518.

8. Jin M, Cataland S, Bissel M, Wu HM. A rapid test for the diagnosis of TTP using SELDI-TOF-mass spectrometry. J Thromb Haemost 2006;4:333–338.

9. Mackie I, Langley K, Chitolie A, et al. Discrepancies between ADAMTS 13 activity assays in patients with TMAs. Thromb Hameost 2013;109:488–496.

10. Peyvandi F, Palla R, Lotta A, et al. ADAMTS 13 assays in TTP. Thromb Haemost 2010;8:361–340.

11. Fuchs TA, Kremer Hovinga JA, Schatzberg D, et al. Circulating DNA and myeloperoxidase indicate disease activity in patients with TMAs. Blood 2012;120:1157–1164.

12. Amin Asnafi A, Jalati MT, Pezeshki SMS, et al. The association between HLAs nad ITP, TTP and HIT. J Pediat Hematol Oncol 2019;41:81–86.

13. Coppo P. Management of TTP. Transfus Clin Biol 2017;24:148–158.

14. Čermáková Z, Blahutová Š, Kořístka M, et al. První zkušenosti jednoho centra s použitím přípravku Octaplas v léčbě pacientky s vrozenou formou TTP. Transfuze Hematol dnes 2012;18:162–164.

15. Stubbs MJ, Low R, McGuckin S, et al. Comparison of rituximab originator (MabThera) to biosimilar (Truxima) in patients with immune-mediated TTP. Br J Haematol 2019;185:912–917.

16. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacuzimab for acquired TTP. N Engl J Med 2016;374:511–522.

17. Coppo P. Treatment of autoimmune TTP in the more severe forms. Transfus Apher Sci 2017;56:52–56.

18. Al-Samkari H, Grace RF, Connors JM. Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired TTP. J Thromb Thrombolys 2018;46:81–83.

19. Vigna E, Petrungaro A, Perri A, et al. Efficacy of eculizumab in severe ADAMTS 13 deficient TTP refractory to standard therapy. Transfus Apher Sci 2018;57:247–249.

20. Dane K, Chaturvedi G. Beyond plasma exchange: novel therapies for TTP. Hematol 2018;1:539–547.

21. Chen J, Reheman A, Gushiken FC, et al. N-acetylcysteine reduces the size and activity of VWF in human plasma and mice. J Clin Invest 2011;121:593–603.

22. Mancini I, Ferrari B, Vaisecchi C, et al. ADAMTS 13-specific circulating complexes as potential predictors of relapse in patients with acquired TTP. Eur J Inter Med 217;39:79–83.

23. Karpman D, Loos S, Tati R, Arvidsson I. HUS. J Inter Med 2017;281:123–148.

24. Desch K, Motto D. Is there a shared pathophysiology for TTP and HUS? J Am Soc Nephrol 2007;18:2457–2460.

25. Laurence J, Haller H, Mannuccio Mannucci P, et al. aHUS: Essential aspects of an accurate diagnosis. Clin Adv Hematol Oncol 2016;14(S11):2–15.

26. Dixon BP, Gruppo RA. Atypical HUS. Pediat Clin N Am 2018;65:509–525.

27. He X, Ardissino G, Patfield S, Cheng LW, Silva CJ, Brigotti M. An improved method for the sensitive detection of shiga toxin 2 in human serum. Toxins (Basel) 2018; Jan 31;10(2); doi: 10.3390/toxins 10020059.

28. Fakhouri F, Loirat Ch. Anticomplement treatment in atypical and typical HUS. Semin Hematol 2018;55:150–158.

29. Dixon BP, Gruppo RA. Atypical HUS. Pediat Cli N Am 2018;65:509–525.

30. Sahutoglu T, Basturk T, Sakaci T, et al. Can eculizumab be discontinued in aHUS? Case report and review of the literature. Medicine 2016;95:31–37.

31.Kerboua KE, Haiba F, Batouche D. C3:CH50 ratio as a proposed marker for eculizumab monitoring in aHUS. J Immunoasay Immunochem 2017;38:178–189.

32. Wong EKS, Kavanagh D. Diseases of complement dysregulation – an overwiew. Semin Immunopathol 2018;40:49–64.

33. Fonseca JE, Mendez F, Catano C, Arias F. Dexamethasone treatment dose not improve the outcome of women with HELLP sy.: a double-blind, placebo controlled, randomized clinical trial. Am J Obstet Gynecol 2005;193:1591–1598.

34. Gumulec J, Šimetka O, Procházka M, et al. Diferenciální diagnostika trombocytopenie v graviditě. Vnitř Lék 2010;56(S1):91–97.

35. Wallace K, Harris S, Adison A, Bean C. HELLP syndrome: Pathophysiology and current therapy. Curr Pharmaceut Biotechnol 2018;19:816–826.

36. Thomas MR, Robinson S, Scully M. How we manage TMAs in pregnancy. Br J Haematol 2016;173:821–830.

37. Wang XD, Zhang S, Li L, et al. Ticagrelor-induced TTP. A case report and review of the literature. Medicine 2018;97:26–31.

38. Krishnappa V, Gupta M, Shah H, et al. The use of eculizumab in gemcitabine induced TMA. BMC Nephrol 2018;19:26–31.

39. Demirsoy ET, Mehtap O, Atesoglu EB, et al. Dasatinib-induced immune mediated TTP. Transfus Apher Sci 2018;57:222–224.

40. Akkeson A, Zetterberg E, Klintman J. At the cross section of TMA and aHUS: A narrattive review of differential diagnosis and a problematization of nomenclature. Therap Apher Dialys 2017;21:304–319.

41. Beck BB, van Spronsen FJ, Diepstra A, et al. Renal TMA in patients with cblC defect: review of an under-recognized entity. Pediat Nephrol 2017;32:733–741.

42. Vaisbich H, Braga A, Gabrielle M, et al. TMA caused by methionine synthase deficiency: diagnosis and teratment pifalls. Pediat Nephrol 2017;32:1089–1092.

43. Tran PN, Tran MH. Cobalamine deficiency presenting with TMA features. A systematic review. Transfus Apher Sci 2018;57:102–106.

44. Massias C, Vasu S, Cataland SR. None of above: TMA beyond TTP and HUS. Blood 2017;129:2857–2863.

45. Villafuerte LHM, Pena PJM, Inigo GP, et al. Severe renal failure and TMA induced by malignant hypertension successfuly treated with spironolactone. Ann Cardiol Angiol 2018;67:208–214.

46. Haram K, Mortensen JH, Mastrolia SA, Erez O. DIC in HELLP syndrome: how much we really know? Maternal Fetal Neonat Med 2017;30:779–788.

47. Zhu J, Chaki M, Lu D, et al. Loss of DGKE in mice causes endothelial distress and impairs glomerulal Cox-2 and PGE2 production. Am J Physiol Renal Physiol 2016;310:F895–F908.

48. Ravindran A, Go RS, Fervenza FC, Sethi S. TMA associated with monoclonal gammopathy. KIidney Int 2017;91:691–698.

49. Rathnayaka N, Ranathunga PAN, Kularelne SA. TMA, HUS and TTP following Hump-nosed Pit Viper envenoming in Srí Lanka. Wilderness Environ Med 2019;30:66–78.

50. Román E, Mendizábal S, Jarque I, et al. Secondary TMAs and eculizumab: a reasonable therapeutic option. Nefrologia 2017;37:478–491.

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