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.