Lecture 8: Platelet Disorders COPY

Question 1

ITP may be part of a broader disease affecting immune regulation such as what?

Answer 1

• HIV infection
• SLE
• Lymphoproliferative malignancy, especially in older pt’s

Question 2

All pt’s with ITP should be screened for what infection; recent research has also linked ITP to what other infective agent?

Answer 2

• All pt’s should be screened for HIV
• Recent reports have linked ITP to H. pylori infection

Question 3

What will blood smear of someone with ITP show?

Answer 3

Decreased platelets and occasional large platelets (megathrombocytes)

Question 4

ITP can be triggered by almost any drug, but is most commonly seen in association with what?

Answer 4

Quinine or Quinidine

Question 5

What are 2 effective therapies for ITP with severe thrombocytopenia or active bleeding is present?

Answer 5

Glucocorticoids and IVIG

Question 6

Which 2nd line immunosuppressive agent will lead to doubling of the platelet count in 40% of pt’s with ITP?

Answer 6

Rituximab

Question 7

Is splenectomy indicated for ITP?

Answer 7

Rarely, only in those w/ significant bleeding unresponsive to immunosuppressive medications

Question 8

What should a CBC of pt with ITP show in terms of platelets, Hgb, Hct, and leukocytes?

Answer 8

• Low platelet count
• Normal Hgb, Hct, and leukocyte count

Question 9

Although pt’s with heparin induced thrombocytopnia do not bleed excessively they have a dramatic risk what complications?

Answer 9

• DVT’sandPE’s
• Unusual clotting problems i.e., portal vein thrombosis or acute arterial occlusion

Question 10

Which type of heparin is more likely to lead to HIT and which is less likely?

Answer 10

• Unfractionated heparin = more likely
• Incidence is 2-3x lower in pt’s receiving LMW heparin

Question 11

What is the “4T Score” used clinically to determine the likelihood of HIT?

Answer 11

• Degree of Thrombocytopenia
• Timing of platelet count fall
• Thrombosis or other sequelae
• Other causes for Thrombocytopenia present

Question 12

Describe the degree of thrombocytopenia associated with 2, 1, or 0 points using the “4T Score” in assessing HIT risk?

Answer 12

• 2 points = platelet count >50% fall and nadir ≥20,000/uL
• 1 point = platelet count 30-50% fall or nadir 10,000-19,000/uL
• 0 points = platelet count <30% fall or nadir <10,000/uL

Question 13

Describe the timing of platelet count fall associated with 2, 1, or 0 points using the “4T Score” in assessing HIT risk?

Answer 13

• 2 points: clear onset btw days 5 and 10 or platelet count decrease at ≤1 day if prior heparin exposure within last 30 days
• 1 point: onset after day 10 or timing unclear, or ≤ day 1 if heparin exposure within past 30-100 days
• 0 points: platelet count fall <4 days without recent exposure

Question 14

Describe the thrombosis or other sequelae category associated with 2, 1, or 0 points using the “4T Score” in assessing HIT risk?

Answer 14

• 2 points: confirmed nw thrombosis, skin necrosis, or acute systemic rxn after IV unfractionated heparin bolus
• 1 point: progressive or recurrent thrombosis, nonnecrotizing (erythematous) skin lesions, or suspected thrombosis not proven
• 0 points: no thrombosis or sequelae

Question 15

Which findings for the category “other causes of thrombosis” are associated with 2, 1, or 0 points using the “4T Score” in assessing HIT risk?

Answer 15

• 2 points = no other cause apparent
• 1 point = another cause is possible
• 0 points = definite other cause

Question 16

How many points using the “4T Score” for risk of HIT is associated with low, intermediate, and high probability of HIT?

Answer 16

• Low = 0-3 points
• Intermediate = 4-5 points
• High = 6-8 points

Question 17

In patients with HIT, heparin should be discontinued and what should be administered?

Answer 17

Direct thrombin inhibitors (i.e., Lepirudin or argatroban)

Question 18

Which findings is the simplest way to differentiate TTP from HUS?

Answer 18

• TTP = MAHA + thrombocytopenia (<50,000) + fever + neurologic sx’s
• HUS = add renal failure to the above

Question 19

How do the hereditary vs. acquired forms of TTP differ?

Answer 19

• Hereditary = mutation of ADAMTS13 gene
• Acquired = autoantibodies directed at ADAMTS13; linked to pregnancy, HIV-infection, chemotherapy and immunosuppressive agents

Question 20

What is the treatment for TTP?

Answer 20

• As in DIC, treat the underlying cause
• Plasmapheresis - life saving in virtually 100% of cases
• Glucocorticoids also recommended

Question 21

How should young patients with TTP-HUS with features suggesting enteric bacterial toxins as the etiology be treated?

Answer 21

Supportively

Question 22

What is the pathologic lesion of TTP; what will be seen on peripheral smear?

Answer 22

• Pathologic lesion is hyaline microthrombi which occlude the capillaries of virtually every organ in the body
• Schistocytes seen on peripheral smear

Question 23

What is the hallmark of essential thrombocythemia and how is the diagnosis made?

Answer 23

• Thrombocytosis that cannot be explained by clinical conditions known to cause a reactive elevation in platelet count
• Dx made by finding persistent platelet counts >600,000 u/L with no other condition present leadin to reactive thrombocytosis

Question 24

What are some genetic findings which can be helpful in diagnosing essential thrombocythemia?

Answer 24

• 50% of pt’s will have JAK2 mutation
• Since thrombocytosis may be seen in CML and PRV, diagnosis further requires that the Philidelphia chromososme be negative and the pt does not have concomitant erythrocytosis

Question 25

What are 3 criteria which would place a patient with essential thrombocythemia in a low-risk category; how should they be treated?

Answer 25

• Those aged <60 year, have no prior thromboembolic event and platelet counts <1,000,000/uLhaveexcellent prognosis
• Should be observed without treatment

Question 26

Pt’s with essential thrombocythemia who are not in the low-risk category should be treated how?

Answer 26

Tx with hydroxyurea + low-dose aspirin

Question 27

Which 2 drugs can be added to reduce platelet count in pt with ET if deemed necessary based on sx’s refractory to salicylates alone?

Answer 27

Pegylated IFN-α or Anagrelide

Question 28

Reactive thrombocytosis is almost always due to what 4 etiologies?

Answer 28

• Iron deficiency
• Inflammation
• Cancer
• Infections