Heparin
Induced Thrombocytopenia
Clinically significant
heparin-induced thrombocytopenia (HIT) is termed Type 2, and is immune
mediated. Type 1 is not immune mediated
and is of no clinical significance. Type
2 occurs primarily on exposure to unfractionated heparin (UFH), even with brief
subcutaneous exposure. Incidence is
lower with low molecular weight heparins (LMWH):
1.
3% with UFH
2.
.3% with LMWH
3.
1.7% with LMWH if
previous UFH
4.
More common in
women
5.
More common in
surgical than medical patients
HIT is not rare. Up to 33% of hospitalized patients receive
heparin. 1 in 8 of patients developing
antibodies evolve to full-blown HIT. 120,000 cases of HIT occur each year in the
The disorder can occur 5-14
days after withdrawal of heparin, therefore if a patient has been on DVT
prophylaxis or is on UFH, and develops a DVT, always check the platelet
count before initiating anticoagulation.
1.
Heparin complexes
with platelet factor 4 forming an antigenic material with antibody
formation. This leads to platelet
activation, formation of thrombus, and thrombocytopenia.
2.
This is a
pro-thrombotic state, and not a bleeding disorder.
3.
Platelet counts
rarely fall below 20,000, and the average nadir is 60,000, therefore any
bleeding is rarely severe.
4.
In 10% the
thrombotic event occurs before the drop in platelet count.
5.
Thrombotic events:
·
75% are venous
thromboses – some with pulmonary embolism
·
10-20% are limb-threatening arterial thromboses.
·
5-10% manifest MI
or stroke
·
hematomas or skin
necrosis at injection sites
·
occasionally an
acute systemic reaction
The first step in establishing
a diagnosis of HIT is recognizing the syndrome.
1.
The appearance of
otherwise unexplained thrombocytopenia.
2.
Thrombosis
associated with thrombocytopenia.
3.
Platelet count
reduction of 50 percent or more from a prior value. 60% of these people develop a thrombotic
event.
4.
Necrotic skin
lesions at heparin injection sites.
5.
Immediate
thrombocytopenia and/or thrombosis in a patient previously exposed to UFH. These patients may appear septic.
These features should raise
the possibility of HIT in any patient begun on heparin therapy within the
preceding five to ten days (discontinued or ongoing), or in a patient receiving
prolonged treatment with low molecular weight heparin. The diagnosis of HIT is
initially made on clinical grounds, because the assays with the highest
sensitivity and specificity may not be readily available and have a slow
turnaround time.
Given that immunologic
confirmation may be unavailable or very slow, it would be useful to identify
those at low risk of HIT with another cause for thrombocytopenia or
thrombosis. In the following table, risk of developing antibodies is evaluated based
on clinical features and history.
Patients in the low risk category are likely to have another cause for
their findings. The remainder must be
treated at greater risk and expense as having HIT:
|
Item |
Score |
I. Thrombocytopenia
|
|
|
Platelet
count fall >50 percent and nadir >20,000 |
2 |
|
Platelet
count fall 30-50 percent or nadir 10-19,000 |
1 |
|
Platelet
count fall <30 percent or nadir <10,000 |
0 |
|
II. Timing of platelet
count fall |
|
|
Clear
onset between days 5-10 or platelet count fall </= 1 day if prior heparin
exposure within the last 30 days |
2 |
|
Consistent
with fall at 5-10 days but not clear (eg, missing platelet counts) or onset
after day 10 or fall </= 1 day with prior heparin exposure within the last
30-100 days |
1 |
|
Platelet
count fall at <4 days without recent exposure |
0 |
|
III. Thrombosis or
other sequelae |
|
|
Confirmed
new thrombosis, skin necrosis, or acute systemic reaction post-IV
unfractionated heparin bolus |
2 |
|
Progressive
or recurrent thrombosis, non-necrotizing (erythematous) skin lesions, or
suspected thrombosis which has not been proven |
1 |
|
None |
0 |
|
IV. Other causes for
thrombocytopenia present |
|
|
None
apparent |
2 |
|
Possible |
1 |
|
Definite |
0 |
Pretest scoring
system for heparin-induced thrombocytopenia
How to use this
scoring system: A score (from 0 to 2) should be determined for each of the
above categories, resulting in a total potential score from zero to eight. The
pretest probabilities for the presence of heparin-induced thrombocytopenia
based on this scoring system are as follows:
Pretest
probability
Score 0 to 3: Low
Score 4 to 5: Intermediate
Score 6 to 8: High
Adapted from Lo GK, Juhl D, Warkentin TE, et al.
Evaluation of pretest clinical score (4 T's) for the diagnosis of
heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost
2006; 4:759.
1.
Stop UFH
2.
LMWH contraindicated.
3.
Platelets
contraindicated unless active bleeding (rare).
4.
Use IV alternative
thrombin inhibitor such as Agatroban or Lipirudin, or Fondaparinux to an end
point PTT of 1.5-2.5.
5.
Once the patient
is on an alternative IV anticoagulant and platelet count has risen to 100,000,
warfarin can be started. If warfarin is
given prior to this point, there is risk of warfarin-induced limb gangrene.
1.
Pendleton RC. The “must knows” of heparin-induced thrombocytopenia. Audio Digest Anesthesiology 2007; 49(5).
2.
Ketteler ER. Heparin-induced thrombocytopenia: what the
surgeon needs to know. Audio Digest
General Surgery 2007; 54(3)
3.
Coutre S. Heparin induced thrombocytopenia. UpToDate online ver. 15.2
4.
Lo GK, Juhl D,
Warkentin TE, et al. Evaluation of pretest clinical score (4 T's) for the
diagnosis of heparin-induced thrombocytopenia in two clinical settings. J
Thromb Haemost 2006; 4:759.