Extracorpuscular Hemolytic Anemias Flashcards
Classifications of hemolysis
- acute vs chronic
- inherited vs acquired
- intravascular vs extravascular
- intracorpuscular vs extracorpuscular (intrinsic vs extrinsic)
acute
rapid onset, shorter time course
chronic hemolysis
slow, with compensation from bone marrow
premature destruction of structurally and functionally normal RBCs due to mechanisms outside of the RBCs
extracorpuscular hemolytic anemia
Causes of Intracorpuscular Hemolysis
- membrane defects
- enzyme defects
- hemoglobinopathies
- PNH
Causes of Extracorpuscular Hemolysis
- non-immune causes: microangiopathic hemolytic anemias, infectious agents, mechanical forces
- immune causes: alloimmune hemolytic anemias, autoimmune hemolytic anemias
caused by a condition that leads to physical or mechanical RBC damage
non-immune hemolytic anemias
- microangiopathic, macroangiopathic
abnormalities in the microvasculature
microangiopathic
abnormalities in the heart or large blood vessels
macroangiopathic
two other causes on non-immune hemolytic anemias
- infectious agents
- chemical and physical agents: chemicals, drugs, venom, thermal injury
microangiopathic hemolytic anemia
- intravascular hemolysis = RBC fragmentation
- thrombocytopenia
thrombotic microangiopathies (TMAs)
- damage occurs when RBCs quickly pass through turbulent areas of small blood vessels partially blocked by microthrombi
- combination of MAHA and thrombocytopenia in the appropriate clinical setting
PBS Morphologies of MAHAs and TMAs
- keratocytes (horn cells)
- helmet cells
- triangulocytes
- microspherocytes
Top 4 scary microangiopathic hemolytic anemias
- thrombotic thrombocytopenic purpura
- hemolytic uremic syndrome
- disseminated intravascular coagulation (DIC)
- HELLP syndrome
What causes thrombotic thrombocytopenic purpura?
a deficiency of ADAMTS13
- protease responsible for cleaving ‘ultra-large’ multimers of von Willebrand Factor, which are involved in coagulation
ULVWF can trigger this
inappropriate clotting which leads to ischemia
this causes RBC fragmentation and trapping of platelets
TTP = results in hemolysis, severe thrombocytopenia
- neurologic dysfunction, fever, and renal failure may also occur
Peripheral smear findings of TTP
schistos and polychromasia
urinalysis of TTP
protein, RBCs, casts if extensive renal damage
- Tx: plasma exchange
AKA ‘hamburger disease’
hemolytic uremic syndrome
Hemolytic Uremic Syndrome
- caused by bacterial toxins (Shiga) - stimulates microvascular thrombi
- presents w acute gastroenteritis and bloody diarrhea
- damage to glomerular endothelial cells => acute renal failure
- Tx: fluid replacement, renal support (why not antibiotics?)
~10% are atypical HUS that have other causes
inappropriate complement activation
HELLP Syndrome
- hemolysis, elevated liver enzymes (transaminases), and low platelet count
- complication in some pregnancies, correlation w pre-eclampsia, and eclampsia
the inappropriate activation of the coagulation system results in clots throughout the microvasculature
DIC
- organ damage and bleeding
- many causes: malignancies, infections, acute leukemias, obstetric complications, tissue damage, transfusion rxns, venoms, etc.
Mechanical causes of MAHAs
- prosthetic cardiac valves
- circuits (ECMO)
- vascular malformation
- malignant hypertension
- exercise (or hobby-induced hemoglobinuria)
immune hemolytic anemia
- shortened red cell survival due to an Ab-mediated mechanism
> autoimmune: Ab specificity against one’s pwn RBC antigens
> alloimmune: Ab specificity against RBC antigens of another person
> drug-induced: multiple mechanisms
autoimmune hemolytic anemia
- can be some complement activation
- results from immune system dysregulation + loss of immune tolerance, exposure to antigen similar to self, etc
- if all of complement cascade is fixed to RBC => intravascular cell lysis
- if complement is only partially fixed = macs recognize Fc receptor of Ig and/or C3b complement - phagocytose RBC = extravascular RBC destruction
if all of complement cascade is fixed to RBC vs if complement is only partially fixed
- if all of complement cascade is fixed to RBC => intravascular cell lysis
- if complement is only partially fixed = macs recognize Fc receptor of Ig and/or C3b complement - phagocytose RBC = extravascular RBC destruction
most common type of autoimmune hemolytic anemia
warm autoimmune hemolytic anemia
antibody characteristics of warm autoimmune hemolytic anemia
- most are IgG
- react best at 37 degrees C
- may fix complement (but only up to C3)
- idiopathic cause (unknown)
- secondary WAIHA (~70%)
- Tx: steoids, splenectomy
cold autoimmune hemolytic anemia
- Ab characteristics = IgM, optimal reactivity at lower than 30 degrees C (~4C), and can bind complement
- fix entire complement cascade
- leads to the formation of membrane attack complex => RBC lysis in the vasculature
- typically only complement found on cells
- primary CAIHA = cold agglutinin disease
- secondary ‘’ (90%) = mycoplasma pneumonia infection, viral infections (mono)
lab findings for autoimmune hemolytic anemia
- decreased Hb
- increased retics
- increased serum bilirubin, lactate dehydrogenase
- decrease haptoglobin
- PBS: poly, spherocytes +/- agglutination
direct Ab test for autoimmune hemolytic anemia
- determines if RBCs are coated with Abs or complement
- can help to establish immune cause for hemolysis
Alloimmune hemolytic anemia
- hemolytic transfusion rxns
- hemolytic disease of the fetus and newborn
hematologic emergencies
- microangiopathic hemolytic anemia (> or equal to 1+ schisto)
- suspected hemolytic anemia with > 1+ sphero
