Pharmacy & Therapeutics - November 2008 - (Page 643)

Heparin-Induced Thrombocytopenia DIAGNOSIS The diagnosis of HIT is based on both cliniPlatelet cal and serological findings. HIT antibody seroconversion, along with thrombocytopenia or other clinical manifestations, such as skin lesions at heparin injections sites or acute sysPF4/heparin IgG alpha granule temic reactions (fever, chills, cardiorespiratory complex distress) after intravenous (IV) bolus administration, are necessary to confirm a positive diagnosis of HIT.13 Clinically, HIT should be first suspected when a patient receiving heparin, typically for 5 to 14 days, experiences an unexplained drop in the platelet count, usually a decline of 50% or more from baseline, along with moderate microparticles thrombocytopenia with a median platelet count Fc receptor of 50 to 60 × 109 cells/L. However, the nadir platelet counts can range anywhere from 15 × 109 to 150 × 109 cells/L in 90% of patients.11 Figure 1 Pathogenesis of heparin-induced thrombocytopenia. Platelet factor Less frequently, thrombocytopenia can pres4 (PF4) contained in platelet alpha granules is expressed on the platelet cell ent within 24 hours (as in rapid-onset HIT), or surface (top left). Following administration, heparin binds to PF4; this conit can be delayed by up to 20 days after heparin formationally modified complex then attaches to anti-heparin/PF4 antibodies has been stopped (as in delayed-onset HIT).14 (most frequently IgG) at its Fab binding domain (top right). The large heparin– Thrombocytopenia has also been reported with PF4 complex allows the IgG antibodies to cross-link via its Fc portion and a single administration.15 occupy FcγIIa receptors, found on the platelets cell surface, thereby activating To aid in the identification of patients with the platelets and causing further expression of PF4 and release of proHIT, clinicians can use a pretest probability thrombotic microparticles (bottom right to left). IgG= immunoglobulin. scoring system known by the simple (From Levy JH, Hursting MJ. Hematol Oncol Clin North Am 2007;21:65–88. mnemonic, the “4 T’s” (Table 2).16,17 Each charReproduced with permission from Elsevier.3) acteristic feature of HIT—such as Thrombocytopenia, Timing, Thrombosis and the absence of oTher explanations—is given a score ranging from 0 to 2. bodies is more likely (a greater than 80% probability). The sum of each component is used to determine a pretest • Scores of 4 to 5 indicate possible HIT with potentially probability score: other causes; testing for antibodies is the most useful strategy for these patients. • Scores of 3 or below suggest a low probability of HIT; antibodies are unlikely (less than a 5% probability). One component of the pretest probability score is the iden• With high scores of 6 or more, the presence of HIT antitification of other causes of thrombocytopenia. This is par- Table 2 Pretest Probability of HIT: The “Four T’s” 2 Points Thrombocytopenia Timing of onset of platelet fall (or other sequelae of HIT) >50% platelet count fall to nadir ≥ 20,000 Days 5–10 or ≤ day 1 if prior heparin exposure within the last 30 days Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV unfractionated heparin bolus None evident 1 Point 30%–50% platelet count fall or nadir 10,000–19,000 >Day 10 or timing not clear (missing platelet counts) ≤ day 1 with prior heparin exposure within the last 30–100 days 0 Points <30% platelet count fall or nadir <10,000 < Day 4 without recent exposure Thrombosis or other sequelae Progressive or recurrent None thrombosis, erythematous skin lesions, or suspected thrombosis (not proven) Possible Definite oT her cause(s) of platelet fall A score (from 0 to 2) should be determined for each category above, resulting in a total potential score from 0 to 8. Pretest probability score: High 6 to 8; Intermediate 4 to 5; and Low 0 to 3 Data from Lo GK, Juhl D, Warkentin TE, et al. J Thromb Haemost 2006; 4:759;16 and Warkentin TE. Circulation. 2004;110(18):e454–e458.17 Vol. 33 No. 11 • November 2008 • P&T® 643

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Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

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