The management of a disease starts with an accurate diagnosis. Physicians are trained to come up with a list of differential diagnoses that stand up to scrutiny so that one disease after another can be checked off as further investigations take place, leaving the one correct diagnosis to remain.
It is therefore imperative that physicians have the tools to make quick and accurate diagnoses. In fact, many diseases can be diagnosed only if they meet certain criteria using certain diagnostic tools. In these situations, the decision is binary: the patient either has the disease or does not.
However, the reality is that many diseases do not return a binary result and are sometimes treated speculatively according to the physician’s best judgment.
Genetic diseases such as sickle cell disease (SCD) are usually diagnosed via genetic testing. However, SCD is unique in that there are a number of methods physicians use to diagnose the disease. Some diagnostic techniques double as means to monitor disease progression.
Searching for Signs
Arishi and colleagues presented the various techniques used to detect SCD in a literature review published in Micromachines.
The first is a full blood count (FBC). An FBC is one of the most frequently ordered laboratory tests; it is quick, efficient, and yields important data. The main advantage of ordering an FBC is that the hemoglobin count should be abnormally low in patients with SCD. Red blood cells (RBCs) and hematocrit levels tend to be low, while white blood cells (WBCs) and platelets tend to be elevated.
“Sickling of RBCs is the primary pathologic event in SCD,” Faes and colleagues wrote in Blood. “Under hypoxic conditions, sickle RBCs undergo a dramatic change in morphology resulting from polymerization of abnormal hemoglobin (Hb) tetramers.”
Although an FBC can quickly point a physician in the right direction (at the very least, the anemic picture should require immediate action), an FBC is insufficient to diagnose SCD on its own.
Read more about SCD diagnosis
Another diagnostic tool is a polymerase chain reaction (PCR) test. “Polymerase chain reaction is one of the most powerful diagnostic techniques, where special enzymes are used to amplify specific parts of the genetic materials to millions of copies, using specific primers,” Arishi et al wrote.
PCR-based techniques, such as high-resolution melting (HRM) analysis, are simple and cost-effective in the mass screening for the SCD genotype. This is important in parts of the world where the incidence of SCD is high and mass screening may be helpful in identifying patients who have the disease without realizing it.
Monitoring the Progression of SCD
Research and innovation in SCD diagnosis and management are happening all the time, and one development of note is the mechanical differentiation of sickle cells.
In SCD, RBCs are deformed and fragile and thus impair blood flow. However, it is precisely this feature of RBCs that allows scientists to differentiate sickle cells via a novel technique. This technique involves using optical tweezers to capture RBCs by dragging them through a viscous fluid (human AB plasma) for the purpose of determining the elasticity of the cells.
For patients with SCD on hydroxyurea, the deformability of the cells was found to be very similar to normal control cells. Hence, this novel technique using optical tweezers can be used to monitor treatment response to hydroxyurea but cannot be used to differentiate between various types of hemoglobin diseases.
Read more about SCD treatment
As mentioned, some diagnostic techniques for detecting SCD can also be used to monitor disease progression. The main goal of SCD management is the prevention of acute, painful crises. It is also important to note that patients with SCD are at a higher risk of stroke, pulmonary disease, cardiac disease, and renal disease. Hence, the onus is on the physician to ensure that the patient’s condition does not deteriorate in any of these areas.
The management landscape for patients with SCD has undergone tremendous changes in the positive direction in the last few decades, and patients with SCD finally have the opportunity to live more normal lives than ever before. However, this means diagnostic measures must quickly give way to measures to monitor disease progression.
“Specialized comprehensive care, including regular screening assessments and monitoring for disease manifestations, is required from identification by newborn screening through adulthood,” Hoppe and Neumayr wrote in Hematology/Oncology Clinics of North America.
Faes C, Ilich A, Sotiaux A, et al. Red blood cells modulate structure and dynamics of venous clot formation in sickle cell disease. Blood. 2019;133(23):2529-2541. doi:10.1182/blood.2019000424
Hoppe C, Neumayr L. Sickle cell disease: monitoring, current treatment, and therapeutics under development. Hematol Oncol Clin North Am. 2019;33(3):355-371. doi:10.1016/j.hoc.2019.01.014
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