What is the management approach for a 14-year-old boy with transfusion-dependent thalassemia (a genetic disorder affecting hemoglobin production) presenting with generalized tonic-clonic seizures (GTCS) and fever?

Management of a 14-Year-Old Boy with Transfusion-Dependent Thalassemia Presenting with GTCS and Fever

Immediate Priorities: Rule Out Life-Threatening Complications

This patient requires immediate assessment for iron-induced cardiac complications, hypocalcemia from hypoparathyroidism, and CNS infection, as these are the most critical causes of seizures with fever in transfusion-dependent thalassemia that directly impact mortality.

Initial Emergency Assessment

• Obtain immediate bedside echocardiography to exclude acute decompensated heart failure, as cardiac iron overload is a leading cause of death in thalassemia and can present with seizures 1
• Check serum calcium, phosphate, magnesium, and parathyroid hormone levels immediately, as acquired hypoparathyroidism from iron overload in parathyroid glands commonly causes seizures in thalassemia patients 2
• Perform lumbar puncture if any signs of meningismus or altered mental status persist beyond the immediate post-ictal period, as transfusion-dependent patients have infection risk 3
• Obtain troponin I levels, as 12% of patients post-GTCS have elevated troponin, with higher risk in cardiac iron overload 4
• Measure creatine kinase (CK), as 59.4% of GTCS patients have elevated CK, and rhabdomyolysis occurs in 1.9% 4

Seizure Management

• Initiate levetiracetam as first-line antiepileptic therapy at 60 mg/kg/day (up to 3000 mg/day) divided in two doses, as it is effective for generalized tonic-clonic seizures and has minimal drug interactions with iron chelators 5, 6
• Avoid valproic acid if possible due to potential hepatotoxicity in patients who may have underlying liver disease from iron overload or viral hepatitis 1, 3
• Continue seizure prophylaxis until the underlying cause is identified and corrected 2

Specific Thalassemia-Related Complications to Address

If Hypocalcemia/Hypoparathyroidism is Confirmed

• Start oral calcium supplementation immediately with calcitriol (active vitamin D) to correct hypocalcemia 2
• Obtain head CT without contrast to evaluate for basal ganglia, frontal subcortical white matter, lentiform nucleus, and cerebellar calcifications, which are pathognomonic for chronic hypocalcemia in thalassemia 2
• Seizures will resolve with calcium correction and antiepileptic drugs can be discontinued once calcium normalizes 2

If Cardiac Complications are Present

• Transfer immediately to a specialized thalassemia center with integrated cardiology and hematology expertise, as this is a medical emergency where delay can be life-threatening 1
• Initiate continuous intravenous deferoxamine at 50 mg/kg/day (24 hours/day, uninterrupted) if acute decompensated heart failure is confirmed 1
• Add deferiprone 75 mg/kg/day in 3 divided doses as soon as possible for combined chelation therapy 1
• Maintain continuous electrocardiographic and hemodynamic monitoring 1
• Avoid aggressive diuretic therapy as thalassemia patients require adequate preload; use minimal diuretics only 1

Ongoing Thalassemia Management Optimization

Transfusion Protocol Review

• Verify pre-transfusion hemoglobin is maintained at 9-10 g/dL and post-transfusion at 13-14 g/dL 3
• Ensure transfusions occur every 3-4 weeks on a regular schedule 3
• Confirm all blood products are leukoreduced and Rh/Kell-matched 7
• Check for alloantibodies, as 16.9% of transfused thalassemia patients develop them 7

Iron Chelation Assessment

• Obtain cardiac MRI with T2 technique* to quantify cardiac iron burden (T2* <20 milliseconds indicates high risk) 8, 3
• Measure liver iron concentration (LIC) by MRI to guide chelation intensity 3
• Check serum ferritin levels (should be monitored every 3 months) 8
• If patient is on deferiprone, obtain complete blood count to assess for neutropenia risk 3, 9
• Consider switching to deferoxamine if neutropenia is present or if concurrent medications increase neutropenia risk 1, 9

Infection Workup for Fever

• Obtain blood cultures, complete blood count with differential, and C-reactive protein 3
• Consider respiratory viral panel if upper respiratory symptoms present, though specific viral identification does not change FS management 10
• Screen for hepatitis B and C status if not recently documented, as chronic viral hepatitis affects 4.4-85.4% of thalassemia patients depending on region 1
• Initiate broad-spectrum antibiotics immediately if fever persists beyond 24 hours or if neutropenia is present 3

Common Pitfalls to Avoid

• Do not assume anemia indicates iron deficiency and give iron supplementation, as thalassemia patients are at risk for iron overload despite anemia 8
• Do not delay cardiac assessment thinking seizures are purely neurological, as cardiac iron overload can present with seizures and has 50% one-year mortality if untreated 1
• Do not continue deferiprone if neutropenia develops, especially during acute illness 1, 9
• Do not use deferasirox in acute settings with potential renal compromise, as it has not been evaluated in acute decompensated heart failure 1
• Do not discharge without confirming calcium levels, as hypoparathyroidism is a treatable cause of recurrent seizures in thalassemia 2

Endocrine Screening

• Perform thyroid function tests, fasting glucose, and gonadotropin levels as annual endocrine screening is recommended in transfusion-dependent thalassemia 3