All Megakaryocytic Macrothrombocytopenia Are Not ITP

RM. Subbaiah*

Consultant Clinical Haematologist, Kauvery hospital, Trichy, Tamilnadu, India

*Correspondence: drrms5@yahoo.co.in

Background

Thrombocytopenia with adequate megakaryocytes in marrow, other possible causes being ruled out constitutes a diagnosis called immune thrombocytopenia (ITP). Hence it is a diagnosis of exclusion and an immune mediated mechanism explains the clinical consequence.

Case Presentation

A 48-years-old female with moderate degree thrombocytopenia was managed with steroids for 1.5 years by a local medical practitioner. She reported no overt bleeding or other symptoms. Physical examination was unremarkable. Labs revealed a normocytic anaemia, mild reticulocytosis, moderate thrombocytopenia, mildly raised serum LDH and mild indirect bilirubinemia. Direct Coombs test was negative. USG abdomen revealed a mild splenomegaly however liver was normal. Peripheral smear revealed normocytic red cells with stomatocytes and giant platelets. A diagnosis of Sitosterolemia was suspected and sample for NGS (next generation sequencing) was ordered which picked up a homozygous mutation in ABCG5 gene confirming the same.

Steroids were tapered and stopped. Patient was initially not satisfied as she felt lethargic with steroid withdrawal which may hamper the physician to do so many times. She was started on Ezetimibe 10 mg every night which helps in reducing sterol absorption and thereby reducing possible clinical manifestations. Anemia and thrombocytoenia improved.

Discussion

Cholesterol is animal fat and Phytosterol is plant fat, Sterolin is a transport protein which helps in in restricting excess phytosterol in the body with a preference to xenosterols [1]. At intestines it restricts excess absorption by transporting them back to intestine. At liver cells it secretes them into bile and there by excreting it via intestines. Sterolin is encoded by ABCG5 and ABCG8 genes [2]. In Sitosterolemia, due to mutation in ABCG5 or ABCG8 genes, Sterolin is defective, above job is not done and plant fat accumulates in the body which may cause atherosclerosis, xanthomas, deranged liver function, non-immune hemolysis and macrothrombocytopenia [3]. Clinical phenotypes in sitosterolemia range as per nonsense mutations in either ABCG5 or ABCG8 genes [4]. Treatment options are restriction of phytosterol rich foods, sterol absorption inhibitor Ezetimibe, bile acid sequestrant such as cholestryramine and as alast resort a partial ileal bypass surgery may be considered [5].

Steroids are a double-edged sword and they must to be used only if there is a strong indication and data to support the same. Like an antibiotic stewardship, steroid stewardship is less discussed and it may reduce its inadvertent usage. A simple peripheral smear examination (which is cost effective) may give enormous information if the viewer knows what to pick up from the stained slide in the given clinical scenario.

References

  • Nghiem-Rao TH, Patel SB. Investigating sitosterolemia to understand lipid physiology. Clin Lipidol. 2013;8(6):649-58.
  • Myrie SB, Steiner RD, Mymin D. Sitosterolemia. In: Adam MP, Ardinger HH, Pagon RA (Ed.), GeneReviews®, 2013.
  • Su X, Shao Y, Lin Y, Zhao X, Zhang W, Jiang M, et al. Clinical features, molecular characteristics, and treatments of a Chinese girl with sitosterolemia: A case report and literature review. J Clin Lipidol. 2019;13(2):246-50.
  • Wang J, Joy T, Mymin D, Frohlich J, Hegele RA. Phenotypic heterogeneity of sitosterolemia. J Lipid Res. 2004;45(12):2361-7.
  • Yoo EG. Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management. Ann Pediatr Endocrinol Metabol. 2016;21(1):7.

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