Multiple Organ Failure Syndrome Complicating Heparin-Induced Thrombocytopenia.
Authors: Frame James N. , Davis Elaine A. , Wang Ying , Emmett Mary S. , Malapur Ashna R. 
Published: April 2020

Abstract
Background: To date, multiple organ failure complicating HIT has been reviewed in a limited patient (pt.) numbers in the medical literature.
Objectives: (1) To describe the clinical features of pts. with HIT who developed the failure of ≥ 2 organs termed multiple organ failure syndrome (MOFS); (2) to determine the prevalence/incidence of MOFS HIT in a cohort of CAMC HIT Registry/open heart surgery (OHS) pts.
Design: Retrospective case series identified from an IRB-approved HIT Registry. Setting: Tertiary-care medical center.
Patients: 19 patients ≥ 18 yrs who presented from 1.1.00 to 12.31.04 with HIT ± thrombo-embolic complications (TEC) confirmed by serological (HPF4 ELISA, GTI) or functional (HIPA) HIT assays during (n=18) or after (n=1) a recent hospitalization with UFH exposure. Mean age: 71 yrs. (range, 49–84); women: 47%. UFH exposure settings (n): CABG alone (6) or with valve replacement (4), valve replacement alone or RV repair (1 each), aortic dissection repair (1), embolectomy or SBO (2 each), Whipple procedure (1; non-CA), atrial fibrillation (1). Measurements: Classification of MOFS: failure of ≥ 2 organs [e.g., brain, GI tract, liver, kidney, heart, lung (due to PE)] as modifications of the methods of Lefering R. et al (2002) and the Society of Thoracic Surgeons National Adult Cardiac Surgery Database, Version 2.52.1; platelet counts, clinical outcomes.
Results: The prevalence of MOFS in HIT Registry pts. was 4.7% (19/404). During this time, the incidence of MOFS complicating OHS HIT pts. in the total OHS pts. was 0.12% (13/11,018). HIT was first suspected a mean of 10d (range, 1–38) from initial UFH exposure and a mean of 4.7d (range, &lt;1d-25) after UFH was D/C’d where overall platelet counts [mean, 74x109/L, (range, 22- to 125-)] showed a 66% decrease from baseline [mean, 218 x 109/L, range (95- to 498-)]. At this time, 12 (63%) pts. had thrombocytopenia alone, 7 (37%) pts. had both thrombocytopenia and TEC, and 13 (68%) pts. had a total 19 organ failures (OF).: 1 OF: 8 pts.; 2 OF’s: 4 pts.; and 3 OF’s: 1 pt. At the time HIT was first suspected, the kidney (47%) and brain (32%) were the most frequent sites of organ failure. After the time HIT was first suspected and diagnosed, 17 (89%) pts. had developed ≥ 1 additional new OF: 1 OF: 7 pts.; 2 OF’s: 5 pts.; 3 OF’s: 5 pts. The liver (39%), kidney (23%) and GI tract (19%) were the most frequent sites of new OF’s. The mean/median overall number of organ failures/pt. were 2.6/2.0 (range, 2 to 4). Direct thrombin inhibitor (DTI) therapy was initiated in 17 (90%) at a mean of 2.5d (SD: 4.0) (range, 0–13) from the date HIT was first suspected: lepirudin (9) or Argatroban (8); (2 were not treated due to family wishes or late recognition). Lepirudin was switched to Argatroban in 2 pts. due to worsening renal failure and Argatroban was switched to lepirudin in 2 pts. due to worsening liver failure. The mean length of DTI therapy was 8.8 d (range, 1–20). Compared with non-MOFS HIT Registry pts. (n=395), MOFS HIT pts. had more fatal outcomes [95% (18/19) vs. 11% (45/395); p = 3.2x 10−15], major bleeding events [26% (5/19) vs. 6.3% (25/395); p = 0.008], and amputations [11% (2/19) vs. 1.5% (6/395); p = 0.047].
Conclusions: Although uncommon, MOFS may be the initial manifestation of HIT and is associated with catastrophic outcomes. Compared to non-MOFS HIT pts., MOFS HIT pts. had an increased rate of fatal outcomes, major bleeding events, and rates of amputation. In a subset of HIT pts., MOFS hampered the delivery of utilized DTI’s. Our data also suggest the need for earlier HIT recognition and DTI interventions.