Lecture 4 - Normocytic Anemia Flashcards
DDX for normocytic anemai?
Ancemia of chronic disease Acute blood loss Multifactorial anemia Renal-failure associated anemia Aplastic anemia Hemolysis (hemolytic anemia)
2nd MC anemia?
Anemia of chronic disease (ACD)
Lab description of ACD?
Normochromic
Normocytic
Hypoproliferative
May be microcytic (late sign)
With ACD what determines the severity and characteristics of the anemia?
The underlying disease
What is the key pathophysiologic principle of ACD?
Disturbance in iron homeostasis mediated by chronic inflammation
Hepcidin released from liver in presence if IL-6
Why does the inflammation process cause anemia?
Inflammatory process leads to decreased iron uptake from GI tract and retention of iron w/in the macrophages as ferritin
Inflammatory processes cause a 2 pronged attack, what is it?
- Decreased iron availability in the bone marrow leads to reduced RBC production-hypoproliferation
- Reduced RBC survival (increased destruction)
How sever is the anemia with ACD?
Usually its mild but is often associated with other anemic processes
Lab findings for ACD?
Normocytic: MCV 80-100 Low iron Low transferrin Low TIBC HIGH ferritin
TX for ACD?
Treat the disease
Blood transfusion
EPO if symptomatic and Hb <10g/dL
Iron supplementation for ACD?
Not generally recommended if no iron deficiency
Charts on
Slides 18 and 19, maybe give them a look
What type of anemia is acute blood loss?
Normocytic anemia
- youre blood is fine you just dont have enough of it
With a hemorrhage pt you cannot trust?
CBC, they are getting IV fluids and blood products as part of their therapy and it will throw off their stuff
What is multifactorial anemia?
You have multiple causes for your anemia
Often Iron and B12 or iron and acd etc
Who gets renal failure associated anemia?
Prolonged renal failure:
- GFR < 30mL/min
It is a normocytic anemia
Erythropoietin, what is it good for?
Absolutely nothing!
Probably inaccurate however we cant count on it for diagnosis of renal failure associated anemia as it looks normal until Hb < 10
What is the tx for renal failure associated anemia?
Chronic synthetic erythropoietin agents (ESAs)
Hypoproliferative anemia is a prominent feature in?
Hematologic diseases described as bone marrow failure states
What is aplastic anemia?
It is a condition Bone marrow failure caused by:
Abnormal expression of stem cells leading to hypoplastic bone marrow.
Pancytopenia ensues
Primary and secondary aplastic anemia?
Primary:
-MC IgG autoantibody directed against the stem cell
Secondary:
- inherited (fanconi’s)
- acquired (chemo, radiation et)
Bone marrow disorders that cause pancytopenia?
- Aplastic anemia
- Myelodysplasia
- Acute leukemia
- Myelofibrosis
- Infiltrative disease
- (lymphoma, myeloma, carcinoma)
- Megalobastic anemia
Non-marrow disorders that cause pancytopenia?
- hypersplenism
- SLE
Clinical features of aplastic anemia?
- Anemia: Weakness, fatigue, pallor
- neutropenia - infection
- thrombocytopenia - bleeding
- P/E (pallor, purpura, petechiae)
- bimodal distribution (15 -25 yo then 60+ yo)
Labs for aplastic anemia?
Severe anemia
Pancytopenia (hallmark)
Decreased reticulocytes
Normal RBC
How is the diagnosis for aplastic anemia made?
CBC - pancytopenia
Bone marrow bx - hypocellular bone marrow
What is fanconi’s anemia?
Inherited form of aplastic anemia
Highly variable phenotypic expression of autosomal recessive trait or x-linked disorder
Fanconi’s anemia is characterized by?
Pancytopenia
Congenital malformations
Major causes of aplastic anemias
Slide 29, give it a gander
Tx for aplastic anemia?
Varies by age
20 y/o: bone marrow transplant (curative)
> 45y/o: immunosuppression, let body fix itself
20-45y/o: shooter preference
Prognosis for aplastic anemia?
<50y/o: 70% 5 yr survival
>70y/o: 50% 5 yr survival
Severe unresponsive aplastic anemia have 1 yr untreated mortality rate of 70%
What are hemolytic anemias?
Condition in which RBCs are destroyed and removed from circulation
- result is fewer mature RBCs which causes anemia
Broad range of etiologies
Classifications for hemolytic anemias?
Intrinsic: defect in RBC (hereditary)
Extrinsic: external to RBC
Lab descriptions of hemolytic anemias?
Peripheral Blood Smear
- spherocytes - round, lack concavity and central pallor
- schistocytosis - fragmented/destroyed rbc
- helmet cells
- target cells
- reticulocytis
Labs for hemolytic anemias?
Haptoglobin : L Indirect bilirubin : H Hemoglobinuria : H LDH : H Reticulocytes : L/Normal
I am an acquired clonal stem cell D/o, what am I?
My MC mutation is PIG-A gene
Paroxysmal nocturnal hemoglobinuria (PNH)
What is a PIG-A gene?
Gene responsible for some stuff… CD55 and CD59…
Result is RBC are susceptible to complement-mediated hemolysis
Clinical manifestation of PNH?
Episodic dark cola-colored urine (wake up pee)
Prone to thrombosis (veins > arteries)
Stem cell disorder
What conditions are associated with PNH?
It is a stem cell d/o so:
Aplastic anemia
Myelodysplasia
Acute myeloid leukemia
Hallmarks (Labs) for PNH?
LDH - H
Urine hemosiderin - +
Haptoglogin - L
iron def
Best screening test for PNH?
Flow cytometry
- def of CD55 and CD59 on RBCs
Key words for PNH diagnosis?
- Episodic hemoglobinuria
- Hemolytic anemia
- Thrombosis (hypercoagulable state)
- Flow cytometry (screening)
Tx of Paroxysmal Nocturnal Hemoglobinuria
Referral
Eculizumab - reduce hemolysis Anticoagulants Iron Bone marrow transplant Prednisone
MC hemolytic anemia to to RBC membrane defect?
Hereditary spherocytosis
What is going on with hereditary spherocytosis?
an abnormailty in spectrein or actin
Basically the RBC membrane doesnt flex like it should so they are rigid and dont pass through small fenestrations in spleen
Leads to badness (i mean hemolysis)
What type of anemia does hereditary spherocytosis cause?
Chronic hemolytic anemia
Clinical findings for hereditary spherocytosis?
Autosomal dominant disorder (fam hx)
Dx’d in childhood
Chronic hemolysis causes
- jaundice,
- splenomegaly
- pigmented gallstones
Labs for hereditary spherocytosis?
Microcytosis or normocytic and increase MCHC
Reticulocytis
Spherocytes
Neg coomgs (antibody test)
Osmotic fragility test - increased
What is the only condition that has increased MCHC?
Hereditary spherocytois
so if you see elevated MCHC pick this one!!!
Hereditary spherocytosis is intrinsic or extrinsic?
Intrinsic (its the RBC membrane that is fucked)
Tx for hereditary spherocytosis?
Supportive care
Folic acid 1mg/d
Splenectomy (that’ll teach the spleen)
This d/o causes acute hemolytic anemia with hemoglobinuria when taking the anti-malaria drug primaquine
G6PD deficiency
MC enzymatic d/o of RBC?
G6PD
X-linked enzyme defect
What are heinz bodies?
Oxidized Hgb denatures to form precipitants called heinz bodies
These damage RBC membrane and the spleen takes them out
Seen with G6PD
Pathophysiology of G6PD?
Oxidative stress
- cellular damage occurs from radical oxygen species that are not fully neutralized by anti-oxidants
G6PD folks cant handle the stress
Drugs that affect G6PD?
Antimalarials
Sulfonamides
Nitrofuratonin
And some misc stuff
Tx for G6PD?
Avoid that shit
Who gets G6PD deficiency?
10-15% of AA males
Labs for G6PD?
Normal between episodes
During episodes
- reticulocytosis
- indirect bilirubin
- bite cells
- heinz bodies
What is sickle cell anemia?
Autosomal recessive disorder
Characterized by point mutation of beta globin chain gene
Sickling
What causes hemolytic crisis for sickle cells pts?
Splenic sequestration of sickled cells
Epidemiology of Sickle Cell Anemia?
8% of AA are carriers, 1 in 400 has Sickle Cell Disease
Clinical findings of Sickle cell anemia?
Usually Show up in 1st year of life
Chronic hemolytic anemia
Pain (acute vaso-occlusion from clusters)
Acute chest syndrome
What is acute chest syndrome?
Fevers
Chest pain
Hypoxemia
Pulmonary infiltrates
Howel-jolly bodies
Hallmarks of hyposplenism due to auto-infarct and vaso occlusion (sickle cell)
(Nuclear remnants w/in RBCs that are usually removed by spleen and target cells)
Thats all cool, it looks like some shit let on the RBC when you look at a microscope
Lab findings for sickle cell
Chronic hemolytic anemia
howell-jolly bodies
Chronic reticulocytosis
How is sickle cell confirmed?
Hb electrophoresis
Tx for sickle cell?
Supportive care
Hydroxyurea
Transfusion
Pneumococcal vacc
Proposed sickle cell treatments?
L-glutamine
Rivipansel
Crizanlizumab
See slide 60-62 if you care, it wont be a question b/c they are still in trials
Hospital therapy for sickle cell crisis?
IV DVT prophylaxis Diphenhydramine NSAIDs Opioid therapy
Autoimmune hemolytic aneima (AIHA)
Acquired autoantibodies to RBC
It is an extrinsic defect
MC AIHA?
“Warm” AIHA
IgG antibodies react at normal body temps and destroy RBCs
Cold AIHA?
Aka cold agglutinin disease
IgM antibodies react at reduced body temps
Clinical feature of autoimmune hemolytic anemia?
- Episodic associated w physiologic stress
- Rapid onset anemia
- fatigue, angina, dypsnea, palpitations
- pain w eating/drinking cold stuff
- spherocytosis
+ COOMBS test
Why does AIHA have positive Coombs?
B/c its autoimmune and thats what Coombs is fore
Warm AIHA tx?
Refer to hematology
Immunosuppression
Splenectomy
Transfusions (complicated)
Cold AIHA tx?
Refer to hematology
Supportive
Avoid cold
Rituximab
What is microangiopathic hemolytic anemias (MAHA)?
Group of d/o
Intravascular hemolysis due to RBC fragmentation (traumatic destruction)
Hallmark of MAHA?
Fragmented cells on PBS
- schistocytosis
- helmet cells
Pts w hemolytic anemia are more prone to?
Infections liek parvovirus and strep
Infections may trigger hymolysis due to “unique mechanisms” i.e. magic
Malaria
JK he just had a title slide of this, no info
They say blood is thicker than water
So what? So is toothpaste
