254. Thrombocytopenias

Question 1

Thrombocytopenia

• 4 general categories of etiology
• definition of mild, moderate, severe

Answer 1

1. Lack of production
2. Destruction
3. Redistribution
4. Congenital Disorder

Normal: 150-400K/uL
Mild: 100-149K/uL (minimal bleeding risk, 2.5% of healthy population)
Moderate: 50-99K/uL (minimal risk spontaneous bleeding, but bleeding with trauma/invasive procedures)
Severe: <50K/uL (spontaneous bleeding, bruising, petechiae)

Question 2

Immune Thrombocytopenia Purpura

• what is it
• key CP (3)
• Secondary causes (4)
• epi - with differences
• tx (not on FSM exam)

Answer 2

Auto-Ab’s (GP IIb/IIIa) against platelets = destruction

1. Isolated Thrombocytopenia
2. Normal Blood Smear
3. Increased MKs on bone marrow biopsy

Secondary causes: Lupus, Malignancy (CLL), HIV, HCV

epi: high in kids, old adults >75 (M>F), at repro age (F>M)
Kids: self-limiting disease preceded by viral illness, rare bleeding
Adults: no preceding infection, tx recommended if platelets <30K, high rates of relapse (75% <12mo)

tx:

1. Steroids
2. IV Ig
3. Rituximab
4. Tpo receptor agonists
5. Splenectomy

Question 3

Heparin-Induced Thrombocytopenia

• mechanism
• CP, typical time course
• tx (not on exam)

Answer 3

Heparin interacts with Platelet Factor 4 = form neoepitope = IgGs made against it
CP: 5-14 days after starting heparin
- new or worse thrombosis since onset of thrombocytopenia
- isolated thrombocytopenia (normal coags)
tx: discontinue ALL heparins, tx with direct thrombin inhibitors (argatroban, bivalirudin)

Question 4

Thrombotic Microangiopathies

• cause
• triad for HUS
• pentad for TTP

Answer 4

Cause: endothelial activation/damage = thrombosis in microvessels
HUS: renal failure, thrombocytopenia, hemolytic anemia
TTP: renal failure, thrombocytopenia, hemolytic anemia, fever, neuro sx (AMS)

Question 5

What are 3 different general categories for deficient platelet production?

Answer 5

1. Lack of production = bone marrow
   - Aplasia: primary (aplastic anemia, myelodysplasia) vs secondary (chemotx, radiation, viral)
   - Myelophthisis (cancer, myelofibrosis, osteopetrosis) - distract bone marrow from making platelets
2. Lack of production = liver failure
   - no TPO = no platelet
3. Lack of production = insufficient nutrients
   - no vit b12, folate, copper

Question 6

What are 2 categories for thrombocytopenia due to redistribution?

Answer 6

1. Sequestration (in body, not in blood)
   - splenomegaly (portal HTN, infiltrative lymphoma, infection, HbSS/HbSC; usually only mild thrombocytopenia)
2. Dilution (increase denominator blood volume)
   - pregnancy (increased BV, 10-15% reduction in platelet count)
   - massive fluid resuscitation (massive transfusions without platelets, large amounts crystalloid fluid)

Question 7

What are 2 examples of antibody-mediated neonatal thrombocytopenia?

Answer 7

1. Alloantibody immune thrombocytopenia (NAIT) - mom has anti-baby platelet Ab’s
2. Passive anti-platelet Abs from mom to fetus (mom has ITP)

Question 8

What are two examples of Congenital Thrombocytopenias?

• CP
• defect
• inheritance
• sx/syndrome

Answer 8

1. Bernard-Soulier Syndrome
   - Large platelets (macrothrombocytopenia)
   - Defect GPIb-V-IX (vWF receptor, part of platelet cytoskeleton)
   - AR
   - sx: moderate-severe bleeding
2. Wiscott-Aldrich
   - small platelets (microthrombocytopenia)
   - Defect WAS gene (WASp protein)
   - XLR (usually only male pts)
   - Syndrome: immune deficiency (recurrent infections), eczema, microthrombocytopenia