Incidence Of Heparin-induced Thrombocytopenia Research Articles

Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis.

Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019. Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01). SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Incidence and Predictive Factors of Heparin-Induced Thrombocytopenia: A Comprehensive Analysis Using National Inpatient Data

Introduction: Heparin-induced thrombocytopenia (HIT) is a serious complication associated with heparin therapy, characterized by an immune reaction involving antibodies against heparin-platelet factor 4 (PF4). This immune complex formation triggers platelet activation, blood clotting, and reduced platelet counts. Several factors, including previous heparin exposure, duration of exposure, and certain comorbidities, have been examined as potential risk factors for HIT development. In this study, our objective was to determine the incidence of HIT and identify predictive factors associated with its occurrence. Methods: We conducted an analysis using the National Inpatient Sample (NIS) data from 2020 to investigate the incidence of HIT during that year and its correlation with specific comorbidities. Patient identification was based on the International Classification of Diseases (ICD-10) code D75.82. The incidence and associated comorbidities were evaluated using multivariate logistic analysis with Stata 17. Results: Among the 32,355,827 adult patients admitted throughout the United States in 2020, a total of 11,380 cases of HIT were identified. The incidence of HIT was significantly higher in male patients, obese individuals, those with acute kidney injury (AKI), chronic kidney disease (CKD), type II diabetes mellitus (DMII), heart failure (HF), primary hypercoagulable states, and autoimmune diseases such as systemic lupus erythematosus (SLE). The highest risk of developing HIT was observed in patients with thrombophilia (OR 4.17, 95% CI 3.66-4.75, P = .000), AKI (OR 3.53, 95% CI 3.19-3.91, P = .000), and HF (OR 2.10, 95% CI 1.90-2.33, P = .000). Among autoimmune diseases studied, only SLE was associated with an increased odds ratio for developing HIT (OR 1.60, 95% CI 1.06-2.41, P = .026). Conclusion: The incidence of HIT varies and is influenced by the presence of specific comorbidities. Further studies are recommended to investigate additional factors that may increase the likelihood of HIT development. This information could aid in validating and implementing standard precautionary measures in patients at higher risk of developing HIT.

Trends in Heparin-Induced Thrombocytopenia in the Pre-Pandemic and Peak-Pandemic Era, and Impact of COVID-19 on Mortality; An Analysis Via the National Inpatient Sample

Introduction: The recent pandemic of COVID-19 caused a significant upheaval in access to healthcare and resources across the world. The COVID-19 infection has also been associated with a hypercoagulable state that can alter multiple coagulation pathways and cause various cerebrovascular and cardiovascular insults, thus requiring the need for heparin products. While a recent study found a decreasing trend of Heparin-induced thrombocytopenia(HIT) between 2011-2014, there have yet to be any recent studies investigating the pandemic's role on HIT trends and the overall effect of COVID-19 on the mortality of these patients. We, therefore, used the National Inpatient Sample (NIS) to assess the impact of the pandemic on HIT. Methods: The 2016-2020 NIS, a set of yearly discharge records released in de-identified form with various patient characteristics, discharge and procedural codes, was used for our study. We included cases with a diagnosis for HIT via the International Classification of Diseases, Tenth Revision (ICD-10) code “D7582”. Patients with COVID-19 and other comorbidities that can influence the outcomes were also identified via their respective ICD-10 codes from past studies. The incidence of HIT per 100,000 hospitalizations between 2016-2020 was compared and linear-by-linear analysis was used to assess trends, as in previous studies. We further proceeded to compare the trends in mortality rates among HIT patients. Finally, the odds of mortality among HIT patients with and without COVID-19, restricting the sample to HIT patients from 2020, were estimated via multivariable regression models. SPSS 29.0 was used for our analyses, and a p-value &amp;lt;0.05 was set for statistical significance. Results: Our study included a total of 72930 cases of HIT between January 1st 2016- December 31st 2020, with 16780 cases in 2016, 16450 cases in 2017, 14590 cases in 2018, 12980 cases in 2019, and 12130 cases in 2020. The overall adjusted incidence of HIT dropped between 2016-2019 from 55.6 cases per 100,000 (in 2016) hospitalizations to 43.0 cases per 100,000 hospitalizations (in 2019). However, a rise was seen in 2020 with 43.9 cases per 100,000 hospitalizations (ptrend&amp;lt;0.01). On average, HIT was reported in 49.1 cases per 100,000 adult hospitalizations. However, in 2020, among the 12130 cases of HIT, there were 1745(14.4%) COVID-19 positive patients. The adjusted incidence of HIT in 2020 without COVID-19 cases of HIT was 37.6 cases per 100,000 hospitalizations. The adjusted analysis (excluding COVID-19 positive HIT cases), showed a continuous decrease in incidence of HIT between 2016-2020 (Figure 1a). Meanwhile, the mortality rates among HIT patients were 10.2% in 2016, 11.9% in 2017, 11.0% in 2018, 10.5% in 2019 and 16.2% in 2020 (ptrend&amp;lt;0.01). However, in 2020 the mortality rate among non-COVID-19 positive HIT patients was 10.4%, with no statistical differences between the years (ptrend=0.440) (Figure 1b). Finally, among the HIT cases of 2020, concurrent presence of COVID-19 was linked with a higher odds of mortality (50.4% vs. 10.4%, aOR 8.471, 95% CI 7.405-9.690, p&amp;lt;0.01). Conclusion: Our study provides a fresh analysis of the burden of the COVID-19 pandemic on the incidence and outcomes of HIT in the United States. While a decreasing incidence of HIT was seen between 2016-2020 for cases without COVID-19, in 2020, patients with the virus contributed to a rise in the overall incidence and mortality rates. COVID-19 infection has a massive impact on coagulation profiles, and while our data covers the pre-vaccination period, we strongly advocate for research via future NIS databases to better understand the progress of the pandemic on HIT in 2021 and onwards.

Incidence of Heparin-Induced Thrombocytopenia in Non-Surgical Patients

Introduction: Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin exposure. HIT occurs when Platelet Factor 4 (PF4) forms a complex with heparin, resulting in the formation of autoantibodies. HIT occurs more frequently in surgical patients compared with non-surgical patients due to the inflammatory release of PF4 and perioperative heparin exposure. Previously, unfractionated heparin (UFH) has been compared to low molecular weight heparin (LMWH) solely among surgical patients which has been correlated with a higher incidence of HIT relative to LMWH. However, there is little data regarding UFH versus LMWH in non-surgical patients. The purpose of this study was to determine whether there was a significant difference in the incidence of HIT between these two forms of anticoagulation in non-surgical patients. We also sought to delineate differences in incidence of HIT with respect to BMI, gender, and age. Methods: This is a retrospective study that included all patients admitted to 14 hospitals within Hospital Corporation of America's (HCA) North Florida Division between January 2016 and September 2022. Data was retrieved and analyzed by HCA statisticians. Patient selection was based not only on whether they had been diagnosed with HIT, but various other factors including age, weight, gender and type of anticoagulation (LMWH vs UFH). Patients who had undergone surgery or even been hospitalized within the six months had been excluded. Other excluded conditions include disseminated intravascular coagulation (DIC), hemolytic-uremic syndrome (HUS), immune thrombocytopenic purpura (ITP), drug induced systemic lupus erythematosus (DILE), and systemic lupus erythematosus (SLE). Results: A total of 2,061 patients were included. Unfractionated heparin group was significantly associated with the likelihood of the patient being diagnosed with HIT (χ 2 = 184.06, p &amp;lt; 0.0001). The odds ratio is 0.237, indicating that patients who received unfractionated heparin were 4.219 (1/0.237) times as likely to develop HIT as patients who received LMWH. When controlling for age, sex, and BMI, age was significantly associated with the likelihood of the patient being diagnosed with HIT (χ 2 = 8.423, p &amp;lt; 0.01). The odds ratio was 1.010, indicating that with each additional year of age, patients were 1.010 times as likely to develop HIT. BMI was also significantly associated with likelihood of HIT (χ2 = 4.892, P &amp;lt; 0.03), indicating that obesity was identified as a potential factor associated with the development of HIT. Female were less likely to develop HIT when compared to men overall (χ2 = 7.238, P &amp;lt; 0.05). Conclusions: HIT is a rare but important cause of morbidity and mortality in patients exposed to heparin containing products. This study explored the profile of HIT incidence in non-surgical patients receiving UFH versus LMWH and in young versus older age groups. Here we provide evidence that a long-standing understanding regarding the incidence of HIT in surgical patients holds true in strictly non-surgical patients. Additionally, we have acquired evidence that age may very well play a role in HIT.

When HIT Testing Hurts- the Financial and Clinical Repercussions of Heparin Induced Thrombocytopenia Testing: A Single Center Analysis

Introduction: Thrombocytopenia is a common inpatient hematologic concern. Most often, thrombocytopenia is a multifactorial phenomenon, without one clear cause. Heparin Induced Thrombocytopenia (HIT) is a rare but serious hematologic consequence of exposure to heparin. In many hospitalized patients, heparin is routinely used as venous thromboembolism (VTE) prophylaxis or for therapeutic anticoagulation. The incidence of HIT is approximately 0.5-1.0% in patients exposed to unfractionated heparin (UFH). Though rare, there seems to be over-testing of HIT antibody in the inpatient setting. As such, there is potential for high cost with low yield and false positives that alter patient management, resulting in prolonged hospital stays and further complications in patient care. Methods: This was a retrospective, observational study reviewing the indications, results, and patient characteristics of cases in which HIT testing was ordered. Indications for testing and influence of results on management were determined based on clinical documentation. The tests of interest included HIT antibody testing and Seratonin Release Assay (SRA). We analyzed how many times a HIT antibody was positive with a negative result in the SRA. We also determined whether there was an increased length of stay in patients who had HIT testing ordered. The study population included patients who were admitted to University of Florida Shands Medical Center, an academic institution in Jacksonville, FL in 2022. All patients were &amp;gt;18 years of age. Results: 190 patients were identified, for whom 190 HIT antibody tests were ordered and 75 SRAs. All patients who had a SRA performed had exposure to low dose heparin or therapeutic high dose heparin. Out of 190 patients, HIT testing was positive in 30 patients (15.8%). SRA testing was performed on 75 patients despite only 30 positive HIT tests. The true positives were 10 patients who had positive SRA confirmatory testing out of 190 patients with suspected HIT. Based on the results of confirmatory testing, the false positive fraction of HIT testing was 66%. When analyzing the 190 patients who underwent HIT testing, the average length of stay was 14 days. On average, a hospital stay in the US is 5.5 days and evaluation of HIT results in 8.5 additional days of hospital admission at our institution. The prolonged length of stay for HIT testing is likely impacted by awaiting SRA results along with other factors. Conclusion: This analysis examines the relative over-testing for HIT at a single institution. Compared with the known incidence of positive HIT tests, there is a significant number of positive HIT antibody tests at our hospital. The data further reveals a high probability of a false positive HIT antibody test results in the hospitalized patient, possibly due to immune reactivity. Of 190 patients suspected with HIT, only 10 patients had a positive confirmatory SRA, indicating that only 5% of suspected patients truly had HIT. This demonstrates that 95% of the time HIT assays ordered did not provide clinically useful information. From the time work up was initiated to the time of discharge, the average stay length was 14 days in a patient suspected with HIT. Cost burden of HIT testing was evaluated. Each HIT panel is $153.83 and each confirmatory SRA test is approximately $250, at a commercial laboratory. Taken together, the total average cost per patient with suspected HIT is $413.83 in diagnostic testing. Prolonged hospital stay contributes to approximately $25,000 increase in hospital stay per patient being evaluated for HIT. This does not include the cost of further work up or interventions. Changing to an alternate anticoagulant such as Argatroban increased costs by nearly $1,500 per case and this number increased further when adding the daily coagulation panel required while on this drug. In other studies, this cost has been estimated to add $90,000 to the hospital stay. Prolonged hospital stays are also associated with unintended incidents such as GI bleeding leading to blood transfusions, invasive testing (such as endoscopy/colonoscopy) and increased morbidity to the patient. We will use this information to implement a tool in our Electronic Medical Record (EMR) that will require answering the 4T score in order to establish high pre-test probability, prior to ordering HIT antibody testing at the University of Florida in Jacksonville.

Incidence and clinical outcomes of heparin-induced thrombocytopenia: 11year experience in a tertiary care university hospital.

Heparin-induced thrombocytopenia (HIT) is a rare immuno-mediated adverse reaction with high thrombotic and mortality risk. To evaluate incidence and outcomes of HIT cases diagnosed at a tertiary care hospital from 2007 to 2018. A retrospective study was conducted. Patients with suspected HIT underwent 4Ts score assessment and anti-heparin PF4 IgG antibodies ELISA screening test. If the latter was positive, platelet aggregation test (PAT) was performed. If the latter was positive, any form of heparin was stopped, alternative anticoagulants were started and then overlapped with warfarin. HIT incidence was calculated by dividing HIT cases by the mean yearly number of admitted patients over 11years. Follow-up was 90days. Among 2125 screening tests, 96 (4.5%) were positive with confirmatory PAT in 82/90 (3.8% for missing data in 6). Median age was 75; 39 patients were surgical and 51 medical. The median 4Ts score was 5. Unfractionated heparin was employed in 34 (37%). HIT incidence was 0.16/1000/patient/years (95% CI: 0.12-0.23) in surgical and 0.15/1000/patient/years (95%: 0.12-0.20) in medical patients. HIT with thrombosis (HIT-T) was observed in 31 patients (0.05/1000/patient/years 95% CI: 0.04-0.1), with venous thromboses in 25 (80%). HIT without thrombosis was observed in 59 patients (0.1/1000 patient/years; 95% CI: 0.08-0.13, twofold vs HIT-T). All cause mortality was 25.5% (95% CI: 17.6-35.4), major bleeding 7.7% (95% CI:3.2-15.3), and thromboembolic complications 3.3% (95% CI:1.1-9.3). HIT is a rare event with high mortality, despite the use of non heparin anticoagulants.

Heparin Induced Thrombocytopenia - Pathophysiology, Diagnosis and Treatment: A Narrative Review.

Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated complication following heparin exposure and is considered to be the most severe adverse reaction to heparin treatment that is not associated with bleeding. Development of autoantibodies against platelet factor 4 (PF4) - heparin complex constitutes the basis of the pathophysiological changes in patients suffering from HIT, which then binds to the surface of platelets and monocytes, thus provoking their activation and subsequent aggregation, ultimately leading to the formation of thrombosis. Formation of arterial and venous thrombosis is aggravated by the simultaneous activation of platelets and monocytes with a substantial mortality rate. The incidence of HIT is reported to be significantly lower in pediatric patients compared with adults. Diagnosis of HIT in pediatric population remains a clinical entity supplemented by laboratory evaluation. The positive predictive value of laboratory evaluation is further elevated by the use of scoring systems and predictive models used for hastening the diagnosis of HIT. Use of alternative anticoagulants like direct thrombin inhibitors and factor Xa inhibitors form the mainstay of treatment in cases of HIT, however, more prospective studies would be required in the pediatric population to delineate definitive guidelines for proper management of patients in this age-group. This article delivers diagnostic and treatment approach in case of patients with HIT, wherein the pathophysiology, clinical manifestations, diagnostic approach and the management of patients with HIT has been described.

Heparin-Induced Thrombocytopenia in Chronic Hemodialysis Patients.

Heparin-induced thrombocytopenia (HIT) is a disorder originating from exposure to heparin and has a spectrum of presentation ranging from asymptomatic positive antibodies to thrombotic complications. When symptomatic, it is associated with morbidity and mortality. The incidence of HIT in the ESRD population is yet to be defined. End-stage renal disease (ESRD) patients are at particular risk due to constant exposure to heparin. The main treatment of HIT is to avoid heparin and pursue alternative anticoagulants. Since 1 of the main advantages of heparin in ESRD patients is the ease of its use due to non-renal clearance, the use of alternative anticoagulants poses yet another challenge for this population due to cost, availability, and adverse effects on ESRD patients. Argatroban seems like the best alternative to heparin in hemodialysis (HD) patients due to its liver clearance. Despite having limited studies in HIT, direct oral anticoagulants (DOACs) were added as a potential treatment for HIT, with apixaban favored in kidney dysfunction as it is the least dependent on kidney clearance. Other treatment modalities exist but are still being studied in ESRD patients. The presence of HIT antibodies is not always associated with clinical syndrome, and some studies suggested that heparin antibodies are transient, and the reintroduction of heparin is still being evaluated as a treatment option. Hence, HIT is a challenging diagnosis in ESRD patients, a population that has frequent exposure to anticoagulants, and a risk/benefit ratio should be weighed between the risk of progression to symptomatic HIT and the benefit of switching to a non-heparin anticoagulant bearing in mind the difficulties associated with the latter.

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 &lt; 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 (HIT) in patients with severe COVID-19

Abstract Introduction To prevent and treat thrombotic complications in patients hospitalized with severe COVID-19 infection, anticoagulation treatments primarily with heparin and low molecular weight heparin have been recommended. Heparin-induced thrombocytopenia (HIT) is a rare but conceivably fatal reaction to heparin that is characterized by a sudden drop in platelet count accompanied by new onset of thrombosis 4-10 days after heparin exposure. The purpose of this retrospective study was to investigate the prevalence of thrombocytopenia and HIT in hospitalized COVID-19 patients, as well as their association with mortality. Methods 3,672 plasma samples were collected from patients admitted to the first wave of COVID-19 in our institution at New York City (March to May 2020). All patients admitted with a platelet count of less than 150 k/ul were assigned to the thrombocytopenic group. In addition, two groups with similar demographics and normal platelet counts were randomly selected based on discharge outcome: alive vs. deceased (n= 88 per group). PF4 IgG Elisa and heparin neutralization were carried out in accordance with the manufacturer's instructions. A positive HIT result required an optical density (OD) greater than 0.4 and heparin neutralization greater than 50%. Statistical analysis was done in R studio (V.1.4.1717) to analyze demographics (age, gender, ethnicity), initial laboratory data, anticoagulation on admission, and thrombosis. Results Only 86 of the 3,672 (2.3%) patients admitted had thrombocytopenia. Only 1 of the 86 patients tested positive for HIT (1.1% ). 4 cases of the non-survivors (4.5%) tested positive for HIT compared to none of the survivors in the two groups with normal platelet counts. One of these 4 cases had a history of thrombosis (DVT). Interestingly, the PF4 Elisa ODs in non-survivors were significantly higher than in survivors (0.09 vs. 0.06, p-value&amp;lt; 0.001). Although the platelet count did not differ significantly between the two groups, the mean platelet volume (MPV) on admission and its maximum peak during hospitalization were significantly higher in non-survivors than in survivors. Conclusions We only found HIT positive cases among non-survivors, implying that HIT is associated with COVID severity. The incidence of HIT in severe COVID-19 patients appears to be higher than the pre-COVID-19 historical rates of HIT in hospitalized patients (&amp;lt;1%). Although thrombocytopenia is relatively uncommon in COVID-19 patients, the MPV was significantly higher in non-survivors, suggesting that platelet activation and destruction may explain the higher rate of HIT in COVID-19.

Early‐onset heparin‐induced thrombocytopenia after cardiac surgery: Should we lose sleep?

Unfractionated heparin remains the preferred anticoagulant, bar none, for cardiac surgery requiring cardiopulmonary bypass (CPB).1 With the ubiquitous use of unfractionated heparin and the universal fall in platelet count that accompanies CPB, concern for heparin‐induced thrombocytopenia (HIT) arises frequently following cardiac surgery, even though the incidence of HIT in this setting is only 0.5%–1%.2

Comparison of HIT Tests in Patients with COVID-19 and Thrombocytopenia.

Thrombosis and coagulopathy have been found to be the most prevalent complications in patients with COVID-19. Thromboprophylaxis to prevent thromboembolic events is recommended for hospitalized COVID-19 patients. Heparin-induced thrombocytopenia (HIT) is a known complication of heparin use. This study aimed to determine the incidence of HIT among admitted patients with confirmed COVID-19 by PCR. In this study, two different HIT assays, rapid immunoassay (STic Expert HIT, Stago) and H-PF4 specific enzyme-linked immunosorbent assay (Asserachrom® HPIA – IgG), were performed. Of 200 patients with confirmed COVID-19, we identified 49 patients who met the possibility of HIT (low platelet count and high D-Dimer level). Only five (10.2%) had a positive HIT rapid test. However, none of the tested samples tested positive by ELISA. Thrombosis was reported in two of five (40%) patients. Further extensive studies are required to determine the prevalence and clinical significance of a positive HIT test among patients with COVID-19.

Abstract 10166: Incidence and Outcomes of Heparin-Induced Thrombocytopenia Among Patients Undergoing Left Ventricular Assist Device Implantation

Background and Objectives: Heparin-induced thrombocytopenia (HIT) increases the risk of thromboembolic and bleeding events. HIT is also a well-known complication in patients undergoing left ventricular assist device (LVAD) implantation, although most studies are limited to case reports/series and single-center experiences. The main objective of this study is to examine the incidence and impact of HIT on outcomes in LVAD implants using a nationwide database. Methods: Using the National Inpatient Sample database (2007-2014), we identified patients ≥ 18 years that underwent LVAD implants using ICD-9 codes. LVAD implants were stratified by the presence of HIT. The primary and secondary endpoints were the impact of HIT on mortality and other outcomes respectively. Results: Out of the 15,083 LVAD implantations, HIT occurred in 331 (2.2%). Although not statistically significant, the annual incidence of HIT rose from 1.3% in 2009, peaked at 3.3% in 2012 and decreased to 2.0% (ptrend = 0.6171). In-hospital mortality (OR 2.21, 95% CI 1.30-3.74, p = 0.0034) and post-operative DVT/PE (OR 2.45, 95% CI 1.09-5.51, p = 0.0303) were significantly associated with HIT. Our analysis did not show any differences in the incidence of vascular complications, post-op stroke/TIA, hemorrhage requiring transfusion and acute kidney injury between HIT and non-HIT group. The HIT group stayed longer in the hospital (30 vs 27 days, p &lt; 0.0001) and incurred higher total hospital charges ($695,834 vs. $640,089 p &lt; 0.0001). Conclusion: Among patients undergoing LVAD implants, HIT was associated with higher risk of in-hospital mortality, post-op DVT/PE, higher hospital charges and longer hospital stay.

Rivaroxaban and apixaban for the treatment of suspected or confirmed heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an adverse hematologic drug reaction that results in thrombocytopenia. This potentially life-threatening event is due to the administration of heparin products, such as unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). The incidence of HIT occurs in <0.1%-7% of hospitalized patients treated with heparin products, with a risk of thrombosis as high as 50%. In 2018, the American Society of Hematology (ASH) recommended the utilization of direct oral anticoagulants (DOACs) in clinically stable patients at average bleeding risk with HIT. The objective of this study was to evaluate the prescribing patterns of rivaroxaban and apixaban for the treatment of suspected or confirmed HIT. This was a retrospective chart review from January 2013 through October 2019 at the University of Chicago Medicine. Twelve patients were identified to have received a DOAC for suspected or confirmed HIT. Rivaroxaban was utilized in seven (58%) patients, six of whom received argatroban prior to starting rivaroxaban. Five (71%) of these patients were started on the recommended dose of rivaroxaban for VTE. Apixaban was utilized in five (42%) patients; four patients were started on argatroban and transitioned to apixaban. One patient was started on the suggested dose of apixaban for VTE. After starting DOACs for suspected HIT, no patients had new thrombosis during hospitalization. Eight patients (67%) followed up at our institution within 6months of their discharge date. No subsequent thrombi formation were identified for any of these patients. The results of this study add to the expanding literature regarding the safety and efficacy of DOAC use in HIT, and indicate DOACs are being increasingly utilized for the treatment of confirmed or suspected HIT.

ACUTE HEPARIN-INDUCED THROMBOCYTOPENIA WITH DELAYED IN-STENT SUBACUTE THROMBOSIS OF DRUG ELUTING STENTS, INTRACARDIAC THROMBOSIS, BIVENTRICULAR HEART FAILURE, AND HYPOXIA

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a fatal complication in patients with an average exposure of one to two weeks or can be rapid (< 24hrs) on re-exposure. In susceptible patients, antibodies directed against platelet factor 4 and heparin complexes cause HIT with thrombosis (HITTS). An average incidence of HIT is 0.1%-5% in patients on heparin therapy [1] CASE PRESENTATION: A 73-year-old female with a history of coronary disease, hypertension, and hyperlipidemia came to an outside hospital with a persistent cough, dyspnea, and acute hypoxia. She was treated for acute heart failure exacerbation and non-ST segment elevation myocardial infarction (NSTEMI) based on workup. An echocardiogram (ECHO) revealed an ejection fraction (EF) of 50%. She underwent staged percutaneous coronary intervention (PCI) and placement of an everolimus-based stent in the left anterior descending artery (LAD) followed by another stent in the left circumflex artery (LCX) after three days. Following stent placements, she went into pulmonary edema and was placed on noninvasive ventilation and was transferred to our institute to further manage acute hypoxic respiratory failure. Her hypoxia worsened, requiring endotracheal intubation, vasopressor support. She was treated for heart failure exacerbation and pneumonia. A repeat ECHO revealed two right ventricular thrombi with a severe decline in biventricular EF (Figure A). Anticoagulation with heparin was started, followed by a decline in platelet count > 50% due to HIT on day two, and was switched to argatroban (Figure B). Blood work showed NSTEMI, and a coronary angiogram revealed in-stent thrombosis of both stents (Figure C). Repeat successful PCI to LAD, and LCX with thrombus aspiration was completed. The patient had a complicated clinical course and never recovered DISCUSSION: As age increases, the risk of HIT gets higher [1]. HIT increases early mortality by 50% and embolic events by 20%-50%[2,3]. An increased HIT risk in females with cardiopulmonary bypass, hemodialysis, and vascular surgery was observed [4]. Venous thrombosis may be associated with surgery and arterial thrombosis with cardiovascular disease [5]. HIT antibody rate in patients with ACS is high and can induce symptoms in the absence of thrombocytopenia [6]. The odds of early stent thrombosis are < 1%[7]. The occurrence of thrombosis during therapeutic heparin anticoagulation is a concern for HITTS regardless of platelet counts and duration of therapy. Acute NSTEMI due to in-stent and intracardiac thrombosis due to HITTS is rare CONCLUSIONS: HITTS should be suspected in coronary thrombosis of unknown origin. Immediate heparin discontinuation and alternate anticoagulation are a must in HITTS, which can present with normal platelet counts REFERENCE #1: Hogan M, Berger JS. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vasc Med. 2020;25(2):160-73 REFERENCE #2: Solanki J, Shenoy S, Downs E, Palkimas S, Goldman S, Sharma AM. Heparin-Induced Thrombocytopenia and Cardiac Surgery. Semin Thorac Cardiovasc Surg. 2019;31(3):335-44 REFERENCE #3: Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program. 2006;408-414. doi:10.1182/asheducation-2006.1.408 DISCLOSURES: No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Tushar Tarun, source=Web Response No relevant relationships by Ritika Verma, source=Web Response

Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly Implanted Mechanical Circulatory Support Devices.

Heparin exposure and device-related thrombocytopenia complicate the diagnosis of heparin-induced thrombocytopenia (HIT) in patients receiving mechanical circulatory support (MCS). To improve anticoagulation management for patients with newly implanted MCS devices, incidence of confirmed HIT needs to be further characterized. The purpose of this study is to describe the incidence of HIT and clinical utility of the 4Ts score in patients with newly implanted MCS devices. This is a retrospective analysis of MCS patients receiving unfractionated heparin from 2014 to 2017. The primary end point was incidence of laboratory-confirmed HIT. Strong positive, likely positive, low probability, and negative HIT categories were established based on heparin-induced platelet antibody (HIPA) and serotonin release assay (SRA). Secondary end points include characterization of platelet trends, argatroban use, incidence of HIT among each of the MCS devices, and utility of 4Ts score. A total of 342 patient encounters met inclusion criteria, of which 68 HIPA tests and 25 SRAs were ordered. The incidence of HIT was 0.88% (3/342) and 4.4% (3/68) in patients with suspected HIT. Of the 68 HIPA tests, 3 (4.4%) were considered strong positive and 3 of the 25 SRAs were positive. Median 4Ts score was 4 [2.5-4] and optical density 0.19 [0.11-0.54]. The positive predictive value for the 4Ts score was 0.15 (CI = 0.03-0.46) and negative predictive value, 0.93 (CI = 0.82-0.98). HIT occurs infrequently with newly implanted MCS devices. The 4Ts score appears to have a high negative predictive value for ruling out HIT.

Diagnosis and Management of Heparin Induced Thrombocytopenia — Are We Choosing Wisely?

Introduction :Thrombocytopenia is a common problem in hospitalized patients. One of the rare but fatal causes of thrombocytopenia is Heparin Induced Thrombocytopenia (HIT), a complex immune disorder in which heparin leads to the production of IgG antibodies, targeting platelet factor 4 (PF4). Not diagnosing HIT when it is present or mistakenly diagnosing HIT when it is absent, both carry significant risks (eg, life-threatening thrombosis or life-threatening bleeding, respectively). Various institutional reviews have reported that clinicians tend to have a high suspicion and low threshold to order laboratory workup for HIT though the incidence of HIT is noted to be only 5%. The American Society of Hematology Choosing Wisely Guidelines 2014 recommend against testing for HIT in individuals at low risk, defined by a 4T score ≤ 3.The primary objective of our study was to examine compliance with guidelines at our institution. Secondary objectives were to assess correlation between 4T's score, HIT antibody and Serotonin Release Assay (SRA) in diagnosis of HIT, impact of Hematology consult on following appropriate guidelines.Methods:Patients with requests for HIT antibody testing between 1/1/2015 - 12/31/2016 were identified from laboratory records. A retrospective chart review was conducted on 92 patients who met criteria. Data collected included admitting department, clinical probability based on 4T's score, result of HIT antibody including optical density (OD), result of SRA, placement of Hematology consult, initiation of novel anticoagulant (NOAC). Using the algorithm below (Fig 1) , compliance with guidelines was analyzed. Data were tabulated by means of simple frequencies for single items, or in 2- or 3-way combinations.Results:Of the 92 charts reviewed, 38 (41.3%) patients had a low clinical probability based on 4T's score and yet had HIT antibody test ordered (table 1). Of these, heparin was stopped in 21 (55.3%) patients and NOAC was initiated in 10 (26.3%) patients (table 2) which is not recommended as per existing guidelines. Interestingly, of the 38 patients with low probability, 19 (50.0%) had OD between 0.4 - 1.99 with 1 positive SRA. Among 43 (46.7%) patients with intermediate clinical probability, 29 (47.5%) patients were HIT positive. Of these, 18 patients with OD < 2 and 21 patients with OD between 0.4 - 1.99 had SRA ordered which is not in compliance with guidelines, however 6 of these patients had positive SRA. 11 (12%) of the 92 patients had high clinical probability, and of these, in patients with OD> 2, SRA was positive 100% of the times; where as in patients with OD between 0.4 - 1.99 SRA was positive only in 45.5% patients. Hematology oncology service was consulted for 44 (47.8%) patients with positive HIT of which 7 had high probability, 22 had intermediate probability and 15 had low clinical probability; heparin was stopped and NOAC was initiated in 5(71%), 12 (54%), and 8 (53%) patients in each of these groups respectively which once again is not in compliance with existing guidelines. Majority of patients were admitted to ICU, however only 3.8% of ICU patients who had HIT antibody ordered had confirmed diagnosis of HIT.Conclusion:Compliance with Choosing Wisely Guidelines and recommended diagnostic algorithm for HIT at our institution is low, and potentially associated with significant harm to the patient due to overtesting and overtreatment. Hematology Oncology consult did not necessarily improve compliance with guidelines, although decision about NOAC were made prior to consult in most cases. However, while there was concern for overdiagnosis and wasteful resources, our study also noted that there were few patients with low clinical probability and intermediate clinical probability with OD between 0.4-1.99 with positive SRA. Limitations of our study is the small sample size and single institution based data. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cost Reduction with Enoxaparin Vs. Heparin for Prophylactic and Therapeutic Use: A Retrospective Analysis in a Community Hospital Setting

BackgroundMost hospitals still use Unfractionated Heparin as the primary agent for Venous Thromboembolism (VTE) prophylaxis and therapy in the inpatient setting due to ease of use and insignificant cost. However, the incidence of Heparin-Induced Thrombocytopenia (HIT) has led to questions about other options for prophylaxis and therapeutic use in the hospital, with more recent data showing that Enoxaparin is safer in terms of incidence of HIT. This study examines the cost-effectiveness of Enoxaparin compared to Heparin for prophylactic and therapeutic usage in a community hospital.MethodsWe conducted a retrospective chart review of patients that had HIT panels ordered at the Inspira Health Network, Vineland campus (an approximately 262 bed community hospital located in southern New Jersey that services a population of approximately 61,050) from the period of April 1, 2015 through December 31, 2016. The starting date represents the time from which Enoxaparin became the primary alternative anticoagulant available at this hospital. Records of the total usage and cost of Heparin and Enoxaparin for the specified time period were collected from the hospital pharmacy database for evaluation, as were records of Heparin-Induced Thrombocytopenia (HIT) panels. The information was analyzed to establish whether or not a significant proportion of HIT panels was ordered for patients on Heparin versus Enoxaparin. Annual cost-savings for the hospital were extrapolated by using the comparative incidences of HIT panels and associated costs, including increased inpatient length of stay, hematology consultation, use of an alternative anticoagulant, and complications of Heparin-Induced Thrombocytopenia and Thrombosis (HITT). These variables were multiplied by the incidence rate for each specified drug and usage in order to determine the daily cost for each drug.ResultsThe overall use of Enoxaparin did not result in a significant decrease in the ordering of HIT panels in the hospital, with a relative rate ratio of 0.948 (95% Confidence Interval: 0.336, 2.21). However, when the data was stratified to reflect prophylactic and therapeutic usages of Enoxaparin and Heparin, there was a marked difference in the use of therapeutic Intravenous (IV) Heparin as opposed to therapeutic Enoxaparin. The rate ratio of HIT panel ordering when using therapeutic Enoxaparin instead of IV Heparin was 0.118 (0.006, 0.625). These numbers were used to extrapolate the total daily cost of Enoxaparin and IV Heparin; therapeutic Enoxaparin cost $30.62, while IV Heparin cost $161.94. IV Heparin use was associated with a higher incidence rate of HIT panel orders, and subsequently a higher daily cost due to the likelihood of increased length of stay, use of alternative anticoagulation, request for expert consultation, and complication of HITT.ConclusionEnoxaparin is associated with a significant cost-saving when used for therapy for patients with venous thromboembolism, when compared to IV Heparin. DisclosuresNo relevant conflicts of interest to declare.

Recent Trends in the Incidence of Heparin-Induced Thrombocytopenia: Data from the 2009-2014 National Inpatient Sample

BackgroundUse of Low-Molecular Weight Heparin (LMWH) has increased in the US hospitals after the release of generic enoxaparin in 2010. Quality improvement projects and various professional bodies have advocated the use of LMWH over unfractionated heparin because of its superiority over unfractionated heparin for VTE prevention and because of its decreased incidence of Heparin-induced thrombocytopenia (HIT). We used a large administrative database to assess the recent trends of HIT to assess the impact of these interventions in adult hospitalized patients.MethodsWe used the 2009-2014 National Inpatient Sample database, which is the largest publicly available all-payer inpatient database in the US, to identify patients ≥18 years with primary and secondary diagnoses of HIT (International Classification of Diseases, 9th Revision, Clinical-Modifications [ICD-9-CM] code 289.84). Annual incidence of HIT was calculated for each year 2009-2014, fitted into a log-linear model and compared using Monte Carlo permutation test to study the changes in trend. Statistical analyses were done using STATA version 13.0 and Joinpoint Regression Program version 4.5.0.1.ResultsA total of 129,761 adult patients with a diagnosis (both primary and secondary) of HIT were identified during the study period. The proportion of patients who developed HIT was unchanged at 0.06 cases per 100 admissions with an annual percent change (APC) of -2.1 which was statistically not significant (95% CI: -5.7 to 1.6, p=0.02) (Figure 1). Despite the increasing awareness and ease of testing for HIT, the annual incidence of HIT with thromboses (HITT) also remained unchanged (Figure 2). There was however, an increasing total cost of hospitalization from $132,535 in 2009 to $174,253 in 2014 (APC: 6.17, 95% CI: 4.1 to 8.3, p<0.05) even when adjusted for yearly inflation (Consumer Price Index, Bureau of Labor Statistics). However, overall inpatient mortality and length of stay remained unchanged at 9.5% and 13.7 days (Table 1).ConclusionDespite ongoing push towards use of LMWH and country-wide quality improvement projects to encourage the use of LMWH over UFH in hospitalized patients, our data shows that the incidence of HIT remains unchanged from 2009 to 2014. Similarly, the rates of HITT and outcomes (mortality and length of stay) remain unchanged. Given the rising healthcare costs of HIT admissions and flat incidence curves, the need for more effective preventative and early diagnostic strategies, along with cost effective management options are urgently warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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.