1. Pathogenesis of HIT
Heparan sulfate B-lymphocyte Heparin
Endothelial cell
Resting platelet
GpIIb/ IIIa
HIT antibody
PF4
Fc receptor
Endothelial cell activation
Microparticles
Monocyte Fibrinogen
Thrombin Activated platelet
Tissue factor

2. Platelet Activation in HIT
Resting Platelet HIT-activated Platelet
Procoagulant, platelet-
derived microparticles

3. Schematic Figure of the Serotonin Release
Assay (platelet activation assay)
Heparin/PF4 Complex
HIT-IgG
Radiolabeled serotonin
released from platelets

4. Schematic Figure of Solid-phase
PF4/Heparin-EIA (immunoassay)
wash wash
Patient serum or plasma is Add alkaline phosphatase- Add
added to microtiter plates conjugated goat substrate
coated with PF4 and heparin antihuman IgG
COLOR
heparin Alkaline phosphatase-
PF4/heparin HIT-IgG
PF4 (from serum or plasma) conjugated goat
complex
antihuman IgG

5. Clinical Features of HIT
Onset Typically 5-10 days after starting heparin
(<1 day if recent heparin exposure)
Platelet count nadir Typically 20-150 x 109/L
• Median platelet count nadir ~ 60
• Sometimes, platelet count falls by >50%, but
remains >150
Platelet count recovery Median time to platelet count >150 = 4 days
(90% by 1 week)
Complications Thromboembolic events: venous > arterial
Incidence of HIT 1%-3% with 1-2 weeks of unfractionated
heparin (UFH) prophylaxis post-surgery

6. Thrombosis Is Common in HIT
Median platelet count nadir ≈ 60 x 109/L
40
Number of Patients With HIT
No HIT-associated
thrombosis
30
HIT-associated Standard definition
thrombosis of thrombocytopenia
(150 x 109/L)
20
10
0
3 5 10 15 20 30 50 70 100 150 200 300 500 1000
Platelet Count Nadir (x 109/L)

7. Economic Consequences of HIT
*
• A cost analysis model suggests a range of $38,046 to $52,164
estimated mean hospital cost per patient having HIT

8. 9 Patients With HIT
Post-Orthopedic Surgery
1000
Patients with HIT (n=9)
* Unilateral lower-limb DVT +2 SD
Platelet Count x 109/L
800 ** Bilateral lower-limb DVT
A Arterial clot
Normal Postoperative
Platelet Counts
PE Pulmonary embolism (mean + 2 SD)
600
Mean
400 * -2 SD
**
200 **
PE
A ** * PE
PE
day 17
0 * *
Pre 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Postoperative Day

9. HIT Complicating Orthopedic Surgery:
Platelet Fall >50% Day 4 to 14
1000
UFH, n=7
Platelet Count x 109/L
LMWH, n=2 +2 SD
Normal Postoperative
800 Platelet Counts
*DVT (mean + 2 SD)
600
* Mean
*
400
-2 SD
200
* *
*
150 x 109/L (standard definition of thrombocytopenia)
0
Pre 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Postoperative Day