Case series of octogenarians with sickle cell disease

To the editor:

Survival of patients with sickle cell disease (SCD) has increased progressively since the 1980s.^1-5  Patients with SCD in their sixth or seventh decade have been described previously.⁶  This report describes 4 patients with SCD who survived beyond the age of 80 years. Three of these were US citizens enrolled in the Sickle Cell Center of Thomas Jefferson University. The center and all its projects were approved by the institutional review board (IRB). The report of the fourth Brazilian patient was approved by the IRB of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti. Table 1 lists the demographic and clinical characteristics of these patients, and Table 2 shows their most recent (within 3-5 years) key laboratory data at a time when they were in a stable steady state.

Old age in the general population usually refers to life expectancy of people beyond what is presumed to be the life expectancy of human beings. Specific numbers that define old age, however, vary greatly among countries, cultures, habitats, and social sciences. Thus, there are official definitions, popular definitions, subgroup definitions, and so forth. Gerontologists define subgroups in a number of ways^7,8 ; however, the subgroup definitions that seem to be in common use are young-old (65-74 years), middle- or older-old (75-84 years), and oldest-old (≥85 years).⁸  Using these definitions, 3 of our patients are older-old and 1 is oldest-old. These definitions may replace those that are categorized by age measured in decades, such as quinquagenarian (50-59 years).

Analysis of the data in Tables 1 and 2 shows expected and unexpected features of SCD and identifies certain parameters that may contribute to longevity. Although our report of 4 patients over the age of 80 years is anecdotal in nature, certain demographic and clinical features are unusual. In comparison, a previous prospective study in patients enrolled in the Sickle Cell Center at Jefferson showed that the mean age of death of 17 women with SS who died during 5 years of observation was 39.1 ± 14.87 years.⁹  The cohort of patients with Hb SC disease at Jefferson included 172 men and women. Twenty-one (12%) of those patients were women who died at a mean age of 49.6 ± 13.22 years. In one Brazilian institution, the mean age of women with Hb SC disease at death was 28.15 ± 9.11 years (Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, unpublished data).

The obvious feature is that all described patients are women. Sex is known to influence longevity both in the general population and in patients with SCD. Previous studies showed that the mortality rate in children with SCD is similar for boys and girls.^10-13  The divergence in the mortality rate between the sexes in favor of females becomes apparent in adults.^4,10  The reason why adult women with SCD live longer than men is not known. One possibility is relatively lower blood viscosity due to lower Hb and hematocrit levels in women.

Some of the features our patients had are known to be associated with good prognosis. These include the infrequent VOCs that required hospitalization; no history of strokes; no previous history of ACS, except in the Brazilian patient; low white blood cell count; low hemoglobin level; and normal biochemical parameters.

Another common feature in our patients is that none of them was on hydroxyurea (HU) because none met the inclusion criterion of at least 3 VOCs that required hospitalization in the immediate previous year and because HU is not approved for Hb SC disease. Nevertheless, the Hb F levels (12% in patient A and 8.8% in patient B) are relatively high. The beneficial cutoff level of Hb F has not been well determined and verified. The primary end point of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) was not the level of Hb F but the frequency of VOCs.¹⁴  Two years after starting HU in the MSH study, the mean Hb F level in the HU group was 8.6% ± 6.8 compared with 4.7% ± 3.3 (P = .0001) in the placebo group.¹⁵  It is generally believed, however, that the higher the level of Hb F, the milder the SCD. Platt et al²  analyzed the risk factors for death in patients with SS in the Cooperative Study of Sickle Cell Disease and found that SS patients with Hb F levels >8.6% had better survival than those with Hb F levels <8.6%. It should be noted that the Hb F levels in patients A and B (Table 2) are the average of previous recent determinations. Higher Hb F levels are often seen in younger years (eg, the Hb F level of patient B was 12.2% when she was 64 years old), and Hb F levels and leukocyte counts are known to decrease with age.¹  Accordingly, the relatively high endogenous levels of Hb F in patients A and B may have contributed to their longevity.

The utilization of blood transfusion differed among the 4 patients. Patient A received blood transfusion to keep her Hb level >7 g/dL due to her cardiac complications. She developed iron overload treated with deferasirox that was later discontinued due to an increase in serum creatinine level. Patient B refused blood transfusion unless it was absolutely necessary. Patient C had a Hb level of >9 g/dL and rarely required blood transfusion. The diagnosis of Hb SC disease in patient D was made at the age of 76 years when she presented with severe symptomatic anemia with a Hb level of 6 g/dL. Workup of the anemia revealed Hb SC disease, and she was started on simple transfusion. Within a few months, she developed ACS and was placed on chronic blood transfusion. Later, she developed the second episode of ACS, which was fatal.

Another common feature among the 4 patients is the family support and adherence to medication intake, appointments, and referrals. This adherence was based on the observations of the many providers they had, including the authors.

In addition to the common features, each patient had specific favorable lifestyle factors in addition to those mentioned in Table 1. Patient A is married, and her husband is highly supportive. Although Patient B was a widow for several years before her death, her son was very supportive. Patient C was a widow with five children; her oldest daughter was very supportive. Patient D was married and had two daughters who lived with her and took excellent care of her.

Despite the longevity of these patients, they did suffer from complications of their disease and from serious comorbidities, shown in Table 1. Comorbidities encompass both sickle and nonsickle complications that may emerge in older age. Over 20 comorbidities affecting patients with SCD have been described.¹⁶  Cognizance of the complexity of SCD and its polymorbidities and the implementation of preventative, educational, counseling, and prompt intervention measures may ameliorate the associated complexities of the disease and improve the quality of life of its victims.

In summary, the patients described had similar desirable features of SCD, despite their different ancestries, cultures, and countries. Their lifestyle of no smoking, no or occasional alcohol, normal body mass index, compliance, and excellent family support were, most likely, important contributors to their longevity. All these factors taken together indicate that these 4 women may provide a blueprint of how to live a long life, despite having a serious medical condition like SCD.