Extrinsic Defects Leading to Increased Erythrocyte Destruction- Nonimmune causes

Question 1

What are some extrinsic, non immune causes of erythrocyte destruction in the differential diagnosis?

Answer 1

• Microangiopathic hemolytic anemias
  *TTP
  *HUS
  *HELLP syndrome
  *DIC
  *Traumatic cardiac hemolytic anemia
  
  • Exercised induced hemoglobinuria
• Hemolytic anemia caused by Infectious agents
  
  • Malaria
  • Babesia
    *Clostridial sepsis
  • Bartonella
• Hemolytic anemia due to RBC injury
  
  • drugs or chemicals
  • venoms
    *extensive burns (thermal injury)

Question 2

What is a common feature in the non-immune, extrinsic hemolytic anemias?

Answer 2

• the presence of a condition that causes physical or mechanical injury to the RBC

Question 3

What is a characteristic feature of microangiopathic hemolytic anemias?

Answer 3

• Intravascular RBC fragmentation and thrombocytopenia
  
  • caused by mechanical shearing in the BV due to micro thrombi or endothelial cell injury

Question 4

What are laboratory findings in MAHA?

Answer 4

• decreased hemoglobin and platelets
• increased reticulocyte count
• schistocytes, polychromatic, and nRBC in severe cases
• markedly increased LDH
• increased total and indirect bilirubin
• decreased haptoglobin
• hemoglobinemia
• hemoglobinuria
• proteinuria, hematuria and casts

Question 5

What are the key features of TTP?

Answer 5

• rare, life-threatening
• abrupt onset of hemolysis, thrombocytopenia
• neurologic dysfunction, fever, and renal failure

Question 6

What is the cause of TTP?

Answer 6

• defect in the vWF cleaving protein ADAMTS13
• the normal function of ADAMTS13 is to cleave the ultra long vWF multimers into smaller multimers that have less hemostatic potential
• acts as a potent antithrombotic agent

Question 7

What is inherited TTP called?

Answer 7

• Upshaw Shulman Syndrome
• severe ADAMTS13 deficiency caused by mutations in the gene

Question 8

What is the typical platelet count in TTP?

Answer 8

• 10-30

Question 9

What is one way in which TTP can be differentiated from DIC?

Answer 9

• the coagulation tests are usually within the reference intervals in TTP

Question 10

What is the treatment for idiopathic TTP?

Answer 10

• plasma exchange with removal of the autoantibody and infusion of ADAMTS13 from plasma
• Rituximab is also given

Note: patients with secondary TTP do not respond well to plasma exchange (except for preganancy, autoimmune and ticlopidine use cases)

Question 11

What is the treatment for inherited TTP?

Answer 11

• infusion of plasma to replenish the ADAMTS13

Question 12

What is the cause of hemolytic uremic syndrome?

Answer 12

• MAHA with thrombocytopenia (mildly decreased) and acute renal failure due to damage of the endothelial cells in the glomeruli
• Typical HUS:
  
  • shiga- toxin producing bacteria
  • preceded by acute, bloody gastroenteritis
• Atypical HUS:
  *unregulated activation of the complement pathway

Question 13

What is the treatment for typical and atypical HUS?

Answer 13

• Typical: supportive therapy
• atypical: do NOT respond to plasma exchange.
  *Eculizumab (antibody C5) shows some efficacy

Question 14

How can HELLP syndrome be differentiated from DIC?

Answer 14

• HELLP will have a normal PT and PTT while DIC will not

Question 15

What are typical findings in DIC?

Answer 15

• prolonged PT and PTT
• low fibrinogen
• increased d-dimer levels