A pain crisis is similar, with one key difference: Hematocrit levels do not drop precipitously. It is not always possible to distinguish between a sickle cell crisis and a pain crisis within the first few hours of presentation. However, prompt recognition and rapid treatment of an acute flare-up (with analgesia, oxygen, hydration, and a search for the precipitating cause) can sometimes prevent the drop in hematocrit associated with a sickle cell crisis.7
Treatment and follow-up
A rapid response to flare-ups is a key reason for primary care physicians and patients with SCD (or their parents) to develop a close relationship. Physicians caring for such patients must ensure that they receive adequate pain management, control of sickling events, and, when necessary, access to emergency services without delay. Blood transfusions are needed to treat severe anemia, which may develop as a result of an infection or enlargement of the spleen.
Beyond the crisis. Management of SCD involves more than responding to crises. Magnesium, taken regularly, can stabilize red cell membranes, and hydroxyurea, which increases fetal hemoglobin, may reduce the frequency of attacks.8 Screening for folate and B12 deficiency should be considered prior to supplementation.9 Bone marrow transplantation and gene therapy are being explored, as well.10
Growing awareness of SCD and improvements in disease management have extended the life expectancy of patients with the disease in recent years to the mid-40s, on average.11 Advances in our understanding of SCD, however, have done little to reduce the incidence of the disease.6
Part of the problem is that sickle cell trait—like carrier status of other genetic diseases identified at birth—is often forgotten or overlooked by the time the patient reaches reproductive age. Family physicians can help by educating parents of a newborn with an SCD diagnosis—or with sickle cell trait—about the risks of passing on the disorder. It is equally important to advise teens and young adults to find out whether they or their partners are carriers, stressing the need for both parties to be tested before they marry or start a family.
Thalassemia
Originally described by Thomas Cooley in 1925,12 thalassemia is named for the Greek word for sea (thalassa)—reflecting the fact that for many years, those most affected lived in the vicinity of the Mediterranean Sea.13 Unlike SCD, which is caused by a qualitative problem involving the beta chain of hemoglobin, thalassemia is characterized by quantitative defects in the synthesis of either the alpha or beta hemoglobin chain.
Thus, thalassemia is a spectrum disorder designated in part by the chain of hemoglobin (alpha or beta) that is affected. The HbVar Database of Human Hemoglobin Variants and Thalassemia Mutations (http://globin.bx.psu.edu/hbvar/) lists hundreds of mutations associated with various subtypes, with particular forms of the disease found in certain ethnic groups.
The number of Americans affected by thalassemia is not known. It is estimated, however, that 15% of African Americans (the US population with the highest incidence of any form of thalassemia) are affected by alpha thalassemia.14 The incidence of beta thalassemia among Mediterranean, African, and Middle Eastern populations ranges from about 5% to 25%.15
Inheritance
Most people have 4 genes for the alpha chain of hemoglobin (2 from each parent) and 2 genes for the beta chain of hemoglobin (one maternal and one paternal). The severity of the disorder typically depends on the number of genes affected.
Individuals in which one alpha gene is missing or damaged are silent carriers, while those with 2 affected genes may have a subclinical anemia, often mistaken for iron deficiency anemia. Those in which 3 alpha genes are missing or defective have hemoglobin H disease, a serious condition that causes an enlarged liver and spleen and hemolytic anemia. When all 4 alpha genes are affected, the result is hydrops fetalis, a condition that leads to the death of the fetus or newborn.16
Beta thalassemia—the group of disorders caused by reduced or absent synthesis of the beta chains of hemoglobin—is further classified as minor, intermediate, or major (also known as Cooley’s anemia). People with minor beta thalassemia are typically asymptomatic; those with major thalassemia are severely affected, and often die by the age of 20 years.17
Testing
Routine neonatal screening can detect both alpha and beta thalassemia and identify asymptomatic carriers. Confirmation testing is widely available by hemoglobin electrophoresis. Antenatal testing can be performed via amniocentesis or chorionic villus sampling, and is indicated in countries in which thalassemia is relatively prevalent. In the United States, we typically take a family history and may screen the parents for carrier status.18