Diagnosis of Sickle Cell Disease and Effect on QoL


Expert hematologists review the presentation and diagnosis of sickle cell disease and the resulting effect of anemia and hemolysis on a patient’s quality of life.


Jeffrey D. Lebensburger, DO, MSPH: Sickle cell disease is diagnosed at birth. In the mid-1970s, New York became the first state to use newborn screening, and that’s how we diagnose sickle cell, and by 2006, all states in the US were able to diagnose sickle cell in any infant. When any child is born, they get their heel stick, either a hemoglobin electrophoresis or HPLC [high-performance liquid chromatography] is performed, and that will come back with a diagnosis of sickle cell. Now, there is some confusion in these newborn screenings in that the first letter that’s shown is hemoglobin F because that’s the most prevalent form of hemoglobin in a newborn. However shortly after that, you’ll see [hemoglobin] S, and that tells you there’s a sickle cell component. We would suggest that you look at the newborn screening, it should have what the diagnosis is, but if there’s any question, call the local pediatric hematologist because it’s important when you see that newborn screening that if this patient does have sickle cell, or one of our sickle cell disease types, they are seen quickly by a pediatric hematologist.

It is very important they are seen within a few months by a pediatric hematologist. It is also important to go ahead and start hydroxyurea. When infants are diagnosed with sickle cell disease, or even if there’s any question of whether this could be a sickle cell disease type, it’s important for a primary care provider to start penicillin prophylaxis.

After a newborn screening identifies the patient with sickle cell, there is a period of some level of protection because all infants are born with a very high level of fetal hemoglobin. For infants, it’s usually going to be acute complications that will present, such as fever, which can be a life-threatening issue because patients with sickle cell are at risk for pneumococcal bacteremia. However, we do begin to see that around 1 year of age, patients begin to develop pain events. They can develop acute chest syndrome, and that can progress throughout one’s lifetime to multiple sickle cell events. All of our patients with sickle cell disease are at high risk for developing acute complications, especially if they have one of the severe phenotypes, or if they’re not on any disease-modifying therapy. This can occur intermittently and unexpectedly for patients. Unfortunately, there’s also an underlying issue with patients with sickle cell having chronic complications, and these are organ-specific complications. For example, with the CNS [central nervous system], they are high risk for having either silent cerebral infarcts, TIAs [transient ischemic attacks], or overt strokes. We can have pulmonary disease or cardiac complications, including pulmonary hypertension. We can have renal disease, including chronic kidney disease, as well as other organs where chronic events occur. All these events can occur throughout the lifetime, so we think of it as a paradigm where there are acute events, which can be an unexpected complication requiring a patient to be hospitalized, but also underlying chronic disease. This is a little harder and needs to be closely evaluated to make sure we are not having our patients progress to a chronic organ disease.

John J. Strouse, MD, PhD: There are several ways that the quality of life of people with sickle cell disease is affected by their anemia and hemolysis. When we ask people with sickle cell disease what gives them trouble, they typically list 3 things. At the top of the list is pain, next is fatigue, and the third issue is cognitive impairment or cognitive dysfunction that affects their daily life. We know that hemolysis, by releasing free hemoglobin and impairing nitric oxide bioavailability, causes vasoconstriction, and that can trigger the vaso-occlusion of sickle cell disease. Hemolysis also increases the adhesiveness of red blood cells, and that increased adhesiveness can contribute to complications like vaso occlusion and pain. The anemia itself likely contributes quite a bit to people’s fatigue and decreased exercise tolerance. When it comes to the cognitive impairment, that’s more complicated. We do know that anemia is associated with cognitive issues, particularly when it comes to working memory and processing speed. That might be part of it. The anemia also is associated with silent cerebral infarcts, which are associated with poor performance on a number of tests of cognitive function, including a full-scale IQ. To summarize, we think that anemia and hemolysis both increase the vaso-occlusive complications, and that the anemia itself contributes to fatigue and cognitive impairment in people with sickle cell disease.

When people have pain, it impacts their daily quality of life when they’re outpatients. People cannot perform their usual activities because of severe pain, and it also leads to acute health care utilization. People have emergency department or day hospital visits, where they get treated with intravenous opioids for severe pain, which interferes with their ability to both enjoy life and to participate in their usual activities. When someone comes to the emergency department, about 40% of the time, they’ll end up being hospitalized, which can last anywhere from a couple of days to a week or 10 days for particularly severe episodes of pain. Extended hospitalizations interfere with the quality of life and activities of daily living as well. Sickle cell disease can contribute to vision and hearing problems as well. We do see a large proportion of people who develop some retinopathy related to their sickle cell disease. This can impair their visual acuity and require treatments for proliferative retinopathy, typically treatment with laser or cryotherapy to eliminate the blood vessels that are prone to bleed and lead to vision loss, and also to tack down the back of the retina. We see an increased incidence of impaired hearing in people with sickle cell disease, which can be various mechanisms, with the most common probably being sickle cell vaso occlusion that affects the inner ear. Men who have more severe anemia are more likely to have episodes of priapism. Those episodes, in addition to causing pain, can lead to injury of the penis and sexual dysfunction. There’s a relatively high incidence of impotency in men with sickle cell disease.

Sophie M. Lanzkron, MD, MHS: Life expectancy in sickle cell disease is still shortened. We know that it’s probably 25 to 30 years shorter for people with sickle cell disease than it is in the general African American population in this country. Although it has gotten much better; in the 1970s, the average life expectancy was about age 17. We now know that for people with the most severe form, hemoglobin SS, they live into the fourth or fifth decade of life on average. There is this broad spectrum where I have patients who are living well into their 70s. One of the things I hear often from my patients who are adults is that they were told as children that they wouldn’t live until their fifth birthday, 10th birthday, 20th birthday. They’re used to hearing this often, especially my older patients, so they are often not interested in talking about life expectancy because they’ve heard it all before and they’ve lived past so many of those milestones. I think it’s different for the younger generation of patients who are coming up into the adult world now. We talk about today, and hope that as we have new therapies available, that their world will be very different. Many of the kids with hemoglobin SS disease are now coming to us on hydroxyurea, and we really have no idea what effect that’s going to have on long-term survival. There are pretty good data that hydroxyurea can improve overall survival. When we talk about prognosis, one of the key things is not necessarily life expectancy, but the risk of developing chronic pain that I think is important to talk about with patients early so it doesn’t become a surprise as they grow older. I don’t spend a lot of time talking about life expectancy because my patients have heard it all before and stop believing me when I start talking about the ages to which they might live.

Transcript edited for clarity.

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