Chapter 5: Hemolytic Anemias Flashcards
What is the average lifespan of an erythrocyte?
120 days
What facilitates the normal destruction of RBCs?
The reticuloendothelial system (BM, liver, and spleen)
What is heme broken down into?
protoporpherin which becomes bilirubin and iron which is recycled.
What happens to globin from degraded RBCs?
It broken into amino acids which are excreted.
What are hemolytic anemias?
Anemias caused by increased Red cell
destruction.
Why does hemolytic anemia not present clinically until average red cell life is less than 30 days?
Because the bone marrow can compensate and produce 6-8 times the normal amount of RBCs masking the hemolysis.
How are hemolytic anemias classified?
Hemolytic anemias are either hereditary or acquired.
What are the clinical features of hemolytic anemias?
(1) pallor
(2) mild jaundice
(3) splenomegaly
(4) pigmented urine (urobillogen) (possibly kidney failure)
(5) Bilirubin gallstones.
(6) occasionally ulcers around the ankle (SSD)
What are the laboratory features of increased Red cell breakdown?
(1) increased serum bilirubin. (more for intravascular)
(2) increased urine urobillogen
(3) increased fecal stercobilinogen
(4) serum haptoglobins absent
(5) Increased LDH
(6) Plasma and urine Hgb increased
(7) Urine hemosiderin (intravascular hemolysis).
What are the laboratory features of increased RBC production?
(1) Reticulocytosis
(2) Myeloid:erythroid BM ratio of 1:1 or lower.
What are the RBC laboratory findings associated with damaged red cells?
(1) microspherocytes, elliptocytes, fragments
(2) autohemolysis
(3) Shortened RBC lifespan.
What are the two main locations of hemolysis?
(1) Extravascular via the reticuloendothelial system (liver and spleen)
(2) intravascular.
What are the key laboratory features of intravascular hemolysis?
(1) hemoglobinemia
(2) hemoglobinuria
(3) Hemosiderinuria
(4) Methaemaalbuminemia
What is the most common hereditary hemolytic anemia among northern europeans?
Hereditary spherocytosis.
What is the pathogenesis of hereditary spherocytosis?
Mutations to proteins involved in the interaction between cytoskeleton and membrane cause loss of RBC membrane. As RBCs circulate they become increasingly spherical. Eventually they get stuck in the microcirculation of the spleen and they die.
What are the clinical features of HS?
(1) Autosomal dominant (usually)
(2) Fluctuating jaundice (particularly with Gilbert’s disease)
(3) Splenomegaly in most patients
(4) Pigment gallstones
(5) aplastic crises (often precipitated by parvovirus infection)
What are the hematological findings with HS?
(1) Anemia
(2) microspherocytosis
(3) Reticulocytes 5-20%
What findings help diagnose HS?
(1) osmotic fragility
(2) Autohemolysis that is corrected by glucose
What is the treatment for HS?
Splenectomy, however this should not be done in younger patients or in patients with mild disease.
What is hereditary elliptocytosis?
A disease with similar clinical and lab features to HS, except for the appearance on a blood film. it also tends to be milder.
What causes hereditary elliptocytosis?
A mutation effecting the association of spectrin dimers into tetramers.
What is south-east asian ovalocytosis?
A red cell abnormality with cells that are rigid and resist invasion by malarial parasites. Most cases are asymptomatic. (mutation of the Band 3 protein)
How does G6PD effect RBCs?
G6PD renders RBCs susceptible to oxidant stress because it impairs their ability to form NADP.
What is the epidemiology of G6PD deficiency?
G6PD is X linked and affects mostly west african, mediterranian, middle eastern, and south-east asians. It imparts some resistance to malaria.
What are the clinical features of G6PD deficiency?
(1) Acute hemolytic anemia
(2) Neonatal jaundice
(3) Rarely a congenital non-spherocytic hemolytic anemia.
How is G6PD diagnosed?
(1) enzyme assay
(2) mid crisis contracted and fragmented ‘bite’ cells
How is G6PD treated?
Whatever agent precipitated the anemic crisis is treated. Blood transfusion may be necessary if the anemia is severe enough.
What other Pentose phosphate shunt deficiencies can lead to hemolytic anemia?
Glutathione deficiency
What glycolytic defects can lead to hemolytic anemia?
several that are all uncommon. They lead to non-spherocytic hemolytic anemia. Pyruvate kinase is the most common of them.
How is pyruvate kinase deficiency inherited?
Autosomal recessive
What are the clinical features of PK deficiency?
(1) widely varying anemia
(2) mild symptoms (right shift in oxygen binding due to rise in 2,3-DPG.)
(3) prickle cells
(4) autohemolysis not corrected by glucose.
What are autoimmune hemolytic anemias?
Anemias characterized by antibodies against self red cells. They give a positive coombs test.
How are AI hemolytic anemias classified?
AI hemolytic anemias are classified into warm and cold types.
What are warm autoimmune hemolytic anemias?
Red cells coated with Ig (usually IgG) and complement are taken up by RE macrophage which remove part of the membrane. This cuases spherocytosis and eventually Red cell destruction in the spleen by the RE system.
What are the clinical features of warm hemolytic anemia?
(1) variable hemolytic anemia
(2) enlarged spleen
(3) remission and relapse
(4) with thrombocytopenic purpura its Evan’s syndrome
(5) can be caused by methyl dopa therapy
What are the Lab findings of warm AI hemolytic anemia?
(1) Typical signs of hemolytic anemia
(2) Positive direct Coomb’s test
How is warm AI hemolytic anemia treated?
(1) Remove the underlying cause
(2) Corticosteroids (good if caused by IgG not complement)
(3) Immunosuppression
(4) Monoclonal antibodies (rituximab anti-CD20)
(5) Splenectomy in severe refractory cases
(6) Folic acid in severe cases
(7) Blood transfusion
What are cold AI hemolytic anemias?
Auto antibody attaches to red cells in the cooler peripheral blood. Usually IgM that fixes complement leading to both intravascular and extravascular hemolysis.
With what is monoclonal cold AIHA associated?
idiopathic (possibly lymphoproliferative disorders)
WIth what is Polyclonal Cold AIHA associated?
infection such as mononucleosis or mycoplasma.
What are the clinical features of cold AIHA?
(1) Chronic Hemolytic anemia aggravated by cold
(2) Mild jaundice
(3) mild splenomegaly
(4) bluish discoloration on the tips of the nose, ears, fingers, and toes.
What are the lab findings in Cold AIHA?
(1) Positive Coombs for complement only
(2) Typical signs of hemolytic anemia
(3) very little spherocytosis.
What is paroxysmal cold hemoglobinuria?
acute hemolysis after exposure to the cold. lysis occurs after rewarming. involves auto antibodies against blood group P antigen.
What is alloimmune hemolytic anemia?
Hemolytic anemia caused by antibodies in one individual against antigen from another. (ABO, Rh, etc.)
What are the three kinds of drug induced hemolytic anemia antibodies?
(1) Ab against drug-red cell membrane complex
(2) deposition of complement after formation of drug antigen complex
(3) true idiopathic AI hemolytic anemia.
What are red cell fragmentation syndromes?
Conditions in which physical damage is done to red cells.
What are causes of fragmentation syndrome?
(1) abnormal surfaces (artificial implants)
(2) atriovenous malformations
(3) microangiopathic hemolytic anemia
What are the causes of microangiopathic hemolytic anemia?
fibrin strands due to
1) DIC
(2) thrombocytopenic purpura (TTP
(3) Vasculitis
(4) polyarteritis nodosa
(5) Burns
What causes march hemaglobinuria?
damage to red blood cells between the small bones of the feet due to prolonged marching or running.
What is PNH?
It is a disorder in which deficient synthesis of the GPI anchor causes loss of DAF and MIRL on the RBC membrane. This leads to complement mediated lysis of RBCs,
What are the clinical features of PNH?
(1) Hemosiderinuria (and potentially iron deficiency)
(2) Thrombosis (acts on platelets too)
(3) Bone marrow hypoplasia
How is PNH diagnosed?
Flow cytometry for CD55 (DAF) and CD59 (MIRL).
How is PNH treated?
(1) Eculizumab (ab against complement C5)
(2) Iron therapy (for associated iron deficiency)
(3) Stem cell transplant (definitive)
(4) immunosuppression.
What are the three principle causes of intrinsic hemolytic anemia?
(1) disorders of the Red cell membrane
(2) Metabolic hemolysis (G6PD, PKD, oxidative drugs)
(3) Disorders of hemaglobin synthesis (sickle cell, thalassemias)
What are the hemolytic disorders of the cell membrane?
(1) hereditary spherocytosis
(2) Hereditary elliptocytosis
(3) Stomatocytosis
(4) Acanthocytosis
(5) Paroxysmal Nocturnal Hemaglobinuria
What are the Immune hemolytic anemias?
(1) Auto immune hemolytic anemia (Warm and Cold)
(2) Alloimmune hemolytic anemia
(3) Transfusion reactions
(4) Erythroblastosis fetalis
What are the infectious conditions which lead to hemolytic anemia?
(1) malaria
(2) Babesiosis
(3) Clostridial sepsis
What are the categories of extrinsic hemolysis?
(1) microangiopathic conditions
(2) Immune hemolytic anemias
(3) Infectious conditions
How does hypersplenism lead to hemolysis?
enlarged spleen traps RBCs and they die early.
How is MCV calculated?
MCV = hct/rbc count (x10)
How is MCH calculated?
MCH = Hgb/ rbc count (x10)
How is MCHC calculated?
MCHC = Hgb/Hct (x100)
What are the first two proteins bound by Hgb in the serum?
Haptoglobin and then albumin (methalbumin)
Why are some coomb’s tests negative for hemolytic anemia?
Because the spleen can remove ab coated RBCs
What can cause hemoytic anemia with low retic count?
parvovirus that knocks out erythropoietic cells.
What is the differential diagnosis with warm AI hemolytic anemia?
Lymphoma, malignancy, SLE, RA, drug induced, idiopathic.`
What is the differential diagnosis of cold AI hemolytic anemia?
Viral infections, mycoplasma, lymphoma, malignancy, SLE, RA, idiopathic.
What has the better prognosis warm or cold HA?
Cold is chronic and seasonal while warm has a much poorer prognosis.
What enzyme deficiency can lead to microangiopathic hemolytic anemia via vWF?
AdamTS13,
