Hemolytic Anemia Flashcards by Meghan May

What is hemolytic anemia?

RBC destruction resulting in loss of RBC mass and release of cellular contents that can be inherited or aquired

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What are some inherited forms of hemolytic anemia?

– RBC membrane disorders
– RBC enzyme deficiencies
– Hemoglobinopathies

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What are some acquired hemolytic anemias?

– Autoimmune (antibody mediated) hemolysis
– Mechanical trauma
– Infections
– Chemical
– Splenic sequestration

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Hemolysis can occur extravascular or intravascular which is more common?

Extravascular: Spleen&raquo_space;»> liver, bone marrow

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What labs are used to identify hemolytic anemia?

Normocytic anemia
Reticulocytosis
↑ LDH (lactate dehydrogenase), AST (aspartate aminotransferase), potassium from release of cellular contents
Bilirubinemia: Unconjugated bilirubinemia (indirect)
Hemoglobinemia (free hgb in plasma): More pronounced in intravascular hemolysis and Scavenged by haptoglobin (↓ hapto)
DAT (direct antiglobulin test)

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What types of urine screens could you do for hemolytic anemia?

Hemoglobinuria and Hemosiderinuria (most often seen with intravascular hemolysis)

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What can cause a “false positive” for hemolytic anemia?

“phlebotomy induced”

hemolysis from hyperkalemia

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Clinical features of hemolysis?

anemia and Hyperbilirubinemia

sometimes other symptoms related to cause

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It is not uncommon for patients with hemolytic anemia to have baseline hemoglobin of 6-7 g/dL without symptoms why?

chronic hemolytic conditions (eg sickle
cell anemia, thalassemia, pyruvate kinase deficiency) can often tolerate extreme anemia with minimal symptoms

Acute changes in red blood cell volume are poorly tolerated

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What are some clinical features of Hyperbilirubinemia?

Jaundice is detectable in most fair-skinned individuals when bilirubin exceeds 2.5 mg/dL
Scleral icterus can be detected by experienced physicians when bilirubin exceeds 1.7 mg/dL
Increased risk of bilirubin gallstone (pigmented)

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What are some rare complications of hemolytic anemia?

Pigment induced kidney injury from heme
Folate deficiency due to increased utilization
Increased risk of venous and arterial thrombosis related, including venous thrombosis of atypical sites (portal vein, cerebral venous sinus)

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Splenomegaly, hepatomegaly related to extra-medullary hematopoiesis is seen with which types of hemolytic anemia?

Thalassemia, PK deficiency, Hereditary spherocytosis

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Skeletal changes related to expansion of marrow ‘chipmunk facies’, convex bones is seen with which hemolytic anemia?

Beta thalassemia major

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What hemolytic anemia has asplenia?

sickle cell anemia

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Microangiopathic hemolytic anemia is seen with what causes of hemolytic anemia?

Seen in TTP, HUS, DIC, malignant hypertension, CREST syndrome, vasculitis, HELLP syndrome

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What does Microangiopathic hemolytic anemia cause?

Microvascular infarction causing acute kidney injury, liver disease, abdominal pain, fever, mental status changes, thrombocytopenia, rash, hemorrhagic diarrhea

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35 yo female with mild jaundice, splenomegaly, low Hb (9.4) and spherocytes on blood smear

What would happen to her MCHC?

Increase due to spherocytes becoming dehydrated as they move through the vessels causing increased concentration of Hb

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What are spherocytes?

• Normal-sized RBCs with increased hemoglobin concentration that are less flexible, trapped in
spleen causing shortened life span

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What are the Spherocytic hemolytic anemias?

Hereditary spherocytosis

* Autoimmune hemolytic anemia (AIHA) - warm and cold

What are the Congenital RBC membrane disorders?

• Hereditary spherocytosis and Hereditary elliptocytosis

both are Characterized by defects in structural cytoskelton proteins

What test is MOST important for differentiating between the causes of spherocytosis?

Direct antiglobulin test which tells you whether the RBCs have Ab or complement attacking them

Most common inherited hemolytic anemia in US

1/5000

Hereditary spherocytosis

What goes on genetically with Hereditary spherocytosis?

75% autosomal dominant and 25% sporatic: recessive and new mutations

Primary defects described in: ankyrin (most common), α/β-spectrin, band 3, band 4.2 and most patients have deficiencies in both ankyrin AND spectrin due to a protein imbalance

Clinical hereditary spherocytosis presentation?

Wide variability in severity of hemolysis

Splenomegaly

Aplastic crisis: Parvovirus infects/kills erythroid precursors

What tests can be used to diagnose hereditary spherocytosis?

* Family history * Peripheral blood review (spherocytes) with negative direct antiglobulin test * Osmotic fragility not used much anymore

Treatment for hereditary spherocytosis?

* Depends on clinical severity * Managing chronic hemolysis, Gallstones and Jaundice * Aplastic crisis * Splenectomy: complete (in adults) and partial (in children < age 6)

If a DAT is positive with spherocytes on the blood smear, jaundice, fatigue, splenomegaly what does the pt probably have?

Autoimmune hemolytic anemias (AIHAs) – Warm autoantibodies → 37°C – Cold autoantibodies → 0-5°C Host antibodies reactive with autologous RBCs

Which is more common warm or cold AIHA?

``` Warm-autoantibody type (~80%) – Idiopathic/Primary (60%) – Secondary: Lymphoproliferative disorders, Autoimmune disorders, Non-hematopoietic neoplasms ie. Ovarian cancer and Drugs, ie. α-methyldopa, cephalosporins ```

What causes cold AIHA?

* Idiopathic | * Secondary: Postinfectious, ie. Infectious mononucleosis, Mycoplasma) and Lymphoproliferative disorders

What is the pathogenesis of warm AIHA?

Extravascular hemolysis • Antibody mediated (IgG) OR • Complement mediated (classical pathway) • Spherocyte production

What is the pathogenesis of cold AIHA?

– IgM binds in cold and IgM-mediated agglutination impeding blood flow and RBC injury

How does warm look on blood smear?

* Spherocytes | * Polychromasia

How does cold look on blood smear?

Cold Agglutinins: Usually do not cause anemia but may cause obstructive symptoms

– Symptoms of anemia • Mild → Severe (with massive hemolysis) – Organomegaly Which AIHA?

Warm

– Symptoms of anemia • Mild → Severe (with massive hemolysis) – Acrocyanosis – Raynaud phenomenon

Cold

Cold comes in chronic and acute forms what is the difference?

* Acute form occurs 2-3 weeks into infectious illness (EBV/Mycoplasma) * Chronic form is associated with lymphoproliferative disorders

Congenital Red cell enzyme disorder?

Glucose 6-phosphate dehydrogenase deficiency (Pentose Phosphate pathway)

G6PDH deficiency causes what to happen in the biochem pathway?

Defect in the pathway responsible for reducing oxidants – Build up in G-6-P – Decreased glutathione production – Inability to reduce oxidant stressors

How are RBCs affected by Increased susceptibility to oxidant stress?

RBCs affected; resulting in a hemolytic anemia of variable clinical severity • Denatured hemoglobin (Heinz bodies) directly damage the RBC → intravascular hemolysis • Heinz bodies are removed in the spleen → extravascular hemolysis and BITE cells

What are some causes of oxidant stress?

* Infection * Fava beans * Drugs: dapsone, sulfonamides, primaquine, nitrofuantoin, quinolones

* 400 million people affected worldwide * Common in malarial endemic areas * X-linked disorder

G6PDH deficiency

What should you do to diagnose G6PDH deficiency?

peripheral blood smear NADPH fluorescence quantitative assay

What can cause fragmented RBCs?

Mechanical trauma to RBCs: heat, defective cardiac valves, microangiopathic hemolytic anemias, malignant hypertension, thrombotic thrombocytopenic purpura

What is Paroxysmal nocturnal hemoglobinuria (PNH)?

Rare Acquired mutation in PIGA gene (X chromosome) resulting in decreased GPI-linked proteins

Pathogenesis of Paroxysmal nocturnal hemoglobinuria?

Lack of GPI-linked anti-complement proteins makes cells suspectible to complement lysis Stem cell disorder so all myeloid lineages are affected, though RBCs are most sensitive to the C’ lysis

Clinical presentation of Paroxysmal nocturnal hemoglobinuria?

– Chronic low level hemolysis – Acute, episodic hemolysis events – Hemoglobinuria – Venous thromboses

What tests should be used to diagnose Paroxysmal nocturnal hemoglobinuria?

– Flow cytometry for GPI-linked proteins: CD55 (DAF), CD59 examined on WBCs AND RBCs