Hemolytic Anemia

Question 1

Excess hemolysis in spleen leads to

Answer 1

Excess hemolysis in spleen –> hypersplenism –> neutropenia and/or thrombocytopenia

Question 2

Answer 2

as we have increased hemolysis we will have increase in bilirubin and iron.

Question 3

Answer 3

unconjugated bilirubin is result of hemolysis.

converted to urobilirubin to be deficated

Question 4

classifications of hemolytic anemia

Answer 4

Question 5

hemolytic anemis

clin man

Answer 5

Variable symptoms related to anemia
Dependent on abrupt or gradual onset
Fatigue
Dyspnea
Jaundice
Pallor
Splenomegaly
Discoloration of urine
Tea colored
Gallstones

Question 6

Hemolytic anemia

work up / Dx

Answer 6

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

Question 7

Normocytic Intravascular Hemolysis

general

Answer 7

• 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

Question 8

Extravascular Hemolytic anemia:

Intrinsic causes

Answer 8

Membrane defects
Glycolytic defects
Oxidation vulnerability
G6PD deficiency
Hemoglobinopathies
Sickle cell disease

Question 9

Extravascular Hemolytic anemias:

Extrinsic causes

Answer 9

• Immune
  Autoimmune
  Drug toxicity
• Microangiopathic
  Thrombotic Thrombocytopenic Purpura (TTP)
  Disseminated Intravascular Coagulation (DIC)
  Valve hemolysis
• Infection
• Hypersplenism
• Burns

Question 10

Coombs test

Coombs positive

Answer 10

Autoimmune, Rh incompatibility (indirect Coombs)

Question 11

Coombs test

Coombs negative

Answer 11

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

Question 12

Direct coombs test

Answer 12

take whole blood and remove plasma, then add reagent to the RBCs

Question 13

Indirect Coombs test

Answer 13

remove RBCs and test the plasma

Question 14

Immune Hemolytic Anemia

general

Answer 14

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

Question 15

Immune hemolytic anemia

Cold vs Warm

Answer 15

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)

Question 16

AIHA

general and cause

Answer 16

Usually symptomatic
2’ to
Infection
EBV
CMV
HIV
Mycoplasma
Another disease
SLE
Other inflammatory disorders
Drugs
antibiotics most common culprits

Question 17

AIHA

clin man

Answer 17

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

Question 18

Haptoglobin and Hemoglobinuria

Answer 18

• 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

Question 19

Hemolytic Anemia

Testing

Answer 19

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

Question 20

AIHA

Tx

Answer 20

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

Question 21

Prednisone

MOA

Answer 21

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

Question 22

Prednisone

Adverse Rxn

Answer 22

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

Question 23

Rituximab (Rituxan)

MOA and indications

Answer 23

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

Question 24

Rituximab

Adverse effects

Answer 24

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

Question 25

IV Immunoglobulin

MOAand adverse effect

Answer 25

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

Question 26

Cold agglutinin disease

general

Answer 26

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

Question 27

Cold Agglutinin Disease

may be seen with which diseases?

Answer 27

May be seen with:
Waldenstrom’s Macroglobulinemia
Lymphoma
Chronic Lymphocytic Leukemia (CLL)
Mycoplasma pneumonia
Viral infections such as
Mononucleosis
Measles
Mumps
CMV

Question 28

Cold aglutinin disease

S/Sx

Answer 28

• Mottled or numb fingers or toes in cold
• Acrocyanosis
• Episodic low back pain
• Episodic hemoglobinuria (after cold exposure)

Question 29

Cold Agglutinin Disease:

Labs

Answer 29