Mild forms of hemolytic anemia seldom produce any symptoms, as in such individuals the hemoglobin levels also appear to be normal. When the disease progresses gradually, the following symptoms are evident:

• Experiencing headaches
• Feeling more tired than usual
• Feeling tired after exercise
• Concentration problems
• Feeling irritable or cranky

When the disease advances to more severe forms, the affected individuals suffer from the following symptoms [7]:

• Development of blue color in the eyes
• Skin turns pale
• Soreness of tongue
• Lightheadedness, particularly when the individual is in the standing position
• Dyspnea
• Nails become brittle
• Development of tachycardia and angina
• Urine color is dark due to presence of hemoglobinuria

• Hemophilia A

  […] deficiency / Activated protein C resistance / Protein S deficiency / Factor V Leiden - Hyperprothrombinemia acquired: DIC ( Congenital afibrinogenemia, Purpura fulminans ) - autoimmune ( Antiphospholipid ) Other Essential thrombocytosis - clotting factor: Hemophilia [wikidoc.org]

• Splenomegaly

  It results in hemolytic anemia and splenomegaly. Autosomal dominant trait marked by splenomegaly, jaundice, and fragile, spheroid erythrocytes which are prematurely cleared by the spleen; anemia is usually mild; treatment is splenectomy. [icd9data.com]

  The patients suffer from a mild hemolytic anemia (Hb levels ranging from 10 to 12.7g/mL) associated with macrocytosis, reticulocytosis, hyperbilirubinemia, hyperferritinemia and slight splenomegaly. [ncbi.nlm.nih.gov]

  Examination New onset of pallor and anemia Jaundice Gallstones Splenomegaly +/- hepatomegaly INVESTIGATIONS Confirm haemolysis Increased absolute reticulocyte count LDH (elevation is more pronounced in intravascular haemolysis) Indirect Bilirubin (i.e [lifeinthefastlane.com]

  […] hemolytic anemia cold agglutinin disease acrocyanosis (different from Raynaud) painful and blue toes/fingers in the cold “colder” parts of the body symptoms resolve upon warming that part of the body acute hemolytic anemia with the cold Physical exam splenomegaly [medbullets.com]

  AIHA is characterized by hemolytic anemia, which is most often revealed by an unusual weakness and fatigue with tachycardia and exertional dyspnea, and also in some cases by jaundice, dark urine and/or splenomegaly. [orpha.net]

• Anemia

  Diagnosis of hemolytic anemia Diagnosis of hemolytic anemia is performed in four steps: Establish that anemia exists. The diagnosis of anemia has been previously covered. [medicalassistantonlineprograms.org]

  Outcome depends on the type and cause of hemolytic anemia. Severe anemia can make heart disease, lung disease, or cerebrovascular disease worse. Call your health care provider if you develop symptoms of hemolytic anemia. Brodsky RA. [nlm.nih.gov]

  There are differences in the management of various types of hemolytic anemias (see Treatment ). Go to Anemia, Iron Deficiency Anemia, and Chronic Anemia for complete information on these topics. [emedicine.medscape.com]

• Fatigue

  All hemolytic anemias feature varying degrees of fatigue, pallor, and weakness (from asymptomatic disease to life-threatening hemolytic crisis), although some diseases have more specific findings (e.g., venous thrombosis in paroxysmal nocturnal hemoglobinuria [amboss.com]

  However after 12 days of post artesunate treatment, she returned with dark urine, malaise and fatigue. Considering the clinical course and base on a reliable causality assessment scale, post artesunate delay hemolytic anemia was possible. [ncbi.nlm.nih.gov]

• Weakness

  All hemolytic anemias feature varying degrees of fatigue, pallor, and weakness (from asymptomatic disease to life-threatening hemolytic crisis), although some diseases have more specific findings (e.g., venous thrombosis in paroxysmal nocturnal hemoglobinuria [amboss.com]

  A 68-year-old married woman of North-African Jewish descent was admitted to our internal medicine department due to newly diagnosed diabetes, with weakness, presyncope, and blood glucose levels as high as 500 mg/dl. [care.diabetesjournals.org]

  CASE PRESENTATION: A 43-year-old woman with metastatic melanoma presented with severe generalized weakness and fatigue. She has received two cycles of ipilimumab and nivolumab, last administered 3 weeks prior to her presentation. [ncbi.nlm.nih.gov]

  If the problem develops slowly, the first symptoms may be: Feeling weak or tired more often than usual, or with exercise Feelings that your heart is pounding or racing Headaches Problems concentrating or thinking If the anemia gets worse, symptoms may [nlm.nih.gov]

  Presenting symptoms and signs of hemolytic anemia include those common to anemia in general: weakness, fatigue, dizziness, shortness of breath, dyspnea on exertion, tachycardia, palpitations, chest pain, new or accentuated cardiac murmur, and pallor. [accessmedicine.mhmedical.com]

• Sepsis

  While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. [ncbi.nlm.nih.gov]

  ECMO, RRT) infection e.g. severe sepsis, malaria (e.g. blackwater fever), Clostridium perfringens, babeosis hypotonic solutions and drowning toxins e.g. heavy metals (e.g. lead, mercury, copper) e.g. oxidants (e.g. causes of methemoglobinaemia), arsine [lifeinthefastlane.com]

  DIC may occur as result of sepsis secondary to bacterial, or fungal infections. [clinicaladvisor.com]

  Non-immune Hemolytic anemias Infection associated Mechanical HA Acquired membrane defects Chemical & physical agents Malaria G-ve Sepsis Drugs Burns Drowning PNH Liver dis. Cardiac Microangiopathic HA 66. [slideshare.net]

  Clostridium perfringens sepsis may produce a severe episode of acute hemolysis, with virtual opacity of the patient’s plasma due to hemoglobin released by the brisk intravascular hemolysis. I. [medicalassistantonlineprograms.org]

• Weight Gain

  Common side effects may include weight gain, high blood pressure, acne, upset stomach and irritability. Immune globulin (IVIG): An intravenous infusion that decreases the destruction of red blood cells. [cincinnatichildrens.org]

  The patient was an 84-year-old male who was admitted to the emergency room in April 2009 with the chief complaint of increased bilateral lower extremity edema, a 34-pound weight gain over the past month, and worsening anemia. [academic.oup.com]

• Respiratory Distress

  A 1-day-old female baby presented with anemia and respiratory distress. Her hemoglobin level was 9.5 g/dL and the total serum bilirubin level was 5.6 mg/dL. Metabolic acidosis was detected in her blood gas analysis. [ncbi.nlm.nih.gov]

  All six patients were hospitalized for the initial management of babesiosis, and one required intensive care for the acute respiratory distress syndrome and intracranial hemorrhage. [nejm.org]

• Abdominal Pain

  She developed yellowing of the skin and eyes, lethargy, mild abdominal pain, and dry mucous membranes. [ncbi.nlm.nih.gov]

  […] up blood Diarrhea, nausea, vomiting, and abdominal pain Problems with balance Exams and Tests The health care provider will perform a physical exam. [mclaren.org]

  […] veins) Vasoconstriction: headache, pulmonary hypertension Abdominal pain, dysphagia, erectile dysfunction Diagnosis Anemia or pancytopenia → infections and bleeding Signs of hemolysis Flow cytometry: absence of CD55 and CD59 on the surface of RBCs Coombs [amboss.com]

  Less than 30% patients suffer with abdominal pain, abnormal urinary color, jaundice (yellow discoloration of eye white and skin), congestive heart failure, edema, fever, splenomegaly and cardiac arrhythmias. [xpertdox.com]

• Tachycardia

  Hemolytic anemia may be suspected from general findings on a complete medical history and physical examination of your child, such as complaints of tiring easily, pale skin and lips, or a fast heartbeat (tachycardia). [stanfordchildrens.org]

  Presenting symptoms and signs of hemolytic anemia include those common to anemia in general: weakness, fatigue, dizziness, shortness of breath, dyspnea on exertion, tachycardia, palpitations, chest pain, new or accentuated cardiac murmur, and pallor. [accessmedicine.mhmedical.com]

  AIHA is characterized by hemolytic anemia, which is most often revealed by an unusual weakness and fatigue with tachycardia and exertional dyspnea, and also in some cases by jaundice, dark urine and/or splenomegaly. [orpha.net]

  […] common symptoms: Abnormal paleness or lack of color of the skin Jaundice, or yellowing of the skin and eyes Dark color to urine Fever Weakness Dizziness Confusion Intolerance to physical activity Enlargement of the spleen and liver Increased heart rate (tachycardia [chop.edu]

• Jaundice

  Zieve syndrome, a rarely reported disease resulting from alcohol abuse, consists of a triad of symptoms: hemolytic anemia, cholestatic jaundice, and transient hyperlipidemia. [ncbi.nlm.nih.gov]

  Jaundice - When the red blood cells break down, some of the cell contents are changed into bilirubin (bil ih ROO bin). Jaundice (yellowing of the skin or eyes) occurs because of the increase in bilirubin. [stjude.org]

  The existence of a primary form of acquired hemolytic jaundice has been questioned more and FULL TEXT [annals.org]

  Autosomal dominant trait marked by splenomegaly, jaundice, and fragile, spheroid erythrocytes which are prematurely cleared by the spleen; anemia is usually mild; treatment is splenectomy. [icd9data.com]

  […] hemolytic (acquired) D59.9 hematogenous D59.9 (acquired) Jaundice (yellow) R17 ICD-10-CM Diagnosis Code R17 Unspecified jaundice 2016 2017 2018 2019 Billable/Specific Code Type 1 Excludes neonatal jaundice ( P55, P57 - P59 ) hemolytic (acquired) D59.9 [icd10data.com]

• Hepatomegaly

  Following this, a physical examination may reveal hepatomegaly or tenderness in the abdominal region. [symptoma.com]

  Examination New onset of pallor and anemia Jaundice Gallstones Splenomegaly +/- hepatomegaly INVESTIGATIONS Confirm haemolysis Increased absolute reticulocyte count LDH (elevation is more pronounced in intravascular haemolysis) Indirect Bilirubin (i.e [lifeinthefastlane.com]

  Occasionally enlargement of the liver (hepatomegaly) may also occur in some people. [rarediseases.org]

  H1N1 influenza–associated AIHA in children may respond to treatment with oseltamivir and intravenous immunoglobulin. [6] Fetal splenomegaly and associated hepatomegaly could be due to hemolysis, but infections are the most likely cause. [emedicine.medscape.com]

• Fracture

  […] was significant for rate controlled atrial fibrillation, anemia, warm autoantibodies, type II diabetes mellitus treated with oral medication, congestive heart failure, hypertension, chronic venous insufficiency, osteopenia, arthritis, and compression fracture [academic.oup.com]

  2 (pneumonia, including one patient with probable pneumocystis infection) 4 (pneumonia = 1; pulmonary abscess =1; diverticulitis = 1; prostatitis = 1) Non‐infectious (non‐fatal) 2 (neutropenia) 2 (severe pulmonary embolism = 1; spontaneous vertebral fractures [cochranelibrary.com]

• Dizziness

  Signs and symptoms may include fatigue, dizziness, heart palpitations, pale skin, headache, confusion, jaundice, and a spleen or liver that is larger than normal. [nhlbi.nih.gov]

  You are dizzy or more tired than usual. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care. Learn about your health condition and how it may be treated. [drugs.com]

  Presenting symptoms and signs of hemolytic anemia include those common to anemia in general: weakness, fatigue, dizziness, shortness of breath, dyspnea on exertion, tachycardia, palpitations, chest pain, new or accentuated cardiac murmur, and pallor. [accessmedicine.mhmedical.com]

  The most common symptoms associated with hemolytic anemia are as follows: Pale or yellow skin Yellowness of the eyes Unusual fatigue or tiredness Lightheadedness or dizziness Dark or “tea/cola colored” urine Other signs or symptoms may include: Fast heart [luriechildrens.org]

At preliminary levels, complete blood count can provide some insight about the type and nature of the hemolytic anemia. Following this, a physical examination may reveal hepatomegaly or tenderness in the abdominal region. In addition, other blood tests would also be required in order to make a definite diagnosis about the type of hemolytic anemia that has set in and also to identify the causative factor.

The standard types of blood tests that are required in addition to complete blood count include peripheral blood smear, serum haptoglobin, serum lactate dehydrogenase and indirect bilirubin. Of these, serum haptoglobin and serum lactatce dehydrogenase study are considered to be sensitive tests for diagnosing hemolytic anemia. Bone marrow aspiration tests would be necessary in order to evaluate the type of red blood cells produced by the bone marrow [8].

• Hematocrit Decreased

  Decreased Decreased Confirm compensatory RBC production Reticulocyte count Increased Confirm hemolysis Peripheral smear Schistocytes—intravascular hemolysis, RBCs fragmented by shear mechanism Spherocytes—extravascular hemolysis, RBC phagocytosis by [accessmedicine.mhmedical.com]

• Total Bilirubin Increased

  This patient’s anemia was clinically thought to be hemolytic in nature, a diagnosis supported by an elevated total bilirubin, increased lactate dehydrogenase (LD), decreased haptoglobin, and elevated reticulocyte count. [academic.oup.com]

The treatment regime for hemolytic anemia depends on the cause and type of anemia that has set in. The following methods are employed for treating hemolytic anemia:

• Blood transfusions: This is usually required in emergency cases, and is meant for treating severe forms of hemolytic anemia.
• Medications: These are given to suppress an overactive immune system that is causing premature destruction of red blood cells. Initially, the individuals are given corticosteroids for suppressing the immune system; if these don’t work then the individuals are put on other class of drugs such as rituximab and cyclosporine [9].
• Plasmapheresis: In this process, the antibodies are removed by separating the plasma from the blood. This is the treatment of choice when other methods do not yield positive results.
• Surgery: Surgery to remove the spleen may be required in individuals with hemolytic anemia. A healthy spleen is competent enough to fight infection and filter off the damaged red blood cells.

The prognosis of hemolytic anemia largely depends on the type and cause of the condition. Mild cases can be treated and patients can live a healthy life without complications. However, in severe cases, hemolytic anemia can worsen already existing disease conditions such as lung disorders, heart anomalies and cerebrovascular diseases [6].

Hemolytic anemia develops, when the bone marrow is unable to replace the loss of red blood cells. Destruction and removal of red blood cells from the system can occur due to many factors such as underlying disease conditions, infections and toxins. Individuals with sickle cell anemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and thalassemia are at an increased risk of contracting this disease condition [2].

Exposure to various types of toxins or chemical also predisposes an individual to develop such a type of anemia. In addition, other factors such as blood clot in a blood vessel or blood transfusion from an unmatched donor can also favor the development of hemolytic anemia.

It has been estimated that 5% of all anemia represent hemolytic anemia. The condition does not affect any particular type of race; but sickle cell anemia is a common occurrence amongst the African population. Individuals with sickle cell anemia are prone to develop hemolytic anemia and therefore, it is understood that the African people are at an increased risk of developing the same. Hemolytic anemia that occurs as a result of heredity, affects an individual early in life [3].

Under normal physiological conditions, the bone marrow produces red blood cells which are gradually replaced when they complete their lifespan. In condition of hemolytic anemia, there is premature destruction of red blood cells and the bone marrow is unable to replenish the lost stores. Hemolysis occurs as a result of intravascular or extravascular factors [4].

Autoimmune hemolytic anemia results, when the body’s own immune system mistakenly attacks the red blood cells by producing antibodies which prematurely destroy them [5]. The condition can also occur when precursors of red blood cells are destroyed in the bone marrow itself prior to being released into the circulation.

It is not possible to prevent the inherited forms of hemolytic anemia. However, some of the acquired forms can be prevented. This can be done by proper matching of the blood prior to blood transfusions. Rh incompatibility can also be avoided to prevent the development of hemolytic anemia in the newborn [10].

Red blood cells are responsible for carrying oxygen to various body tissues. Normally, lifespan of red blood cells is about 120 days. I condition of hemolytic anemia they are prematurely destroyed. Hemolytic anemia can either be intrinsic or extrinsic in nature. The former type occurs when the healthy red blood cells of the body are destroyed; whereas in the latter type, the bone marrow produces defective type of red blood cells [1].

• Definition: Hemolytic anemia is a condition wherein there is premature destruction of red blood cells that occurs due to infections or various underlying disease conditions. In this disease, the bone marrow cannot replace for the lost stores of red blood cells giving rise to anemia.
• Cause: Various factors such as infections, exposure to toxins and underlying disease conditions can favor the development of hemolytic anemia. Autoimmune hemolytic anemia occurs when the body’s immune system attacks red blood cells considering them as invaders. Genetic defects also predispose an individual to develop hemolytic anemia.
• Symptoms: Symptoms of hemolytic anemia include feeling of tiredness, development of pale skin, blue color in eyes, headaches, thinking problems, light headedness, brittle nails, shortness of breath and sore tongue.
• Diagnosis: Diagnosis of hemolytic anemia is done by blood tests which involve complete blood count, peripheral smear tests, serum haptoglobin, serum lactate dehydrogenase study and indirect bilirubin. In addition, bone marrow aspiration test would also be required.
• Treatment: Blood transfusion is the primary mode of treatment for hemolytic anemia. Medications would also be required in order to suppress the activity of immune system. Plasmapheresis would also be indicated in order to remove the antibodies by separating the plasma from whole blood.

1. Glader BE. Hemolytic anemia in children. Clin Lab Med. Mar 1999;19(1):87-111, vi.
2. Olivieri N. Thalassaemia: clinical management. Baillieres Clin Haematol 1998; 11:147.
3. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol. Apr 2002;69(4):258-71. 
4. Palek J, Jarolim P. Hereditary spherocytosis, elliptocytosis, and related disorders. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. 5th ed. New York, NY: McGraw Hill; 1995:557-63.
5. Izui S. Autoimmune hemolytic anemia. Curr Opin Immunol 1994; 6:926.
6. Erslev AJ. Traumatic cardiac hemolytic anemia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds.Williams Hematology. 5th ed. New York, NY: McGraw Hill; 1995:663-4
7. Packman CH. Hemolytic anemia due to warm autoantibodies. Blood Rev. Jan 2008;22(1):17-31
8. Giannadaki E, Potamianos S, Roussomoustakaki M, et al. Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis. Am J Gastroenterol 1997; 92:1872.
9. Abdulla NE, Ninan MJ, Markowitz AB. Rituximab: current status as therapy for malignant and benign hematologic disorders. BioDrugs. Apr 1 2012;26(2):71-82.
10. Hosono S, Hosono A, Mugishima H, Nakano Y, Minato M, Okada T, et al. Successful recombinant erythropoietin therapy for a developing anemic newborn with hereditary spherocytosis. Pediatr Int. Apr 2006;48(2):178-80.