12. Extrinsic Defects Flashcards
Extravascular Lab Findings
- Increased serum bilirubin
- Increased urine and fecal urobilinogen
- Spherocytes may be seen (due to macrophages plucking abnormalities from RBC)
Extrinisc Hemolytic Anemia can be caused by:
- Immune anemias
- non-immune (infections, mechanical, chemical, physical)
Immune Hemolytic Anemias
and Lab findings
- Alloimmune
- Autoimmune
- Drug-induced
Lab findings:
- spherocytes (HgB normal)
- polychromasia
Alloimmune
- antibodies react to foreign RBC antigens
- Usually associated with transfusions, pregnancy, or transplant
- Acute hemolytic transfusion reactions - usually IgM (ABO incompatibility)
- Delayed hemolytic transfusion reactions - usually IgG (Patient is sensitized by previous exposure, Anamnestic response)
IgM
- large antibodies that activate complement in the plasma
- typically cause intravascular hemolysis
IgG
- small antibodies capable of crossing the placenta
- tags RBC to be hemolyzed in the spleen (Extravascular hemolysis)
Hemolytic Disease of the Newborn
- Alloimmune response of mother against antigens on fetal RBC
- Usually IgG, RH blood group system, anti-D
- Erythroblastosis fetalis
Erythroblastosis fetalis
- hemolytic anemia in newborn infant
- numerous nucleated RBCs
- hyperbilirubinemia
- leads to neural cell death.
- Putting baby under UV light or even sunlight can help bilirubin levels lower.
Autoimmune Hemolytic Anemia
- types
- diagnosis
Warm:
- Secondary to infection, immunologic disorders, pregnancy.
- 70% of AIHA
- Usually IgG
Cold:
- Cold agglutinin
- Paroxysmal cold hemoglobinuria
Diagnosis: Variable anemia, positive DAT, spherocytes, increased poly, increased retic, increased bilirubin.
Cold Agglutinin Syndrome
- Antibody has wide thermal range (optimum 4 degrees C)
- Usually IgM, anti-I specificity
- May be secondary to infections (mycoplasma)
- IgM anti-i secondary to infectious mononucleosis
- RBC clumping at room temperature may cause technical problems in CBC
Paroxysmal Cold Hemoglobinuria
- Very rare
- Associated with viral disorders: measles, mumps, flu, etc.
- Anti-P specificity, biphasic hemolysin (binds at cold temperature but destroys red blood cell at warm temperature)
Drug-Induced Immune Hemolytic Anemia
- Autoimmune
- Drug Adsorption
- Immune Complex
Drug-Induced: Autoimmune
- 70% of all cases of drug-induced hemolytic anemia
- drugs cause patient to make antibodies against self
- IgG antibodies, RBC destroyed in spleen
- Patients may demonstrate antibody long after discontinuing drug
- Seen in hypertensive drugs (Aldomet, l-dopa)
Drug-Induced: Drug Adsorption
- Hapten
- Penicillins, cephalosporins
- Drug is adsorbed to RBC surface
- Drug-RBC complex illicits antibody response
- IgG, extravascular hemolysis
Drug-induced: Immune complex
- Quinidine, phenacetin
- Antibody is formed against drug and forms complex with drug
- Complex adsorbs onto patients RBC and activates complement
- Activated complement = typically associated with intravascular hemolysis
Non-Immune Hemolytic Anemia: Infections
Intracellular - the organism becomes a part of the RBC. (ex: Malaria, Babesiosis)
Extracellular - create toxins that have an effect on the RBC causing them to burst. (Bartonella, Clostridium)
Non-Immune Hemolytic Anemia: Mechanical
March hemoglobinuria- pounding of the feet of marchers caused the red blood cells to be destroyed as they passed through their feet.
Cardiac Prosthesis- heart valve that is foreign to the body
Microangiopathic- destruction in the small vessels. Fibrin strands that cross the vessel act like a chain linked fence.
Microangiopathic Hemolytic Anemia
- TTP
- HUS
Thrombotic Thrombocytopenic Purpura (TTP)
- RBC fragmentation
- Thrombocytopenia
- Neurologic dysfunction
- Fever
- Renal failure
Endothelial damage leads to deposition of platelet thrombi and fibrin
Hemolytic Uremic Syndrome (HUS)
- MAHA
- Thrombocytopenia
- Acute renal failure
- Most commonly found in children (as opposed to TTP which is most common in 30-40 yo)
Non-Immune Hemolytic Anemia:
Chemical
Oxidative - denatures hemoglobin = heinz bodies (usally prevented by Hexose monophosphate shunt)
- Naphthalene (mothballs)
- Individuals deficient in G6PD are particularly susceptible
Examples: heavy metals = Arsenic, lead, copper
Non-Immune Hemolytic Anemia: Venoms
Direct hemolysins
- Brown recluse spider
- Bees and wasps
- Snakes
Non-Immune Hemolytic Anemia: Physical
- Burns - thermal damage to RBCs circulating in the area of burn
- Characteristic budding and microspherocytes
- body quickly clears them
