Hemolytic Anemias Flashcards
hemolytic anemia definition
conditions in which there is an increased destruction of RBCs causing the BM to respond by accelerating production
RBCs destroyed faster than BM can produce them
Wintrobe classification of hemolytic anemias
normocytic, normochromic
general lab findings of hemolytic anemias
normo, normo anemia reticulocytosis, increased IRF marked polychromasia & NRBCs elevated indirect/unconjugated bilirubin normal direct/conjugated bilirubin decreased haptoglobin (intravascular)
general signs & symptoms of hemolytic anemias
jaundice: from increased bilirubin production
gallstones made of bilirubin
dark or red urine due to excretion of plasma hemoglobin (or increased urobilin)
splenomegaly (extra)
general anemia symptoms
Extravascular hemolysis general
RBC destroyed outside blood vessels (spleen (!), liver, BM)
phagocytized by macrophages in the spleen & liver
SPHEROCYTES
Intravascular hemolysis general
destruction of defective RBCs as they circulate release hemoglobin into the plasma decreased haptoglobin hemoglobinuria, hemoglobinemia etc SCHISTOCYTES
normal way RBCs are broken down
- globin is returned to amino acid pool
- iron is separated & stored
- protoporphyrin (heme ring) is broken down into bilirubin (indirect/unconjugated)
- travels to liver via albumin & is converted to conjugated/direct
- secreted as bile & dumped into GI tract where is converted to urobilinogen
- majority excreted in stool some reabsorbed and excreted in the urine
intrinsic defects (categories)
membrane
enzymes
hemoglobin
most are hereditary & usually extravascular hemolysis
extrinsic defects general
antagonist in plasma or soluble factors in environment - toxic to cell & cause hemolysis
physical/mechanical trauma
immune mediated
usually acquired
Hereditary Spherocytosis (HS) general
hereditary hemolytic anemia due to RBC membrane defect
most common inherited anemia among whites
RBCs deficient in spectrin (secondary deficiency in ankyrin)- loss of membrane, decreasing surface to volume ratio = SPHEROCYTES
Lab diagnosis of HS
normo, normo mild anemia spherocytes (!) elevated MCHC (due to spherocytes) reticulocytosis increased osmotic fragility!! (confirmatory test)
Osmotic fragility test
RBCs are incubated in varying concentrations of hypotonic NaCl solutions
spherocytes are unable to expand as much & are lysed at a higher concentration of NaCl than normal
confirmatory test for hereditary spherocytosis
Treatment for HS
mild forms - no therapy
splenectomy
Hereditary Elliptocytosis (HE) general
hereditary hemolytic anemia due to RBC membrane defect
deficiency of alpha-spectrin or beta spectrin are common
90% of patients show no signs of hemolysis
populations with HE
Blacks, equatorial african populations
rare in western populations
laboratory diagnosis of HE
normo, normo
no anemia, no hemolysis (!!)
elliptocytes (usually more than 25%)
Hereditary pyropoikilocytosis (HPP) general
severe subtype of HE
primarily seen in blacks & arabs
severe hemolytic anemia & extreme poikilocytosis
decreased thermal stability of RBCs
2 defects: deficiency of alpha-spectrin & another mutant spectrin = cell destabilization
clinical findings of HPP
present at birth hemolytic anemia hyperbilirubinemia splenectomy striking poikilocytes decreased MCV (25-55) increased thermal sensitivity test
Hereditary Stomatocytosis general
rare! abnormalities in cation permeability in RBC membrane
[intracelluar cations] increases & water enters the cell & overhydratess = stomatocytes
increased bilirubin, moderate reticulocytosis
Energy for mature RBCs
dependent on anaerobic glucose metabolism (no organelles)
Glucose-6-phosphate dehydrogenase deficiency ( G6PD) general
worldwide (mediterranean, africa, china)
x-linked inheritance (fully expressed in males, females with homozygous)
most common inherited enzyme deficiency
asymptomatic except when combined with: oxidizing chemical/drug (fava bean), severe infection, neonatal jaundice
G6PD defect
enzyme defect of the hexose monophosphate pathway
RBCs do not make enough or it cannot function properly
necessary to reduce cellular oxidants = hemoglobin could be oxidized to methemoglobin which precipitates to form Heinz bodies (which are removed and cause bite cells & blister cells)
Lab diagnosis of G6PD
normo, normo anemia Bite cells, heinz body test (supravital stain) reticulocytosis increased unconjugated bili hemoglobinuria/emia screening tests for G6PD
Pyruvate Kinase (PK) deficiency general
most common in norther european ancestry
hereditary hemolytic anemia due to enzyme defect
most common deficiency of the glycolytic pathway
inability of RBC to maintain normal ATP levels = alterations to RBC membrane
loss of K+, gain Na+ & Ca++
deformed or rigid cells that are removed by the spleen
lab diagnosis of PK
normo, normo anemia reticulocytosis echinocytes elevated indirect bili reduced PK
MAHAs
group of clinical disorders characterized by RBC fragmentation in the circulation - intravascular hemolysis
fragmentation occurs as RBCs pass through fibrin deposits inside small blood vessels
characterized by schistocytes, microspherocytes & increased retics
disorders associated with MAHA
Disseminated intravascular coagulation (DIC)
thrombotic thrombocytopenic purpura (TTP)
hemolytic uremic syndrome (HUS)
Hemolytic uremic syndrome (HUS)
multi-system disorder
characterized by triad of clinical findings:
1. hemolytic anemia with RBC fragmentation
2. thrombocytopenia
3. acute nephropathy, including renal failure (clots in kidneys)
Lab diagnosis of HUS
normo, normo mod-severe anemia schistocytes, helmet cells, spherocytes polychromasia, occiasonal NRBC leukocytosis w/ left shift low to markedly low plts hemoglobinemia/uria increased bili, LD decreased haptoglobin
Thrombotic thrombocytopenic purpura (TTP)
syndrome of diverse issues characterized by: hemolytic anemia w/ RBC fragmentation fever thrombocytopenia (
lab diagnosis of TTP
low hemoglobin normo, normo anemia polychromasia, NRBC SCHISTOCYTES Severe thrombocytopenia hemoglobinemia, hemoglobinuria, increased bili & LD, decreased haptoglobin
TTP treatment
plasma exchange with FFP
Cyrosupernantant
DIC
characterized by:
widespread activation of hemostatic system
secondary to: bacterial sepsis, pregnancy complications, neoplasms, trauma etc
easiest way to detect is through coagulation studies
thermal injury
3rd degree burn patients may have severe acute hemolytic anemia
direct effect of heat on spectrin-loss of elasticity & deformability
schistocytes, spherocytes & acanthocytes
exercised induced hemoglobinuria
march hemoglobinuria: associated with strenuous exercise transient hemolysis usually no anemia hemoglobinuria/emia
Infectious agents of hemolytic anemia
malaria- most common cause of hemolytic anemia world wide
bartonellosis
babesiosis
clostridium perfringens
general lab findings of immune mediated hemolytic anemias
normo, normo anemia
spherocytes, schistocytes & polychromasia
reticulocytosis
POSITIVE DAT!!!!!
classification of Immune hemolytic anemias
autoimmune
drug-induced
alloimmune
3 subcategories of autoimmune hemolytic anemias
warm antibody AIHA
cold antibody AIHA
paroxysmal cold hemoglobinuria
Warm autoimmune hemolytic anemia general
most common (70% of AIHA)
2:1 female prevalence
older adults & children
lab diagnosis of WAIHA
normo, normo anemia spherocytes retic, poly, NRBCs increased unconjugated bili POSITIVE DAT
cold autoimmune hemolytic anemia
cold agglutin disease 16-30% of AIHA chronic hemolytic anemia usually >50 yrs older peak at 70 predominance in females
lab diagnosis of CAIHA
normo. normo poly, retic, NRBC spherocytes autoagglutination of RBCs positive DAT increased unconjugated bili
Paroxysmal cold hemoglobinuria
rare acute form of cold generated hemolysis
common in children after viral infection
antibody react & induce hemolysis at lower temps
massive acute hemolysis & hemoglobinuria
DONATH-LANDSTEINER ANTIBODY
Donath-Landsteiner antibody
anti-P antibody
binds in cold temps & causes complement activation upon warming
intracellular hemolysis
lab diagnosis of PCH
DAT weak positive retic spherocytes & schistocytes hemoglobinuria/emia serum bili elevated
Drug induced hemolytic anemia
uncommon acquired cause
drug itself doesn’t cause RBC injury
immune response to drug-induced alteration of RBC
Alloimmune hemolytic anemias
reacts to transfused cells & HDFN
Transfused: acute & delayed
