Figura 1. Baseline angiography of splenic artery. The target distal branches can be seen here.

Figura 2. Distal embolization of splenic artery. Selective angiography from microcatheter after embo...

Figura 3. Chart of platelet count across time. During drug treatment: 25 000 platelets/mm3 (red arro...

INTRODUCION

Immune thrombocytopenic purpura (ITP) is a condition characterized by isolated thrombocytopenia of autoimmune origin. Its clinical signs can be asymptomatic, mild mucocutaneous hemorrhage or severe bleeding. Corticosteroids are the first-line therapy to treat ITP. As a second-line therapy other drugs like rituximab or thrombopoietin receptor agonists (TPO-RAs) have been proposed. Splenectomy is still considered a second-line therapy to treat corticoid-resistant ITP in adults since its response rate is around 60% to 80%. However, despite its low mortality rate, there is a tendency to avoid splenectomy due to its complications (infections, postoperative bleeding). Partial splenic embolization (PSE) has been used as an alternative to splenectomy since it is a minimally invasive procedure that does not require general anesthesia or laparotomy. Togasaki E. et al. described a case series where PSE was safe and effective.

This is the case report of a woman diagnosed with persistent ITP who remained unresponsive to multiple drug therapies. Since her platelet count was low, and risk of bleeding was high, a PSE was performed as a treatment prior to splenectomy to optimize platelet levels, reduce the need for transfusion support, and the risk of postoperative bleeding.

CASE REPORT

This is the case of a 19-year-old woman with a past medical history of treated tuberculosis. She remained on ongoing monitoring by the hematology unit following asymptomatic ITP after treatment with corticoids, gammaglobulines, romiplostim, rituximab, mycophenolate, vincristine, and cyclophosphamide. Since she remained unresponsive to these drugs, splenectomy was decided. The patient had been vaccinated against Streptococcus pneumoniae, Haemophylus influenzae, and meningococcus bacteria. Given the patient’s low platelet count and risk of postoperative bleeding partial splenic embolization was performed to improve platelet levels prior to surgery. The percutaneous procedure was performed 7 days earlier.

Embolization technique

Local anesthesia and sedation were administered. Femoral arterial access was attempted using Seldinger technique. A 6-Fr introducer sheath (Terumo Corporation, Tokyo, Japan) was inserted. A Simmons Sidewinder 2 catheter (Terumo Medical Corporation, Tokyo, Japan) was advanced through the introducer sheath. A selective arteriography of the celiac trunk splenic artery was performed to identify the target branches (figure 1). Afterwards a 2.7-Fr Maestro® microcatheter (Merit) was advanced until it reached the most distal and inferior portion (super-selective) of the splenic artery. Embolization started with polyvinyl alcohol (PVA) Contour® particles (Boston Scientific, Marlborough, Massachusetts, United States) sized 500 microns to 700 microns until achieving a lack of distal splenic flow (figure 2). After the procedure, 1 unit of platelets was transfused before removing the arterial introducer sheath followed by 20 min manual compression to achieve local hemostasis at the puncture site.

Evolution

No vascular complications were reported. Postoperative analgesia with opioids was administered for 48 hours. No signs of hypotension or fever were reported. The patient was treated with ceftriaxone for 48 hours. Afterwards, the patient was transferred to the operating room 7 days later with a platelet count of 160 000 platelets/mm3. Postoperative bleeding was minimum. At hospital discharge, the patient’s platelet count was 400 000 platelets/mm3 (figure 3).

Discussion

Immune thrombocytopenic purpura (ITP) is a syndrome characterized by multiple causal mechanisms that occur in different genetic settings, which determine the heterogeneous response to the treatments available. Thrombocytopenia is mediated by platelet destruction due to antibodies against platelet anti-glycoprotein , and CD T-cell-induced cytotoxicity (1).

Clinical signs of ITP can be asymptomatic or persistent mucocutaneous hemorrhage. Internal bleeding and hemarthrosis are rare (2).

Primary ITP presents with thrombocytopenia (platelet count < 100 000 platelets/mm3) for the lack of an underlying systemic disease and is associated with a normal megakaryocyte count in the bone marrow. On the other hand, secondary ITP presents with thrombocytopenia (platelet count < 100 000 platelets/mm3) and is associated with a recognizable condition (1).

The incidence rate of ITP is between 3.3 and 10 cases/100 000 inhabitants/year in adults (3).

Therapeutic target is to keep platelet count > 30 000 platelets/mm3. Although numerous guidelines have been published with different expert opinions, there is still no consensus on the most adequate management of this condition (1).

In our country, clinical practice guidelines suggest the use of corticosteroids as first-line therapy plus gammaglobulines given the imminent risk of severe bleeding. The total response rate with steroids is between 50% and 80%, and it is estimated that 40% of the patients do not experience any relapses (3).

As second-line therapies, thrombopoietin receptor antagonists, romiplostim, and eltrombopag have been suggested. They have an overall response rate of 79% to 95% while the total response rate of monoclonal antibodies like rituximab is 65% (3-4-5).

Other third-line therapeutic options are highly chemotherapeutic immunosuppressant drugs with response rates of up to 50%. However, individual responses do not usually exceed 30%, and the appearance of adverse events complicates its prolonged use (3-6).

Splenectomy is a second-line therapy to treat ITP that remains unresponsive to drug therapy (7). Its total response rate is between 65% and 80% (8) with a perioperative mortality rate of 0.2% (9).

PSE is a minimally invasive procedure that has been recently implemented as an alternative to splenectomy in patients with steroid-resistant ITP (10). It does not require general anesthesia or laparotomy, and reports have not described the appearance of serious complications. Emi Togasaki et al. retrospectively studied the efficacy profile and long-term results obtained in 91 patients with corticoid-resistant ITP treated with PSE. The total response rate (TRR, platelets > 100 × 109/L) was 51 % (n = 46) while the overall response rate (ORR, platelets > 30 × 109/L) was 84% (n = 76). One year after the PSE, 70% of the patients maintained their platelet counts above the therapeutic target No PSE-related deaths were reported, which is indicative that the procedure was both safe and effective (10).

The most common complication is the so-called post-embolization syndrome due to inflammatory response to tissue necrosis. Its appearance has been reported in up to 30% of the patients. It is self-limiting and usually gone within a week. Treatment is basically symptomatic. Patients treated with partial splenic embolization should be vaccinated against Streptococcus pneumoniae, Haemophylus influenzae, and meningococcus bacteria (11).

CONCLUSION

Case reports and observational trials suggest that partial splenic embolization is a safe and effective procedure with a low rate of complications. In our case, the therapeutic strategy used increased platelet count and reduced procedural risk during splenectomy.

1. Trombocitopenia inmune. Guía de diagnóstico y tratamiento. Sociedad Argentina de Pediatría Subcomisiones, Comités y Grupos de Trabajo. Arch Argent Pediatr 2019;117 Supl 6:S243-S254.

2. British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003 Feb;120(4):574-96. doi: 10.1046/j.1365-2141.2003.04131.x. PMID: 12588344.

3. Hemostasia y Trombosis. Trombocitopenia immune. Sociedad Argentina de Hematología Guías de Diagnóstico y Tratamiento. 2021. Pag 225-243. http://www.sah.org.ar/docs/guias/2021/Hemostasia-y-trombosis-Guia-2021-Libro.pdf.

4. Tsukamoto S, Nakaseko C, Takeuchi M, et al. (2013) Safety and efficacy of romiplostim in patients with eltrombopag-resistant or - intolerant immune thrombocytopenia. Br J Haematol 163(2):286–289. https://doi.org/10.1111/bjh.12483.

5. Ghanima W, Khelif A, Waage A, et al.; group Rs. (2015) Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 385(9978):1653–61. https://doi. org/10.1016/S0140-6736(14)61495-1.

6. Análisis de 200 casos clínicos de púrpura trombocitopénica idiopática. Lilia Adela et al. García–Stivalet LA et al. Aspectos clínicos de la púrpura trombocitopénica. Rev Med Inst Mex Seguro Soc 2014;52(3):322-5.

7. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, Hematology ASo (2011) The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117(16):4190-207. https://doi.org/10. 1182/blood-2010-08-302984.

8. Katkhouda N, Hurwitz MB, Rivera RT, et al. (1998) Laparoscopic splenectomy: outcome and efficacy in 103 consecutive patients. Ann Surg 228(4):568-78. https://doi.org/10.1097/00000658-199810000-00013.

9. Kojouri K, Vesely SK, Terrell DR, George JN (2004) 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 104(9):2623-34. https://doi.org/10.1182/blood-2004-03-1168.

10. Togasaki E, Shimizu N, Nagao Y, et al. Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia. Ann Hematol 97, 655-62 (2018). https://doi.org/10.1007/s00277-018-3232-x.

11. Partial esplenic embolization in thrombocitopenic idiopatic purpura. Description of procedure. MA Valeroa et al. Hernándeza a Hospital Clínico Universitario San Cecilio. Complejo Hospitalario de Granada. Granada. España. Intervencionismo. 2016;16(1):35-420.

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