Pretest Probability of Heparin Induced Thrombocytopenia
Heparin induced thrombocytopenia (HIT) is an antibody mediated adverse effect of heparin that is strongly associated with venous and arterial thrombosis. Major risk factors include exposure to unfractionated high molecular weight heparin for more than 5 days, undergoing surgery and female gender. Diagnostic criteria include:
- Thrombocytopenia
- Onset 5 to 12 days after exposure to heparin
- Exclusion of other causes of thrombocytopenia
- Positive laboratory test for HIT
The incidence of HIT is 2.6% of patients exposed to unfractionated heparin and 0.2% exposed to low molecular weight heparin. Approximately 25% of these patients will develop thrombosis within 30 days. Most cases arise in patients who have not been previously exposed to heparin. In this situation, thrombocytopenia usually occurs 5 to 12 days after heparin initiation. In patients who have been previously sensitized to heparin, platelet counts may decrease within the first three days or even hours after re-exposure. Platelet counts usually decrease more than 50% from baseline and typically fall to 20,000 - 150,000/uL. The nadir is usually reached 5 days after onset of the decline. The thrombocytopenia associated with HIT is not as severe as other drug induced thrombocytopenia and is seldom associated with spontaneous bleeding.
The antibody that causes this syndrome is not directed against heparin alone, but a complex of heparin with platelet factor 4 (PF4). The initial test for HIT is an enzyme linked immunosorbent assay for human platelet factor 4 (H/PF4) IgG antibody. However, before this test is ordered the4Ts score should be calculated to determine the pretest probability of HIT. This score is based on timing and magnitude of platelet count decrease, presence of thrombosis, and alternative causes of thrombocytopenia. The following table summarizes how points are assigned.
| 2 points | 1 point | 0 points | |
| Thrombocytopenia | >50% decrease & nadir of 20,000/uL or greater | 30-50% decrease or nadir of 10,000 to 19,000/uL | <30% decrease or nadir of less than 10,000/uL |
| Timing of platelet count decrease | Clear onset at 5-10 days or at less than 1 day | Consistent with 5-10 day onset or onset after 10 days | Decrease at less than 4 days without recent heparin |
| Thrombosis or other sequelae | New thrombosis or skin necrosis or acute systemic reaction | Progressive or recurrent thrombosis or non-necrotizing skin lesions | None |
| Other causes of thrombocytopenia | None apparent | Possible | Definite |
The score ranges from 0 to 8. A score of 0 to 3 indicates a low pretest probability for HIT of less than 5%. PF4 antibody testing is not needed. A score of 4 to 5 indicates intermediate risk of HIT while a score of 6 to 8 indicates high risk. PF4 antibody testing should be ordered for patients with either intermediate or high risk. Calculation of the 4Ts score prior to PF4 antibody testing decreases the likelihood of false positive results and eliminates unnecessary testing.
Reference
Min-Shen Y, Wolfe H and Barman S. Evaluating thrombocytopenia during heparin therapy. JAMA 2018;319:497-98.
