Hemolytic anemia

Today we discussed hemolysis. These cases are relatively rare, but can cause impressive anema and can be very challenging to manage (and blog about!). A few points:

Hemolytic anemias account for less than 5% of cases of anemia, and have over 200 causes.


Traditional approach to differential is

1) Intracorpuscular 2) Membrane 3) Extracorpuscular


Intracorpuscular- think of what an RBC contains: Hgb, enzymes.

Inherited hemoglobinopathies:
alpha and beta thalassemia, sickle cell disease (SS and SC), unstable hemoglobins

RBC enzymopathies:
Pyruvate kinase def (N.Europe; shows echinocytes)
G6PD def- in males mainly. Inducers of G6PD deficiency related hemolysis:
dapsone, primaquine, sulfamethoxazole (many other obscure drugs), fava beans

Membrane

Hereditary spherocytosis: N europe (1/2000). 75% AD. Has spherocytosis, osmotic fragility
Hereditary elliptocytosis

Extracorpuscular

Inherited RBC antigen abnormalities

Immune-mediated hemolysis: Shown in above picture
Autoimm- warm (IgG), cold (IgM or IgG). Associated with autoimmune conditions, immunodeficiency, lymphoproliferative disorders, malignancy, infection (For cold, mycoplasma, EBV, HSV. For warm, CMV).
Alloimmune- active (e.g. transfusion, transplant), passive (e.g. in newborns)

Metabolic:
Renal failure- esp echinocytes
Hepatic failure- esp acanthocytes
Hypophosphatemia
Osmotic hemolysis (dialysis)

Toxins/physical:
aresnic, lead, Wilson's
valvular disease, vegetations
LVAD, intraaortic balloon pump, cardiac bypass, dehisced mechanical valves,
burns, radiation, trauma (e.g. march hemoglobinuria in soldiers)
Venoms (snake, spider)

Drug- induced hemolysis :
May be hapten, innocent bystader (RBCs adsorbed to IC's), or induce warm autoimmune (bad because remains after drug goes)
Drugs (many!)- Classics are alphamethyldopa, cephalosporins, penicillin, quinine, sulfonamides.

Infections:
clostridial sepsis
DIC
Mycoplasma, EBV, CMV
HSV, syphillis
Parasitic: malaria, babesiosis

Thrombotic microangiopathy
DIC, TTP, HUS, HELLP, acute fatty liver of pregnancy, ticlopidine, plavix, calcineurin inh


Some points on a "hemolysis history"

Age, ethnicity, malaria endemicity
temporal onset (for acquired vs congenital cause)
anemia symptoms
hemolysis symptoms (flank pain, hemoglobinuria, biliary colic)
PMHx (autoimm, rheum, malignancy, infectious, thrombosis)
FHx (hemolysis, splenectomy, pigment stones)
Meds/foods: Drug induced (or 'DIHA' as hematologists call it), TTP instigators, G6PD triggers
Transfusion hx


Focused physical

fever, tachycardia, hypotension
scleral icterus, pallor, jaundice
SLE features
lymphadenopathy
organomegaly, Murphy's sign

Lab:

1) For hemolysis itself:

Reticulocytosis, blood film changes (fragments, spherocytes, etc), plasma hemoglobinemia, high unfractionated bili, high LDH (nb- AST may be high, not ALT), low haptoglobin (both intra and extravascular). If all RBC production stops, expect Hgb fall of ~10/wk. If faster, probably destruction (e.g. hemolysis) happening

2) For potential causes

CBC, retics, blood film, DIC testing, ABO type and screen (i.e. indirect AT), DAT, cold agglutinin testing
Others: PNH, HB electrophoresis, osmotic fragility, sickle testing, 02 affinity testing, HIT, blood cultures, viral titres.


Management:

Depends on reason for hemolysis. If autoimmune, general principles are

1) avoid transfusion unless absolutely necessary, but involve the blood bank . transfusion medicine early- may be extremely difficult or impossible to find appropriate units
2) If cold autoimmune: warm extremities, warm IV fluids, steroids, plasmapheresis
3) If warm autoimmune: steroids, IVIG, plasmapheresis. Splenectomy in refractory cases
4) Try to reverse underlying cause if possible


Some links:

Click here for interesting NEJM case and image on cold agglutinin disease
For the serious connaisseur, click here for a review of autoimmune hemolytic anemias