Lecture 4: Normocytic Anemias Flashcards
Normocytic anemias: DDx (6)
(1) Acute blood loss
(2) Primary bone marrow disorders
(3) Anemia of chronic disease/ inflammation (AOCD)
(4) Splenomegaly
(5) Hemolytic anemia with low or normal retic count
(6) Endocrine disorders
Anemia of Inflammation: Definition
Mild or moderate anemia that is persistent for greater than 1 to 2 months in patients with the associated conditions
- Infection
- Malignancy
- Endocrine disorders
- Immune disorders (SLE, RA)
- Others: HIV, DM, heart failure
Pathophysiology of Anemia of inflammation (4)
(1) Epo production is inhibited, so inappropriately low levels
(2) increased levels of inflammatory cytokines
(3) alterations in iron metabolism
(4) suppression of erythropoiesis
Anemia of inflammation: lab values
- Serum Fe: low to normal
- TIBC: Low to low-normal
- % iron sat: low
- ferritin: normal to high
- MCV: low to normal
- RDW: normal to high
T/F Iron replacement is necessary for anemia of inflammation.
FALSE; erythrocyte-stimulating agent can be given associated with hypertension and thrombosis
What is the pathogenesis of Aplastic Anemia?
Bone marrow failure
What is pancytopenia? What is it associated with?
hematopoietic stem cell injury associated with aplastic anemia
Aplastic Anemia: Causes (6)
- Idiopathic ( >50%): autoimmune, T-cell mediated
- Drugs (Chloramphenicol, sulfanomides, chemotherapy, etc.)
- Industrial and agricultural chemicals (benzene), radiation
- Congenital (FA)
- Infection (EBV, hepatitis, HIV, etc)
- Pregnancy
Aplastic Anemia: DDx (4)
- Other bone marrow failure syndromes
~ Myelodysplasia
~ Leukemias
~ Metastatic disease to the bone marrow
- Splenomegaly/portal HTN
- Severe B12 or Iron deficiency
- Autoimmune disorderClinical features of Aplastic Anemia
- Bleeding and ecchymoses (thrombocytopenia)
- Frequent infections, usually bacterial (neutropenia)
- Fatigue, pallor, decreased exercise tolerance, CV compromise (anemia)
What is not seen with Aplastic Anemia?
Splenomegaly/Hepatomegaly
Aplastic Anemia:Lab Findings (Peripheral blood and bone marrow)
- Peripheral blood:
~Pancytopenia
~variable, may be very severe
- Bone marrow
~ Hypocellular marrow
~ Cytogenetics are normalWhat condition does the normal cytogenetics finding in Aplastic anemia distinguish against?
Myelodisplastic syndrome; cytogenetics would be abnormal
Aplastic Anemia- Management (4)
(1) Prompt hematology referral if suspected
(2) Immunosuppressive therapy
- ATG, cyclosporine, corticosteroids
(3) Supportive care
- Recognition and tx of infections
- RBC and platelet transfusions if symptomatic
(4) Allogenetic bone marrow transplantation
What percentage of people survive Aplastic Anemia with immunotherapy?
75%
What is likely the cause of death in Aplastic Anemia?
Bleeding and infection
What percentage of people survive with Aplastic Anemia beyond one year with supportive therapy only? With bone marrow transplantation?
30-35%; 80-90%
What virus causes Aplastic Crisis? What does this virus do? How do you treat it?
Parovirus; arrests erythropoiesis; blood transfusion
When is Aplastic Crisis especially life threatening?
In patients with sickle cell anemia or hereditary spherocytosis that are heavily dependent on erythopoiesis due to the reduced lifespan of the red cells
What is Hemolytic Anemia?
Accelerated rate of red cell destruction beyond the ability of the bone marrow to fully compensate
What are the two main causes of hemolysis?
Intrinsic RBC defects (inherited) Extrinsic causes (acquired)
What is hemolysis?
Premature or accelerated destruction of RBCs (<100 days)
- elevated retic count
- may be well compensated by increased red cell production by the bone marrow
What happens to RBC with age? (3)
(1) Decreased membrane lipid component
(2) Spherocytic shape
(3) Less pliability and deformability
What are the hereditary hemolytic disorders (intrinsic)? (4)
(1) RBC enzyme defects (metabolic)
(2) RBC membrane defects
(3) Hemoglobinopathies
(4) Thalassemias
What are the acquired hemolytic disorders (extrindic)? (6)
(1) Immune hemolytic anemias
(2) Splenomegaly
(3) Microangiopathic hemolytic anemia
(4) PNH
(5) Direct toxic effect (malaria, clostridial infections)
(6) Spur cell anemia
In what other way can hemolytic disorders be classified? What do each entail?
According to anatomic site of RBC destruction
- Extravascular:
~ RBC destruction by macrophages in the liver
and spleen (more common)
~ Splenomegaly
- Intravascular
~ RBC destruction occuring primarily in the blood
vessels
~ Release of contents in the plasma
~ Hemoglobinuria, hemoglobinemia
- Overlap
Hemolytic Anemia: Clinical Presentation (8)
(1) Anemia
(2) Hypotension, syncope
(3) Pallor
(4) Jaundice, scleral icterus
(5) Gallstones secondary to increased bilirubin (chronic)
(6) Splenomegaly
(7) Hemoglobinuria
(8) Ulcers (sickle cell)
What additional studies would you get for hemolytic anemia? (3)
(1) Hemoglobin electrophoresis
(2) G6PD assays
(3) Bone marrow aspirate/biopsy
What is the most common cause of hereditary hemolytic anemia in Caucasians. What is it a deficiency of?
Hereditary Spherocytosis; membrane proteins
Hereditary Spherocytosis facts (4)
(1) Often the hemolysis is well compensated
(2) Very diverse clinical presentation
(3) History of gallstones is common
(4) Splenectomy is often effective
