Effi cacy of splenectomy in primary immune thrombocytopenia

Introduction. Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. Splenectomy is one the most effective treatment methods for this disorder.

Aim — to evaluate the effi cacy and safety of a splenectomy in patients with primary immune thrombocytopenia.

Subjects and methods. 111 patients (31 males, 80 females) with primary immune thrombocytopenia who were hospitalized to perform laparoscopic splenectomy were included in a prospective study conducted at the National Research Center for Hematology from 2015 to 2019. Disease duration from onset to splenectomy was from 1 month to 51 years. Response to the splenectomy, complications, and correlation with immediate preoperative platelet count were analyzed.

Results. Complete response was achieved in 79 (71.2 %) cases, a partial response was achieved in 11 (9.9 %) cases, and in 21 (18.9 %) cases there was no response. Immediate preoperative platelet count was signifi cantly higher in patients with complete response in comparison with the group with no response, median (95% CI): 47 (35–58) vs 16 (9–20), p < 0.001.

Multivariate analysis (logistic regression) was performed. According to this regression, a risk factor for an unfavorable response was detected — males > 60 years of age, p = 0.05; RR (95% CI): 2.0 (0.9–7.1). A predictor of unfavorable response was identifi ed – immediate preoperative platelet count < 23 × 109/l (cutoff point determined in ROC-analysis); p = 0.001, RR (95% CI): 2.5 (1.1–8.6). The probability of complete response was lower with the number of treatment lines prior to splenectomy (weak inverse correlation: r S = −0.30; p = 0.01). The frequency of postoperative complications was 12.6 %. According to our follow-up data, a complete response was preserved in 66/79 (83.5 %) of patients, with a follow-up of 2.7 years.

Conclusion. Splenectomy is an effective and safe treatment method for ITP. Factors of unfavorable response were identifi ed: males > 60 years of age and immediate preoperative platelet count < 23 × 109/l. It is safe to perform splenectomy regardless of effectiveness of preoperative splenectomy treatment and platelet count.

1. Melikyan A.L., Egorova E.K., Pustovaya E.I., et al. Interim results of epidemiological study of idiopathic thrombocytopenic purpura in adults in the Russian Federation: Intermediate results. Gematologiya i Transfusiologiya. 2019; 64(4): 436–46. DOI: 10.35754/0234-5730-2019-64-4-436-446. (in Russian).

2. Moulis G., Palmaro A., Montastruc J.L., et al. Epidemiology of incident immune thrombocytopenia: A nationwide population-based study in France. Blood. 2014; 124(22): 3308–15. DOI: 10.1182/blood-2014-05-578336.

3. Schoonen W.M., Kucera G., Coalson J., et al. Epidemiology of immune thrombocytopenic purpura in the general practice research database. Br J Haematol. 2009; 145(2): 235–44. DOI: 10.1111/j.1365-2141.2009.07615.x.

4. Melikyan A.L., Pustovaya E.I., Tsvetaeva N.V., et al. National clinical recommendations for diagnosis and therapy of idiopathic thrombocytopenic purpura (primary immune thrombocytopenia) in adults (2016). Gematologiya i Trasfusiologia. 2017; 62(1, suppl. 1): 1–60. DOI: 10.18821/0234-5730-2017-62-1-S1-1-60. (in Russian).

5. Melikyan A.L., Pustovaya E.I., Egorova E.K., et al. Differential diagnosis of thrombocytopenes. Oncohematologiya. 2017; 12(1): 78–87. DOI: 10.17650/1818-8346-2017-12-1-78-87. (in Russian).

6. Fogarty P.F., Tarantino M.D., Brainsky A., et al. Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012; 28(1): 79–87. DOI: 10.1185/03007995.2011.644849.

7. Neunert C., Noroozi N., Norman G., et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: A systematic review. J Thromb Haemost. 2015; 13(3): 457–64. DOI: 10.1111/jth.12813.

8. Neunert C., Terrell D.R., Arnold D.M., et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019; 3(23): 3829–66. DOI: 10.1182/bloodadvances.2019000966.

9. Provan D., Arnold D.M., Bussel J.B., et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019; 3(22): 3780–817. DOI: 10.1182/bloodadvances.2019000812.

10. Brown T.M., Horblyuk R.V., Grotzinger K.M., et al. Patient-reported treatment burden of chronic immune thrombocytopenia therapies. BMC Blood Disord. 2012; 12: 2. DOI: 10.1186/1471-2326-12-2.

11. Chater C., Terriou L., Duhamel A., et al. Reemergence of splenectomy for ITP second-line treatment? Ann Surg. 2016; 264(5): 772–7. DOI: 10.1097/SLA.0000000000001912.

12. Vianelli N., Palandri F., Polverelli N., et al. Splenectomy as a curative treatment for immune thrombocytopenia: A retrospective analysis of 233 patients with a minimum follow up of 10 years. Haematologica. 2013; 98(6): 875–80. DOI: 10.3324/haematol.2012.075648.

13. Kuter D.J., Bussel J.B., Lyons R.M., et al. Effi cacy of romiplostim in patients with chronic immune thrombocytopenic purpura: A double-blind randomised controlled trial. Lancet. 2008; 371(9610): 395–403. DOI: 10.1016/S0140-6736(08)60203-2.

14. Bussel J.B., Provan D., Shamsi T., et al. Effect of eltrombopag on platelet countsand bleeding during treatment of chronic idiopathic thrombocytopenic purpura: A randomised, double-blind, placebo-controlled trial. Lancet. 2009; 373(9664):641–8. DOI: 10.1016/S0140-6736(09)60402-5.

15. Ojima H., Kato T., Araki K., et al. Factors predicting long-term responses to splenectomy in patients with idiopathic thrombocytopenic purpura. World J Surg. 2006; 30(4): 553–9. DOI: 10.1007/s00268-005-7964-0.

16. Katkhouda N., Grant S.W., Mavor E., et al. Predictors of response after laparoscopic splenectomy for immune thrombocytopenic purpura. Surg Endosc. 2001; 15(5): 484–8. DOI: 10.1007/s004640000355.

17. Hani M.N.B., Qasaimeh G.R., Bani-Hani K.E., et al. Laparoscopic splenectomy: Consensus and debatable points. South African J Surg. 2010; 48(3): 81–4. DOI: 10.7196/sajs.419.

18. Delaitre B., Maignien B. Splénectomie par voie coelioscopique. 1 observation (letter). Presse medicale. 1991: 20(44): 2263.

19. Kojouri K., Vesely S.K., Terrell D.R., et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: A systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004; 104(9): 2623–34. DOI: 10.1182/blood-2004-03-1168.

20. Dolan J.P., Sheppard B.C., DeLoughery T.G. Splenectomy for immune thrombocytopenic purpura: Surgery for the 21st century. Am J Hematol. 2008; 83(2): 93–6. DOI: 10.1002/ajh.21029.

21. Rijcken E., Mees S.T., Bisping G., et al. Laparoscopic splenectomy for medically refractory immune thrombocytopenia (ITP): A retrospective cohort study on longtime response predicting factors based on consensus criteria. Int J Surg. 2014; 12(12): 1428–33. DOI: 10.1016/j.ijsu.2014.10.012.

22. Keidar A., Feldman M., Szold A. Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count. Am J Hematol. 2005; 80(2): 95–100. DOI: 10.1002/ajh.20433.

23. Cai Y., Liu X., Peng B. A novel method for laparoscopic splenectomy in the setting of hypersplenism secondary to liver cirrhosis: Ten years’ experience. World J Surg. 2014; 38(11): 2934–9. DOI: 10.1007/s00268-014-2652-6.

24. Chen X., Peng B., Cai Y., et al. Laparoscopic splenectomy for patients with immune thrombocytopenia and very low platelet count: Is platelet transfusion necessary? J Surg Res. 2011; 170(2): e225–32. DOI: 10.1016/j.jss.2011.06.031.

25. Kaufman R.M., Djulbegovic B., Gernsheimer T., et al. Platelet transfusion: A clinical practice guideline from the AABB. Ann Intern Med. 2015; 162(3): 205–13. DOI: 10.7326/M14-1589.

26. Zaja F., Barcellini W., Cantoni S., et al. Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: Results of a retrospective, observational GIMEMA study. Am J Hematol. 2016; 91(5):E293–5. DOI: 10.1002/ajh.24341.

27. Provan D., Stasi R., Newland A.C., et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010; 115(2): 168–86. DOI: 10.1182/blood-2009-06-225565.

28. Neunert C., Lim W., Crowther M., et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011; 117(16): 4190–207. DOI: 10.1182/blood-2010-08-302984.

29. Thanarajasingam G., Vaidya R., Erie A., et al. Accessory splenectomy for refractory immune thrombocytopenic purpura. Am J Hematol. 2011; 86(6): 520–3. DOI: 10.1002/ajh.22011.

30. Wan X., Wang W., Liu J., et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014; 14: 135. DOI: 10.1186/1471-2288-14-135.

31. Boyle S., White R.H., Brunson A., et al. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood. 2013; 121(23): 4782–90. DOI: 10.1182/blood-2012-12-467068.

32. Thomsen R.W., Schoonen W.M., Farkas D.K., et al. Risk of venous thromboembolism in splenectomized patients compared with the general population and appendectomized patients: A 10-year nationwide cohort study. J Thromb Haemost. 2010; 8(6): 1413–6. DOI: 10.1111/j.1538-7836.2010.03849.x.

33. Ruggeri M., Tosetto A., Palandri F., et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014; 12(8): 1266–73. DOI: 10.1111/jth.12636.

34. Chaturvedi S., Arnold D.M., McCrae K.R. Splenectomy for immune thrombocytopenia: Down but not out. Blood. 2018; 131(11): 1172–82. DOI: 10.1182/blood-2017-09-742353.

35. Rørholt M., Ghanima W., Farkas D.K., et al. Risk of cardiovascular events and pulmonary hypertension following splenectomy — A Danish populationbased cohort study from 1996–2012. Haematologica. 2017; 102(8): 1333–41. DOI: 10.3324/haematol.2016.157008.

36. Rodeghiero F., Ruggeri M. Short- and long-term risks of splenectomy for benign haematological disorders: Should we revisit the indications? Br J Haematol. 2012; 158(1): 16–29. DOI: 10.1111/j.1365-2141.2012.09146.x.

37. Legrand A., Bignon A., Borel M., et al. Perioperative management of asplenic patients. Ann Fr Anesth Reanim. 2005; 24(7): 807–13. DOI: 10.1016/j.annfar.2005.05.002.

38. Thai L.H., Mahévas M., Roudot-Thoraval F., et al. Long-term complications of splenectomy in adult immune thrombocytopenia. Medicine. 2016; 95(48): e5098. DOI: 10.1097/MD.0000000000005098.

39. Yong M., Schoonen W.M., Li L., et al. Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database. Br J Haematol. 2010; 149(6): 855–64. DOI: 10.1111/j.1365-2141.2010.08176.x.

40. Suvajdzic N., Zivkovic R., Djunic I., et al. Health-related quality of life in adult patients with chronic immune thrombocytopenia in Serbia. Platelets. 2014; 25(6): 467–9. DOI: 10.3109/09537104.2013.831065.

41. Rodeghiero F. A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP. Br J Haematol. 2018; 181(2): 183–95. DOI: 10.1111/bjh.15090.