Selective Splenic Artery Embolization for the Treatment of Thrombocytopenia and Hypersplenism in Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Iori Anna Paola , Brown Karen , Araten David J. , Scalzulli Emilia , Torelli Giovanni Fernando , De Propris Maria Stefania , Girmenia Corrado , Salvatori Filippo Maria , Zelig Orly , Foa Robin , Luzzatto Lucio 
Published: October 2019

Abstract
Abstract 4408
PNH is a hemolytic disorder resulting from dysregulation of complement on the rbc, and is associated with immune mediated marrow failure and marked hypercoagulability. Thrombosis can be prevented with anticoagulation or the complement inhibitor eculizumab, and it often involves the hepatic, portal, and splenic veins. This can result in an increase in portal pressure and complications that we term the “Thrombosis-Splenomegaly-Thrombocytopenia” syndrome (TST). TST is frequently associated with abdominal pain, and thrombocytopenia may be simultaneously exacerbated by marrow failure. Particularly, thrombocytopenia can complicate efforts at anticoagulation, leaving the patient exposed to the risk of further events. In some patients thromboses can reversed with tPA, but others will not be candidates because they have presented late after their thromboses. Ablating splenic function would be desirable: however, with a high risk of perioperative thrombosis, surgical splenectomy may be hazardous, particularly in patients who have already had thrombosis, and will confer a risk of sepsis. Here we report on 4 patients with PNH and late-presenting TST. We referred these 4 patients for selective splenic artery embolization (SSAE), which involves cannulating branches of the splenic artery– beyond the hilum– and introducing gelfoam and microcoils. We planned a multi-session stepwise approach: we started with the inferior branches of the splenic artery, to decrease the risk of pleural effusions. We planned to infarct no more than 1/3 of the spleen at any one time and to allow weeks to months for recovery. We routinely administered vaccinations and discontinued anticoagulation temporarily, and patients were given prophylactic antibiotics, fluids, analgesics, and antipyretics, and they were observed in the hospital with a back-up surgical team. Prior to the procedure, the median platelet count was 17 and the median spleen size was 22 cm. Patients 1–4 were treated with 3,2,1, and 3 procedures respectively, which resulted in a significant reduction in spleen volume in all 4 patients. The post procedure platelet counts were respectively 123, 12, 44, and 90, which represented a significant increase for all patients except patient 2, who remained thrombocytopenic; since there was evidence of bone marrow failure, she underwent a successful unrelated SCT. Patients 1,2, and 4 all had had abdominal pain before the procedure, which very significantly improved after recovery from the procedure, which we attribute to decreased venous return from the spleen into the portal circulation. Patients 1–3 were treated before eculizumab was available and patient 1, 3, and 4 are now on it. Patient 4 is a special case in that she had been on eculizumab for several months prior to the SSAE, but had had only a partial reduction in the red cell transfusion requirement; C3d deposition on rbcs was documented by flow cytometry, and it was thought that extravascular hemolysis was limiting her response to eculizumab, as has been described. Of note, her hemoglobin began to rise after the embolization procedure, concurrent with the increase in the platelet count, and a significant further reduction in the red cell transfusion requirement, suggesting that partially reducing splenic function markedly reduced C3-mediated extravascular hemolysis. Of the 9 procedures performed on these 4 patients, only one was complicated by a clinically significant left sided pleural effusion, which was drained by thorascope. All patients are doing well between 3.5 and 11 years after their procedures. We conclude that SSAE, when performed by an experienced interventional radiologist, is relatively safe in patients with PNH and TST, it produces sustained correction of hypersplenism without the risk associated with surgery or the asplenic state, and can be of benefit to patients on eculizumab who have hypersplenism.
Pt Age at diagnosis Lowest plt count pre-SSAE Spleen size (cm) pre-SSAE Abdominal pain pre-SSAE Bone marrow Plt count post SSAE Spleen size post SSAE Abdominal pain after recovery from SSAE Complications of SSAE Follow up (yrs) 1 30 42 21 + Hypercellular Megakaryocyte aggregates 123 12 No Abd pain and fever 10 2 18 19 19 + Hypocellular Megas reduced 12 12 No Pain, pleural effusion SCT 3 27 14 36 – Erythroid hyperplasia Megas adequate 44 NA No Abd pain 11 4 26 <10 22 + Normocellular Megas adequate 90 12 No None 3.5

Disclosures:
No relevant conflicts of interest to declare.