hemo julia Flashcards
Anemia =
RBC, Hematocrit and Hemoglobin decrease
Present with pallor, fatigue, weakness, dyspnea, palpitations, heart failure – any or all symptoms
How does anemia occur?
Acute blood loss (trauma)
Chronic blood loss
- Usually from GI tract – such as bleeding ulcers or carcinoma, etc.
- From Gyn – increased menses, postmenopausal bleeding, etc.
Increased destruction of RBCs = hemolytic anemias
Decreased or impaired production
Impaired production of RBCs by…
problem in proliferation of stem cells (e.g., aplastic anemia)
problems of proliferation and maturation of erythroblasts
defective DNA synthesis (e.g. Megaloblastic anemia)
defective heme synthesis (e.g Iron deficiency anemia)
defective globin synthesis (e.g. thalassemia)
Hemolysis: intra vs extravascular
= broken down/burst RBC
Intravascular hemolysis (in vessels)
- Common causes include mechanical trauma (e.g., prosthetic heart valves), PNH, and severe G-6-PD deficiency.
-Characterized by hemoglobinemia, hemoglobinuria, and decreased serum haptoglobin
- no splenomegaly
Extravascular hemolysis (spleen)
- presentation = anemia, splenomegaly, jaundice
- cause: Changes that make red cells less deformable, leading to their premature destruction in the spleen
- ex: Hereditary spherocytosis, Autoimmune hemolytic anemia, Thalassemia, Sickle cell disease
Hereditary causes of hemolysis
RBC membrane problems (hereditary spherocytosis)
- Defects in membrane proteins like ankyrin and spectrin cause RBCs to lose their biconcave shape, becoming spherical without normal central pallor. (very fragile and breakdown easily)
- hemolysis as they pass through the spleen
Enzyme disorders (e.g., G-6-PD deficiency)
-reduces RBCs ability to protect themselves against oxidative injuries
- Episodic hemolysis caused by exposures that generate oxidant stress
- triggers: ingestion of oxidant drugs (chloroquine), fava beans, or infections.
Hgb disorders:
- sickle cell anemia
- Thalassemia (alpha and beta)
Acquired causes of hemolysis
RBC membrane problem (paroxysmal nocturnal hemoglobinuria)
- Acquired mutation in the PIGA gene = RBCs more susceptible to complement-mediated lysis
Antibody mediated: antibodies and/or complement binding to the surface of RBCs and destroying our RBcs
- warm antibody
- cold agglutinin ds
- cold hemolysin
Mechanical trauma (e.g prosthetic heart valves)
Others include infections, drugs, toxins, splenic sequestration
Hemolytic anemia, General labs
Life span of the RBC is less than the normal of 120 days.
There is usually bone marrow erythroid hyperplasia = compensating response to…
- loss of RBC
- release of erythropoietin (EPO) produced by kidney
Lab findings:
- Decreased RBC lifespan.
- Increased bilirubin
- Hemosiderosis.
- Reticulocytosis (elevated reticulocyte count) that indicates active RBC production
- breakdown of RBCs releases heme, which is converted into unconjugated bilirubin
- Excess iron from hemolysis is stored as hemosiderin in tissue
Coombs tests
Coombs tests = always used in work-up of hemolytic anemias
- helpful in diagnosing autoimmune hemolytic anemia
Direct – rbc cells tested for surface antibodies
Indirect – serum tested for antibodies
Hereditary Spherocytosis
= Autosomal dominant genetic defect affecting RBC membrane proteins such as Ankyrin and spectrin
RBCs will be round without normal central pallor
==> These spherocytes are fragile and break down.
G-6-PD deficiency
G-6-PD = an enzyme which converts glucose-6-phosphatase
- Rate limiting step of pentose phosphate pathway
- Genetics: X-linked or recessive.
==> Hemolysis may occur after eating some types of food (classically Fava beans) or use of oxidant drugs ( chloroquine or infections)
- enzyme deficiency reduces RBCs ability to protect themselves against oxidative injuries. Episodic hemolysis caused by exposures that generate oxidant stress
Usually either recessive or X-linked
Morphologically RBCs will show HEINZ bodies which is precipitated/denatured hemoglobin
Sickle cell anemia
= Hemoglobinopathy
- Heterozygous versions are usually asymptomatic; need HOMOZYGOTES
- Protection against Malaria
Recall normal globin chains are alpha2 beta 2 ~~~~~> Sickle cell anemia is a BETA chain defect (amino acid substitution)
- cells become stiff and sticky under hypoxic conditions
There may be jaundice, pain, vaso-occlusive disorders (sickle cells get “stuck” in vessels).
There is also susceptibility to infections such as Strep. pneumonia or Salmonella osteomyelitis
Sickle cells trapped in sinusoids –> Spleen can basically become non-functional (auto infarct) –> infections with encapsulated microorganisms are more prevalent since the spleen is important in dealing with these types of microorganisms.
- Vaso-occlusive crises (painful episodes) -> Sickled cells can’t move smoothly through small blood vessels, so they can get stuck and block blood flow
- MICROVASCULAR OBSTRUCTION
- ISCHEMIC TISSUE DAMAGE
- Susceptibility to ENCAPSULATED bacterial infections due to splenic dysfunction… Sickle cells can get trapped in the spleen, damaging it. The spleen is an important organ for fighting infections, especially encapsulated organisms
- Streptococcus pneumoniae
- Salmonella osteomyelitis
Thalassemia
Hgb Alpha or Beta chain problems, aka deficient synthesis
- Inherited deficiency
Morphology: “Crew cut” skull X-ray because of erythroid hyperplasia expanding bone
Alpha:
- one missing gene: no sx
- four missing genes: hydrops fetalis - usually fatal (fetus does not make it to term) … If born, infant will have severe hemolytic anemia, edema (hydrops), massive hepatosplenomegaly
beta: varying degrees of severity
- one: mild anemia
- two: severe anemia
paroxysmal nocturnal hemoglobinuria
= Acquired mutation of PIGA (gene for enzyme needed to make certain RBC membrane complement regulatory proteins) = acquired RBC membrane disorder
- RBCs more susceptible to complement-mediated lysis
Not always paroxysmal or nocturnal
Don’t need to know too much about this
Immunohemolytic Anemias
Immunohemolytic Anemias = antibodies and/or complement present on RBC surface
= autoantibodies that react with red blood cells at temperatures ≥ 37° C (warm antibody hemolytic anemia) or < 37° C (cold agglutinin disease)
- May not be auto-immune, can be causes by certain drugs
warm IgG (will not hemolyze at room temperature)
- may be idiopathic or secondary to malignancies (i.e. lymphomas and leukemias)
cold agglutinin IgM (will hemolyze at room temperature)
- Mycoplasma pneumoniae, HIV, mononucleosis
cold hemolysin IgG
- e.g. cold paroxysmal hemoglobinuria (very rare subtype of autoimmune hemolytic anemia, caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria
- typically after exposure to cold temperatures
Hemolytic Anemias due to Trauma overview
-Mechanical Heart Valves:
Microangiopathies:
- Thrombotic Thrombocytopenic Purpura (TTP): pentad - of fever, thrombocytopenia, anemia, renal and neurological manifestations, deficiency of enzyme ADAMTS-13
- Hemolytic Uremic Syndrome (HUS): usually follows E. coli GI infections in children + acute kidney injury!!!!
