Complications	Monitoring tests	Ages to test	Frequency	Comments
Anemia	Complete blood count with differential	All	Every 6 months Monthly if receiving transfusions	Pretransfusion Hb goal: 9 to 10.5 g per dL (90 to 105 g per L) Posttransfusion Hb goal: 11 to 12 g per dL (110 to 120 g per L)
Cardiac complications, such as arrhythmia and heart failure	T2*-weighted cardiac MRI	Starting at 10 years	Every 2 years if T2 ≥ 30 ms Annually if T2 ≥ 10 ms and < 30 ms Every 6 months if T2 < 10 ms	Iron chelation therapy has been shown to reverse cardiac dysfunction
	Echocardiography and electrocardiography	Starting at 10 years	Annually if LVEF ≥ 56% Every 4 to 6 months if LVEF < 56%	—
Endocrine disorders	Hypothyroidism: thyroid-stimulating hormone	≥ 9 years	Annually	Treat per society and local institutional standards
	Hypoparathyroidism: calcium, phosphate, vitamin D, and parathyroid hormone	≥ 9 years	Annually	—
	Diabetes mellitus: fasting glucose or A1C	≥ 9 years	Annually	—
	Adrenal insufficiency: corticotropin (adrenocorticotropic hormone) stimulation test	≥ 9 years in those with iron overload or growth hormone deficiency	Every 1 to 2 years	—
Extramedullary hematopoiesis	Physical examination to assess for facial and bone deformities, pseudotumors, and hepatosplenomegaly Imaging based on clinical suspicion	All	Every visit	Pseudotumors may improve with transfusions, hydroxyurea, irradiation, or surgery Splenectomy may be indicated for clinically significant splenomegaly (symptomatic splenomegaly, hypersplenism with clinically significant cytopenias, or iron overload from frequent transfusions that cannot be managed with chelation therapy) Patients should be immunized against Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis before splenectomy
	Dental examination	All	Annually	Evaluate for facial deformities affecting teeth, palate, and mandible
Growth delay	Height (measure standing and sitting height when possible) Weight Head circumference	All	Annually Every 3 to 6 months during puberty or long-term transfusion therapy	If growth delay (< 3rd percentile) is identified, IGF-1 and IGFBP-3 measurements and growth hormone stimulation testing should be performed Consider other causes of growth delay in workup (chelation therapy toxicity, other hormonal or nutritional disorders) Treat per society and local institutional standards
	Bone age radiography	9 to 17 years	Annually	—
Leg ulcers	Skin examination	All	Every visit	More common in patients with NTDT Treat per society and local institutional standards; consider referral to wound care specialist
Liver dysfunction, fibrosis, cirrhosis, and hepatocellular carcinoma	Liver function tests (including AST, ALT, bilirubin)	All	Every 3 to 6 months Monthly if undergoing transfusion or if AST or ALT > 5 times the upper limit of normal	Chelation therapy has been shown to reverse hepatic fibrosis and inflammation
	R2*-weighted MRI	Starting at 10 years	Every 2 years if LIC < 3 mg per g Annually if LIC is 3 to 15 mg per g Every 6 months if LIC > 15 mg per g	An LIC of 3 to 7 mg per g is considered an adequate goal in treating iron overload in patients with thalassemia
	Liver ultrasonography	≥ 18 years	Annually Every 6 months if diagnosed with cirrhosis	Ultrasonography can also assess for portal hypertension, gallstones, or biliary disease Transient elastography can identify and determine the stage of fibrosis
	Alpha fetoprotein	≥ 40 years or if cirrhosis is diagnosed	Every 6 to 12 months	—
Osteoporosis	Bone mineral density with dual-energy x-ray absorptiometry	≥ 10 years	Every 1 to 2 years	Encourage physical activity, smoking cessation, and adequate calcium intake for prevention Initiate bisphosphonate therapy with calcium, vitamin D, and zinc supplementation for diagnosed osteoporosis Hormone therapy, transfusions, iron chelation therapy, and hydroxyurea, if indicated, may prevent osteoporosis
Pubertal delay	Tanner staging	9 to 17 years	Annually	Treat pubertal delay per society and local institutional standards
	Menstrual history	≥ 9 years	Annually	—
	Follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol	≥ 9 years	Annually	Obtain if concerned for pubertal delay or secondary hypogonadism
Pulmonary hypertension	Echocardiography	Starting at 10 years	Every 1 to 2 years	Tricuspid valve velocity > 3 m per second necessitates cardiac catheterization to confirm diagnosis Potentially beneficial treatments include transfusions, hydroxyurea, sildenafil (Revatio), anticoagulation, and controlling iron overload
Reproductive health, infertility and pregnancy	Assess for infertility	≥ 14 years	Annually	80% to 90% of patients with TDT have hypogonadotropic hypogonadism, although fertility may be possible with induction of ovulation or spermatogenesis Assistive reproduction technology may be necessary
	Assess patient’s desire for pregnancy	Child-conceiving age	Annually	Ideally, pregnancy in patients with thalassemia should be planned because of the potential risks to mother and child Discuss contraception if pregnancy is not desired Prepregnancy  Provide counseling on the risks of pregnancy and methods for prenatal diagnosis  Optimize health and risk management (assess iron overload status; cardiac, liver, thyroid function; viral infection status; appropriate immunizations)  Discontinue iron chelation therapy (deferoxamine [Desferal] may be used in second and third trimesters)  Discontinue bisphosphonates (6 months prior), hormone therapy, hydroxyurea, angiotensin-converting enzyme inhibitors; switch anticoagulants to heparins  Start folic acid supplementation During pregnancy  Assess cardiac, liver, and thyroid function each trimester  Screen for gestational diabetes at 16 and 28 weeks’ gestation  Monitor fetal growth with serial ultrasonography beginning at 24 to 26 weeks  More frequent transfusions may be needed  Thromboprophylaxis with low-molecular-weight heparin; aspirin for patients who have had a splenectomy After pregnancy  When the patient is no longer breastfeeding, bisphosphonates, hormone therapy, and iron chelation therapy may be restarted (deferoxamine is safe during breastfeeding)  Thromboprophylaxis for 7 days after vaginal delivery or 6 weeks after cesarean delivery Discuss contraception
Systemic iron overload	Ferritin	All	Every 3 months	Ferritin ≥ 1,000 ng per mL (1,000 mcg per L) in patients with TDT or ≥ 800 ng per mL (800 mcg per L) in patients with NTDT warrants chelation therapy
Thrombosis	Assess risk at time of inpatient admission, surgery, or pregnancy	All	As necessary	Higher risk in adults and in individuals with splenectomy, beta-thalassemia intermedia, history of thrombosis, pulmonary hypertension, platelet count > 500 × 103 per μL (500 × 109 per L), or Hb < 10 g per dL (100 g per L) Consider prophylactic anticoagulation in high-risk patients Consider aspirin in patients with NTDT and splenectomy if platelet count > 500 × 103 per μL
Transfusion-related infections	Hepatitis B, hepatitis C, HIV	All, if receiving transfusions	Annually	Patients should be immunized against hepatitis A and B before initiating transfusions Treat infections per society and local institutional standards