Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation

Abstract

Objective This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. Methods Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. Results Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/μL (median peak platelet count, 1403 K/μL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. Conclusions After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post–total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.

Portal Vein Thrombosis May Be More Strongly Associated With Islet Infusion Than Extreme Thrombocytosis After Total Pancreatectomy With Islet Autotransplantation

“…[34][35][36][37][38] In the TPIAT literature, one small study showed a universal increase in thrombopoietin a few days after surgery, followed by a marked platelet count rise. 16 The data presented here in association with the IBMIR and thrombopoietin production physiology described above suggest that the observations of nearly universal post-TPIAT thrombocytosis likely occurs through both increased proinflammatory platelet production and postsplenectomy mechanisms. 16 Previous work has examined the utility of drugs like heparin, 21 lowmolecular-weight dextran sulfate, 22,39 and melagatran 33 in TPIAT but primarily evaluated whether they reduce IBMIR and thus improve islet survival.…”

“…Hematologic outcomes including TE and thrombocytosis and management strategies for each have only recently been examined, despite this procedure's long history. 13,15,16,26 In this retrospective review of a large contemporary TPIAT cohort containing both pediatric and adult patients, we examined ExT and TE to determine their rates, potential links to portal vein measurements, and the success of current mitigation strategies. Pediatric and adult patients differed notably in terms of platelet trends, TE, and pharmacologic strategies to manage thrombocytosis.…”

“…[9][10][11][12] However, only recently have researchers explored hematologic effects of TPIAT, including risks for thrombosis and extreme thrombocytosis (ExT, platelets >1000 × 10 9 /L), some unique to this procedure. [13][14][15][16] Portal vein thrombosis (PVT) risk has been Original Clinical Science-General Background. Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein.…”

“…9-12 However, only recently have researchers explored hematologic effects of TPIAT, including risks for thrombosis and extreme thrombocytosis (ExT, platelets >1000 × 10 9 /L), some unique to this procedure. 13-16 Portal vein thrombosis (PVT) risk has been found to be associated with increased portal pressures (PPs) and high tissue volume (TV), but its relationship with thrombocytosis and antiplatelet therapy is unknown. 17…”

Hydroxyurea Pharmacokinetics in Pediatric Patients After Total Pancreatectomy With Islet Autotransplantation

“…Total pancreatectomy with islet autotransplantation is a complex but potentially curative surgery for debilitating chronic or acute recurrent pancreatitis, with a few unique side effects. Extreme thrombocytosis frequently occurs postoperatively and is hypothesized to be because of in part a combination of splenectomy, inflammatory response to infusion of islets into the portal vein, and increased thrombopoietin levels 6,7,32–34 . In some pediatric centers that perform this surgery, including ours, hydroxyurea is started for platelet cytoreduction and aspirin for antiplatelet therapy in an effort to reduce postoperative portal vein thrombosis risk.…”