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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025

Jan-.
Hemolytic Anemia
Authors

Caitlin Baldwin1; Jyotsna Pandey2; Olubunmi Olarewaju3.

Affiliations

1 Jefferson Northeast
2 Central Michigan University College of Medicine
3 Jefferson Northeast

Last Update: July 24, 2023.

Continuing Education Activity

Hemolytic anemia is a class of anemia that is caused by the destruction of red blood cells,
increased hemoglobin catabolism, decreased levels of hemoglobin, and an increase in efforts of
bone marrow to regenerate products. This activity reviews the evaluation and treatment of
hemolytic anemia and highlights the role of an interprofessional team in evaluating and
treating patients with this condition.

Objectives:

Review the types and causes of hemolytic anemia

Describe the typical histological findings on blood smear that can aid in diagnosis of the
type of hemolytic anemia.

Outline the management options available for several categories of hemolytic anemia.

Explain the importance of a thorough evaluation by the interprofessional team to improve

the diagnosis and treatment of hemolytic anemias.

Access free multiple choice questions on this topic.

Introduction
Anemia is a decrease in hemoglobin levels from an individual's baseline; however, sex-specific
and race-specific reference ranges to make a diagnosis are often used when baseline
hemoglobin is not known. The World Health Organization (WHO) criteria for anemia in men is
less than 13 g/dL, whereas it is less than 12 g/dL for women. There are revised criteria for
anemia in men and women with complications of chemotherapy as well as age and race. Even
"special populations" such as athletes, smokers, older adults, or those living at high altitudes
have suggested different ranges.

The critical issue in evaluating any form of anemia is to recognize treatable causes early. This is
crucial because hemoglobin, an iron-rich protein, is what helps red blood cells (RBC), carry
oxygen from the lungs to the rest of the body. The biconcave shape of RBCs themselves allows
for it to provide optimal respiratory exchange. If the body is unable to provide oxygen to the
body, one may experience symptoms of weakness, lethargy, dizziness, headaches, shortness of
breath, or arrhythmias.

Anemia is often subcategorized into microcytic, normocytic, and macrocytic based on

mean corpuscular volume (MCV). As there are numerous types of anemia, this laboratory
parameter allows clinicians to formulate a practical diagnostic approach.

Hemolytic anemia is classified as normocytic anemia with an MCV of 80 to 100 fL. It is a

form of low hemoglobin due to the destruction of red blood cells, increased hemoglobin
catabolism,
decreased levels of hemoglobin, and an increase in efforts of bone marrow to regenerate
products.

Hemolytic Anemias can be further subdivided into intrinsic and extrinsic causes.[1][2]

Etiology
There are numerous causes of hemolytic anemia, which have several ways that can be
broken down to include acute and chronic disease, immune vs. non-immune mediated,
intravascular or extravascular, inherited or acquired, and intracorpuscular or
extracorpuscular.

Intracorpuscular causes refer to abnormalities in the red blood cell itself. A red blood cell can be
internally damaged when the solubility of hemoglobin is altered (hemoglobinopathy), the
structure of the membrane or cytoskeleton is changed (membranopathy), or its metabolic
abilities (enzymopathy) is decreased. Examples of hemoglobinopathies include sickle cell
disease (SCD) and thalassemias. SCD is caused by a beta-globin gene mutation leading to
polymerization of hemoglobin-S, sticking, and, therefore, hemolysis. Thalassemia is the most
common cause of hereditary hemolytic anemia and is caused by partial or complete lack of
synthesis of one of the major alpha or beta globin chains of hemoglobin A.[3]

Membranopathies include hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). HS

is often autosomal dominant; however, non-dominant and recessive traits have been seen. It
has been seen in all racial groups. HS has been documented as a rare disease, however, due
to limited knowledge as the onset and severity vary considerably, as well as, the lack of
specific lab tests, make it a difficult disease to study. HE is a heterogeneous red cell
membrane disordered where the autosomal dominant inheritance can lead to a spectrum of
presentations from asymptomatic to life-threatening.[4][5]

Several RBC enzymopathies alter the shape of RBCs and cause nonspherocytic hemolytic
anemias.
[2] G6PD deficiency and pyruvate kinase deficiency (PKD) both fall into this category. PK is the
rate- limiting enzyme in RBC energy production, whereas G6PD is involved in the processing of
carbohydrates and plays a protective role from reactive oxygen species in RBCs.[6] G6PD
deficiency is an X-linked inherited disorder, almost exclusively seen in males, that causes
hemolysis often with certain medications or foods such as fava beans and aspirin.[3]

Alternatively, extracorpuscular causes refer to defects that were influenced by external factors,
including mechanical, immune-mediated, or infectious. RBC transfusions can cause both acute
and delayed hemolytic reactions. Mechanical trauma to RBCs is seen with microthrombi, fibrin,
or valve shearing forces. Pathogens such as malaria and babesiosis are known to destroy
RBCs as well as medications like dapsone, that can be used to treat these diseases, also have
deleterious effects as it has oxidant potential.

Epidemiology
Two databases exist which provide a systematic exclusion of the population of people that are
not “normal”: NHANES-III (the third U.S. National Health and Nutrition Examination Survey)
database and the Scripps-Kaiser database.

Through these databases, one can see there is no difference in hemoglobin values of men from
20 to 59 or women 20 to 49. This assists in studying patient populations whose values do fall
out of the norm from these ranges.

African Americans are found to have a lower limit of normal hemoglobin concentration, lower
serum transferrin saturation, higher serum ferritin levels, lower bilirubin levels, and lower
leukocyte counts. This is thought to be due to the higher frequency of alpha-thalassemia and
G6PD deficiency in the black population. G6PD deficiency is known to affect millions of people
worldwide.[7][8][9]
Although it can be seen worldwide, HE is most predominantly seen in malaria-endemic
regions of West Africa.[5] Several forms of anemia are seen in these regions, as it is often
thought to be protective against malaria.

Overall hemolytic anemias cover a broad range of age groups, races, and both genders as
several subcategories can be acquired or inherited.

Pathophysiology
Hemolytic anemia is the destruction of RBCs. Normally, red blood cells have a lifespan of 120
days. This process can be something chronic that has occurred over time or acute and life-
threatening. It can be further subdivided as to where the hemolysis is taking place -
intravascularly or extravascularly.

When a red blood cell is unable to change shape as it passes through the spleen, it will
become sequestered and phagocytosis will occur. This is seen in hemoglobinopathies such
as sickle cell disease.

Destruction can also occur with inherited protein deficits (membranopathies ie hereditary
spherocytosis), fragmentation [microangiopathic hemolytic anemias ie. thrombotic
thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), HELLP],
increased oxidative stress or decreased energy production (enzymopathies ie. G6PD
Deficiency), antibodies binding with RBC’s resulting in phagocytosis (immune-mediated), drug-
induced hemolysis, infections, or direct trauma (conga drums).[10]

Histopathology
A peripheral blood smear should be studied when there is concern for hemolysis. One would
look for abnormal red blood cells such as schistocytes, spherocytes, or bite cells.[10]

RBC shape is crucial in diagnosis. A distinctive blood smear may even be sufficient for the
diagnosis of a type of hemolytic anemia. This can be seen in cases such as hereditary
elliptocytosis or Southeast Asian ovalocytosis.

However, other hemolytic anemias may have similar features such as red cell
fragmentation, as seen in microangiopathic hemolytic anemia (MAHA) and mechanical
hemolytic anemia from leaking prosthetic valves.

Oxidant damage produces specific types of red blood cells, therefore, aiding in the diagnosis
from a blood smear. Keratocytes or "bite" cells, "blister" cells, and irregularly contracted cells
must be differentiated from spherocytes as it will alter one's diagnosis.[9]

History and Physical

A patient with anemia may present with shortness of breath, weakness, fatigue, arrhythmias
such as tachycardia, or can present asymptomatic. Those with anemia caused by cell
destruction or hemolysis may also present with jaundice or hematuria. If symptoms have been
going on for longer periods, lymphadenopathy, hepatosplenomegaly, cholestasis may even
be seen.

Specific physical exam findings may be able to lead a clinician to a suggested diagnosis. If a
patient presents with diarrhea and hemolytic anemia, one may consider hemolytic uremic
syndrome.
Hematuria, in conjunction with labs supportive of hemolytic anemia, could be a sign of
paroxysmal nocturnal hemoglobinuria (PNH).[10]

A thorough history must be taken, and a physical exam performed as these clues can
connect the information to form a diagnosis.

Evaluation
Although a patient may present with physical characteristics that may lead a clinician down
the path to diagnosing hemolytic anemia, laboratory markers are key. Results that will help
confirm hemolysis are an elevated reticulocyte count, increased lactate dehydrogenase
(LDH), elevated unconjugated bilirubin, and decreased Haptoglobin.

LDH is found intracellularly, therefore when RBCs rupture, this value increases. Haptoglobin
binds free hemoglobin. Therefore as this protein is fully bound with what little hemoglobin is
left, it results in decreased levels of overall Haptoglobin. Unconjugated bilirubin is elevated as
the body is unable to eliminate it as quickly as it is produced with the destruction of RBCs.

Warm and cold agglutinins can further differentiate whether the cause is immune-
mediated. A direct antiglobulin test (DAT) must be performed.[10]

Hemoglobin concentration, or degree of anemia, can be used as an indicator of the extent of

hemolysis that occurs in sickle cell disease (SCD). The inverse correlation of low hemoglobin
concentration to a high degree of hemolysis has been supported by evidence of clinical
measures such as LDH, reticulocyte count, and indirect bilirubin.[11]

Treatment / Management
Depending on the severity of illness, immediate interventions, including blood
transfusions, plasmapheresis, or diuresis, may need to be performed depending on the
cause of hemolytic anemia.

Blood transfusions are always the mainstay of treatment when there is severe anemia,
especially when there is active bleeding. Once hemolysis is the known cause of anemia, or if
no emergent intervention is required, more specific treatment modalities may be followed.
However, the treatment will always vary depending on the cause.

If the cause is initially unclear, performing a direct antiglobulin (Coombs) test can be
used to differentiate between an immune or non-immune cause of hemolysis.

For patients with SCD, blood transfusions, hydroxyurea, erythropoiesis-stimulating agents,

and bone marrow transplants are possible options with demonstrated effect.[11]

A blood smear should be performed, especially when G6PD deficiency is being ruled out as it
can be performed more rapidly than an assay. Additionally, there is the possibility of a false
negative assay, while the smear is still suggestive of G6PD deficiency.[9] Once the diagnosis
is known, patients must avoid medications and foods that will worsen the oxidative process.

As the most feared complication of PNH is a thromboembolic event, some recommend

starting prophylactic anticoagulation; however, further studies must be performed to
create a proper treatment regimen as well as define who would benefit most from this
anticoagulation.[3]

Splenectomy, steroids, monoclonal antibodies, or immunosuppressants have been used as

late treatment options for certain diseases such as autoimmune hemolytic anemias, HS, and
SCD.[10] [12]

Differential Diagnosis
One of the main laboratory values that aids in the diagnosis of hemolytic anemia is an
elevated reticulocyte count, as the bone marrow is attempting to produce increased amounts
of RBCs. This can be seen in other disease processes such as blood loss anemia; therefore,
one must be cautious in taking a thorough history as well as evaluating other lab values that
should also be altered, including LDH, haptoglobin, and indirect bilirubin.

Hemolysis can be seen in many rare conditions from paroxysmal nocturnal hemoglobinuria to
blood transfusions or mechanical circulatory support; therefore, a wide differential must be
ruled out.[3] However, to assist one in making this distinction, there have been case reports
that help
separate intravascular hemolysis from diseases such as PNH, from those like heart valves
with mechanical prosthesis as kidney injury is less seen in the latter unless there is
underlying kidney disease.[13]

Prognosis
Overall the development of anemia increases the risk for mortality in many clinical diseases
such as chronic kidney disease, heart failure, and malignancy. This is seen in the publication
of landmark trials such as TRICC, TRISS, and TRACS as their goals were to see what was the
lowest level of anemia that could be tolerated without increasing mortality.

The prognosis for hemolytic anemias again varies on the cause of the illness as well as how
early it is diagnosed and managed appropriately.

Studies have shown that patients with SCD had poorer outcomes. Specifically, hemoglobins of
less than 8 g/dL are more likely to have complications during admissions, such as strokes, and
increased mortality.[11]

Patients who are diagnosed with autoimmune hemolytic anemia with marked anemia at onset
are at increased risk of multiple relapses as well as more often seen to be refractory to
multiple lines of treatment.[12]

As the main treatment for G6PD deficiency is the avoidance of oxidative stressors, the
disease is rarely fatal. However, these patients are more predisposed to sepsis and
complications from infections.[14]

Complications
Hemolytic anemia can affect multiple organ systems throughout the body. As RBCs are
destroyed, their products cause a chain of reactions that lead to further complications.

In SCD, the chronic hemolysis that occurs decreases the amount of oxygen that can be
delivered, further leading to tissue hypoxia. As tissues are deprived of blood and, therefore,
oxygen, patients can experience fatigue and muscle pain. The worse the degree of anemia has
shown worse clinical outcomes in patients with SCD.[11]

The risk of ischemia and thrombotic complications can be seen in any case of hemolysis as
there are more complications being studied from the toxic effects of circulating free
hemoglobin and iron.

Thromboembolism is the most common cause of death in paroxysmal nocturnal

hemoglobinuria (PNH). 15% to 44% of these patients will have at least one thromboembolic
event during their disease course. Thalassemia and SCD both are found to have a
hypercoagulable state caused by an abnormal phospholipid membrane asymmetry, which has
been linked to increased hemolysis and thrombosis.[3]

Excess hemoglobin and iron from hemolysis also are seen to cause complications in the
kidneys. Iron and hemosiderin deposition in the kidneys with intravascular hemolysis, such as
in PNH, have shown decreases in kidney function.[13]

Both liver disease and neurological deficits can be seen in Wilson disease if it is not diagnosed
and treated early. Hemolysis is one of the most important presenting symptoms in a child or
young adult with Wilson disease.[15]

Many people with HS are not diagnosed until adulthood when they begin to present with
complications. They can often be seen to have recurrent cholelithiasis, and in the most
severe cases, which are often found to be recessive, will need regular blood transfusions.
[5]

Consultations
While initial labs and workup for hemolytic anemia can be performed by a primary care
provider, hematology should be consulted for newly diagnosed hemolysis. These patients have
the ability to decompensate acutely and may require urgent interventions with the
coordination of multiple teams for medications and infusions.

Deterrence and Patient Education

Hemolytic anemia has many subsets within its disease process. Patients often require a full
team of medical professionals and specialists to treat their class of hemolytic anemia. While
many have medications that can be taken or simple deterrence from triggers to avoid any
complications, others can have serious consequences. Patients must be educated on the
symptoms of worsening clinical status or the beginnings of infections that can lead to further
morbidity due to their disease process.

Enhancing Healthcare Team Outcomes

While the initial workup for hemolytic anemia can begin with a general practitioner in a non-
urgent setting or even an emergency physician, a thorough diagnosis and continued treatment
can be difficult and challenging. An interprofessional team that incorporates a hematologist is
often crucial. Once specific lab markers and blood smears are obtained and reviewed, the
cause of hemolytic anemia can be determined. When a patient presents to the emergency
department compromised and decompensated, blood transfusions may need to be given when
the cause is unknown. However, if a thorough workup is able to be performed, it is crucial to
systematically diagnose the cause of hemolytic anemia as the treatment for one category may
be harmful in another. Furthermore, as the treatment is diverse among hemolytic anemias, the
morbidity and mortality outcomes vary just as much.

Review Questions

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topic. Click here for a simplified version.

Comment on this article.

References
1. Tefferi A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc.
2003 Oct;78(10):1274-80. [PubMed: 14531486]
2. van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte
enzyme abnormalities of glycolysis. Blood. 2005 Dec 15;106(13):4034-42. [PubMed:
16051738]
3. L'Acqua C, Hod E. New perspectives on the thrombotic complications of haemolysis.
Br J Haematol. 2015 Jan;168(2):175-85. [PubMed: 25307023]
4. Xue J, He Q, Xie X, Su A, Cao S. Clinical utility of targeted gene enrichment and
sequencing technique in the diagnosis of adult hereditary spherocytosis. Ann Transl
Med. 2019 Oct;7(20):527. [PMC free article: PMC6861754] [PubMed: 31807509]
5. Narla J, Mohandas N. Red cell membrane disorders. Int J Lab Hematol. 2017 May;39
Suppl 1:47-
52. [PubMed: 28447420]
6. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood
hemoglobin concentration? Blood. 2006 Mar 01;107(5):1747-50. [PMC free article:
PMC1895695] [PubMed: 16189263]
7. Beutler E, West C. Hematologic differences between African-Americans and whites: the
roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular
volume. Blood. 2005 Jul 15;106(2):740-5. [PMC free article: PMC1895180] [PubMed:
15790781]
8. Bain BJ. Diagnosis from the blood smear. N Engl J Med. 2005 Aug 04;353(5):498-507. [
9. Phillips J, Henderson AC. Hemolytic Anemia: Evaluation and Differential Diagnosis. Am
Fam Physician. 2018 Sep 15;98(6):354-361. [PubMed: 30215915]
10. Ataga KI, Gordeuk VR, Agodoa I, Colby JA, Gittings K, Allen IE. Low hemoglobin increases
risk for cerebrovascular disease, kidney disease, pulmonary vasculopathy, and mortality in
sickle cell disease: A systematic literature review and meta-analysis. PLoS One.
2020;15(4):e0229959. [PMC free article: PMC7122773] [PubMed: 32243480]
11. Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel
M, Montillo M, Röth A, Zeerleder SS, Berentsen S. Diagnosis and treatment of
autoimmune hemolytic anemia in adults: Recommendations from the First
International Consensus Meeting. Blood Rev. 2020 May;41:100648. [PubMed:
31839434]
12. Qian Q, Nath KA, Wu Y, Daoud TM, Sethi S. Hemolysis and acute kidney failure. Am J
Kidney Dis. 2010 Oct;56(4):780-4. [PMC free article: PMC3282484] [PubMed: 20605299]
13. Frank JE. Diagnosis and management of G6PD deficiency. Am Fam Physician. 2005
Oct 01;72(7):1277-82. [PubMed: 16225031]
14. Walshe JM. The acute haemolytic syndrome in Wilson's disease--a review of 22 patients.
QJM. 2013 Nov;106(11):1003-8. [PubMed: 23842488]
Disclosure: Caitlin Baldwin declares no relevant financial relationships with ineligible companies.

Disclosure: Jyotsna Pandey declares no relevant financial relationships with ineligible companies.

Disclosure: Olubunmi Olarewaju declares no relevant financial relationships with ineligible companies.
Figures

Reticulocytes, Polychromatic, polychromatophilic, red blood cell, Romanowsky, Stain,

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Brief Bullet Points on Hemolytic Anemia from "Essentials of Haematology"

Definition & Overview

• Hemolytic anemia results from excessive red blood cell (RBC) destruction, leading to
reduced RBC lifespan.
• Can be intrinsic (due to RBC membrane defects, enzyme deficiencies, or
hemoglobinopathies) or extrinsic (due to immune destruction, infections, or toxins).

Classification of Hemolytic Anemia

1. Hereditary Hemolytic Anemia

o Membrane defects: Hereditary spherocytosis, hereditary elliptocytosis.
o Enzyme defects: Glucose-6-phosphate dehydrogenase (G6PD) deficiency,
pyruvate kinase deficiency.
o Hemoglobinopathies: Sickle cell anemia, thalassemia.
2. Acquired Hemolytic Anemia
o Immune-mediated: Autoimmune hemolytic anemia (AIHA), alloimmune
hemolysis (e.g., transfusion reactions).
o Non-immune causes: Paroxysmal nocturnal hemoglobinuria (PNH), infections
(e.g., malaria), drug-induced hemolysis.

Pathophysiology

• RBC destruction can occur intravascularly (within blood vessels) or extravascularly

(mainly in the spleen).
• Common mechanisms include:
o Defective RBC membranes (spherocytosis).
o Oxidative stress causing Heinz body formation (G6PD deficiency).
o Complement-mediated destruction (PNH).
o Antibody-mediated destruction (AIHA).

Clinical Features

• Pallor, jaundice (from bilirubin released during RBC breakdown).

• Splenomegaly due to increased RBC destruction.
• Dark urine (hemoglobinuria in intravascular hemolysis).
• Fatigue, dyspnea, and tachycardia due to anemia.

Laboratory Findings

• Peripheral blood smear: Spherocytes, schistocytes, polychromasia, Heinz bodies (in

G6PD deficiency).
• Increased reticulocyte count: Bone marrow compensatory response.
• Elevated bilirubin & lactate dehydrogenase (LDH): Indicating RBC breakdown.
• Decreasedhaptoglobin: Haptoglobin binds free hemoglobin in intravascular hemolysis.
 • Direct Antiglobulin Test (DAT/Coombs test): Positive in autoimmune
hemolysis.
• Specific tests:
o Osmotic fragility test: Positive in hereditary spherocytosis.
o Fluorescent spot test: Used for G6PD deficiency.
o Ham test & flow cytometry: Used for PNH.

Management

• Supportive care: Folic acid supplementation, transfusions if severe.

• Specific treatments:
o Hereditary spherocytosis: Splenectomy.
o G6PD deficiency: Avoid oxidant drugs (e.g., sulfonamides, fava beans).
o Autoimmune hemolytic anemia: Corticosteroids, immunosuppressants.
o PNH: Eculizumab (complement inhibitor).

Let me know if you need more details on any specific type of hemolytic anemia!

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Detailed Overview of Hemolytic Anemia from "Essentials of Haematology"

Definition & Overview

• Hemolytic anemia is characterized by increased red blood cell (RBC) destruction

exceeding bone marrow production.
• It can be hereditary (intrinsic) or acquired (extrinsic).
• RBC destruction occurs intravascularly (within blood vessels) or extravascularly (by
macrophages in the spleen, liver, or bone marrow).

Classification of Hemolytic Anemia

1. Hereditary Hemolytic Anemia

o Membrane defects:
▪ Hereditary spherocytosis: Mutation in RBC membrane proteins
(spectrin, ankyrin).
▪ Hereditary elliptocytosis: Oval-shaped RBCs, usually asymptomatic.
o Enzyme defects:
▪ G6PD deficiency: RBCs vulnerable to oxidative stress.
▪ Pyruvate kinase deficiency: Causes ATP depletion and RBC destruction.
o Hemoglobinopathies:
▪ Sickle cell disease: Mutated hemoglobin S causes RBC sickling.
 ▪ Thalassemia: Reduced or absent globin chain synthesis.
2. Acquired Hemolytic Anemia
o Immune-mediated hemolysis:
▪ Autoimmune hemolytic anemia (AIHA): Antibodies against RBCs
(warm and cold AIHA).
▪ Alloimmune hemolysis: Occurs in transfusion reactions or hemolytic
disease of newborns.
o Mechanical hemolysis:
▪ Microangiopathic hemolytic anemia (MAHA): RBC fragmentation due
to mechanical trauma (seen in DIC, TTP, HUS).
▪ Cardiac hemolysis: From prosthetic heart valves.
o Infectious causes:
▪ Malaria: Parasite-induced hemolysis.
▪ Clostridium infections: Toxin-induced RBC destruction.
o Drug-induced hemolysis: Certain antibiotics, antimalarials, and chemotherapy
drugs.
o Paroxysmal nocturnal hemoglobinuria (PNH): Complement-mediated
hemolysis due to PIGA gene mutation.

Pathophysiology

• Hemolysis can be intravascular or

extravascular:
Parameter Intravascular Extravascular Hemolysis
Hemolysis Macrophages of spleen, liver, bone
marrow
Location Within circulation
PNH, transfusion reactions, Hereditary
Causes
microangiopathic hemolysis spherocytosis,
Splenomegaly Absent autoimmune hemolysis
Plasma Present
Increased Normal/slightly elevated
hemoglobin
Hemoglobinuria Present Absent
Serum
Decreased Decreased
haptoglobin
LDH levels Increased Increased
Indirect Increased Increased
bilirubin
• Key Mechanisms of Hemolysis:
o Defective RBC Membranes: Hereditary spherocytosis leads to loss of
deformability, trapping RBCs in the spleen.
o Oxidative Stress: In G6PD deficiency, RBCs are prone to oxidative
damage,
forming Heinz bodies.
 o Complement-Mediated Destruction: Seen in PNH, leading to nocturnal
hemoglobinuria.
o Antibody-
Mediated
Destruction: Warm
AIHA (IgG-
mediated) occurs
Clinical Features at body
temperature, while
• General cold AIHA (IgM-
Symptoms:
Fatigue, occurs
o mediated) weakness,
in pallor.
Jaundice
o cold (due to increased bilirubin from RBC breakdown).
environments.
o Dark urine (hemoglobinuria in intravascular hemolysis).
o Splenomegaly (in extravascular hemolysis).
• Crisis States:
o Aplastic crisis: Transient bone marrow suppression (often due to parvovirus
B19).
o Hemolytic crisis: Sudden increase in RBC destruction.
o Megaloblastic crisis: Due to folate deficiency in chronic hemolysis.

Laboratory Findings

• Peripheral blood smear:

o Spherocytes (hereditary spherocytosis, AIHA).
o Schistocytes (MAHA, DIC).
o Heinz bodies (G6PD deficiency).
o Target cells (thalassemia).
• Reticulocyte count: Increased (bone marrow compensatory response).
• Unconjugated bilirubin: Elevated (increased RBC breakdown).
• Serum lactate dehydrogenase (LDH): Increased (released from lysed RBCs).
• Serum haptoglobin: Decreased (binds free hemoglobin).
• Direct Coombs Test (DAT): Positive in AIHA.
• Osmotic fragility test: Positive in hereditary spherocytosis.
• G6PD enzyme assay: Detects G6PD deficiency.
• Flow cytometry for PNH: Detects CD55/CD59 deficiency.

Management of Hemolytic Anemia

1. General Supportive Care

o Folic acid supplementation to support RBC production.
o Blood transfusions in severe anemia.
o Iron chelation if chronic transfusions are required (e.g., in thalassemia).
 2. Specific Treatments
o Hereditary spherocytosis: Splenectomy in severe cases.
o G6PD deficiency: Avoid oxidative triggers (fava beans, sulfonamides).
o Autoimmune Hemolytic Anemia:
▪ Corticosteroids (first-line treatment).
▪ Rituximab or splenectomy in refractory cases.
o PNH: Eculizumab (complement inhibitor).
o MAHA (TTP, HUS, DIC): Plasma exchange, corticosteroids, or anticoagulation
based on cause.

Conclusion

Hemolytic anemia is a diverse group of disorders requiring precise diagnosis based on clinical
features and laboratory investigations. Treatment varies based on underlying cause, ranging from
supportive care to targeted therapy like immunosuppressants, enzyme replacement, or
splenectomy.