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| DRUG WATCH |
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| Year : 2023 | Volume
: 55
| Issue : 5 | Page : 335-337 |
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Deferasirox causing duodenal ulcer leading to upper gastrointestinal bleed and hemorrhagic shock in a child with beta-thalassemia major
Anu Tresa, Guruprasad Hassan Shankar, Bhakti U Sarangi, Ajay Walimbe
Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India
| Date of Submission | 20-Mar-2023 |
| Date of Decision | 14-Jul-2023 |
| Date of Acceptance | 29-Aug-2023 |
| Date of Web Publication | 02-Nov-2023 |
Correspondence Address:
Bhakti U Sarangi
Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune - 411 043, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijp.ijp_151_23
Iron chelators have significantly reduced the morbidity associated with iron overload and improved the quality of life in children with beta-thalassemia major. A 5-year-old female child with beta-thalassemia major on recurrent transfusions and oral chelation with deferasirox was brought with repeated episodes of frank hematemesis and progressive lethargy. Her evaluation revealed anemia, leukocytosis, and deranged liver function with coagulopathy. She was given red blood cell and plasma transfusions with liver supportive medication and proton-pump inhibitor (PPI) infusion. Her upper gastrointestinal endoscopy revealed multiple ulcers in all three parts of the duodenum, which in the absence of any other likely etiology were attributed to prolonged use of oral deferasirox. The child improved with the above-mentioned measures. Chelation therapy was withheld for 2 weeks and restarted at a lower dose using enteric-coated preparation while PPIs were given for 8 weeks. She showed sustained improvement and remained well on follow-up.
Keywords: Deferasirox, duodenal ulcer, hemorrhage, thalassemia
How to cite this article:
Tresa A, Shankar GH, Sarangi BU, Walimbe A. Deferasirox causing duodenal ulcer leading to upper gastrointestinal bleed and hemorrhagic shock in a child with beta-thalassemia major. Indian J Pharmacol 2023;55:335-7 |
How to cite this URL:
Tresa A, Shankar GH, Sarangi BU, Walimbe A. Deferasirox causing duodenal ulcer leading to upper gastrointestinal bleed and hemorrhagic shock in a child with beta-thalassemia major. Indian J Pharmacol [serial online] 2023 [cited 2023 Nov 28];55:335-7. Available from: https://www.ijp-online.com/text.asp?2023/55/5/335/389231 |
| » Introduction | |  |
Iron chelation is one of the cornerstones of long-term care of transfusion-dependent thalassemia patients, and deferasirox has become the first-line monotherapy chelating agent in recent years. Although long-term safety and efficacy have been established, rare adverse effects of deferasirox can be potentially fatal.[1] We hereby report a case of transfusion-dependent beta-thalassemia major on long-term chelation therapy with deferasirox presenting in the emergency room (ER) with massive hematemesis.
| » Case Report | | |
A5-year-old girl diagnosed with beta-thalassemia major on regular transfusions presented to the ER with two episodes of large frank hematemesis. She also had poor oral intake and progressive lethargy for a day before admission. She was on chelation therapy with deferasirox since 2 years of age (current dose 500 mg once a day at 41.6 mg/kg/day). She had tachycardia, bounding peripheral pulses, epigastric tenderness, and nontender hepatomegaly. The spleen was not palpable. The rest of the systemic examination was normal. She received 2 crystalloid boluses (10 + 10 ml/kg), which improved her hemodynamic status. Pretransfusion hemoglobin from the previous record was 9 g/dl. Initial workup revealed anemia with neutrophilic leukocytosis, deranged renal function tests indicating a prerenal involvement, coagulopathy with the elevation of PT/INR, and severely elevated (>5 times) transaminases [Table 1].
Management and outcome
She was transfused 15 ml/kg of packed red cell volume followed by a unit of fresh-frozen plasma (at 15 ml/kg). Hemodynamic status normalized with these measures without any inotrope requirement. For acute liver failure, she received N-acetylcysteine infusion. Pantoprazole was infused for upper gastrointestinal (GI) hemorrhage. Postadmission, no further episodes of hematemesis were noted. Emergency diagnostic upper GI endoscopy revealed multiple postbulbar ulcers in all three parts of the duodenum. The ulcers demonstrated a yellow base, and flattened duodenal folds were noted as well [Figure 1]a and [Figure 1]b. In view of coagulopathy, a biopsy was not taken to check for Helicobacter pylori. Factors considered that may have contributed to liver involvement included deferasirox-induced drug toxicity and ischemic injury to the liver due to shock. | Figure 1: (a and b) Multiple ulcers with yellow base noted in the postbulbar region
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The child remained hemodynamically stable through the hospital stay, and she was transferred out of ICU care after 48 h. Liver enzymes showed a decreasing trend on day 2, and coagulopathy normalized on day 3.
Considering the possibility of deferasirox-induced ulcers, chelation therapy was withheld for 2 weeks and then restarted at a lower dose using enteric-coated preparation. Proton-pump inhibitors were given for 8 weeks. She was noted to be well on follow-up.
| » Discussion | | |
GI bleeding is uncommon in this setting; rather, the concerns are of a hypercoagulable state leading to thromboembolic phenomena. However, thalassemia is known to cause complex changes in hemostasis, including a reduction in the protein C, protein S, and antithrombin III levels, and hemorrhagic manifestations have also been noted although less commonly.[2] Hypersplenism causing thrombocytopenia, liver disease due to iron overload, and adverse effects of chelating agents (deferiprone) may precipitate bleeding manifestations.[3] Other abdominal emergencies in thalassemia relating to adverse effects of medications include the rare possibility of gastric/duodenal ulcer due to deferasirox, which may lead to upper GI bleeding or perforation.
Peptic ulcer disease, being uncommon in children compared with adults, often GI ulcer as a cause of pediatric acute abdomen, is overlooked. Etiologic considerations like H. pylori, stress-induced gastric injury, and medication-related (NSAIDs and corticosteroids) gastritis may have to be taken into account.
Deferasirox is a tridentate chelator that binds to the ferric form of iron. It has an oral bioavailability of 70%, with an elimination half-life ranging from 8 to 16 h, allowing for once-a-day dosing. It has good efficacy as shown by the ratio of the amount of iron excreted to that which can be theoretically bound (15%–27%). A dose of 30 mg/kg/day is needed to achieve a negative iron balance.[1] Long-term studies of up to 5 years have demonstrated safety and efficacy.[4] It is usually well tolerated, with more common adverse effects being gastrointestinal disturbances which usually do not last more than a week. Rare but serious adverse effects that have been reported include hepatic failure, acute kidney injury, cytopenias, and gastrointestinal hemorrhage.[2]
Bauters et al. reported a 10-year-old female with beta-thalassemia major, with a gastric ulcer after 5.5 years of deferasirox treatment and presented with hematemesis.[5] In our report as well, the complication occurred many years[3] after initiation. The child did not have any history of gastrointestinal symptoms in the past. It is important to rule out concomitant H. pylori infection as a contributing factor in such presentations; however, in view of coagulopathy, we were unable to perform a duodenal biopsy. The liver and renal involvement in our case could have been due to hemorrhagic shock or an additional complication of deferasirox.
As in any other emergency, stabilization of the airway, breathing, and circulation takes the first priority in children with upper GI bleed. In hemorrhagic shock, it is appropriate to try and limit crystalloid resuscitation to avoid further hemodilution in an already anemic patient. The degree and rapidity of blood loss need to be ascertained, and transfusion of packed RBC may be performed as part of resuscitation itself. NG tube insertion helps to confirm the presence of intragastric blood and determine the rate of ongoing bleeding. Once additional risk factors for bleeding are investigated and the child is stabilized, upper GI endoscopy comes next to determine the etiology.
Given the rarity and long duration of time after which deferasirox-induced ulcers have been reported, there are currently no recommendations about concomitant administration of proton-pump inhibitors or H2 receptor blockers for the prevention of the said complication. In conclusion, gastric/duodenal ulcer is a rare but potentially life-threatening complication of the use of deferasirox as a chelating agent in beta-thalassemia major and must be considered a differential diagnosis of acute abdomen in this setting.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| » References | | |
| 1. | Cappellini MD. Long-term efficacy and safety of deferasirox. Blood Rev 2008;22 Suppl 2:S35-41.  |
| 2. | Naithani R, Chandra J, Narayan S, Sharma S, Singh V. Thalassemia major – On the verge of bleeding or thrombosis? Hematology 2006;11:57-61. |
| 3. | Jamuar SS, Lai AH, Tan AM, Chan MY, Tan ES, Ng IS. Use of deferiprone for iron chelation in patients with transfusion-dependent thalassaemia. J Paediatr Child Health 2011;47:812-7. |
| 4. | Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A, et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: Efficacy and safety during 5 years' follow-up. Blood 2011;118:884-93. |
| 5. | Bauters T, Mondelaers V, Robays H, Hunninck K, de Moerloose B. Gastric ulcer in a child treated with deferasirox. Pharm World Sci 2010;32:112-3. |
[Figure 1]
[Table 1]
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