Incidence Of Heparin-induced Thrombocytopenia In Patients Research Articles

Heparin-Induced Thrombocytopenia Is Associated with Higher in-Hospital Mortality after Left Ventricular Assist Device Placement: A Retrospective Cohort Study from National Inpatient sample2016-2019

Background: Heparin is widely used to implant and maintain left ventricular assist devices (LVAD). Heparin-induced thrombocytopenia (HIT) is a severe complication that can hamper successful LVAD implantation or maintenance. The incidence and outcomes of HIT among hospitalized patients undergoing principal LVAD procedures are not well studied. Purpose: We hypothesized that HIT is not associated with increased or decreased odds of in-hospital mortality in LVAD. Methods: This is a retrospective cohort study from principal LVAD hospitalizations between January 1, 2016, and December 31, 2019, using the 2016-2019 National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. Our study sample included any hospitalizations with LVAD, as a principal procedure, aged 18 years or older, using the ICD 10 procedural codes validated in previous studies. Results: From 2016 to 2019, a total of 2924 (weighted N =13,205) hospitalizations with the principal procedure as LVAD were identified. Among them, 21.96% (n= 642) were females, and 78.04% (n = 2281) were males (p < 0.001), and 1.47 % (n=43) developed HIT. MeanThe mean age was 56.8 ± 13.3 years. Moreover, 60.7% of total LVAD were performed in Whites, 26.6% in Blacks, 7% in Hispanics, and 2% in Asians. 2111 (72.2%) hospitalizations had a Charlson comorbidity index (CCI) of three or higher. Compared to non-HIT, those who had HIT, were similar in age (mean age: 55.6 vs. 56.8; p=0.542), had lower CCI of three or higher (53.5% vs. 72.5%, p=0.015), but higher in-hospital mortality (23.3% vs 9.4%, p=0.006). Multivariate regression analysis showed that, compared with non-HIT, HIT had a significantly increased odds of in-hospital mortality (aOR: 3.37; 95% CI: 1.61, 7.01; p=0.001) after controlling for age, race, regional location of the hospital, hospital bed capacity, income, insurance provider, and Charlson comorbidity index. From 2016 to 2019, the annual incidence of principal LVAD per 100,000 hospitalizations have been stable at 10.1 in 2016, 10.8 in 2017, 10.2 in 2018 and 10.0 in 2019 (p-trend=0.475). Conclusion: The incidence of HIT in patients undergoing LVAD is low. However, HIT carries significantly higher in-hospital mortality in patients getting LVAD. The incidence of LVAD procedures has been stable over recent years.

Incidence of Heparin Induced Thrombocytopenia in Patients Undergoing Implantation of Durable and Non-Durable Mechanical Circulatory Support Devices

Purpose Unfractionated heparin exposure in patients undergoing mechanical circulatory support device (MCSD) implantation increases the risk for developing heparin-induced-thrombocytopenia (HIT). The false positive rate of HIT in this population using current standard testing is unknown. Postoperative and device related thrombocytopenia complicate the HIT diagnosis. Methods A retrospective analysis of patients undergoing MCSD pre-implantation assessment or implantation of MCSD (October 2014 - August 2020) was performed. The primary objective was to assess the incidence of HIT with positive PF4 IgG ELISA (PF4) and serotonin release (SRA) assays. False positive HIT was defined as PF4 ≥0.4 optical density (OD) and negative SRA. Argatroban usage was also assessed. Results 366 patients with 512 tests were analyzed. PF4 tests were performed in 128 patients (158 tests) undergoing pre-implantation assessment, 136 patients (185 tests) with non-durable devices (primarily Impella®), and 102 (169 tests) patients with durable devices (72 ventricular assist devices, 30 total artificial hearts). 25% (92/366) of patients had positive PF4 ≥0.4 OD and had subsequent SRA performed (92 patients, 122 tests). True positive HIT was documented in 13% (12/92) of PF4 positive patients consisting of 1 pre-implantation, 9 non-durable MCSD, and 2 durable MCSD patients. The mean PF4 for true positive HIT was 2.2±0.7 OD. False positive HIT was documented in 15% (19/128) of pre-implantation patients (mean PF4 0.9±0.6 OD), 14% (19/136) of non-durable MCSD patients (mean PF4 0.8±0.5 OD), and 41% (42/102) of durable MCSD patients (mean PF4 1.1±0.6 OD). Argatroban was administered in 40% (37/92) of patients with a positive PF4 and 67% (25/37) of patients with a negative SRA. Conclusion Without clinical suspicion of HIT, preoperative PF4 testing is not recommended. Patients with non-durable MCSD devices are at the highest risk of developing HIT (7%). Although a PF4 ≥0.4 OD is considered a positive screening test for HIT, a higher threshold should be considered for MCSD patients. To our knowledge, this is the first in depth assessment of the incidence of HIT in patients undergoing pre-implantation evaluation for both non-durable and durable MCS devices.

Heparin-induced thrombocytopenia during extracorporeal life support: incidence, management and outcomes.

Heparin-induced thrombocytopenia (HIT) is a severe antibody-mediated reaction leading to transient prothrombosis. However, its incidence in patients on extracorporeal life support (ECLS) is not well described. The aim of this systematic review was to report the incidence of HIT in patients on ECLS, as well as compare the characteristics and outcomes of HIT in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and veno-venous ECMO (VV-ECMO). An electronic search was performed to identify all studies in the English literature examining outcomes of patients with HIT on ECLS. All identified articles were systematically assessed using specific inclusion and exclusion criteria. Random effects meta-analysis as well as univariate analysis was performed. Of 309 patients from six retrospective studies undergoing ECLS, 83% were suspected, and 17% were confirmed to have HIT. Due to the sparsity of relevant retrospective data regarding patients with confirmed HIT on ECLS, patient-based data was subsequently collected on 28 patients from case reports and case series. Out of these 28 patients, 53.6% and 46.4% of them underwent VA-ECMO and VV-ECMO, respectively. Patients on VA-ECMO had a lower median platelet count nadir (VA-ECMO: 26.0 vs. VV-ECMO: 45.0 per µL, P=0.012) and were more likely to experience arterial thromboembolism (VA-ECMO: 53.3% vs. VV-ECMO: 0.0%, P=0.007), though there was a trend towards decreased likelihood of experiencing ECLS circuit oxygenator thromboembolism (VA-ECMO: 0.0% vs. VV-ECMO: 30.8%, P=0.075) and thromboembolism necessitating ECLS device or circuit exchange (VA-ECMO: 13.3% vs. VV-ECMO 53.8%, P=0.060). Kaplan-Meier survival plots including time from ECLS initiation reveal no significant differences in survival in patients supported on VA-ECMO as compared to VV-ECMO (P=0.300). Patients who develop HIT on VA-ECMO are more likely to experience more severe thrombocytopenia and arterial thromboembolism than those on VV-ECMO. Further research in this area and development of standardized protocols for the monitoring, diagnosis and management of HIT in patients on ECLS support are warranted.

Platelet Trends Are Not Predictive of Heparin Induced Thrombocytopenia in Patients on Extra Corporeal Membrane Oxygenation

Introduction: Extracorporeal membrane oxygenation (ECMO) is a form of a cardiopulmonary bypass circuit that is utilized for patients in dire need of cardiac or pulmonary support. The circuit exposes blood to artificial surfaces which leads to platelet activation, clotting and thrombocytopenia. The addition of heparin is required in order to prevent clots from forming along the circuit. Heparin-induced thrombocytopenia (HIT) and heparin induced thrombocytopenia and thrombosis (HITT) are serious adverse effects of heparin treatment characterized by formation of antibodies to heparin platelet factor 4 (PF4) complexed with heparin which leads to thrombocytopenia and a greatly increased risk of arterial and venous thrombosis. The well-established incidence of HIT ranges from 0.5-5% in patients exposed to heparin for more than four days. The reported incidence of HIT in ECMO patients ranges from less than 1% to 8.3%. However this data comes from only a few studies with small sample sizes. Our institution has a large lung center and as a result ECMO is utilized frequently. When patients are suspected to have HIT, they are taken off heparin and switched to a different anticoagulant. For patients without HIT, the switch to a different anticoagulant is unnecessary and exposes the patient to additional risks such as a higher risk of bleeding. Our aim was to calculate the incidence of HIT and HITT at our institution. Furthermore we wanted to examine the platelet trends of all patients on ECMO specifically comparing and contrasting the patients who are deemed true HIT positive vs. all other patients on ECMO.Methods: We conducted a retrospective analysis of all patients on ECMO at Temple University Hospital from July 1, 2012 to December 31, 2017. The data for this study was drawn from the T'PAU (Temple Population Access Utility) research data warehouse that has successfully merged data from the Epic EMR and the McKesson administrative system that houses important summary data on inpatient admissions going back through July 2012. Our inclusion criteria consisted of all patients on ECMO who had a clinical suspicion of HIT and thus had a screening test sent for HIT, the ELISA polyclonal IgG testing against PF4. The diagnosis of HIT or HITT was confirmed by PF4 antibody positivity with an optical density (OD) >1.0, serotonin release assay (SRA) positivity or a positive PF4 antibody test >0.4 and the presence of thrombosis. Linear mixed-effects model was used to estimate and compare platelet count change over time between true HIT patients and patients who tested negative for the HIT ELISA.Results: There were 164 patients on ECMO between July 1st, 2012 and December 31, 2017. A total of 77 patients had the HIT ELISA sent while on ECMO. Of those, 15 patients had a positive test result (OD > 0.4) and 62 had a negative test result. Of the patients with positive results, 5 patients had an OD > 1.0. Three of the 10 patients with an OD < 1.0 were found to have thrombosis. Therefore 8 patients had true HIT out of a total of 164 patients on ECMO, for an incidence of 4.88%. There was no difference of the change of platelet count over time between the HIT (n=8) and non-HIT (n=62) groups (P=0.98).Conclusion: The incidence of HIT in our ECMO patient population is similar to the incidence of HIT in all patients who have been exposed to heparin for four or more days. Patients requiring ECMO are very ill and with the accompanying thrombocytopenia that develops with the initiation of ECMO, the clinical suspicion for HIT is high. Unlike the majority of hospitalized patients, patients on ECMO are a unique population and platelet count trends are not necessarily a clinically reliable indicator for HIT. Our research supports that the full clinical picture should be taken in account when suspecting HIT in patients on ECMO, especially when considering a change in anticoagulation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence of heparin-induced thrombocytopenia in lower-extremity free flap reconstruction correlates with the overall surgical population

Lower-extremity free flap reconstruction is a growing trend in the management of lower extremity wounds. Heparin-induced thrombocytopenia (HIT) is a significant risk to free flap reconstruction. The purpose of this study was to investigate the incidence of HIT in patients receiving lower-extremity free flap surgery. We conducted a retrospective, single center, IRB approved cohort study in which we reviewed all patients who received lower-extremity free flap surgeries between 2011 and 2016. The 4T and HIT Expert Probability (HEP) scores were calculated to assess the likelihood of HIT. One hundred patient charts revealed three patients with HIT. One patient was excluded due to a prior diagnosis of HIT. HIT incidence in patients receiving lower-extremity free flaps was between 1% and 3%, which is consistent with the national average. 4T scores indicated that two of three HIT-positive patients had a high probability of HIT (approximately 64%), and one of three HIT-positive patients had an intermediate probability (approximately 14%). HEP scoring indicated that all the three (100%) patients had HIT. These data suggest that the incidence of HIT in patients receiving lower-extremity free flaps correlates with the incidence of HIT nationally. The use of available scoring methods and other algorithms, combined with patient history helps to assess the immediate perioperative risks of HIT in the absence of rapid immunologic confirmatory tests. This knowledge can allow for successful free flap salvage or for performance of free flaps in patients with a history of HIT.

Is the incidence trend of heparin-induced thrombocytopenia decreased by the increased use of low-molecular-weight-heparin?

BackgroundThe increasing trend of using low-molecular-weight-heparin (LMWH) versus unfractionated heparin (UFH) in hospitalized adult patients is raising concerns about the incidence of heparin-induced thrombocytopenia (HIT).MethodA retrospective study analyzed the requests for heparin-induced antibodies by enzyme-linked immunosorbent assay (ELISA) among adult hospitalized patients during the period from January 2011 to December 2013. These patients received either UFH or LMWH for prevention or therapeutic indications. Those with positive immune-mediated HIT were identified and considered as case patients.ResultThe usage of LMWH and UFH and development of HIT was determined during the study period. The incidence of HIT in patients receiving UFH and those receiving LMWH was 4.09 per thousand patients and 0.48 per thousand patients, respectively, (p<0.0001) with an overall incidence of 2.49 per thousand patients.ConclusionThe increased trend of using LMWH over UFH among hospitalized adult patients was observed and can be said to contribute to the diminished overall incidence of HIT.

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Introduction: Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin treatment characterized by formation of antibodies to heparin–platelet factor 4 (H–PF4) complexes. Clinically, patients with HIT demonstrate a fall in platelet count of more than fifty percent, occurring 5–10 days after the start of heparin treatment; some also develop HIT related thrombosis (HITT). Cardiopulmonary bypass (CPB) is associated with platelet activation, thrombocytopenia and the release into the plasma of large amounts of PF4, as well as exposure to high doses of unfractionated heparin (UFH). Up to 50% of patients develop antibodies to H–PF4 complexes following CPB. However, less than 3% of those patients develop actual HITT, characterized by a second episode of thrombocytopenia 5-10 days after CPB ("P1 pattern" reported by Pouplard et al.). ECMO is a modified CPB circuit that critically ill patients may be exposed to for days and weeks. The incidence of HIT in patients undergoing ECMO is unknown. Furthermore, clinical scores used to diagnose HIT may not be useful in ECMO patients given the high prevalence and persistence of thrombocytopenia caused by artificial circuit and underlying disease. We sought to determine the incidence of HIT/HITT and platelet patterns potentially suggestive of HIT in a cohort of ECMO patients at our institution Methods: After IRB approval, a prospectively collected data set encompassing all ECMO patients from 2009 to 2012 at our institution was reviewed. To compare platelet trends, we only included patients who survived longer than 48 hours after ECMO initiation. Patients were tested for HIT based on presence of thrombocytopenia and clinical suspicion. Institutional criteria defines patients as "HIT positive" if they meet any of the following serological criteria: HIT ELISA Ab(+)/SRA(+); HIT ELISA Ab(-)/SRA(+); HIT ELISA(+) with optical density (OD)>1. "HIT positive" patients with evidence of thrombosis were considered as having HITT. Patients who didn't meet these criteria, or were not tested due to lack of clinical suspicion, were considered "HIT negative". Daily platelet counts were recorded for 10 days inclusive of day of ECMO initiation. Statistical analysis was done using the Wilcoxon rank sum test and Fisher exact test as appropriate for the data sets. Results: 85 patients underwent ECMO from 2009 to 2012. 68 (80%) patients survived longer than 48 hours after ECMO initiation. Of those, 50 patients(73.5%) were tested for HIT ELISA, SRA or both. 4 patients were deemed "HIT positive" and 3 of those patients had documented thrombo-embolic events (HITT) based on predefined criteria (HIT and HITT incidence in the study group of 5.9% and 4.4% respectively). HIT positive patients were significantly younger (53.1 vs. 37.5 years, p=0.048) and had a trend toward higher average HIT ELISA OD (1.246 vs. 0.258, p=0.056). Only significantly different average platelet count between "HIT negative" and "HIT positive group" was at day 10 (163 vs. 53.7, p=0.024).This difference remained significant when we excluded patients from "HIT negative" group who were not tested for HIT ELISA, SRA or both (127.9 vs. 53.7, p=0.033). No other platelet parameter, such as average highest platelet count, platelet nadir, days to nadir and percentage platelet drop, differed significantly between the groups. However, plots of average daily platelet counts suggests a potentially revealing pattern in "HIT positive" group, where a gradual drop to platelet nadir (post ECMO day 5-6) is followed by a period of persistently depressed platelet counts (days 6-10). Conclusions: Incidence of both HIT and HITT is relatively high in patients who survive ECMO for longer than 48 hours at our institution. Traditional clinical scores for diagnosis of HIT such as "4 Ts", or presence of "P 1" platelet pattern (typical of HIT in cardiac surgery patients) are not useful in ECMO patients. Pattern of depressed platelet counts after nadir may be suggestive of HIT in these patients.