Captopril-induced bone marrow suppression in two cardiac patients with trisomy 21

Abstract

Neutropenia is an infrequent complication following administration of the angiotensin-converting enzyme (ACE) inhibitor, captopril. Most reports have been in adult patients, with rare reports in the pediatric population. We report two cases of neutropenia following captopril use in cardiac patients with trisomy 21. As this was not seen in patients without Down's syndrome, we postulate that patients with trisomy 21 have bone marrow which is "at risk" for suppression, and, thus warrant close evaluation while on such medications.

Effect of Angiotensin II on Hematopoietic Progenitor Cell Proliferation

“…Further, a rare but noted side effect of treatment with ACE inhibitors is neutropenia. This side effect has been observed in 0.3% of patients using this therapy [23][24][25][26][27]. Although other mechanisms have been proposed, lowering of blood AII by ACE inhibitors might contribute to this clinical observation [28].…”

Agranulocytosis Associated With Trandolapril-Verapamil Combination

“…ACE inhibitors, which are used for the treatment of congestive heart failure and hypertension, have been reported to cause neutropenia as a side effect, though rarely. The most commonly reported cases in the literature mainly include neutropenia cases induced by captopril [9][10][11][12][14][15] , with some cases associated with the use of enalapril [16] and ramipril [17] . There are two basic mechanisms in drug-induced neutropenia and/or agranulocytosis [18][19][20][21][22] :…”

Captopril‐induced pancytopenia in a premature newborn

“…Bone marrow failure associated with captopril use is a rare but important side‐effect of this drug. Some of the risk factors for the development of captopril‐associated pancytopenia have been well defined, namely, renal dysfunction, excessive dosage (> 6 mg/kg per day), collagen vascular disease, concurrent use of immunosuppressive agents and Down syndrome with its associated marrow abnormalities 5,6 . This condition is relatively common in renal transplant recipients who are taking the drug.…”

“…Some of the risk factors for the development of captopril-associated pancytopenia have been well defined, namely, renal dysfunction, excessive dosage (> 6 mg/kg per day), collagen vascular disease, concurrent use of immunosuppressive agents and Down syndrome with its associated marrow abnormalities. 5,6 This condition is relatively common in renal transplant recipients who are taking the drug. In many of these cases, pancytopenia is thought to be a doserelated complication caused by accumulation of the drug through defective renal tubular excretion.…”