RBC disorders 2 Flashcards

1
Q

Causes of Normocytic anemiascorrected reticulocyte count <3%

A
Acute blood loss
Early iron deficiency and ACD
Aplastic anemia
Chronic renal failure
malignancy
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2
Q

normocytic anemia intrinsic defects

A

Membrane defect
Abnormal Hb
Enzyme deficiency

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3
Q

normocytic anemia extrinsic defects

A

Trauma (e.g. aortic stenosis, prosthetic valves)

Immune destruction

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4
Q

Mechanism and labs for normocytic extravascular hemolysis

A

Rbc phagocytosis by splenic and hepatic macs
Igg bound, with or without c3b
Abnormal shape (e.g. spherocytosis, sickling)

Laboratory findings:
Increase unconjugated bilirubin
Increased serum LDH

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5
Q

Mechanism and labs for normocytic intravascular hemolysis

A
intravascular hemolysis
Rbc phagocytosis by splenic and hepatic macs
Hemolysis occurs within blood vessels
Enzyme deficiency (g6pd)
Mechanical trauma
Complement/immune destruction
Laboratory findings:
Increase unconjugated bilirubin (minimal)
Increased serum LDH
Decreased serum haptoglobin
hemosiderinuria
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6
Q

Basic hereditary spherocytosis points

A
Autosomal dominant
USA 1/5,000
Intrinsic defect  . . . Where would the hemolysis occur?
Mutations in ankyrin most common
Band 3, spectrins, protein 4.2
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7
Q

hereditary spherocytosis clinical features

A
Clinical features
Jaundice
Gallstones
Splenomegaly
Aplastic crisis in children
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8
Q

Hereditary spherocytosis lab findings

A
Laboratory findings
Normocytic anemia
Increased MCHC
Increased osmotic fragility (rupture in hypotonic solution)
Elevated LDH and bili

Not all spherocytes are due to genetic disease
Warm autoimmune hemolytic anemia, ABO incompatibility, etc

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9
Q

Hereditary elliptocytosis

A

Autosomal dominant
Defect in spectrin tetramers or 4.1
Mild anemia
splenomegaly

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10
Q

Sickle cell anemia basic features

A

Autosomal recessive missense mutation
Valine substitution for glutamic acid in beta-globin chain
Heterozygote (HbAs) – 10% of blacks – no anemia
Hbss anemia (60% Hbs is threshold for disease)

Predominantly extravascular hemolysis
Hbs molecules aggregate.   Triggers:
low ph 
low oxygen tension
Volume depletion
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11
Q

sickle cell clinical findings

A
Clinical findings:
Dactylitis
Acute chest syndrome (most common cause of death)
Stroke
Gallstones
priapism
Aseptic necrosis of femoral head
Aplastic crisis (ass. With parvovirus)
Autosplenectomy (splenomegaly by 2 yo, then loses function) – Howell-jolly bodies
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12
Q

three complications of sickle cell

A

Susceptibility to infections:
due to dysfunctional spleen
Strep pneumonia, other encapsulated organisms
Osteomyelitis by salmonella paratyphi

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13
Q

renal findings with sickle cell

A

Sickle may occur in peritubular capillaries
Microhematuria
Renal papillary necrosis

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14
Q

sickle cell treatment

A

Treatment:
Infectious prophylaxis
Pain management
Transfusion – acute chest syndrome, aplastic crisis

Preventive measures: 
Hydroxyurea
Immunizations
Pneumococcal vaccine
Folic acid supplementation
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15
Q

G6PD deficiency basic features

A
recessive X--linked pattern 
affects 22% of U.S. blacks
females are asymptomatic 
older RBCs usually affected 
young RBCs have normal or near normal levels
> 100,000,000 worldwide
over 100 genetic variants known 
most represent amino acid substitutions
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16
Q

G6PD deficiency pathophysiology

A
Pathophysiology
Glutathione (reduced state) protects RBCs and their membranes from oxidants
Oxidative Damage → hemolysis
Inciting causes:
Infection
Drugs: primaquine, sulfas, 
Other compounds – in fava beans, etc.
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17
Q

G6PD Mediterranean

A

↓ enzyme activity throughout life span of RBCs
drug + Hb → production of H2O2
accumulating H2O2 injures RBC → hemolysis
Oxidized hemoglobin precipitates (Heinz bodies)
“bite cells” – macrophage removal of damaged membrane

more severe

18
Q

G6PD deficiency clinical and lab findings

A

Clinical and laboratory findings:
sudden onset back pain and delayed hemoglobinuria
Susceptibility to infections (impaired MPO – no nadph)
normocytic anemia
Heinz bodies
RBC enzyme analysis after hemolytic episode has resolved
*g6pd levels are ~normal in retic and young cells

19
Q

Immunohemolytic anemia basic features

A

Extrinsic hemolytic anemia with intra- or extravascular hemolysis

Warm agglutinins
Cold agglutinins
complement
Drug induced
Paroxysmal Cold Hemoglobinuria (PCH)
20
Q

Immunohemolytic warm agglutinin

A

Most common hemolytic anemia - extravascular.
Igg-coated rbc’s are phagocytosed by splenic macrophages
~ 50% idiopathic
associated with SLE, collagen vascular diseases (SLE), CLL, malignant lymphoma (esp. Hodgkin’s), viral infections, etc.

21
Q

Immunohemolytic cold agglutinin

A

intra- or extravascular hemolysis
causes include: Mycoplasma pneumoniae, infectious mononucleosis, CLL, drugs, etc.
Raynaud’s phenomenon common

22
Q

immunohemolytic compliment mediated hemolysis

A

C3b coated rbc are phagocytosed by liver macs – extravascular
Rbc’s coated by c5-c9 membrane attack complex – intravascular

23
Q

Immunohemolytic lab finding and clinical presentation

A

Jaundice
Hepatosplenomegaly
Raynaud’s phenomenon

Positive dat
Positive indirect
Unconjugated hyperbilirubinemia
Hemoglobinuria
Decreased haptoglobin
Normocytic anemia
Rbc agglutination (igm)
24
Q

drug induced hemolytic anemia

A
Antibody (IgG) to drug binds to RBC membrane
prototype is penicillin
extravascular hemolysis
direct coombs positive
“innocent bystander”
Drug–anti-drug immune complex 
IgG or IgM bind complement
IgG → extravascular hemolysis
IgM → intravascular hemolysis
drugs: quinidine, quinine, INH, sulfonamides
25
treatment of drug induced HA
Discontinue offending drug Corticosteroids/immunosuppression Splenectomy IVIG – igg coated macrophages can not phagocytize rbcs
26
Paroxsysmal Nocturia Hemoglobinuria basic info
Acquired membrane defect in myeloid stem cells – mutation in pig-a gene Mutation causes loss of decay accelerating factor (DAF) Daf normally destabilizes c3 and c5 convertase adhering to rbc’s, plt, neutrophils Intravascular complement mediated lysis
27
Paroxsysmal Nocturia Hemoglobinuria presentation and labs
Episodic hemoglobinuria May lead to iron def Increased risk of thrombosis (platelet frags) Increased risk of AML Labs: Normocytic anemia with pancytopenia Decreased haptoglobin Increased serum/urin hb
28
traumatic hemolysis
Cell Fragments: schistocytes, burr cells, helmet cells Disseminated intravascular coagulation (DIC) RBCs damaged by fibrin buildup or clots in small vessel lumen other causes: long distance running artificial heart valves thrombotic thrombocytopenia purpura
29
non immunologic hemolytic anemia
``` hypersplenism microangiopathic hemolytic anemia (MAHA) microorganisms, i.e. malaria, babesia, Clostridium perfringens snake venoms, i.e. cobra venom chemical, i.e. plumbism physical, i.e. burns ```
30
Alloimmune Hemolytic Anemia causes
transfusion reaction | Hemolytic disease of the newborn (HDN)
31
Alloimmune Hemolytic Anemia - transfusion reaction
``` donor and recipient blood is incompatible intra- and/or extravascular hemolysis free hemoglobin toxic to kidney cells laboratory findings DAT anemia depending on severity total and indirect bilirubin elevated haptoglobin ↓ LDH ↑ ```
32
Alloimmune Hemolytic Anemia - Hemolytic disease of the newborn
``` maternal antibodies > baby's RBCs anemia and hyperbilirubinemia Laboratory findings positive DAT ↑ total and indirect bilirubin LDH ↑ initially hematocrit and hemoglobin may be within normal limits ```
33
anemia associated with renal disease
Renal Disease (Uremia) Normochromic, normocytic mild anisocytosis sometimes hypochromic, microcytic burr cells – shrunken RBCs with irregular projections (echinocytes) usually present when BUN is twice normal possible mechanisms: bone marrow suppression hemolysis from impaired renal excretion coagulation defects (in severe disease) leading to blood loss impaired erythropoietin production from renal endocrine failure
34
anemia with neoplasia
usually normochromic and normocytic unless there is: blood loss hemorrhage a myelophthisic process mild hemolytic component often present severe with some lymphomas possibly due to the altered endothelium of malignant tissues (a set-up for DIC)
35
Macrocytic anemias (MCV >100 μm3)
Megaloblastic: Folate or b12 deficiency Nonmegaloblastic: alcoholism
36
B12 deficienct causes
``` Causes: Pernicious anemia Pure vegan diet Malnutrition Malabsorption: ↓ Intrinsic factor ↓ Gastric acid ↓ Intestinal absorption ```
37
folate deficiency causes
``` DECREASED INTAKE Malnutrition Etoh Goat milk Infants/elderly ``` MALABSORPTION Celiac Bacterial overgrowth ``` DRUG INHIBITION 5-FU MTX Tpm-sfx Phenytoin Ocp’s etoh ```
38
Megaloblastic Anemia Pathogenesis
Delayed nuclear maturation Affects all rapidly dividing cells Cellular RNA and protein synthesis unabated
39
Pernicious Anemia
Type II hypersensitivity: Autoimmune destruction of parietal cells (85-90%) Antibodies that block B12-if binding (60-75%) Blood group A individuals Achlorhydria
40
Folate deficiency anemia
Similar lab findings to b12 def Decreased serum and RBC folate (best test) Treatment: Intramuscular injections of b12 Oral administration of monoglutamic folic acid
41
Non Megaloblastic Macrocytosis
Mcv 105 ±10 Anemia may not necessarily be present Etoh most common cause Liver disease (increased cholesterol)