Heparan sulfate

Endothelial cell

B-lymphocyte Heparin

Resting platelet

PF4

Activated platelet

Microparticles

Monocyte

End

othe

lial c

ell a

ctiv

atio

n

HIT antibody

Tissue factor

Thrombin

Fibrinogen

Fc receptor

GpIIb/ IIIa

Pathogenesis of HIT

Platelet Activation in HIT

Resting Platelet HIT-activated Platelet

Procoagulant, platelet-derived microparticles

Heparin/PF4 Complex

HIT-IgG

Radiolabeled serotonin released from platelets

Schematic Figure of the Serotonin Release Assay (platelet activation assay)

Patient serum or plasma is added to microtiter plates coated with PF4 and heparin

heparin

PF4PF4/heparincomplex

HIT-IgG(from serum or plasma)

Add substrate COLOR

Alkaline phosphatase-conjugated goat antihuman IgG

Add alkaline phosphatase-conjugated goat antihuman IgG

wash wash

Schematic Figure of Solid-phase PF4/Heparin-EIA (immunoassay)

Clinical Features of HIT

1%-3% with 1-2 weeks of unfractionatedheparin (UFH) prophylaxis post-surgery

Incidence of HIT

Thromboembolic events: venous > arterialComplications

Median time to platelet count >150 = 4 days (90% by 1 week)

Platelet count recovery

Typically 20-150 x 109/L• Median platelet count nadir ~ 60• Sometimes, platelet count falls by >50%, but

remains >150

Platelet count nadir

Typically 5-10 days after starting heparin (<1 day if recent heparin exposure)

Onset

Num

ber

of P

atie

nts

With

HIT

0

10

20

30

40

10 100 1000 3 20 30 50 70 150 15 5 300 500 200

Platelet Count Nadir (x 109/L)

Median platelet count nadir ≈ 60 x 109/L

No HIT-associatedthrombosis

HIT-associatedthrombosis

Standard definitionof thrombocytopenia

(150 x 109/L)

Thrombosis Is Common in HIT

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

*

**

9 Patients With HIT Post-Orthopedic Surgery

day 17

0

200 Pla

tele

t C

ount

x 1

09/L

Pre 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Postoperative Day

400

600

800

1000

Mean

+2 SD

-2 SD

PE

PE

PE

Patients with HIT (n=9)

Bilateral lower-limb DVTArterial clot

Unilateral lower-limb DVT

Pulmonary embolism

Normal Postoperative Platelet Counts(mean + 2 SD)

*

******

* **

*

PE

PE

A

A

0

200

Pla

tele

t C

ount

x 1

09/L

Pre 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Postoperative Day

400

600

800

1000

Mean

+2 SD

-2 SD

Normal Postoperative Platelet Counts(mean + 2 SD)

UFH, n=7LMWH, n=2

150 x 109/L (standard definition of thrombocytopenia)

**

*

*

*

*DVT

HIT Complicating Orthopedic Surgery: Platelet Fall >50% Day 4 to 14