Anemia Flashcards
Anemia
🡓 in RBC count, Hct +/or Hgb
history + clinical signs important to help differentiate true from relative anemia
chronic anemias (develop slowly) may have few outward clinical signs
acute anemias usually present with outward clinical signs
Classifications based on:
- RBC indices
- Bone Marrow response
- pathologic mechanism
Faux Anemias
Pseudoanemia = collecting whole blood samples through IV fluid lines
Relative anemia = excess plasma volume
- anemia of newborn
3 Ways to Classify of Anemia
1) based on RBC indices
- MCV + MCHC
2) based on BM response
- regenerative v nonregenerative
3) based on major pathophysiologic mechanism
- loss (hemorrage)
- destruction (hemolysis)
- 🡓 production (reduced or defective erythropoiesis)
Anemia by RBC Indices
MCV + MCHC
- by convention, characterization of cell size is stated 1st followed by characterization of Hgb concentration
Some common types of anemias observed:
- normal MCV + MCHC = normocytic, normochromic anemia
- 🡑 MCV + 🡓 MCHC = macrocytic, hypochromic anemia
- 🡓 MVC + 🡓 MCHC = microcytic, hypochromic anemia
hyperchromia (🡑 MCHC) is always a false 🡑
Anemia by Bone Marrow Response
Regenerative:
- BM working appropriately to resolve anemia
- evidence of BM response in peripheral blood
Nonregenerative:
- BM not working appropriately to resolve anemia
- no evidence of BM response in peripheral blood
Regenerative Anemia
By Bone Marrow Response
Expect to see 🡑 polychromasia on peripheral blood smear + reticulocytosis
- other possible findings
classic pattern = macrocytic, hypochromic anemia based on MCV + MCHC
presence of a BM resoponse suggests either hemorrhage/hemolysis
Nonregenerative Anemia
By Bone Marrow Response
classic pattern = normocytic, normochromic anemia based on MCV + MCHC
multiple potential causes:
- something outside the marrow is affecting marrow function
- marrow is damaged/diseased
has enough time passed for the marrow to respond to anemia?
Anemia by Pathophysiologic Mechanism
loss (hemorrhage)
destruction (hemolysis)
🡓 production (🡓/defective erythropoiesis)
Anemia from Loss
Hemorrhagic Anemia
- anemia from blood loss can be chronic or acute
- source may be obvious or occult
Broad causes:
- damage to vasculature
- coagulation abnormalities
- severe thrombocytopenia
- parisitism
Acute Hemorrhage
clinical signs depend on amount of blood lost, period during whichc bleeding occured + site of hemorrhage
lab findings:
- Hct inititally within RI
- splenic contraction may temporarily compensate Hct by delivery of high hct blood into circulation
- blood volume subsequently restored via shifting of IF into vasculature
- 🡓 in RBC + Hct + Hgb will become evident
- evidence of regeneration evident 3-5 days after event
- plasma protein should start to normalize witihin 2-3 days after loss
- values should return to RI within 1-2 weeks following acute, single episode
if over 1/3 blood volume lost rapidly = hypovolemic shock can develop
Chronic Hemorrhage
anemia occurs slowly 🡒 clinical signs?
Lab findings:
- likely to have 🡓 plasma proteins
- nonregeneratie anemia common at time of diagnosis
blood loss associated with parasitism or GI ulceration often chronic
Anemia from RBC Destruction
Hemolytic Anemia
extravascular hemolysis (phagocytosis of RBCs by macrophages, typically within spleen) is by far more common than intravascular hemolysis (RBC rupture within BVs)
with acute hemolysis, clinical signs commonly overt bc no time for physiologic adaptation
Hemolytic Anemia Lab Findings
Extravascular v Intravascular
usually strong evidence of BM regeneration in peripheral blood (not expected in horses)
normal to 🡑 plasma proteins
often see evidence of Hgb:
1) extravascular = hyperbilirubinemia, bilirubinuria, clinical icterus
- important clue on serum biochem analysis
2) intravascular= hemoglobinemia, hemoglobinuria
- if hemoglobinemia occurs, MCHC may be falsely 🡑 d/t hemolysis
Abnormal RBC morphology may be present + help support hemolysis as cause of anemia
- spherocytes, heinz bodies, RBC parasites, etc.
Extravascular Hemolysis
phagocytosis of RBCs by macrophages within spleen
hyperbilirubinemia typically present
- don’t expect to see hemoglobinemia + hemoglobinuria
+/- splenomegaly
Mechanisms:
- antibody +/or complement mediated
- 🡓 RBC deformability
- abnormally 🡑 cellular phagocytic activity
- inherited erythrocyte defects
Antibody &/or Complement Mediated
Extravascular Hemolysis
antibodies/complement bind to RBCs 🡒 recognized by macrophage receptors 🡒 complete/partial phagocytosis of RBCs by macrophage
IMHA
Immune-mediated hemolytic anemia (IMHA)
Primary v Secondary
usually IgG mediated
- if IgM mediated 🡒 may see agglutination
Primary IMHA - body produces anti-RBC antibodies that cause early RBC removal
- true autoimmune hemolytic anemia (AIHA)
- no stimulus/cause identified
- diagnosis of exclusion
- most common in dogs
Secondary IMHA - immune response has inciting cause:
- infectious agents
- toxins
- drugs
- paraneoplastic syndrome
- vaccines?
Diagnosis:
1) expected BW findings:
- anemia (often severe)
- spherocytes
- regenerative response
- hyperbilirubinemia
2) May be present/helpful:
- agglutination
- Coombs test +
Coombs Test
Direct Antiglobulin Test
A + result is formation of RBC agglutination
- this result + supportive findings supports diagnosis of IMHA
Limitations:
- can’t be performed in patient that has autoagglutination
- can’t be used as stand-alone test to diagnose IMHA
- false negatives + false positives can occur
- requires species-specific tests components
- doesn’t differentiate primary v secondary IMHA
🡓 RBC deformability
Extravascular Hemolysis
less deformable RBCs sequestered by spleen + removed:
- RBC shapes formed from fragmentation injury
- oxidant damage
- parasitized erythrocytes
- spherocytes from IMHA + other process
🡑 Cellular Phagocytic Activity
Extravascular Hemolysis
hemophagocytic neoplasms 🡒 ex. hemangiosarcoma + hystiocytic sarcoma
Hemophagotic Syndrome:
- abnormal behavior by tissue macrophages
- generally secondary to neoplasia
Intravascular Hemolysis
lysis of RBCs within BVs 🡒 releasing Hgb into plasma
usually peracute or acute onset
may see hemoglobinemia, hemoglobinuria, hyperbilirubinemia
Mechanisms:
- complete-mediated lysis
- physical injury
- oxidative damage (sometimes)
- osmotic lysis
- other membrane alterations
Complement-Mediated Lysis
Intravascular Hemolysis
Membrane attack complex (MAC)
- some transfusion reactions
- some cases of neonatal isoerythrolysis
- some cases of IMHA
Physical Injury
Intravascular Hemolysis
- fragmentation injury
- 🡑 RBC fragility
- oxidative damage
- osmotic lysis
- other membrane alterations
Anemia from 🡓 Production
most present as non-regenerative anemia
- classic pattern = normocytic, normochromic anemia w/ lack of reticulocytosis
BM can’t keep up with normal body demand for blood cells:
- primary (intra-marrow cause) v secondary (extra-marrow cause)
- BM evaluation may be necessary to delineate cause
Extra-Marrow Causes
Anemia from 🡓 Production
- inflammatory/chronic disease
- chronic renal disease
- nutrient deficiency
- “hypo-“ endocrinopathies
Inflammatory Disease
Extra-marrow Causes
especially chronic inflammation 🡒 AKA Anemia of Inflammatory Disease (AID) or Anemia of Chronic Disease (ACD)
most common non-regenerative anemia of domestics species
milld to moderate, often normocytic + normochromic anemia
Mechanisms:
- hepcidin production 🡒 redices iron availability
- blunted EPO release + erythroid response to EPO
- shortened RBC lifespan
Intra-marrow Causes
Anemia from 🡓 Production
- aplastic anemia
- myelophthisis
- FeLV-induced erythroid hypoplasia
- prescursor-dirtected immune-mediated anemia (PIMA) 🡒 Pure red cell aplasia (PRCA)
Hepcidin
binds ferroportin 🡒 causing its internalization within cell
1) 🡓 iron export from macrophages
2) IC iron 🡑, leading to:
- 🡓 iron absorption from intestinal lumen
- 🡓 iron uptake by erythroid precursors
Net effects 🡒 hepcidin prevents iron absorption + locks iron away in storage
Chronic Renal Disease
Extra-Marrow Causes
mild to severe, normocytic + normochromic anemia
must correlate with biochem findings indicative of renal disease/insuffiency
main mechanism = 🡓 EPO d/t loss of renal cells
Nutrient Deficiency
Extra-Marrow Causes
Iron Deficiency Anemia:
- chronic external blood loss
- inadequate dietary intake
Copper Deficiency:
- copper needed i proteins essential for iron transport
- results in functional iron deficiency
classic pattern = microcytic + hypochromic anemia
Decreased Production
Intra-marrow Causes
Damage to 1+ of following:
- hematopoietic stem cells
- BVs/sinusoids
- BM stromal cells
may be reversible or irreversible
may or may not affect multiple cell lines
Aplastic Anemia
Intra-marrow causes
thought to be d/t stem cell injury
🡓 in RBCs, WBCs, platelets expected
Numerous causes:
- infectious
- drugs + toxins
- therapeutic or env. irradiation
- idiopathic
Myelophthisis
Intra-Marrow Causes
replacement of normal marrow hematopoeitic cells with non-hematopoietic issue, neoplastic tissue or inflammation
often presents as pancytopenia
FeLV-Induced Erythroid Hypoplasia
- felv targets + damages erythroid stem cells + progenitor cells
- may be macrocytic + normochromic or normocytic + normochromic anemia
- numerous abnormalities or erythroid cells
Prescursor-Directed Immune-Mediated Anemia (PIMA)
may be primary or secondary immune-mediated disease
- directed against precursor cells
BM evaluation typically reveals 🡑 # of immature RBC forms, which may not progress past a certain level of maturation
some cases respond to immunosuppressive therapy
Pure Red Cell Aplasia (PRCA)
considered a severe form of PIMA
non-regenerative anemia with markedly 🡓 (<5%) or absent erythroid precursors in marrow
