It is almost an axiom in medicine that diagnosing a condition as early as possible often leads to better outcomes. Some conditions, like food poisoning, are immediately apparent. However, some diseases are dangerously insidious and are in fact more lethal due to their ability to go undetected for years; cancers such as cholangiocarcinoma come to mind.
Then we have a category of diseases that are not immediately obvious but should be detectable once symptoms manifest in earnest. Sickle cell disease (SCD) falls into this category. Although patients with SCD can be asymptomatic for long periods of time, the presence of painful vaso-occlusive crises would normally lead physicians down an investigative path toward a conclusive diagnosis of this condition.
SCD is classified as a rare disease because it only affects approximately 100,000 individuals in the United States. Its global prevalence is around 3 million.
This disease is driven by point mutations in the HBB gene that codes for the β-subunit. In SCD, nucleotide substitution occurs and amino acids are altered, resulting in the formation of hemoglobin S (HbS). The HbS is rigid and sickle-shaped; crucially, it has a low affinity for oxygen. This means that circulatory oxygenation is impaired.
Read more about SCD epidemiology
Although the most prominent symptoms of SCD are vaso-occlusive crises, the poverty of circulatory oxygenation can cause a number of complications. These include organ failure due to progressive ischemia, cerebrovascular disease, retinopathy, and priapism. In pregnant women, common complications include preeclampsia and preterm delivery.
Epidemiological studies indicate that individuals with an Afro-Caribbean background are at a higher risk of developing SCD. In Sub-Saharan Africa, the mortality rate is exceedingly high, reaching up to 80% by the time a patient turns 5 years of age. The most common cause for this alarmingly high mortality rate is the lack of comprehensive medical care, as well as the risk of infections such as invasive pneumococcal disease and malaria.
Of course, physicians must have adequate diagnostic tools to detect SCD; even the most acute clinical suspicions matter little without an internationally validated diagnostic tool.
An Arsenal of Diagnostic Tools
One of the most important aspects of the consultation process is taking a detailed history. Some physicians who are relatively new in the field have the unfortunate tendency to skim over the history-taking process in favor of technologically advanced procedures such as computed tomography (CT) or magnetic resonance imaging (MRI).
Nevertheless, experienced physicians understand the incredible value of a history well-taken; some estimate that 70% of what one needs to know can simply be gathered via a good patient interview. In SCD, family history is crucial, since it is an inherited disorder. Physicians should also understand any complications of this disease (both acute and chronic). The key to a good history is to ensure that relevant questions are asked to rule out potential differential diagnoses (such as metabolite disturbances, diabetes mellitus, and thalassemia).
Read more about SCD diagnosis
After a detailed history has been taken, physicians typically move on to collect a full blood count. As a medical doctor, I noticed that physicians routinely take a full blood count, whether it was strictly indicated or not. The logic goes that a full blood count is important even if it simply reveals that there is nothing wrong (plus it is relatively cheap).
In SCD, a full blood count would immediately reveal anemia, specifically hemolytic anemia. This means that red blood cell count, hemoglobin, and hematocrit levels tend to be low. In known cases of SCD, patients who receive hydroxyurea treatment may have an elevated mean corpuscular volume. Physicians may also detect an increase in red cell distribution width due to the different subpopulations of erythrocytes.
Another test that is cheap and effective is a solubility sickling test. The principle behind this test is that HbS is insoluble in the presence of a concentrated phosphate buffer, sodium dithionate, and a hemolyzing agent. These agents cause the HbS to crystallize and precipitate the cells. This test is best compared with negative and positive controls, which should make its abnormal appearance all the more obvious.
Hemoglobin electrophoresis is another key test in detecting hemoglobin variants. It utilizes an electrical field to cause electrically charged molecules to migrate. Hemoglobin variants can be identified by using different pH and mediums.
“Hemoglobin electrophoresis can differentiate between HbS and HbC, which are the most clinically significant variants,” Arishi and colleagues wrote in Micromachines.
One of the most powerful modern diagnostic techniques we have is polymerase chain reaction. This method utilizes special enzymes to amplify certain parts of a piece of genetic material. The availability of this test has made a significant difference in the field of prenatal and neonatal care. A number of polymerase chain reaction techniques are used in the mass screening of SCD genotypes, as they can be used to detect βs mutations.
“Regardless of the methods implemented, the outcomes must be correlated with the clinical picture,” Arishi and colleagues cautioned.
In an age of increasingly effective and cheap diagnostic procedures for detecting SCD, physicians have a golden opportunity to detect and diagnose this condition early, saving lives in the process.
References
Brandow AM, Liem RI. Advances in the diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022;15(1):20. doi:10.1186/s13045-022-01237-z
Arishi WA, Alhadrami HA, Zourob M. Techniques for the detection of sickle cell disease: a review. Micromachines (Basel). 2021;12(5):519. doi:10.3390/mi12050519
