Blood facts

Question 1

Explain the different shapes of the Hgb and Mgb curves.

Answer 1

Mgb is hyperbolic b/c it is monomeric (only one heme subunit). Hgb is sigmoid because of heme-heme interactions.

Question 2

Physiologic influences on O2 disassociation curve?

How does high altitude get compensated?

Physiologic compensation for chronic left shift?

Answer 2

Left shift (O2 binds more tightly):

• low temperature
• low H+ / high pH
• low 2,3-BPG

Right shift:

• high temperature
• high H+ / low pH
• high 2,3-BPG

Chronic high altitude compensation involves increased 2,3-BPG.

Physiologic compensation for eg hereditary right-shifted Hgb is increased EPO and polycythemia.

Question 3

Sickle cell anemia: mutations and charges of HbA, HbS, HbC

Answer 3

HbA: normal, has glutamate in beta-chain (negative charge)

HbS: has valine instead of glutamate (neutral charge)

HbC: has lysine instead of lysine instead of glutamate (positive charge)

Question 4

Pure red cell aplaisa: Signs and Tx

Answer 4

Normocytic anemia with absent erythroid precursors but other lineages preserved. Can result from parvovirus B19 or cytotoxic/autoantibody response from a thymoma.

Question 5

Heparins, LMWH, Direct Xa inhibitors, DTIs

Examples - what are they used for?

Answer 5

• Heparin - unstable angina, DVTs. Inhibits both thrombin and Xa via ATIII
• LMWH - easier to dose and administer (subq) than heparin. Inhibits mostly Xa via ATIII.
• DTI - “rudins” and Argatroban/Dabigatran. Used for HIT patients, and for eg unstable angina when you can’t use heparin.
• Direct Xa inhibitors - “xabans”. Used instead of warfarin, no bridge period req’d.

Question 6

Fibrinolysis inhibitors (4) and mechanisms

Answer 6

• Plasminogen activator inhibitor I (endothelium) and II (placenta)
  
  • inhibit urokinase and tPA
• Lysine analogs: Aminocaproic acid and tranexamic acid
  
  • competitive inhibitor for plasminogen and plasmin
• Carboxypeptidase B - thrombin-activatable fibrinolysis inhibitor
  
  • Thrombin-thrombomodulin complex activates protein C and TAFI; TAFI inhibits plasmin
  • (so thrombin-thrombomodulin has both anti- and proccoagulant properties)

Question 7

What kind of mutations result in alpha-thalassemia and beta-thalassemia?

Answer 7

Alpha-thalassemia: allele deletions

Beta-thalassemia: defects in mRNA processing (splicing etc).

Question 8

How do you reverse Warfarin emergently?

Answer 8

Fresh frozen plasma. (Also vitamin K injection.)

Question 9

CML vs leukemoid reaction

Answer 9

Both have elevated circulating immature WBC forms, but few blasts.

CML has: basophilia and low alk phos

Leukemoid will have normal-elevated alk phos.

Question 10

What gene is defective in paroxysmal nocturnal hemoglobinuria? Cause of death?

What tx?

Answer 10

Death from thromboembolism. PIGA, which anchors

DAF/CD55 - degrades C3 convertase, and

protectin/CD59 - binds MAC

Tx is eculizumab, which binds C5, inhibiting its cleavage, can’t form MAC.

Question 11

Sarcoidosis: signs

Answer 11

Noncaseating granulomas.

Hilum of lung, uveitis.