From the Guidelines
The sickling window in sickle cell disease refers to the specific range of oxygen saturation where red blood cells are most likely to undergo sickling, typically between 40-60% oxygen saturation. This concept is crucial in understanding the pathophysiology of sickle cell disease, as described in the guideline on the peri-operative management of patients with sickle cell disease 1. At this intermediate level of deoxygenation, hemoglobin S molecules polymerize and form rigid fibers that distort the red blood cell into the characteristic sickle shape.
Key points to consider:
- Above this window (higher oxygen levels), hemoglobin remains properly saturated and cells maintain their normal disc shape
- Below this window (severe deoxygenation), most cells have already sickled
- Understanding this concept is clinically important because patients with sickle cell disease should avoid situations that might place their oxygen saturation in this dangerous range, such as high altitudes, extreme physical exertion without proper hydration, or environments with reduced oxygen
- Healthcare providers monitor oxygen saturation carefully during procedures and illnesses to keep patients above this sickling window, as recommended in the guideline 1
The severity of sickle cell disease varies according to genotype and within genotype, with HbSS, HbSß0-thalassaemia, and HbSD disease being associated with severe sickle cell disease, early onset of painful crises, and severe anaemia 1. Fetal haemoglobin (HbF) reduces the polymerisation of the HbS molecules, and offers some protection in sickle cell disease, with patients with high HbF levels (> 8%) tend to have mild phenotype with fewer symptoms 1.
In clinical practice, avoiding the sickling window is crucial to prevent sickling and its associated complications, and healthcare providers should be aware of the factors that can influence oxygen saturation in patients with sickle cell disease, as outlined in the guideline 1.
From the Research
Definition of Sickling Window
- The sickling window refers to the range of oxygen tensions at which sickling of red blood cells occurs in sickle cell disease patients [ 2 ].
Factors Influencing the Sickling Window
- Physiological modulators of oxygen affinity, such as pH and 2,3-diphosphoglycerate, can affect the sickling window [ 2 ].
- Antisickling agents, including GBT440, can alter the oxygen affinity of hemoglobin and cause a left-shift of the Point of Sickling (PoS), indicating improved deformability at lower oxygen tensions [ 2 ].
Measurement of Sickling Window
- The oxygenscan method can measure RBC deformability as a function of pO2 and produce clinically relevant parameters, including the Point of Sickling (PoS5%) [ 2 ].
- The sickling window can be assessed using high-throughput methods, such as semiquantitative measurement of hemoglobin polymer in single RBCs as a function of oxygen [ 3 ].