positive (spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. this is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the rbc and leads to its rupture. although the osmotic fragility test is no longer considered the gold standard for diagnosing hereditary spherocytosis, as it misses ~25% of cases). acidified glycerol lysis test: positive (a newer version of the osmotic fragility test that adds glycerol to a hypotonic solution. this produces lysis, a positive test, quicker that the traditional saline version). supportive blood work: mean cell volume (mcv): normocytic (normal range: 80-100fl), or slightly lower. spherocytes are slightly smaller than normal biconcave red blood cells. mean corpuscular hemoglobin concentration (mchc): increased (normal range: 31-36% hb/cell). this is secondary to less water being in the cell. red blood cell distribution width (rdw): increased (normal range: 11-15%). the spherocytes create variation in the size of the red blood cells on average, thus expanding the distribution. red blood cell count (rbc): sometimes increased early (normal range males: 4.3-5.9 million/mm3; normal range females: 3.5-5.5million/mm3). the loss of surface area per cells cause the body to mass produce red blood cells. the spleen will filter spherocytes out and change this value. reticulocytes: increased (normal range: 0.5%-1.5% of the rbc listed above). the body to mass produces red blood cells (reticulocytes being young erythrocytes) even as the spleen filters spherocytes out. this is known as reticulocytosis. unconjugated bilirubin: increased (normal range: 0.2-1.2 mg/dl). this is caused by heme released into the hepatosplenic circulation by macrophages that have phagocytosed erythrocytes. the unconjugated bilirubin is not soluble in water (blood), so it binds to albumin, and is processed in the liver. haptoglobin (free): decreased (normal range: 41–165 mg/dl). this is caused by hemoglobin binding to haptoglobin, thus making it no longer "free." lactate dehydrogenase (ldh): increased (normal range: 110-295u/l in children). this is due to extravascular hemolysis. peripheral blood smear: directly shows spherocytes on microscope. eosin-5-maleimide binding test: positive (reduced mean fluorescence), as the test will demonstrate a reduced ability of the eosin-5-maleimide dye to bind to erythrocyte plasma membrane proteins. the process relies upon flow cytometry. gold standard test that produces results at low cost within ~2 hours. in chronic cases, patients who have taken iron supplementation, have heterozygous hemochromatosis, or received numerous blood transfusions, iron overload may cause additional health issues. measuring iron stores is sometimes considered part of the diagnostic approach to hereditary spherocytosis in older patients presenting with heart muscle damage of unknown etiology or liver disease without apparent cause. imaging ultrasound is often used to evaluate the dimensions of the spleen, and also the gallbladder in preparation for functionally curative splenectomy with or without cholecystectomy. treatment although research is ongoing, currently there is no genetic-level cure for the myriad of mutations that cause the various presentations of hereditary spherocytosis. common current management focuses on interventions prevent the body from inappropriately destroying the functional spherocytes produced by erythrocyte progenitor cells within the bone marrow. typical treatment options include: splenectomy (operative): this is the operative removal of the entire spleen by a surgeon, thus stopping the extravascular hemolysis, but also removing the immune functions the spleen naturally provide to the body. partial splenectomy (operative): this is when only a section of the spleen is removed, instead of the entire organ. the goal is to lower the extravascular hemolysis to a level compatible with homeostasis of the patient, while preserving the immune function of the spleen's presence. research on outcomes is currently ongoing, and is routine at children's hospitals within the united states of america. splenic ablation (interventional radiology): this option is non-operative, and is when an interventional radiologist (instead of a surgeon) uses radiologic techniques to coil or cauterize vasculature within the splenic circulation. there are various points in the circulatory pathway where the treatment can be applied to produces varying amounts of retained viability of the spleen, thus giving the option to attempt to preserve splenic immune function. all operative and interventional treaments require the immunization of hs patients against the influenza virus, sars-cov-2, and encapsulated bacteria such as streptococcus pneumoniae and meningococcus. antibiotics are no longer recommended for maintenance use, even in post-splenectomy hs patients. since the spleen is important for protecting against encapsulated organisms, sepsis caused by encapsulated organisms is a possible complication of splenectomy. additional elective treatments offered: surgical removal of the gallbladder. experimental treatment: bone marrow transplant (heme-oncology intervention): the replacement of the bone marrow with bone marrow from an individual without spherocytosis. the transplanted progenitor cells do not have the genetic mutations found in individuals with hereditary spherocytosis, and therefore do not produce spherocytes. this results in an individual with biconcave-disc-shaped erythrocytes. this treatment is not standard of care, and is not offered as it has only been documented incidentally during treatment for other diseases, such as myelodysplastic sydnrome. symptomatic treatments: folic acid supplementation. complications common complications hemolytic crisis, with more pronounced jaundice due to accelerated hemolysis (may be precipitated by infection). aplastic crisis with dramatic fall in hemoglobin level and (reticulocyte count)-decompensation, usually due to maturation arrest and often associated with megaloblastic changes; may be precipitated by infection, such as influenza, notably with parvovirus b19. folate deficiency caused by increased bone marrow requirement. pigmented gallstones occur in approximately half of untreated patients. increased hemolysis of red blood cells leads to increased bilirubin levels, because bilirubin is a breakdown product of heme. the high levels of bilirubin must be excreted into the bile by the liver, which may cause the formation of a pigmented gallstone, which is composed of calcium bilirubinate. since these stones contain high levels of calcium carbonates and phosphate, they are radiopaque and are visible on x-ray. hyperglycemia with concomitant low hemoglobin a1c levels. hemoglobin a1c (glycated hemoglobin) is a test for determining the average blood glucose levels over an extended period of time, and is often used to evaluate glucose control in diabetics. the hemoglobin a1c levels are abnormally low because the life span of the red blood cells is decreased - providing less time for the non-enzymatic glycosylation of hemoglobin. thus, even with high overall blood sugar, the a1c will be lower than expected. iron overload. leg ulcer. deep vein thrombosis (dvt). cardiovascular disease. research modern ongoing research interests: experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy. bone marrow transplant. paradoxical endurance-based athleticism associated with hereditary spherocytosis. evolution of spherocytic erythrocyte adaptation in those of northern european and japanese descent. increased ability to defend against viral infections in hereditary spherocytosis patients.