Hereditary spherocytosis natural history, complications and prognosis
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- Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Natural History
- Disease severity and age of presentation — HS can present at any age and with any severity, with case reports describing a range of presentations, from hydrops fetalis in utero through diagnosis in the ninth decade of life. [1][2][3]
- The majority of affected individuals have mild or moderate hemolysis or hemolytic anemia and a known family history, making diagnosis and treatment relatively straightforward. Individuals with significant severe hemolysis may develop additional complications such as jaundice/hyperbilirubinemia, folate deficiency, or splenomegaly.
Hemolytic anemia — A classification for HS has been developed based on the severity of anemia and markers of hemolysis (reticulocyte count and bilirubin) [4][5]; it characterizes patients as having one of the following:
●HS trait – Normal hemoglobin and reticulocyte count
●HS (20 to 30 percent of cases) – Hemoglobin 11 to 15 g/dL; reticulocytes 3 to 6 percent; bilirubin 17 to 34 micromol/L
●Moderate HS (60 to 75 percent of cases) – Hemoglobin 8 to 12 g/dL; reticulocytes >6 percent; bilirubin >34 micromol/L
●Severe HS (5 percent of cases) – Hemoglobin 6 to 8 g/dL; reticulocytes >10 percent; bilirubin >51 micromol/L
- Neonates may have a relatively normal hemoglobin level at birth that is followed by development of severe anemia, especially during the first three weeks and, in some cases, the first year of life, when the erythropoietic response may not be adequate. According to one review, more than half of neonates with HS are not anemic during the first week of life [6]. However, anemia can develop after several days, and is most likely to be severe during the second or third week of life. Some infants require chronic transfusions during the first year; however, transfusion dependence beyond the first year of life is unusual.
- In older children and adults, the presentation may be that of an incidental finding of hemolysis, hemolytic anemia, or spherocytes on the blood smear (picture 2), or the individual may be symptomatic from anemia, splenomegaly, pigment gallstones, or jaundice. Jaundice due to severe hemolysis is less common after the newborn period.
- In some cases, co-inheritance of another disorder affecting RBC survival such as sickle cell disease or thalassemia can influence the severity of anemia and make diagnosis more challenging. [7]
Complications
Exacerbations of anemia in certain settings:
●Infections that impair RBC production in the bone marrow and thus diminish the capacity to compensate for chronic hemolysis may lead to a period of aplasia. A commonly cited cause of transient aplastic crisis is parvovirus B19 infection; other viral or bacterial infections may also cause transient aplasia. This is because individuals with chronic hemolysis are highly dependent on the accelerated production of new RBCs by the bone marrow, and they can experience a rapid drop in hemoglobin level when the bone marrow is unable to compensate for hemolysis. If an individual with HS develops a precipitous decline in hemoglobin level or reticulocyte count, testing for parvovirus infection is appropriate.
●Conditions that increase the size of the spleen, such as infectious mononucleosis, may cause increased splenic pooling of RBCs and/or increased hemolysis.
●Individuals who develop folate, vitamin B12, or iron deficiency may be unable to produce sufficient RBCs to compensate for those lost by hemolysis.
●Anemia may worsen during pregnancy, as the RBC mass and plasma volume expand to meet the physiologic needs of the pregnancy. Attention to folic acid supplantation and iron stores are also important so as not to impair RBC production.
●Individuals who experience a decline from their baseline hemoglobin level and/or reduction in baseline reticulocyte count are likely to require more frequent monitoring and/or additional testing, details of which will depend on the associated symptoms and laboratory findings.
Complications of hemolysis — Common complications of hemolysis include neonatal jaundice, splenomegaly, and pigment gallstones.
●Rarely, hemolysis may be severe enough to cause extramedullary hematopoiesis and/or growth delay.[8][9] A small subset of these children may be at risk for iron overload due to increased iron absorption and/or transfusions, although the majority of patients with HS do not develop iron overload.
●Other rare complications that have been reported include leg ulcers, priapism, neuromuscular disorders, cardiac disease, and gout; in some cases, these may represent coincidental rather than causal associations.[10]
Neonatal jaundice — HS may present in the neonatal period with jaundice and hyperbilirubinemia, and the serum bilirubin level may not peak until several days after birth. Some experts have proposed that HS is underdiagnosed as a cause of neonatal jaundice.[11] A requirement for phototherapy and/or exchange transfusion during this period is common.
Hyperbilirubinemia may be exacerbated by concomitant Gilbert syndrome.
Splenomegaly — Splenomegaly is rare in neonates, but can often be seen in older children and adults with HS. Early reports of family studies found palpable spleens in over three-fourths of affected members, but this may reflect a skewed population with the most severe disease. In these studies, the relationship between disease severity and splenic size was not linear.[12]
●There is no evidence of an increased risk of splenic rupture.
Pigment gallstones — Pigment (bilirubin) gallstones are common in individuals with HS and may be the presenting finding in adults. Gallstones are unlikely before the age of 10 years but are seen in as many as half of adults, especially those with more severe hemolysis. Gallstones appear to be more common in individuals with Gilbert syndrome.[13]
Obstructive jaundice or cholecystitis is treated similarly to that in individuals without HS. If cholecystectomy is performed, it may be worthwhile to discuss whether splenectomy was also planned, as the procedures could be combined; however, splenectomy should not be routinely performed during cholecystectomy.[14]
Prognosis
- Overall, the long-term outlook () for people with hereditary spherocytosis (HS) is usually good with treatment.[7] However, it may depend on the severity of the condition in each person.
- People with very mild HS may not have any signs or symptoms unless an environmental "trigger" causes symptom onset.[4] In many cases, no specific therapy is needed other than monitoring for and watching for signs and symptoms.[8] Moderately and severely affected people are likely to benefit from splenectomy.[5]
- Most people who undergo splenectomy are able to maintain a normal hemoglobin level.[4] However, people with severe HS may remain anemic post-splenectomy, and may need blood transfusions during an infection.[5]
- Information about life expectancy in the medical literature appears to be limited. However, we are not aware of reports that state that life expectancy is known to be significantly shortened in people without other medical problems who are managed appropriately. In all people who undergo splenectomy, there is a lifelong, increased risk of developing a life-threatening infection (sepsis).[9] Although most septic episodes have been observed in children whose spleens were removed in the first years of life, older children and adults also are susceptible. Fortunately, taking certain precautions can reduce this risk and can prevent minor infections from becoming life-threatening
References
- ↑ Perrotta S, Gallagher PG, Mohandas N (2008). "Hereditary spherocytosis". Lancet. 372 (9647): 1411–26. doi:10.1016/S0140-6736(08)61588-3. PMID 18940465.
- ↑ Whitfield CF, Follweiler JB, Lopresti-Morrow L, Miller BA (1991). "Deficiency of alpha-spectrin synthesis in burst-forming units-erythroid in lethal hereditary spherocytosis". Blood. 78 (11): 3043–51. PMID 1954389.
- ↑ Eber SW, Armbrust R, Schröter W (1990). "Variable clinical severity of hereditary spherocytosis: relation to erythrocytic spectrin concentration, osmotic fragility, and autohemolysis". J Pediatr. 117 (3): 409–16. PMID 2391596.
- ↑ Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ; et al. (2004). "Guidelines for the diagnosis and management of hereditary spherocytosis". Br J Haematol. 126 (4): 455–74. doi:10.1111/j.1365-2141.2004.05052.x. PMID 15287938.
- ↑ Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ; et al. (2004). "Guidelines for the diagnosis and management of hereditary spherocytosis". Br J Haematol. 126 (4): 455–74. doi:10.1111/j.1365-2141.2004.05052.x. PMID 15287938.
- ↑ Christensen RD, Yaish HM, Gallagher PG (2015). "A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates". Pediatrics. 135 (6): 1107–14. doi:10.1542/peds.2014-3516. PMC 4444801. PMID 26009624.
- ↑ Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ, General Haematology Task Force of the British Committee for Standards in Haematology (2012). "Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update". Br J Haematol. 156 (1): 37–49. doi:10.1111/j.1365-2141.2011.08921.x. PMID 22055020.
- ↑ Bastion Y, Coiffier B, Felman P, Assouline D, Tigaud JD, Espinouse D; et al. (1990). "Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: a case report". Am J Hematol. 35 (4): 263–5. PMID 2239921.
- ↑ Smith J, Rahilly M, Davidson K (2011). "Extramedullary haematopoiesis secondary to hereditary spherocytosis". Br J Haematol. 154 (5): 543. doi:10.1111/j.1365-2141.2011.08692.x. PMID 21517821.
- ↑ Perrotta S, Gallagher PG, Mohandas N (2008). "Hereditary spherocytosis". Lancet. 372 (9647): 1411–26. doi:10.1016/S0140-6736(08)61588-3. PMID 18940465.
- ↑ Christensen RD, Henry E (2010). "Hereditary spherocytosis in neonates with hyperbilirubinemia". Pediatrics. 125 (1): 120–5. doi:10.1542/peds.2009-0864. PMID 19948573.
- ↑ MACKINNEY AA (1965). "HEREDITARY SPHEROCYTOSIS; CLINICAL FAMILY STUDIES". Arch Intern Med. 116: 257–65. PMID 14315658.
- ↑ del Giudice EM, Perrotta S, Nobili B, Specchia C, d'Urzo G, Iolascon A (1999). "Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis". Blood. 94 (7): 2259–62. PMID 10498597.
- ↑ Ruparel RK, Bogert JN, Moir CR, Ishitani MB, Khan SP, Rodriguez V; et al. (2014). "Synchronous splenectomy during cholecystectomy for hereditary spherocytosis: is it really necessary?". J Pediatr Surg. 49 (3): 433–5. doi:10.1016/j.jpedsurg.2013.05.012. PMID 24650472.