Approach To Anemias Ii

Front 1

Hemolysis: Definition, Types, Categorization of Causes, Diagnosis

Back 1

1. Definition: higher than normal rate of RBC loss but no bleeding
2. Types: Extravascular (RBCs destroyed too soon by RES in spleen), Intravascular (red cells destroyed within vessels)
3. Categorization of Causes: Intravascular vs Extravascular, non-immune vs immune [autoimmune (warm vs cold) vs alloimmune (active vs passive) vs drug]

Front 2

How do you prove hemolysis? (2 steps)

Back 2

1. Step 1: Fast drop in Hb with no bleeding, BF changes, increased plasma-free Hb, elevated bilirubin, lactate dehydrogenase elevated, low serum haptoglobin, urinary hemosiderinuria, Coomb's test *high LDH with low haptoglobin is 90% sensitive
2. Step 2: Where is the lesion (intravascular or extravascular)? Intravascular has absent haptoglobin, normal spleen and schIstocytes; Extravascular has reduced haptoglobin, splenomegaly and sphErocytes

Front 3

What are examples of "inside" and "outside" causes of hemolysis?

Back 3

1. Inside (congenital): Hb disorder (sickle cell), Enzymes, Cytokines
2. Outside (acquired): Ag/Ab complex, electrolytes, toxins, burns, drugs, infections, TMA

Front 4

What are 2 inherited hemoglobin disorders?

Back 4

1. Hemoglobinopathy: Abnormal form of hemoglobin (ex-HbS in sickle cell disease) that leads to normocytic anemia
2. Thalassemia: Reduced rate of production of 1+ globin chains (ex-beta thalassemia) causing microcytic anemia

Front 5

Sickle Cell Disease: Pathophysiology, Complications, Epidemiology,

Back 5

1. Pathophysiology: HbS becomes crystalized when not carrying O2 ->crystals stick to and damage RBC -> RBC leaks water, becomes sickled and sticks to things->sickled RBCs hemolyse easily and block/damage blood vessels
2. Complications: Tissue damage (pain, organ failure), neovascularization with poor quality vessels
3. Epidemiology: >1 in 10 carriers in Toronto

Front 6

Beta Thalassemia: Clinical Phenotypes, Pathophysiology, Complications, Treatment of Complications

Back 6

1. Phenotypes: Silent (carrier with normal phenotype), Trait (slight microcytic anemia), Intermedia (late onset, moderate anemia, minimal transfusions), Major (early onset, severe anemia, lifelong transfusion)
2. Pathophysiology: imbalance in synthesis of alpha- to non-alpha globin chains
3. Complications: Infants (failure to thrive, poor feeding, malaise, splenomegaly, delayed puberty) Adults get iron overload from transfusions (osteoporosis, interility, cirrhosis, diabetes/hypothyroid, cardiac failure)
4. Treatment of Complications: blood transfusion + iron chelation, bone marrow transplant

Front 7

Hereditary Spherocytosis (HS): Pathophysiology, Complications, Treatment

Back 7

1. Pathophysiology: Defects in cytoskeleton of RBCs (ankyrin, spectrin, band 3, protein 4.2) causing them to be non-deformable -> removed by spleen -> splenomegaly + hemolytic anemia
2. Complications: Gallstones, leg ulcers, iron overload
3. Treatment: folic acid, supportive care, splenectomy

Front 8

RBC Enzymopathies: Pathophysiology of Hemolysis, Example

Back 8

1. Pathophysiology of Hemolysis: problem with an enzyme that is part of an anti-oxidant production or protection pathway -> oxidative stress leads to hemolysis
2. Example: G6PD deficiency which affects the glycolysis pathway (an anti-oxidant protective pathway)

Front 9

Allo-Immune Hemolysis: Transfusion Reaction (active) vs Hemolytic Disease of the Newborn (Passive)

Back 9

1. Transfusion Reaction: active reaction=major blood group incompatability, recipient has preformed Ab against transfused products
2. Hemolytic Disease of the Newborn: passive reaction=minor incompatibility, donor or placenta carry antibodies against recipients cells

Front 10

Warm autoimmune hemolysis antibodies: Pathophysiology, Findings, Causes, Treatment

Back 10

1. Pathophysiology: IgG Ab against own RBC causes extravascular hemolysis mainly in spleen
2. Findings: DAT +, spherocytes on blood film
3. Causes: idiopathic, drugs (penicillin, quinidine, quinine), autoimmune (SLE), lymphomas, CLL
4. Treatment: stop drug, folic acid, steroids, splenectomy, rituximab, cytotoxic immunosuppression, transfusion

Front 11

Cold Autoimmune Hemolytic Antibodies: Pathophysiology, Findings, Causes, Treatment

Back 11

1. Pathophysiology: IgM antibodies against RBC that cause intravascular hemolysis with the help of complement and react most strongly at cold temperatures
2. Findings: DAT+ for complement, agglutination on blood film
3. Causes: Infections (EBV, Mycoplasma), B-cell neoplasm (CLL, lymphomas), idiopathic, cold agglutinin disease, cryoglobulins
4. Treatment: warm patient, warm blood, folic acid, plasmapheresis

Front 12

What are causes of non-immune mechanical hemolysis? (7)

Back 12

Electrolytes: renal, hepatic or lipid failure leading to severe hypophosphatemia and osmotic hemolysis
Toxins/Drugs: Arsenic, lead, copper, venoms
Burns
Infections: membrane injury, sepsis (DIC, direct toxic effect), molecular mimicry leading to autoantibodies, parasites (malaria)
TMA/MAHA: Type of thrombotic microangiopathy called microangiopathic hemolytic anemia, coagulopathic (DIC) or non-coagulopathic (HUS, TTP, etc.)
Hypersplenism
Prosthetic heart valve

Front 13

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura: Pathophysiology of TTP, Pathology, Causes, Clinical Pentad of HUS, Treatment of TTP

Back 13

1. Pathophysiology of TTP: mutation in ADAMTS13 which normally cleaves/inactivates vWF, when absent, clots are more likely to form due to increased vWF
Pathology: Hyaline microthrombi in arterioles and capillaries
3. Causes: Idiopathic, E.coli (HUS)
4. Clinical Pentad of HUS: Microangiopathic hemolytic anemia, Thrombocytopenia, CNS abnormalities (seizures, coma), Renal failure, Fever
5. Treatment of TTP: Plasma exchange