96 - Hemolytic Anemias Flashcards
What are the main signs of HA (Hemolytic Anemia) (4)?
- Jaundice
- Discoloration of urine
- Spleno/hepatic- megaly
- Skeletal changes
What do you find in HA lab workup?
- Unconjugated bilirubin and AST increase
- MCV + MCH increase
- LDH increase
- Haptoglobin reduce
What is the definition of HA?
When the rate of RBC destruction exceed the capacity of the BM to produce more RBC
What are the main clinical findings in HS (Hereditary Spherocytosis)?
- Jaundice
- Splenomegaly
- Gallstone
What is the CBC finding that suggests most strongly that the patient might have HS?
MCHC (Mean Corpuscular Hemoglobin Concentration)>34
What is the treatment for HS?
- Mild- no treatment
2. Moderate- postpone splenectomy until after puberty
What does PKD (pyruvate Kinase Deficiency) treatment include?
- Supportive
- Folate
- Iron chelation
- Blood transfusion
- Splenectomy
What is the HA triad for diagnosis?
- Normomacrocytic anemia
- Reticulocytosis
- Hyperbilirubinemia
How can we differentiate between enzymatic and membranous disorders?
Enzymopathies should be considered when coombs negative HA
What is the role of G6PD?
Redox metabolism of all aerobic cells- In RBC its the only source of NADPH
What is the genetic location of G6PD?
X-linked
When challenged by an oxidative agent what do the majority of people with G6PD may present with?
- Neonatal jaundice (NNJ)
2. AHA (Acute HA)
What is the result of inadequately managed NNJ+G6PD deficiency?
Kernicterus and permanent neurological damage
What can cause AHA in people with G6PD deficiency? (3)
- Fava beans
- Infections
- Drugs (antimalarials, sulpho, antibacterials, antipyretic)
What is the prodrome of AHA in people with G6PD deficiency?
Malaise, weakness, abdominal/lumber pain.
After several hours-3 days jaundice and dark urine develop
What do we see in the lab of AHA in people with G6PD deficiency? (5)
- Hemoglobinemia
- Hemoglobinuria
- High LDH
- Low/absent plasma haptoglobin
- High unconjugated bilirubin
What are the typical features of G6PD deficiency blood cells
- Hemighosts (unevenly distributed hemoglobin
- Bite cells
- Heinz bodies
What is the most serious threat from AHA in adults with G6PD deficiency?
Acute renal failureq
Who usually gets affected by aHUS? what will we see?
- Children
2. microangiopathic HA, thrombocytopenia, ARF
What is the mortality rate of aHUS in the acute phase and in the case of progressing to ESRD?
- 15%
2. 50%
What is the treatment of aHUS?
- Eculizumab (anti C5 complement inhibitor) indefinitely to prevent ERSD
- Traditionally plasma exchange was given, but now less.
What are the two situations in which mechanical destruction of RBC occur?
- March hemoglobinuria (marathon runners)
2. Chronic and iatrogenic- Microangiopathic hemolytic anemia due to prosthetic heart valve
What are the most frequent infectious causes of HA?
- Malaria- in endemic areas
2. Shiga toxin-producing E.coli O157:H7- in the rest of the world
How can open wounds/septic abortion lead to HA?
Clostridium perfringens sepsis-> toxin with lecithinase activity
What is the mortality rate due to AIHA (Autoimmune HA) when treated?
5-10%
What is clinical triad of AIHA?
- Abrupt drop in hemoglobin level (up to 4 g/dl)
- Jaundice
- Splenomegaly
How do you call the direct antiglobulin test?
Coombs test
Which lab test is diagnostic for AIHA?
Coombs test. You can use to to determine if its C3 or Ig implicated.
Which disease might have AIHA as its first manifestation?
SLE
Where does the RBC destruction occur in AIHA?
Extravascular hemolysis (spleen, liver, BM)
What is the treatment for severe acute AIHA?
RBC transfusion
What is the treatment for non-life-threatening AIHA?
Prednisone (1 mg/kg per day) + rituximab (anti DC20) (100 mg wk * 4)
How will you treat patients with relapsing AIHA?
Splenectomy
What is CAD (Cold Agglutinin Disease)?
- A form of AIHA which occur in areas exposed to cold temperature.
- It is a chronic condition.
- Usually IgM produced by expanded B lymphocyte clone
- regarded as Waldenstorm macroglobulinemia
How do you treat CAD?
- Mild- avoiding cold temperature
- Rituximab (60% of patients respond to this treatment)
- Blood transfusion
What proved to be ineffective in CAD treatment?
- Splenectomy
2. Prednisone
What is PNH (Paroxysmal Nocturnal Hemoglobinuria) ?
Acquired chronic HA characterized by persistent intravascular hemolysis with occasional or frequent exacerbations.
What is the PNH triad?
- Hemolysis
- Pancytopenia
- Venous thrombosis (may lead to Budd-Chiari syndrome)
Describe a typical complaint of a patient with PNH?
Blood like urine in the first pass of urine in the morning
What kind of anemia do we usually see in PNH?
Normo/macrocytic with reticulocytosis
What is the gold standard for diagnosing PNH?
Flow cytometry for RBC and granulocytes- presenting CD59 and CD55 negative
How do you treat PNH?
Eculizumab + folic acid
or
Blood transfusion
