DIT review - Heme 3

Question 1

What does HELLP syndrome stand for?

Answer 1

• Stands for:
  
  • H - Hemolysis (anemia)
  • EL - Elevated Liver enzymes (RUQ pain, jaundice)
  • LP - Low Platelets (bruising bleeding)
• Preeclampsia + thrombotic microangiopathy
  
  • Hemolysis = thrombi causing schistocytes
  • Liver enzymes = lack of RBCs leads to infarction of liver tissue
  • Platelets = all used up in thrombi

Question 2

Describe the steps of platelet plug formation (trigger, adhesions, activation, aggregation)

Answer 2

• (1) Endothelial damage - transient vasoconstriction
  
  • Via neural stimulation reflex and endothelin (released from damaged cell)
• (2) Platelet adhesion
  
  • Won Willebrand factor (vWF) binds to exposed subendothelial collagen
    
    • vWF from Weibel-Palade bodies of endothelial cells and a-granules of platelets
  • Platelets bind vWF via GPIb receptor and undergo conformational change
• (3) Platelet activation/degranulation
  
  • Platelets shape change causes degranulation with release of:
    
    • ADP – promotes exposure of GPIIb/IIIa receptor on platelet surface
    • TXA2 – synthesized by platelet COX and promotes vasoconstriction and aggregation
    • Ca2+ – needed to activate the coagulation cascade
    • Fibrinogen
• (4) Platelet aggregation
  
  • Platelets link to each other via GP2b3a, using fibrinogen as a linking molecule

Question 3

MOA of Aspirin

Answer 3

• Inhibits the COX, thus halting the synthesis of TXA2
  
  • ASA acts by covalently attaching an acetyl group to COX (both COX-1 and COX-2) enzyme, causing IRREVERSIBLE inhibition (lasts for the life-time of the platelet until new ones are produced in about 1 week)
• Inhibition of TXA2 leads to inhibition of platelet aggregation

Question 4

What are the names of the ADP receptor inhibitors

Answer 4

• Clopidogrel, Ticagrelor, Prasugrel, Ticlopidine
• Sketchy - hot dog grill

Question 5

MOA of ADP receptor antagonists

Answer 5

Inhibiting ADP receptors = decreased expression of GP2b3a = decreased platelet aggregation

Question 6

What are the names of the GP2b3a antagonists

Answer 6

• Abciximab - ABC sports caster
• Eptifibatide - tied game
• Tirofiban - tied game

Question 7

What are the names of phosphodiesterase inhibitors

Answer 7

Sketchy: “Don’t PHOSTER DISINTEREST” sign

Drugs:

• Dipyridamole - two pyramids as top of tent
• Cilostazol - lost the ball

Question 8

MOA of phosphodiesterase inhibitors

Answer 8

• Inhibition of phosphodiesterase leads to increases cAMP within the platelet which will activate protein kinase A, and impairing platelet function and aggregation

Question 9

MOA of GP2b3a antagonists

Answer 9

Block GP2b3a, so it cannot bind fibrinogen = decreased platelet aggregation

Question 10

What is the most common inherited bleeding disorder

Answer 10

von Willebrand disease

Question 11

What will be the lab findings in von Willebrand disease (BT, PT, PTT)

Answer 11

• Increased bleeding time – decreased platelet adhesion
• Increased PTT – vWF normally stabilizes Factor VIII
• Normal PT

Question 12

Treatment of von Willebrand disease

Answer 12

• Desmopressin – increases vWF release from Weibel-Palade bodies of endothelial cells

Question 13

Describe the pathogenesis behind DIC

Answer 13

• Widespread activation of clotting
• This consumes all platelets and coagulation factors, resulting in bleeding

Question 14

Findings in DIC

Answer 14

• Increased bleeding time – low platelets
• Increased PT and PTT
• Low fibrinogen – being used up
• High D-dimer (fibrin split products)
• Schistocytes

Question 15

Causes of DIC

Answer 15

• STOP Making New Thrombi
  
  • Sepsis
  • Trauma
  • Obstetric complications
  • Acute Pancreatitis
  • Malignancy
  • Nephrotic syndrome
  • Transfusion

Question 17

Describe the cause of Immune thrombocytopenia (ITP)

Answer 17

• IgG autoantibodies to GP2b3a
• Antibodies produced by plasma cells of spleen and antibody-bound platelets consumed by macrophages of spleen

Question 18

Findings of immune thrombocytopenia

Answer 18

• Decreased platelet count
• Increased megakaryocytes on bone marrow biopsy

Question 19

Treatment of immune thrombocytopenia

Answer 19

• Steroids and IVIG (autoimmune treatment)
• Splenectomy

Question 20

Describe the defect in thrombotic thrombocytopenic purpura (TTP)

Answer 20

• Platelets used up in pathologic formation of microthrombi in small vessels
• Due to decreased ADAMTS13, enzyme that normally cleaves vWF for degradation
  
  • No vWF degradation = abnormal platelet adhesion = microthrombi

Question 21

Describe the findings in TTP

Answer 21

• Pentad of findings
  
  • Thrombocytopenia = platelets being used up
  • Microangiopathic hemolytic anemia = RBCs sheared by microthrombi
  • Renal insufficiency (thrombi involve vessels of the kidney)
  • Neurological symptoms (confusion, HA, seizures, coma) – thrombi involve vessels of CNS
  • Fever

Question 22

Describe the defect in hemolytic uremic syndrome (HUS)

Answer 22

• Platelets used up in pathologic formation of microthrombi in small vessels
• Commonly caused by Shiga toxin-producing E. Coli O157:H7 (STEC)
  
  • Accompanied with diarrhea

Question 23

Findings in HUS

Answer 23

• Findings (triad):
  
  • Microangiopathic hemolytic anemia
  • Renal insufficiency (thrombi involve vessels of the kidney)
  • Thrombocytopenia

Question 24

Describe the defect in Bernard-Soulier syndrome

Answer 24

• Defect of glycoprotein 1b
• Platelet can’t bind to vWF on collagen = defect of platelet plug formation

Question 25

Findings in Bernard Soulier

Answer 25

* Platelet count is only slightly low – moderate thrombocytopenia * Large platelets

Question 26

Describe the defect in Glanzmann thrombasthenia

Answer 26

* Genetic GP2b3a deficiency * Defect in platelet aggregation

Question 27

Describe the finding in Glanzmann thrombasthenia

Answer 27

Platelet count is normal (they aren’t being destroyed, just can’t aggregate)

Question 28

What is the difference between Leukemia and Lymphoma

Answer 28

* Leukemia: * Malignancy within bone marrow or peripheral blood * Lymphoma: * Malignancy within lymph nodes

Question 29

Describe the basic difference between Hodgkin and Non-Hodgkin lymphoma

Answer 29

Hodgkin - Rare neoplastic cells (Reed-Sternberg cells) which secrete cytokine that draw in inflammatory cells, leading to a mass Non-Hodgkin - Whole mass composed of malignant cells

Question 30

Describe Reed-Sternberg cells and their surface markers

Answer 30

* Large cells with multiple/bi-lobed nuclei with clearing around the nuclei (“owl-eye”) * RS cells are CD15+ and CD30+ * THINK: 2 owl eyes x 15 = 30

Question 31

Which lymphoma is found in a single group of lymph nodes and rarely extranodal vs. multiple lymph node and extranodal involvment

Answer 31

* Hodgkin * Found in a single group of lymph nodes * Extranodal involvement is rare * Non-Hodgkin * Can be in multiple different lymph nodes * Often extranodal (GI tract, thyroid, CNS)

Question 32

Which lymphoma is associated with B-symptoms

Answer 32

Hodgkin - Due to cytokine released by RS cells

Question 33

Describe age distribution of Hodgkin vs. Non-hodgkin lymphoma

Answer 33

Hodgkin - bimodal distribution (peak at 20 and 65 y/o) NHL - variable age range

Question 34

Describe the disease associated with Hodgkin and NHL

Answer 34

Hodgkin - EBV NHL - HIV and autoimmune

Question 35

What is the most common type of Hodgkin lymphoma

Answer 35

Nodular sclerosing type

Question 36

What type of Hodgkin lymphoma has the best prognosis

Answer 36

Lymphocyte-predominant