hemolytic anemias Flashcards
target cell differential
Liver disease →
Splenectomy →
Thalassemia →
Other hemoglobinopathies →
Iron deficiency →
Differential for DAT positive hemolytic anemia
1) False positive
2) AIHA
3) Drug induced auto-immune hemolytic anemia → (antibiotics (cephalosporins, penicillins), CPIs, platinum-based chemo, NSAIDs) – table 1, acute (often within hours).
4) *Delayed hemolytic transfusion reaction → 1-2 weeks after transfusion of RBCs, although the interval can range from 24 hours to 28 days.
5) *Cold agglutinin disease
Therapies that can cause false positive result on DAT
IVIG
RHd
ATG
*daratumumab
Peripheral smear findings w/ AIHA
spherocytes
reticulocytosis
*review peripheral smear image online
Secondary causes of AIHA
Medications (penicillins, methyldopa, cephalosporins) →
CVID →
Lymphoproliferative disease (CLL) →
Connective tissue diseases (SLE)→
Viral infections (EBV, HEV, CMV, HIV) →
Autoimmune disorders (causal?) →
Allogeneic blood transfusion →
Chronic inflammatory disease (IBD) –>
Infectious causes of AIHA
EBV, Hep C, CMV, HIV, *brown recluse spiders, babesia
Initial management of AIHA
pred 1 mg/kg
Management of refractory AIHA
- rituxan
- Immunosuppressive agents, such as cytoxan, mycophenolate, azathioprine, or cyclosporine
- splenectomy as last resort
What is a high titer in cold agluttinin disease?
(1:40) or >99th percentile
Infectious causes of cold agglutinin disease
1) mycoplasma pneumonia (atypical pneumonia)
2) EBV/mono
Secondary causes of cold agglutinin disease
1) Low grade lymphoproliferative disorders (B cell NHL, MGUS, LPL, SLL) ( clone producing monoclonal IgM antibody) (most commonly) → Etiology in most older people unless active infeciton
2) ***Infection (mycoplasma pneumonia (atypical pneumonia) + EBV/mono) →
3) Autoimmune disorder (SLE, RA)
Initial management of cold agglutinin disease
- Cold avoidance (minimize cold rooms, cold water/liquids)
- IF symptomatic critical anemia, see temporizing measures below
- Initial period of observation with strict return precautions
- Indications for treatment (Not all need treatment)
- Symptomatic anemia, fatigue, cold-induced ischemic symptoms interfering with QOL
- ***Not all hemolysis requires treatment (if stable and compensated can continue observation or see how they do after tapering steroids)
Definitive therapy of cold agglutinin disease
BR vs. single agent rituxan depending on burden of disease + toxicity profile
*steroids ineffective
Complement inhibitor approved for cold agglutinin disease 2) target
1) Sutimlimab 2) C1
PCH pathophys
polyclonal IgG developing following viral illness that leads to complement mediated hemolysis
PCH smear
- spherocytes
- *erythrophagocytosis
*see picture online
DAT profile in paroxysmal cold hemoglobinuria
Positive for C3d
Test specific for PCH
donald landsteiner antibody
Differentiating cold agglutinin disease vs. PCH based on DAT
in PCH, C3 remains positive but IgG becomes negative at higher temperatures (in cold agglutinin IgG is always negative)
PCH management
supportive care (self limited)
PNH DAT
negative
DAT negative hemolytic anemia differential
1) TMA’s → (TTP →
HUS + atypical HUS)
2) Drug-induced TMA → (table 5)
3) ***infections (clostridium perfringens, babesiosis, bartonella, leishmania) →
4) Platelet transfusions → Not ABO matched + low grade hemolysis
5) Liver disease →
6) Kidney disease →
7) Spherocytosis →
8) Thalassemia →
9) Sickle cell disease →
10) Delayed hemolytic transfusion reaction →
11) G6PD →
12) B12 deficiency →
13) hemodialysis →
14) hypersplenism
15) Paroxysmal cold hemoglobinuria
Eculizumab SE’s
- headache (improves after 1-2 doses)
- back pain
- nasopharyngitis
- neisseria meningitis
Pegcetacoplan mechanism
C3 monoclonal antibody
*inhibits both intra and extravascular hemolysis
