Rapid Reversal of Severe Thrombocytopenia after Cessation of Diazoxide in a 1.7-Year-Old Girl with Hyperinsulinemic Hypoglycemia

Supamas Harintajinda; Natee Sakornyutthadej; Surapong Lertthammakiat; Sinitdhorn Rujirabanjerd; Warittha Supho

doi:10.69898/jhtm.36.2026.285661

Authors

Supamas Harintajinda Ramadhibodi Chakri Naruebodindra Hospital, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
Natee Sakornyutthadej Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
Surapong Lertthammakiat Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
Sinitdhorn Rujirabanjerd Ramadhibodi Chakri Naruebodindra Hospital, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
Warittha Supho Ramadhibodi Chakri Naruebodindra Hospital, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand

DOI:

https://doi.org/10.69898/jhtm.36.2026.285661

Keywords:

thrombocytopenia, diazoxide, hyperinsulinism, drug-induced thrombocytopenia

Abstract

Background: Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare genetic form of hyperinsulinemic hypoglycemia. While diazoxide is the first-line medical therapy for this condition, it has been associated with several adverse effects, ranging from fluid retention to rare hematologic complications.

Case Description: A 1.7-year-old girl with HI/HA syndrome, confirmed by a monoallelic pathologic variant in the GLUD1 gene (c.1466C>A, p.Pro489His), presented with a sudden onset of generalized ecchymoses, petechiae, and wet purpura. These symptoms emerged three weeks after initiating diazoxide therapy at 5 mg/kg/day. Investigations revealed severe isolated thrombocytopenia (platelet count 4 x 10⁹/L). An elevated immature platelet fraction (10.5%) and a low one-hour corrected count increment following platelet transfusion suggested an immune-mediated destructive process. Diazoxide was immediately discontinued. Following a single platelet transfusion and cessation of the drug, the patient’s platelet count recovered rapidly, normalizing within 48 hours and reaching 487 x 10⁹/L two weeks after.

Conclusion: This case highlights a rare but severe presentation of diazoxide-induced thrombocytopenia in a pediatric patient. Laboratory confirmation of an immune process, most likely via a quinine-type mechanism, is consistent with the patient's rapid recovery. Clinicians should maintain a high index of suspicion for hematologic toxicity among patients treated with diazoxide, as prompt discontinuation of the offending agent leads to rapid clinical and laboratory recovery.

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References

Flanagan SE, Kapoor RR, Hussain K. Genetics of congenital hyperinsulinemic hypoglycemia. Semin Pediatr Surg. 2011;20:13-7. DOI: https://doi.org/10.1053/j.sempedsurg.2010.10.004

Newman-Lindsay S, Lakshminrusimha S, Sankaran D. Diazoxide for neonatal hyperinsulinemic hypoglycemia and pulmonary hypertension. Children (Basel). 2022;10:5. DOI: https://doi.org/10.3390/children10010005

Chen X, Feng L, Yao H, Yang L, Qin Y. Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis. PLoS One. 2021;16:e0246463. DOI: https://doi.org/10.1371/journal.pone.0246463

Welters A, Lerch C, Kummer S, Marquard J, Salgin B, Mayatepek E, et al. Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers. Orphanet J Rare Dis. 2015;10:150. DOI: https://doi.org/10.1186/s13023-015-0367-x

Fukutomi M, Shimodera M, Maeda Y, Iwakura M, Hara M. Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey). Clin Pediatr Endocrinol. 2018;27:131-43. DOI: https://doi.org/10.1297/cpe.27.131

Herrera A, Vajravelu ME, Givler S, Mitteer L, Avitabile CM, Lord K, et al. Prevalence of adverse events in children with congenital hyperinsulinism treated with diazoxide. J Clin Endocrinol Metab. 2018;103:4365–72. DOI: https://doi.org/10.1210/jc.2018-01613

Thornton P, Truong L, Reynolds C, Hamby T, Nedrelow J. Rate of serious adverse events associated with diazoxide treatment of patients with hyperinsulinism. Horm Res Paediatr. 2019;91:25-32. DOI: https://doi.org/10.1159/000497458

Delaflor-Weiss E, Mintz PD. The evaluation and management of platelet refractoriness and alloimmunization. Transfus Med Rev. 2000;14:180-96. DOI: https://doi.org/10.1016/S0887-7963(00)80007-3

Vayne C, Guéry EA, Rollin J, Baglo T, Petermann R, Gruel Y. Pathophysiology and diagnosis of drug-induced immune thrombocytopenia. J Clin Med. 2020;9:2212. DOI: https://doi.org/10.3390/jcm9072212

Bakchoul T, Marini I. Drug-associated thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2018;2018:576-83. DOI: https://doi.org/10.1182/asheducation-2018.1.576

Thus KA, den Boogert WJ, van der Heyden JC. Thrombocytopaenia: a serious side effect of diazoxide. BMJ Case Rep. 2019;12:e231222. DOI: https://doi.org/10.1136/bcr-2019-231222

Eisner EV, Crowell EB. Hydrochlorothiazide-dependent thrombocytopenia due to IgM antibody. JAMA. 1971;215:480-2. DOI: https://doi.org/10.1001/jama.1971.03180160076026

Okafor KC, Griffin C, Ngole PM. Hydrochlorothiazide-induced thrombocytopenic purpura. Drug Intell Clin Pharm. 1986;20:60-1. DOI: https://doi.org/10.1177/106002808602000110

Jeon K, Kim M, Lee J, Lee JS, Kim HS, Kang HJ, et al. Immature platelet fraction: a useful marker for identifying the cause of thrombocytopenia and predicting platelet recovery. Medicine (Baltimore). 2020;99:e19096. DOI: https://doi.org/10.1097/MD.0000000000019096

Benlachgar N, Doghmi K, Masrar A, Mahtat EM, Harmouche H, Tazi Mezalek Z. Immature platelets: a review of the available evidence. Thromb Res. 2020;195:43-50. DOI: https://doi.org/10.1016/j.thromres.2020.06.048

Pereira KN, de Carvalho JAM, Paniz C, Moresco RN, da Silva JEP. Diagnostic characteristics of immature platelet fraction for the assessment of immune thrombocytopenia. Thromb Res. 2021;202:125-7. DOI: https://doi.org/10.1016/j.thromres.2021.03.023

Steibel K, Joris M, Clichet V, Charbonnier A, Desoutter J, Marolleau JP, et al. Evaluation of the immature platelet fraction as a predictive marker of bone marrow regeneration after hematopoietic stem cell transplantation. Int J Lab Hematol. 2025;47:41-50. DOI: https://doi.org/10.1111/ijlh.14358

Arnold DM, Kukaswadia S, Nazi I, Esmail A, Dewar L, Smith JW, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013;11:169-76. DOI: https://doi.org/10.1111/jth.12052

Stanworth SJ, Navarrete C, Estcourt L, Marsh J. Platelet refractoriness--practical approaches and ongoing dilemmas in patient management. Br J Haematol. 2015;171:297-305. DOI: https://doi.org/10.1111/bjh.13597

Marini I, Uzun G, Jamal K, Bakchoul T. Treatment of drug-induced immune thrombocytopenias. Haematologica. 2022;107:1264-77. DOI: https://doi.org/10.3324/haematol.2021.279484

Symchowicz S, Winston L, Black J, Smith M, Calesnick B, Tabachnick II. Diazoxide blood levels in man. J Pharm Sci. 1967;56:912-4. DOI: https://doi.org/10.1002/jps.2600560730

Kizu R, Nishimura K, Sato R, Kosaki K, Tanaka T, Tanigawara Y, et al. Population pharmacokinetics of diazoxide in children with hyperinsulinemic hypoglycemia. Horm Res Paediatr. 2017;88:316-23. DOI: https://doi.org/10.1159/000478696

Adachi J, Mimura M, Minami I, Kakihana K, Watanabe T. Thrombocytopenia induced by diazoxide in a patient with an insulinoma. Intern Med. 2014;53:759-62. DOI: https://doi.org/10.2169/internalmedicine.53.1094

Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157–67. DOI: https://doi.org/10.1056/NEJMra035092

Watanabe H, Nagano N, Tsuji Y, Noto N, Ayusawa M, Morioka I. Challenges of pediatric pharmacotherapy: a narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics. Eur J Clin Pharmacol. 2024;80:167–80. DOI: https://doi.org/10.1007/s00228-023-03598-x

Brar PC, Heksch R, Cossen K, De Leon DD, Kamboj MK, Marks SD, et al. Management and appropriate use of diazoxide in infants and children with hyperinsulinism. J Clin Endocrinol Metab. 2020;105:dgaa543. DOI: https://doi.org/10.1210/clinem/dgaa543

George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program. 2009:153-8. DOI: https://doi.org/10.1182/asheducation-2009.1.153