6.2 Thalassemia and Other Hemoglobinopathies

Thalassemia is underproduction of globin chains, not a sickle polymer. The CPHON nurse’s job is to tell β from α, transfusion-dependent from intermittent, and anemia from the iron that chronic transfusion deposits in heart, liver, and endocrine glands. A 14-month-old who becomes pale as fetal hemoglobin falls, a 6-year-old with maxillary prominence after missed transfusions, and a teenager with delayed puberty on chelation are the same disease family at different stages.

β-thalassemia: major, intermedia, and trait

β-thalassemia major, classically called Cooley anemia, means two severe β-globin mutations and little or no hemoglobin A. After HbF declines in late infancy, children develop progressive hemolytic anemia, irritability, poor feeding, hepatosplenomegaly, and expanding marrow. Without a chronic transfusion program they do not grow, their bones deform, and high-output cardiac strain appears. This is transfusion-dependent thalassemia: planned red-cell support is the backbone of care, not a rescue used only when the child collapses.

β-thalassemia intermedia (often grouped with non-transfusion-dependent β-thalassemia) retains enough β-globin that the child may need only intermittent transfusion during infection, pregnancy in older patients, or growth spurts. Intermedia is not “mild enough to ignore.” These children still load iron from increased absorption and occasional units, still risk pulmonary hypertension and thrombosis, and still develop bone disease. β-thalassemia trait (minor) is a carrier state with microcytosis; it is not a transfusion disease, but it is a counseling diagnosis so families do not treat every low MCV as iron deficiency forever.

A 10-month-old with falling hemoglobin, a huge liver and spleen, and both parents with microcytic “anemia” that never needed iron is β-thalassemia major until hemoglobin analysis says otherwise. Start the diagnostic path (hemoglobin electrophoresis or HPLC, plus α/β genetic testing as directed) while supporting the anemia; do not give iron empirically for every microcytic toddler.

α-thalassemia: gene dose, HbH, and hydrops

Four α-globin genes normally exist. Loss of one is a silent carrier. Loss of two is α-thalassemia trait (cis deletions are more common in some Southeast Asian ancestries and raise hydrops risk in offspring). Loss of three is hemoglobin H (HbH) disease: unstable β4 tetramers, moderate hemolytic anemia, and intermittent transfusion during infection or oxidative stress. Loss of all four is Hb Bart’s hydrops fetalis (γ4 tetramers), usually lethal in utero unless a perinatal plan with intrauterine transfusion is in place. HbH is a living child’s disease; hydrops is an obstetric and neonatal emergency, not a routine clinic hemoglobinopathy.

Ineffective erythropoiesis and the face you can see

When globin imbalance destroys precursors in the marrow, ineffective erythropoiesis follows: the marrow works overtime and still delivers few viable red cells. Erythropoietin stays high. Marrow cavities expand. Extramedullary hematopoiesis grows in liver, spleen, and sometimes paravertebral masses. If transfusion is inadequate to suppress that drive, facial bones expand—maxillary prominence, dental malocclusion, frontal bossing—the chipmunk facies of undertransfused thalassemia major. Cortical thinning and pathologic fracture appear in the same physiology. A 6-year-old who missed a year of planned transfusions and now cannot close the teeth is not a dental-only problem; the transfusion program failed to suppress erythropoiesis.

Chronic transfusion: target as a concept, not a universal number

A chronic transfusion program uses leukoreduced, preferably phenotype-matched red cells to reduce alloimmunization, given on a calendar that keeps the child growing and in school. Pretransfusion hemoglobin targets are center- and protocol-specific. Cooperative programs often aim high enough to suppress ineffective erythropoiesis and prevent bone expansion, and not so high that extra iron and viscosity accrue without benefit. Do not memorize or invent a single gram-per-deciliter figure as an ONCC fact. Teach the principle: too low, the face and bones pay; the local protocol’s pretransfusion target is the number you chart against, not a number you improvise from a website.

A 5-year-old with β-thalassemia major whose pretransfusion hemoglobin has drifted far below the center’s target for months needs a logistics repair—transport, venous access, antibody workup—not a lecture that “thalassemia children are supposed to look pale.”

Iron overload, MRI T2*, and three chelators

Each unit adds iron the body cannot excrete. Iron deposits in the heart (cardiomyopathy, arrhythmia), liver (fibrosis, failure), and endocrine organs (diabetes, hypothyroidism, hypogonadism, delayed puberty, short stature). A 16-year-old on chronic transfusion who has not entered puberty is an iron-endocrine patient until the MRI and endocrine labs say otherwise. Serum ferritin trends are useful but rise with inflammation; they do not map organ iron by themselves. MRI T2* (and related R2/R2* methods) is the noninvasive map of liver and cardiac iron that guides intensification of chelation.

Chelators are not interchangeable nursing scripts:

Teach families why a “normal ferritin week” does not cancel the MRI schedule, and why a sore throat on deferiprone is a same-day count, not a school-clinic strep swab only. Deferoxamine that “tingles the ears” or blurs vision is held and referred, not pushed through the infusion.

HSCT and the brief other hemoglobins

Hematopoietic stem cell transplant from a matched sibling (or other protocol-eligible donor) can be curative for transfusion-dependent thalassemia, ideally before irreversible iron cardiomyopathy. Nursing teaching starts early: infection, graft-versus-host disease as a later-chapter topic, and the reason iron is still chelated around transplant. Gene-addition and gene-editing therapies exist in the field; for CPHON, HSCT is the established curative option to name.

Hemoglobin E is common in many Southeast Asian ancestries. Trait is mild; HbE/β-thalassemia can be as severe as transfusion-dependent β-thalassemia major and is managed on the same transfusion-iron-HSCT map. Hemoglobin C trait is usually silent; HbCC causes mild hemolysis. C matters on this exam mainly as the partner in HbSC disease (previous section). Do not treat every “E” or “C” on an electrophoresis as Cooley anemia, and do not dismiss HbE/β-thalassemia as trait.

The CPHON product in thalassemia is a child whose transfusions actually suppress marrow drive, whose iron is measured in organs not only in ferritin, whose chelator matches its toxicity checklist, and whose family has heard HSCT as a curative conversation at the right time—not after chipmunk facies and a stiff heart have already declared under-treatment.