PPI-INDUCED BICYTOPENIA: MATTER OF CONCERN by RxVichuZ! ;)

This presentation deals with bicytopenia induced by proton pump inhibitors, that were reported and published as a Case Report by researchers from China.
References have been provided as a separate textbox under each slide, for extensive referencing into the same.

1. PPI-INDUCED BICYTOPENIA: RARE, BUT ALARMING PRESENTED BY: VISHNU.R.NAIR, DIVYA SEBASTIAN, PHARM.D INTERNS, NATIONAL COLLEGE OF PHARMACY.

2. PUBLICATION DETAILS TITLE “Neutropenia and Thrombocytopenia induced by Proton Pump Inhibitors: A Case Report” AUTHORS Zheng Yu, Jing Hu, Yaojun Hu DATE OF PUBLICATION 23.11.2018 JOURNAL INVOLVED Drug Safety-Case Reports(Springer)

3. WHY ALARMING? Proton pump inhibitors(PPIs)  widely used medications for treatment of gastrointestinal disorders With ever-increasing use of PPIs  complications & adverse effects have come up! Although cases of “ cytopenia ” have been attributed to PPI therapy Bi-cytopenia has not been documented before Makes this case rare , yet alarming ! Turner T. Proton pump inhibitors. 2018. Available at https: //www.drugwatch.com/proton-pump-inhibitors /. Last accessed on 10 Oct 2018. [ Crossref ] Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroentrology . 2017;152:706–15. [ Crossref ] Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding the complications and risks. Nat Rev Gastroenterol Hepatol . 2017;14:697–710. [ Crossref ] Dury S, Nardi J, Gozalo C, Lebargy F, Deslee G. Agranulocytosis induced by proton pump inhibitors. J Clin Gastroenterol . 2012;46:859. [ Crossref ]

4. CASE DETAILS 85 year old Chinese man  admitted to hospital with C/O dysphagia in 2017 Past medical history details: MEDICAL HISTORY TREATMENT INITIATED BPH(2012) Transurethral resection of prostate Lumbar vertebral compression fracture(2015) Percutaneous vertebroplasty Early squamous cell carcinoma of esophagus(21 months before existing case) Endoscopic multi-band mucosectomy Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

5. CASE DETAILS Diagnosis of squamous cell carcinoma of esophagus (in another hospital) Mucosectomy was performed Patient developed progressive dysphagia Patient received 4 endoscopic dilations Dysphagia recurred after each episode of dilation Severity of dysphagia  rendered patient to be able to swallow only liquids ! Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

6. CASE DETAILS BMI: 18.4 Vital signs were stable CBC  revealed mild anemia, with slightly reduced serum iron & ferritin concentrations: WBC 5.6 * 10 9 cells/L Neutrophil count 4.46 * 10 9 cells/L RBC count 2.97 * 10 12 cells/L Hb 104 g/L Platelet count 135 * 10 9 cells/L Serum iron 5.70 µmol/L Transferin saturation 16.72% TIBC 34.10 µmol/L Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

7. CASE DETAILS Iron deficiency anemia owing to malnutrition suspected Iron sucrose was administered intravenously, intermittently(100 mg, thrice weekly) Esophagoscopy & esophagogram Revealed 2 mm-long benign scar stricture Stent was placed after dilation After dislodgement of stent Dysphagia recurred! Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

8. Case details With each dilation  dysphagia improved, but again recurred!! Finally Pantoprazole sodium(80 mg, i.v infusion, BD) was administered in hospital Esomeprazole (20 mg/day, orally) was administered intermittently at home Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

9. CASE DETAILS On admission to hospital for next dilation Pantoprazole was given again from hospital The following abnormalities were found : HEMATOLOGICAL PARAMETER INITIAL VALUE(AFTER 1 ST HOSPITAL ADMISSION) FINAL VALUE(AFTER PPI INITIATION) Platelet count 135 * 10 9 cells/L 83 * 10 9 cells/L WBC 5.6 * 10 9 cells/L 2.67 * 10 9 cells/L Neutrophils 4.46 * 10 9 cells/L 0.88 * 10 9 cells/L Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

10. CASE DETAILS Bone marrow aspiration smear Revealed “ hypoplastic hematopoiesis ” Pantoprazole was immediately discontinued Values returned to normal within 8 days !!! Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

11. CASE DETAILS Drastic changes in levels of WBC, neutrophils and platelets after administration of pantoprazole. With drug discontinuation Values tend to normalize! Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

12. DISCUSSION Although package inserts of both pantoprazole & esomeprazole indicate risk for neutropenia Occurrence of the same is a rarity! In this case PPI usage led to bone-marrow suppression Led to thrombocytopenia & neutropenia Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

13. DISCUSSION Cross-reactivity between esomeprazole & pantoprazole May have resulted in cytopenia However Neutropenia & thrombocytopenia were directly associated with pantoprazole (evident from Naranjo scale of 5) Gouraud A, Vochelle V, Descotes J, Vial T. Proton pump inhibitor-induced neutropenia: possible cross-reactivity between omeprazole and pantoprazole. Clin Drug Investig . 2010;30:559–63. Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

14. DISCUSSION Mechanisms of PPI-induced cytopenia include: IMMUNE-MEDIATED MECHANISM: In this  drug-induced antibodies  act against circulating hemocytes B . TOXIC MECHANISM: - Involves direct, dose-mediated toxicity to hematopoietic cell s. Heimpel H. When should the clinician suspect a drug- induced blood dyscrasia, and how should he proceed? Eur J Haematol Suppl. 1996;60:11–5. [ Crossref ] Yu Z, Hu J, Hu Y. Neutropenia and Thrombocytopenia Induced by Proton Pump Inhibitors: A Case Report. Drug safety-case reports. 2018 Dec 1;5(1):28.

15. CONCLUSION Proton pump inhibitors  widely used agents for management of gastrointestinal disorders Widespread use of PPIs  increase risk of long-term complications and adverse effects PPIs  might cause leukopenia & thrombocytopenia Neutrophil & platelet counts may normalize days within cessation of PPI administration Since PPI-induced bicytopenia is a rare incident Occurrence of the same may be overlooked in clinical practice Mandates monitoring of hematological parameters during PPI therapy!

16. THANK YOU!!