History

Fact Explanation
History of jaundice or icterus in childhood In hereditary spherocytosis, the red blood cells have abnormal morphology due to the defects of the membrane proteins including spectrin, ankyrin, band 3 and protein 4.2. The cytoskeleton of these cells are unstable and the red blood cells undergo extravascular haemolysis in the spleen. Newborn babies can present with neonatal jaundice in first week of life. [2]
Intermittent nature of jaundice [1] This is due to the haemolysis that increases the unconjugated bilirubin in the blood. [1]
Fever and fatigue Fever is one of the presenting features. [1] Fever may be due to infections triggering the haemolytic crisis. Parvovirus B19 is one such example of an infection that induces haemolytic crisis by inhibiting erythropoiesis. [3] Post splenectomy patients are vulnerable for recurrent infections. Fatigue is associated with intermittent jaundice.
Headache, myalgia, and abdominal pain Aplastic crisis can give rise to these symptoms. [3]
Right upper abdominal pain, radiating to the back across the flanks, associated with non specific symptoms such as dyspepsia, nausea, vomiting This is due to the biliary colic. [1] If there is fever, cholecystitis has to be considered. Pigment gallstone formation is a complication of spherocytosis.
Positive family history of same condition or splenectomy Hereditary spherocytosis has an autosomal dominant inheritance. [2] Occasionally autosomal recessive inheritance is seen.
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011
  3. OH SE, KIM JH, CHOI CH, PARK KH, JUNG JY, PARK YI, PARK MJ. An Adult with Aplastic Crisis induced by Human Parvovirus B19 as an Initial Presentation of Hereditary Spherocytosis Korean J Intern Med [online] 2005 Mar, 20(1):96-99 [viewed 12 July 2014] Available from: doi:10.3904/kjim.2005.20.1.96

Examination

Fact Explanation
Pallor Due to anaemia. [1] As the bone marrow compensates the haemolysis, usually there is mild anaemia. Severe disease may cause marked anaemia. [2]
Icterus [1] Yellowish discolouration of the eyes and mucous membranes due to the elevation of unconjugated bilirubin. [1]
Febrile Infections can trigger a haemolytic crisis, post splenectomy patients are vulnerable to recurrent infections and it may also be due to hyperdynamic circulation resulting from anemia. [1]
Splenomegaly[1,2] Abnormal red blood cells are destroyed by the spleen causing splenomegaly. [2] In mild disease there may be no splenomegaly, and there can be mild to moderate splenomegaly in advanced disease.
Right upper abdominal tenderness If complicated with cholilithiasis due to pigment stones. [1]
Leg ulcers Chronic skin inflammation and ulceration occurs with chronic disease. [2]
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011

Differential Diagnoses

Fact Explanation
Hereditory elliptocytosis Hereditary elliptocytosis is characterized by the presence of elliptical red blood cells in the blood. [3] Its clinical features may be similar to spherocytosis.
Anemia due to other causes Anaemia can be differentiated depending on the investigation findings. Microcytic hypochromic anaemia is seen in iron deficiency, thalassemia [2] and anaemia of chronic disease. Macrocytic anaemia is seen with Folate and Vitamin B12 deficiency, liver disease and alcoholics. Normocytic normochromic anaemia can also be due to anaemia of chronic disease, bone marrow problems and other types of haemolytic anaemias.
Hemolytic Anemia (HA) Haemolytic anaemias are mainly of two types: immune and nonimmune. Immune HA can be autoimmune or alloimmune. Non immune causes may be related to drugs, infections, march haemoglobinuria. Direct and indirect coombs tests are positive in immune haemolytic anaemia. [4]
Biliary colic and cholecystitis Patient can present with right upper abdominal pain, radiating to the back across the flanks, associated with non specific symptoms such as dyspepsia, nausea, vomiting in the case of biliary colic. If there is fever, cholecystitis has to be considered. [1]
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. ELDOR A.. The hypercoagulable state in thalassemia. [online] 2002 January, 99(1):36-43 [viewed 12 July 2014] Available from: doi:10.1182/blood.V99.1.36
  3. GALLAGHER P. G.. Red Cell Membrane Disorders. Hematology [online] 2005 January, 2005(1):13-18 [viewed 12 July 2014] Available from: doi:10.1182/asheducation-2005.1.13
  4. SEKIGUCHI Y, SHIMADA A, IMAI H, WAKABAYASHI M, SUGIMOTO K, NAKAMURA N, SAWADA T, KOMATSU N, NOGUCHI M. A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature Int J Clin Exp Pathol [online] , 7(5):2624-2635 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069955

Investigations - for Diagnosis

Fact Explanation
Full blood count Low haemoglobin due to anaemia can be seen. [2]A hemoglobin of (g/dL) 11-15 indicates mild anemia and 8 - 12 moderate, 6-8 moderately severe and <6 severe. [2] There can be increased mean corpuscular hemoglobin concentration (MCHC) and if there is substantial reticulocytosis mean corpuscular volume may be low or high. [3]
Blood picture Normocytic normochromic anaemia is seen with spherocytes (appear as red blood cells that are smaller than normal on a blood smear) [1] with uniform size and density. There is spectrin deficiency in the membrane of red blood cells, leading to loss of red blood cell surface area, producing spherical shaped red blood cells.
Reticulocyte count As this is a type of haemolytic anaemia reticulocyte count is usually increased. Reticulocyte count may be 3-8% in mild disease, 8% or more than 8% in moderate disease and 10% or more than 10% in severe disease. [2]
Osmotic fragility test [1,2] Red blood cells are incubated for 18-24 hours under sterile conditions at 37°C, and osmotic fragility is checked. Osmotic fragility is increased in hereditary spherocytosis. [1,2]
Bilirubin levels Unconjugated hyperbilirubinemia due to increased haemoglobin breakdown. [2]
Lactate dehydrogenase (LDH) Increased Lactate Dehydrogenase (LDH) is seen. [3]
Direct Coombs test Negative. [2] ( This helps to differentiate HS from autoimmune haemolytic anaemia, where Coomb's test is positive)
References
  1. GOLAFSHAN HA, RANJBARAN R, KALANTARI T, MOEZZI L, KARIMI M, BEHZAD- BEHBAHANI A, ABOUALIZADEH F, SHARIFZADEH S. Evaluation of Red Cell Membrane Cytoskeletal Disorders Using a Flow Cytometric Method in South Iran Turk J Haematol [online] 2014 Mar, 31(1):25-31 [viewed 12 July 2014] Available from: doi:10.4274/Tjh.2012.0146
  2. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  3. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011

Investigations - Fitness for Management

Fact Explanation
Full blood count White blood cell counts and platelets are important as patient may be going into aplastic/ hemolytic crisis, precipitated by an infection. White blood cell count is increased in bacterial infections and lymphocyte count is increased in viral infections. Hypersplenism [1] can occur with reduction in the platelet count. Aplastic crisis due to infections can result in low white cell and platelet counts. [2]
IgM antibodies to HPV B19 HPV B19 infection is associated with the aplastic crisis. [2]
References
  1. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011
  2. OH SE, KIM JH, CHOI CH, PARK KH, JUNG JY, PARK YI, PARK MJ. An Adult with Aplastic Crisis induced by Human Parvovirus B19 as an Initial Presentation of Hereditary Spherocytosis Korean J Intern Med [online] 2005 Mar, 20(1):96-99 [viewed 12 July 2014] Available from: doi:10.3904/kjim.2005.20.1.96

Investigations - Followup

Fact Explanation
Full blood count Level of haemoglobin and platelet count need to be monitored. [1]
Blood picture Spherocytosis [1] will appear during a crisis and settle when trigger is removed.
References
  1. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011

Investigations - Screening/Staging

Fact Explanation
Ultrasound scan of abdomen [1] Cholelithiasis is a complication of spherocytosis. If the patient gives a history of upper abdominal pain, radiating to the back across the flanks, associated with non specific symptoms such as dyspepsia, nausea, vomiting and fever, they should be evaluated for gallstones. Most gallstones are asymptomatic and detected on the ultrasound scan. [1]
Bone marrow biopsy Aplastic crisis [2] can occur during the course of the disease. Bone marrow biopsy and aspirate to rule out aplasia may be needed occasionally.
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. KOBAYASHI Y, HATTA Y, ISHIWATARI Y, KANNO H, TAKEI M. Human parvovirus B19-induced aplastic crisis in an adult patient with hereditary spherocytosis: a case report and review of the literature BMC Res Notes [online] :137 [viewed 17 September 2014] Available from: doi:10.1186/1756-0500-7-137

Management - General Measures

Fact Explanation
Blood transfusion [1] Red blood cell transfusion may be indicated in following conditions: exacerbation of anemia due to blood loss such as in trauma or surgery, hypersplenism, and infection with parvovirus B19. [2]
Treating the precipitating infection Haemolytic crisis can be triggered by infections. [2]
Folic acid As rapid cellular proliferation occurs with haemolysis, oral Folate supplements are given. [1]
Monitoring Regular monitoring is needed for growth failure, [1] complications such as cholelithiasis and post splenectomy sepsis.
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011

Management - Specific Treatments

Fact Explanation
Splenectomy Abnormal erythrocytes are sequestrated and destructed inside the spleen and therefore severe hemolysis needs splenectomy. Severe anemia and extramedullary hematopoiesis are the indications for splenectomy. [3] Postsplenectomy sepsis due to encapsulated organisms such as streptococci and meningococci is the main complication following the surgery. [1] Therefore patients are given prophylactic oral penicillin for a minimum duration of 5 years after the surgery. Partial splenectomy is an option that avoids postsplenectomy sepsis associated with total splenectomy. [2]
Management of complications Cholecystectomy is indicated in symptomatic gallstone disease. [1]
Intravenous immunoglobulin Patients with prolonged severe aplasia and immunodeficiency might need intravenous immunoglobulin. It is usually given for 5 to 10 days. [4]
References
  1. DAS A, BANSAL D, DAS R, TREHAN A, MARWAHA RK. Hereditary spherocytosis in children: profile and post-splenectomy outcome. Indian Pediatr [online] 2014 Feb, 51(2):139-41 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632695
  2. RICE HE, OLDHAM KT, HILLERY CA, SKINNER MA, O’HARA SM, WARE RE. Clinical and Hematologic Benefits of Partial Splenectomy for Congenital Hemolytic Anemias in Children Ann Surg [online] 2003 Feb, 237(2):281-288 [viewed 12 July 2014] Available from: doi:10.1097/01.SLA.0000048453.61168.8F
  3. HASSAN A, BABADOKO AA, ISA AH, ABUNIMYE P. Hereditary spherocytosis in a 27-year-old woman: case report. Ann Afr Med [online] 2009 Jan-Mar, 8(1):61-3 [viewed 12 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763011
  4. OH SE, KIM JH, CHOI CH, PARK KH, JUNG JY, PARK YI, PARK MJ. An Adult with Aplastic Crisis induced by Human Parvovirus B19 as an Initial Presentation of Hereditary Spherocytosis Korean J Intern Med [online] 2005 Mar, 20(1):96-99 [viewed 12 July 2014] Available from: doi:10.3904/kjim.2005.20.1.96