1) Heparin-induced thrombocytopenia (HIT) is caused by antibodies that form in response to heparin-PF4 complexes, activating platelets and increasing the risk of thrombosis. 2) HIT typically occurs 5-10 days after starting heparin, with platelet counts falling by at least 50% and often below 150 x 109/L. Complications include venous and arterial thromboses. 3) Thrombosis is common in HIT, even with mild platelet count drops, and significantly increases hospital costs. Orthopedic surgery patients are at high risk if platelet counts fall after postoperative heparin use.

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