HIT Antibody Positivity
Out of the control cohort of 1265 hospitalized COVID-19 positive patients, 33 had intermediate to high 4T scores and were tested for HIT antibodies. In all COVID-19 patients who were tested for HIT, there was no difference in intermediate 4T scores predicting EIA+ at 26.1% compared to high 4T scores at 33.3% (p= 0.6248). EIA+ in COVID-19 patients with intermediate to high 4T scores at our institution was significantly higher at 24.24% compared to IgG EIA+ in the general population for intermediate to high 4T scores at 10.18% (p=0.00896).16
Of the 33 patients tested for HIT, only 8 patients were EIA+ (study cohort), with characteristics listed in Table 1. Incidence of EIA+ in COVID-19 patients was 0.6%, which is significantly higher than in the general population 0.2%15 (p<0.0001, 95% CI 0.25-1.20%). Serological confirmation of HIT diagnosis in our study cohort was 37.5% which is significantly higher than confirmation of HIT in the general population 5.6%16 (p<0.0001, 95% CI 29.57-85.32%). The mortality rate of the EIA+ study cohort was 50%, significantly greater than the mortality rate of 12% in COVID-19 patients in the control cohort (p=0.0011, CI 9.46-66.53).
Thrombosis Risk
The incidence of thromboembolic events in EIA+ patients in the study cohort was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 patients in the control cohort (p<0.0001, CI 41.96- 86.98%). Of the EIA+ patients in the study cohort who had thrombosis, 28.57% had PE, 57.14% had DVT, 14.28% had a stroke. There was a statistically significant higher incidence of DVT in the study cohort compared to DVT in all COVID-19 patients in the control cohort 4.82% (p=0.0038). There was no difference in incidence of PE or stroke in EIA+ study cohort compared to PE (4.82%, p= 0.0557) or stroke (2.60%, p=0.1731) in all COVID-19 patients in the control cohort.
Hospital Course Analysis
There was no significant difference in demographic distribution between the study cohort of EIA+ patients and the control cohort of all COVID-19 hospitalized patients (Table 3). There was no difference in mortality rate of EIA+ patients based on demographics or risk factors for HIT (Table 4). The average days of anticoagulation received prior to HIT antibody testing was 6.75 days with standard deviation ± 6.43 days, and no difference in mortality rate based on days of anticoagulation before diagnosis of EIA+ (p=0.2362). In the EIA+ study cohort, 25% had exposure to both UFH and LMWH, 25% UFH only, 50% exposure to only LMWH. There was no difference in mortality rate for EIA+ COVID-19 patients based on the type of anticoagulation received, UFH 0%, LMWH 75%, Both 50% (p=0.6571). There was no difference in mortality rate between EIA+ patients who received prophylactic 50% or therapeutic dosage of anticoagulation 50% (p=1.0). After diagnosis with EIA+, 37.5% were transitioned to Argatroban and 62.5% were treated with Bivalirudin. There was no difference in mortality rate of patients who received Argatroban 33.3% compared to Bivalirudin 60% (p=1.0).
HIT antibody testing was sent on average 7.75 days into hospitalization with standard deviation ± 6.16 days. The hospital length of stay (LOS) of EIA+ study cohort patients was 27.9 days with standard deviation ± 7.66 days, which was significantly higher than all COVID-19 patients in the control cohort who had a mean hospital LOS of 9.836 with standard deviation of ± 10.27 days (p=0.0005, 95% CI 7.96 to 28.16).
Hematologic Laboratory Values Analysis
It was statistically significant that having severe thrombocytopenia (platelet count <50k) was not associated with increased mortality 0% whereas moderate thrombocytopenia (platelet count 50k-99k) was associated with increased mortality 100% (p=0.0286). The average days to platelet recovery in EIA+ patients was 6.29 days with standard deviation ± 3.45 days. There was no difference in mortality rate based on the number of days from diagnosis of EIA+ to platelet recovery (p=0.7383). The average highest D-dimer for all EIA+ patients was 14.34 times the upper limit of normal (ULN) with standard deviation of ± 8.52. There was no difference in mortality rate based on highest D-dimer level for EIA+ patients (p= 0.2917).
6 Month Follow up on Discharged EIA+ Patients
Of the 4 EIA+ patients who survived, one (25%) of those patients on follow up had died, increasing the overall mortality rate in the study cohort to 62.5%. This patient (Patient 6 on Table 1) had an acute myocardial infarction as well as hemorrhagic shock. Patient 3 from Table 1 suffered from dry gangrene. Patient 1 and patient 7 had no further complications.
Analysis based on Literature Review
There were 39 HIT antibody patients reported in the literature with HIT antibody testing and had patient specific data. Of those, 23.07% had positive confirmatory testing (6 SRA, 3 HIPAA) which is significantly higher than 5.6%16 in the general population (p=0.00001). The incidence of thrombosis in EIA+ COVID-19 patients in the literature was 56.4% which is significantly higher than reported rates of thrombotic events in in all COVID-19 patients in the literature at 4.8%1 (p=0.00001). Of the EIA+ COVID-19 patients in the literature who reported both 4T scores and confirmatory testing, 0% of low 4Ts score were serologically positive, 44.44% of intermediate 4Ts score were serologically positive, and 37.5% of high 4Ts score were serologically positive with no significant difference of 4Ts score as a predictor for serologically positive HIT (p=0.5839).