Chapter 136. Sickle Cell Disease and Other Hereditary Hemolytic Anemias

The inherited hemoglobin disorders stem from abnormal Hb structure (eg, sickle cell disease [SCD] or abnormal Hb production (eg, the thalassemias). Anemia occurs when destruction of red blood cells outstrips production. Most patients are aware of their dyshemoglobinemia status.

Clinical Features

The most common complaints in SCD (homozygous (HbSS) or sickle trait (heterozygus [HbAS]) patients are pain, localized or generalized, weakness, or infectious complaints. Physical examination findings commonly include pale complexion, venous stasis changes, jaundice, hepatosplenomegaly, anemic cardiac flow murmurs, cardiomegaly, and high output CHF.

Painful vaso-oclusive crisis in the musculoskeletal system or diffusely in the abdomen are the most common presentation to the ED. Crisis occur when sickled RBCs mechanically obstruct blood flow, causing ischemia, organ damage, and infarcts. Crisis-causing stresses include fever or infection (especially encapsulated organisms Haemophilus influenza or Pneumococcus), cold exposure or high altitude, dehydration or overexertion, medication noncompliance, or drug use.

Acute symptomatic anemia results from splenic sequestration or bone marrow failure (aplastic crisis) and presents with weakness, dyspnea, CHF, or shock.

Life or limb-threatening events seen in SCD patients include acute chest syndrome (vaso-occlusive pulmonary insult), stroke, renal infarct, mesenteric infarcts, sepsis, osteomyelitis, pneumonia, or priapism.

Diagnosis and Differential

The degree of illness guides the evaluation of an acute crisis. Although workups should be individualized, the more common protean complaints (pain, weakness, fever) must include a search for a cryptic inciting event. See Table 136-1.

Acute worsening of baseline anemia may suggest increased splenic sequestration if the reticulocyte count is elevated, or bone marrow failure if the reticulocyte count is depressed. Leukocytosis or left shift with increased bands suggests infection. Perform a pregnancy test on women. Assessment of electrolytes allows evaluation of dehydration and renal function. Liver function tests and lipase may help evaluate abdominal pain. Febrile SCD patients without localizing symptoms should have blood cultures, urinalysis, and chest radiographs performed.

Patients presenting with symptoms of acute chest syndrome (chest pain, cough, fever, dyspnea) need immediate evaluation (Table 136-2). Assess oxygenation; type and cross for possible exchange transfusion.

Radiographs of the skeleton are indicated for atypical focal bone pain. Advanced imaging for abdominal pain or for neurologic manifestations are helpful with assessment of these symptoms.

The differential diagnosis includes osteomyelitis, bony infarcts, cellulitis, acute arthritides, pancreatitis, hepatitis, cholecystitis, pelvic inflammatory disease, pyelonephritis, pneumonia, pulmonary embolus, and meningitis.

Emergency Department Care and Disposition

Initial management for acute crisis in SCD patients is primarily supportive, and includes pain management and an assessment for the underlying cause of the crisis (see Tables 136-1 and 136-2).

Oral rehydration should be encouraged if dehydration is suspected. IV crystalloid may be used as an alternative, at 1.5 times maintenance. Opioid pain medications should be administered for severe pain. Individualized treatment plans are warranted for patients with frequent relapses. Supplemental oxygen is indicated for hypoxia. ECG and cardiac monitoring is appropriate for patients with cardiopulmonary symptoms. For symptoms of acute infection, cultures should be obtained and broad spectrum antibiotics administered. Exchange transfusion for acute crisis or complications should be considered in specific circumstances–aplastic crisis, cardiopulmonary decompensation, pregnancy, stroke, respiratory failure, general surgery, and priapism (requires urologic consultation). Admission criteria include pulmonary, neurologic, aplastic, or infectious crises; splenic sequestration; intractable pain; persistent nausea and vomiting; or an uncertain diagnosis. Discharged patients should receive oral analgesics, close follow-up, and instructions to return immediately for temperature above 38°C or worsening symptoms.

Other genetic variants of hemoglobinopathies exist and vary in presentation, from asymptomatic to SCD-like and depend upon the specific abnormality and whether homozygous, heterozygous, or combined with sickle cell trait.

Thalassemias

Thalassemias are hereditary disorders caused by defective synthesis of globin chains, resulting in microcytic, hypochromic, hemolytic anemia. The degree of illness depends upon the type and number of genetic abnormalities.

Patients with β-thalassemia minor have mild microcytic anemia and are generally asymptomatic. Patients with β-thalassemia major (Cooleys anemia), develop hepatosplenomegaly, jaundice, and bony changes. They are at increased risk for infection and may develop severe anemia requiring blood transfusions. Iron overload from transfusions causes significant morbidity and mortality.

Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy of RBCs. This causes Hb precipitation, RBC removal by the spleen and hemolysis. The amount of hemolysis depends on degree of enzyme abnormality. Most patients are asymptomatic until an exposure to an oxidative stress (eg, medication, infection, fava beans) causes hemolysis. Evaluation includes a complete blood count and reticulocyte count, bilirubin levels, serum aminotransferases, and lactate dehydrogenase. Treatment is determined by the patient's overall clinical condition and includes early treatment of infection and may include blood transfusion for severe anemia.

Hereditary Spherocytosis

Hereditary spherocytosis results from an erythrocyte membrane defect creating small inflexible RBCs unable to pass through the spleen resulting in an increased rate of destruction and a compensatory increase in RBC production. Complications include aplastic or megaloblastic crises, cholecystitis or cholelithiasis, splenomegally and hemolysis with jaundice. Treatments include blood transfusions and splenectomy in severe cases.