Hemolytic Anemia Flashcards
Excess hemolysis in spleen leads to
Excess hemolysis in spleen –> hypersplenism –> neutropenia and/or thrombocytopenia
as we have increased hemolysis we will have increase in bilirubin and iron.
unconjugated bilirubin is result of hemolysis.
converted to urobilirubin to be deficated
classifications of hemolytic anemia
hemolytic anemis
clin man
Variable symptoms related to anemia
Dependent on abrupt or gradual onset
Fatigue
Dyspnea
Jaundice
Pallor
Splenomegaly
Discoloration of urine
Tea colored
Gallstones
Hemolytic anemia
work up / Dx
Reticulocytes (% and absolute count) ↑
Bilirubin ↑ (Unconjugated/indirect)
AST ↑
LDH ↑ liverenzymes elevated
Haptoglobin ↓ or absent
Peripheral smear
Schistocytes (fragmented RBCs)
Macrocytes
UA
Hemoglobin
Hemosiderin
Coagulation Studies
Normocytic Intravascular Hemolysis
general
- Direct trauma: bongo drummers, runners’ hemolysis
- Shear stress: defective mechanical heart valves
- Heat damage: thermal burns
- Osmotic lysis following infusion of hypotonic solutions
- Lysis from bacterial toxins (clostridial sepsis)
- G6PD deficiency, TTP, DIC
- Transfusion reaction
- Immune mediated (antibodies)
Nonimmune (transfusion of damaged RBCs) - RBCs phagocytized by macrophages in spleen and liver
- Can occur with any condition that results in abnormal RBC morphology
Extravascular Hemolytic anemia:
Intrinsic causes
Membrane defects
Glycolytic defects
Oxidation vulnerability
G6PD deficiency
Hemoglobinopathies
Sickle cell disease
Extravascular Hemolytic anemias:
Extrinsic causes
- Immune
Autoimmune
Drug toxicity - Microangiopathic
Thrombotic Thrombocytopenic Purpura (TTP)
Disseminated Intravascular Coagulation (DIC)
Valve hemolysis - Infection
- Hypersplenism
- Burns
Coombs test
Coombs positive
Autoimmune, Rh incompatibility (indirect Coombs)
Coombs test
Coombs negative
Intrinsic red cell disease
Abnormal hemoglobin: sickle cell disease, thalassemia
Membrane defect: hereditary spherocytosis
Enzyme defect: G6PD deficiency
Extrinsic disease
Microangiopathic hemolytic anemia
TTP, DIC, prosthetic valve hemolysis
Splenic sequestration
Direct coombs test
take whole blood and remove plasma, then add reagent to the RBCs
Indirect Coombs test
remove RBCs and test the plasma
Immune Hemolytic Anemia
general
Acquired process
Distinct mechanisms:
True autoantibody directed against red cell antigen
molecule present on surface of red cells
Antibody directed against a certain molecule creates a reaction which secondarily damages or destroys RBCs
Immune hemolytic anemia
Cold vs Warm
Antibodies differ in optimum reactivity temps
“cold”
Complement mediated destruction at colder temperature (IgM)
Cold agglutinin disease
“warm”
RBC destruction at body temperature (IgG)
Autoimmune hemolytic anemia (AHIA)
AIHA
general and cause
Usually symptomatic
2’ to
Infection
EBV
CMV
HIV
Mycoplasma
Another disease
SLE
Other inflammatory disorders
Drugs
antibiotics most common culprits
AIHA
clin man and labs
Jaundice
Splenomegaly
Rapid progressing anemia
Peripheral smear: spherocytes
↑ reticulocytes
Indicates bone marrow response to anemia
+ Direct Coombs test
90% of patients
Indirect Coombs test +/-
LDH
Released from lysed RBCs
↓ or absent serum haptoglobin
Haptoglobin and Hemoglobinuria
- Hemolysis releases Hgb which is immediately bound by haptoglobin
- Hgb-haptoglobin cleared from the plasma by liver
- Hgb-haptoglobin binding overwhelms rate of haptoglobin synthesis, haptoglobin levels decrease
- Excess hemoglobin filtered in the kidney and reabsorbed in proximal tubules.
- Hemoglobinuria indicates severe intravascular hemolysis overwhelming absorptive capacity of renal tubular cells
Hemolytic Anemia
Testing
Combination of ↑ LDH and ↓ haptoglobin is 90% specific for diagnosing hemolysis
Combination of normal LDH and serum haptoglobin >25 mg/dL is 92% sensitive for ruling out hemolysis
AIHA
Tx
Hematology consultation- REFER
Acute
Steroids (acute)
Prednisone 1-2 mg/kg/day PO divided BID
May be difficult to crossmatch for blood transfusion due to antibodies
Therapeutic plasmapheresis
If severe anemia without available PRBC match
Rituximab IV weekly x 4 weeks
Refractory
IV Immunoglobulin (IVIG)
As adjunct to other treatments
Splenectomy
Prednisone
MOA
Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability
Suppresses the immune system by reducing activity and volume of the lymphatic system
Pregnancy: Crosses the placenta
Prednisone
Adverse Rxn
Adverse Reactions (more common)
Facial erythema
Flushing/diaphoresis
Fluid retention
Headache
Impaired wound healing
Increased LFTs
Long term use causes adrenal suppression.
Any dosing > 1 week need to taper slowly! so that adrenal glands can wake back up
Rituximab (Rituxan)
MOA and indications
MOA: Thought to eliminate B cells via apoptosis, antibody dependant cytotoxicity, and complement mediated cytotoxicity. Plasma cells responsible for long-term antibody production do not express CD20 and are not eliminated by rituximab
Dug Class: Monoclonal Antibody
Indications For AIHA
Initial therapy with glucocorticoids
Added to glucocorticoids if no improvement
Single agent initial therapy
Single agent for refractory disease
Rituximab
Adverse effects
Adverse Effects
Infusion reaction (usually 1st reaction)
Long term immunosuppression
Reactivation of Hepatitis B
Pre-medications (30 minutes prior)
Acetaminophen
Antihistamine (Benadryl)
Methylprednisolone 100mg IV
IV Immunoglobulin
MOAand adverse effect
MOA:
Interference with certain cell receptors of the reticuloendothelial system for autoimmune cytopenias and ITP
Provides passive immunity by increasing the antibody titer and antigen-antibody reaction potential
Dosing: Varies by diagnosis; SubQ/IV
Pregnancy: Crosses the placenta
Adverse reactions: Hypersensitivity reaction
Cold agglutinin disease
general
Acquired hemolytic anemia due to IgM autoantibody (cold agglutinin)
Increased reactivity at low temperatures
Returns to warm central circulation and IgM antibody detaches leaving behind complement
Leads to sequestration in liver followed by destruction
Occurs in distal circulation (Fingers, nose, ears)
Usually idiopathic
Cold Agglutinin Disease
may be seen with which diseases?
May be seen with:
Waldenstrom’s Macroglobulinemia
Lymphoma
Chronic Lymphocytic Leukemia (CLL)
Mycoplasma pneumonia
Viral infections such as
Mononucleosis
Measles
Mumps
CMV
Cold aglutinin disease
S/Sx
- Mottled or numb fingers or toes in cold
- Acrocyanosis
- Episodic low back pain
- Episodic hemoglobinuria (after cold exposure)
Cold Agglutinin Disease:
Labs
