Delayed-Onset Heparin-Induced Thrombocytopenia and/or Thrombosis Following Open Heart Surgery Hospital Discharge.
Authors: Frame James N. , Lambert April , Davis Elaine A. , Wang Ying , Emmett Mary S. 
Published: April 2020

Abstract
Background: Delayed-onset heparin-induced thrombocytopenia (D-HIT) is reported to present with thromboembolic complications (TEC) and thrombocytopenia from 5d–19d after stopping heparin (UFH) or from 9d–40d following discharge (D/C) from hospitalizations that included UFH exposure. D-HIT has been reported in limited patient numbers after hospital D/C for open heart surgery (OHS).
Objectives: To describe the clinical features and outcomes in patients (pts.) who presented with D-HIT after a recent OHS hospitalization with UFH exposure.
Design: Retrospective case series of D-HIT pts. from an IRB-approved HIT Registry.
Setting: Tertiary-care medical center.
Patients: 25 pts. (≥ 18 yrs) seen from 1.1.99 to 6.30.04 with D-HIT who initially presented with TEC ± thrombocytopenia or thrombocytopenia alone after OHS D/C. OHS procedures (n): CABG alone (23) or with aortic valve replacement (2). Median age: 61 yrs. (range, 35–79); female: 36%. Measurements: platelet cts., results of HIT-Ab to H-PF4 by ELISA (GTI; O.D. ≥ 0.4) or HIPA (≥ 1+ test in all pts.), objectively determined TEC, UFH/LMWH re-exposures, and clinical outcomes.
Results: At initial D-HIT presentation, 15 had TEC alone, 2 had thrombocytopenia alone, and 8 had both a median of 13d (range, 6–51) from the last day of UFH exposure and a median of 8d (range, 2–46) from the OHS D/C date. The overall mean and % decrease in platelet cts. from OHS D/C to D-HIT admission were 103 x 109/L (range, 12–244) and 48% (range, 5–85), respectively. TEC (n) included: PE alone (4) or with DVT (4), DVT alone (5) or with arterial thrombosis (1), acute MI alone (3) or with DVT (1), arterial thrombosis alone (3), stroke (1), and superficial VTE (1). Pts. with thrombocytopenia alone presented with atrial flutter (1) or dyspnea (1) with TEC excluded. At D-HIT presentation, 13/25 pts. were re-exposed to UFH (10) or LMWH (3) for TEC with (5) or without thrombocytopenia (8). This produced a mean 41% (median, 68%) decrease in platelet cts. in 9/13 pts. (7 without prior thrombocytopenia) [mean/median platelet cts. at D-HIT presentation, 265-/243x109/L, (range: 40–473); mean/median platelet ct. nadirs after UFH/LMWH re-exposure, 157-/79x109/L, (range, 8–427)] and no change in 2 pts. with or 2 pts. without thrombocytopenia. Of the 12/25 pts. who were not re-exposed to UFH/LMWH, 6/12 pts.(5 without prior thrombocytopenia) had a mean 32% (median, 50%) decrease in platelet cts. [mean/median platelet cts. at D-HIT presentation, 293-/237x109/L, (range, 88–538); mean/median platelet ct. nadirs during D-HIT admission, 200-/118x109/L, (range, 48–461)] with no change in 2 pts. with or in 4 pts. without thrombocytopenia. After D-HIT was recognized, treatment with a direct thrombin inhibitor (DTI) was administered in all pts: lepirudin alone (15), argatroban alone (7) or after lepirudin (1), or bivalirudin alone (2). Mortality from progressive TEC occurred in 3 pts (all re-exposed to UFH). The mean overall time on a DTI and DTI-warfarin overlap was 8.3d and 5.2d, respectively. 21/22 survivors were D/C’d on warfarin.
Conclusion: In this patient cohort, D-HIT presented with TEC alone (60%) ± thrombocytopenia (32%) or thrombocytopenia alone (8%) at a median of 13d from last UFH exposure and up to 46d after OHS hospital D/C. Our observations expand the spectrum of D-HIT presentations reported to date and re-emphasize the high-index of suspicion necessary to avoid UFH or LMWH re-exposures in at-risk patients.