Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical treatment for patients with debilitating chronic pancreatitis or acute recurrent pancreatitis. The surgery consists of removal of the pancreas, splenectomy, and a choledochojejunostomy or hepaticojejunostomy (roux-en-Y jejunal limb sutured to the bile duct to allow bile to drain into the intestine). In order to mitigate diabetes, the pancreatic islets are enzymatically and mechanically removed from the pancreas and autotransplanted into the liver via portal vein infusion during the procedure.
An enigmatic, but consistent complication of this procedure is a significant and sustained thrombocytosis, higher than observed after splenectomy alone that is sustained for a long period of time. Platelet counts typically rise to >1,000,000 within 1 week of the procedure and remain elevated at >1,000,000 for up to a year or longer. A review of over 100 pediatric patients undergoing TPIAT at the University of Minnesota (the pioneers of the procedure), as well as our own experience at CCHMC, demonstrate that this degree of thrombocytosis is typical. The etiology of the thrombocytosis is poorly understood. We have some data generated locally to suggest that thrombopoietin (TPO) derangement of hepatocyte-derived TPO secretion is possible, but the data is not definitive.
As the etiology of thrombocytosis is unclear, the potential thrombogenicity is also unknown. Of particular concern is the potential for portal vein thrombosis given the manipulation of the portal vein. To date, no natural history studies of patients undergoing TPIAT with untreated thrombocytosis have been done. Therefore, we have elected to follow a therapeutic plan for the thrombocytosis developed at the University of Minnesota using a combination of Hydroxyurea and aspirin. Note that while using this approach in over 100 pediatric patients, the team at the University of Minnesota states (personal communication) that they have had excellent outcomes overall and no significant complications related to therapy.
Hydroxyurea and ASA Management
Pre-operative:
Obtain the following pre-operative labs: ferritin, soluble transferrin receptor, serum iron, TIBC, RBC folate, Vitamin B12, methylmalonic acid, homocysteine risk factor assay, CBC and reticulocyte count, TPO level
Intra-operative:
Bolus 35 units/kg heparin just prior to initiation of islet infusion. Islet prep will also contain total of 35 U/kg heparin.
Initiate a prophylactic heparin drip (10 units/kg/hr) starting intraoperatively, when the intraoperative ACT is <150 seconds AND at the discretion of the surgical team
Post-operative medications and lab monitoring:
Heparin drip (prophylactic) should be continued for 7 days post-operatively
On POD 7, start prophylactic Lovenox SQ for duration of hospitalization. Dose frequency is based on patient weight and pharmacy recommendation.
Start aspirin 2 mg/kg daily (max dose 162 mg – round to nearest 40.5 mg increment) on post-operative day 2
Consider using non-enteric coated aspirin. Aspirin solution given via the J-port of the GJ tube is often used in the immediate post-operative period
Obtain an Aspirin Resistance Test after 2-3 doses of aspirin to ensure there is no aspirin resistance. (Lab only available Monday – Friday, 8AM – 4PM)
If aspirin resistance test is high (indicating inadequate platelet suppression), increase aspirin to 3-4 mg/kg daily (round to nearest 40.5 mg increment) and repeat the test in 2-3 days.
Aspirin should be continued until the patient is off Hydroxyurea for 4 weeks without a significant rise in platelet count
Following discontinuation of aspirin, CBC and reticulocyte count are monitored monthly for 2 months. Re-initiation of anti-platelet therapy and/or hydroxyurea will be triggered by a significant rise in platelet count.
Start Hydroxyurea 25 mg/kg/day daily by post-operative day 5
Adjust Hydroxyruea dose based on platelet count:
Platelet count >750K for 2 weeks: increase dose by ~5 mg/kg to a max of 30 mg/kg. NOTE: the maximum Hydroxyurea dose is typically 2000 mg, but doses up to 3000 mg have been used in select patients with appropriate CBC monitoring
Platelet count 500-750K: maintain the current dose
Platelet count <500K: wean dose by ~5-10 mg/kg
If Hydroxyurea is stopped, monitor platelets biweekly for another 1-2 months. Hydroxyurea should be restarted at the previous dose if platelet rise to >750K for 2-3 weeks.
NOTE: for any of the following, HOLD HYDROXYUREA and restart at a dose 5 – 10 mg/kg less once the count has recovered
ANC < 1500 x 109/L
Absolute reticulocyte count <80 x 109/L, if hemoglobin is <9.0g/dL
Hemoglobin <5g/dL or >20% below baseline, regardless of the ARC
Post-operative labs:
Monitor for potential liver dysfunction by checking PT/INR and aPTT every 8-12 hours (based on clinical acuity)
Monitor anti-thrombin daily and replete to maintain activity >70% (see separate Post TPIAT anti-thrombin guidelines for details regarding dosing)
Monitor CBC with diff, reticulated platelet count and reticulocyte count daily during first week post-op, then repeat CBC with reticulocyte count (and also order reticulated platelet count if in the CCHMC system) weekly to every other week after post-operative day 7. May eventually be transitioned to every 2 weeks CBC with diff with reticulocyte count as outpatient.