Thalassemia Sudawadee Ekwitayawechnukul, MD

Thalassemia Treatment Complication of thalassemia Complication of secondary hemochromatosis Iron chelation Other

Thalassemia Thalassa-sea Emia-blood Chronic disease Genetic disease Prevention Thalassemia trait: 30-50% of Thai population

Severity of thalassemia - no sign and symptom - mild decrease Hb, mild low MCV Thalassemia minor  thal trait,  thal trait, homozygous HbE, HbE trait, Homozygous  thal2 - hepatosplenomegaly - Hb 8-10 g/dL - Hemolysis Thalassemia intermedia Hb H disease,  /E - Huge hepatosplenomegaly - Hb < 7 g/dL Thalassemia major homozygous  thalassemia,  /E

Medical problems of adult thalassemia patients Infection : Pneumococci, gram negative bacterial encapsulated organism, Pythium Iron overload Hypertension Pulmonary thrombo embolism Cardiac arrhythmia, congestive heart failure and pericarditis

Medical problems of adult thalassemia patients Liver cirrhosis and gall stone Extramedullary erythropoiesis Autoimmune hemolytic anemia Growth and endocrine abnormality Chronic leg ulcer : ?zinc deficiency

Complications and therapies for  -thalassemia Rund D et al. N Engl J Med 2005;353:1135–46. Supportive therapy  Transfusion – Leukoreduction – Viral testing  Iron overload – DFO – Deferiprone – Deferasirox  Endocrinopathies – Hormone replacement  Osteoporosis – Osteoclast replacement – Vitamin D Curative therapy  Hematopoietic stem cell transplantation – Bone marrow – Cord blood – Unrelated donor – Non-myeloablative  Experimental therapy – EPO – Fetal hemoglobin modifiers (hydroxyurea, butyrate) – Antioxidants Future therapy  Gene therapy Infection via transfusion Arthropathy Venous thrombosis Delayed puberty and delayed secondary sexual characteristics Testicular or ovarian failure Osteoporosis Short stature Hypopituitarism Excessive melanin skin pigmentation (‘bronze diabetes’) Hypothyroidism / Hypoparathyroidism Pulmonary hypertension and embolism Cardiomyopathy Hemosiderosis and cirrhosis of liver Extrameduallry hematopoiesis Splenomegaly Diabetes mellitus Bone expansion (‘hair on end’)

Complication Iron overload Infection Gall stone Hypersplenism Extramedullary hematopoiesis Pulmonary arterial hypertension Autoimmune hemolytic anemia Chronic leg ulcer

Treatment Folate supplement Transfusion therapy Iron chelation Family planning

Transfusion therapy

Targeted Hb – Low transfusion: pretransfusion Hb>7 – Hypertransfusion: pretransfusion Hb – Supertransfusion: pretransfusion Hb Leukocyte reduce pack red cell – LPRC – LDPRC Premedication – Antihistamine – Diuretic

Secondary hemochromatosis Organ involvement – Cardiac hemochromatosis – Liver cirrhosis – Diabetes mellitus – Hypothyroidism

Iron chelation – regular transfusion – transfusion>20-25 unit – Keep serum ferritin ng/ml – Monitor serum ferritin every 3-6 mo Secondary hemochromatosis

DrugDeferioxamineDefeiproneDeferasirox Usual dose25-40 MKD MKD10-40 MKD Route of administration IV, SC infusionPO Half life20-30 min3-4 hr12-16 hr Frequency5-7 days/wk3 times dailyOnce daily Excretionurinary, fecalurinaryfecal Adverse effectLocal reaction Ophthalmologic Auditory Bone abnormalities Reddish-brown urine GI disturbance Agranulocytosis Neutropenia Arthralgia ↑liver enzyme Reddish-brown urine GI disturbance Rash ↑liver enzyme ↑serum creatinin Cost220 B/500 mg5 B/500 mg530 B/250 mg

Deferioxamine

Continuous intravenous infusion พิจารณาให้เมื่อมี cardiac problem จาก iron overload Dose MKD iv continuous drip 5-7 วัน / สัปดาห์

Deferasirox

คำแนะนำด้านสุขภาพทั่วไป รับประทานอาหารครบ 5 หมู่ หลีกเลี่ยงอาหารที่ มีธาตุเหล็กสูง งดวิตามินเสริมธาตุเหล็ก ออกกำลังกาย แต่หลีกเลี่ยงการออกกำลังกาย ที่มีการกระทบกระแทก เนื่องจากกระดูกเปราะ หักง่าย Vaccination – ในเด็กให้วัคซีนให้ครบตามปกติ – Post splenectomy-pneumococcal vaccine – HBV vaccine – Influenza vaccine

คุณภาพชีวิตของผู้ป่วย Thalassemia การเข้ารับการรักษาในสถานพยาบาล การศึกษา / ทำงาน สิทธิการรักษา การวางแผนครอบครัว

Prevention is better than cure