Rates Of Heparin-induced Thrombocytopenia Research Articles

Heparin-induced thrombocytopenia associated with low-molecular-weight heparin: clinical feature analysis of cases and pharmacovigilance assessment of the FAERS database.

Background: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used anticoagulants for the management of arterial and venous thromboses. However, it is crucial to be aware that LMWH can, in rare cases, lead to a dangerous complication known as heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the pharmacovigilance and clinical features of HIT associated with LMWH, as well as identify treatment strategies and risk factors to facilitate prompt management. Methods: We extracted adverse event report data from the FDA Adverse Event Reporting System (FAERS) database for pharmacovigilance assessment. Case reports on LMWH-induced thrombocytopenia dated up to 20 March 2023 were collected for retrospective analysis. Results: Significantly elevated reporting rates of HIT were shown in adverse event (AE) data of LMWHs in the FAERS database, while tinzaparin had a higher proportional reporting ratio (PRR) and reporting odds ratio (ROR) than other LMWHs, indicating a greater likelihood of HIT. Case report analysis indicated that a total of 43 patients showed evidence of LMWH-induced thrombocytopenia with a median onset time of 8days. Almost half of the events were caused by enoxaparin. LMWHs were mainly prescribed for the treatment of embolism and thromboprophylaxis of joint operation. Patients with a history of diabetes or surgery appeared to be more susceptible to HIT. Clinical symptoms were mostly presented as thrombus, skin lesion, and dyspnea. Almost 90% of the patients experienced a platelet reduction of more than 50% and had a Warkentin 4T score of more than 6, indicating a high likelihood of HIT. In all patients, LMWHs that were determined to be the cause were promptly withdrawn. Following the discontinuation of LMWHs, almost all patients were given alternative anticoagulants and eventually achieved recovery. Conclusion: LMWH-induced thrombocytopenia is rare but serious, with increased risk in patients with diabetes or a surgical history. Prompt recognition and management are crucial for the safe use of LMWHs.

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< 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 (<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.

The Effect of Digitization on the Safe Management of Anticoagulants.

Background Anticoagulants are high-risk medications and are a common cause of adverse events of hospitalized inpatients. The incidence of adverse events involving anticoagulants has remained relatively unchanged over the past two decades, suggesting that novel approaches are required to address this persistent issue. Electronic medication management systems (eMMSs) offer strategies to help reduce medication incidents and adverse drug events, yet poor system design can introduce new error types. Objective Our objective was to evaluate the effect of the introduction of an electronic medical record (EMR) on the quality and safety of therapeutic anticoagulation management. Methods A retrospective, observational pre-/poststudy was conducted, analyzing real-world data across five hospital sites in a single health service. Four metrics were compared 1-year pre- and 1-year post-EMR implementation. They included clinician-reported medication incidents, toxic pathology results, hospital-acquired bleeding complications (HACs), and rate of heparin-induced thrombocytopenia. Further subanalyses of patients experiencing HACs in the post-EMR period identified key opportunities for intervention to maximize safety and quality of anticoagulation within an eMMS. Results A significant reduction in HACs was observed in the post-EMR implementation period (mean [standard deviation [SD]] =12.1 [4.4]/month vs. mean [SD] = 7.8 [3.5]/month; p = 0.01). The categorization of potential EMR design enhancements found that new automated clinical decision support or improved pathology result integration would be suitable to mitigate future HACs in an eMMS. There was no significant difference in the mean monthly clinician-reported incident rates for anticoagulants or the rate of toxic pathology results in the pre- versus post-EMR implementation period. A 62.5% reduction in the cases of heparin-induced thrombocytopenia was observed in the post-EMR implementation period. Conclusion The implementation of an EMR improves clinical care outcomes for patients receiving anticoagulation. System design plays a significant role in mitigating the risks associated with anticoagulants and consideration must be given to optimizing eMMSs.

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.

Predictive value of HIT-antibodies detection for new thrombosis in heparin-induced thrombocytopenia

Objective To investigate the predictive value of HIT-antibodies(HIT-Ab) detection for new thrombus in suspected Heparin-Induced thrombocytopenia (HIT). Methods Retrospective cohort study. 472 suspected HIT patients were collected from July 2016 to November 2018, and all subjects underwent a 4Ts score and were sent for HIT-Ab tests. According to the results of HIT-Ab, there were four groups: 412 cases of negative HIT-Ab (0-0.9 U/ml), 45 cases of weak-positive HIT-Ab (1.0-4.9 U/ml), 12 cases of moderate-positive HIT-Ab (5.0-15.9 U/ml), and 3 cases of strong-positive HIT-Ab (≥16.0 U/ml) respectively. Ultrasound or CT examination was used to confirm new thrombosis as a standard to evaluate the value of HIT-Ab for predicting new thrombus. The diagnostic efficacy of HIT-Ab for HIT was evaluated in clinically confirmed HIT. Results The incidence rates of new thrombus in each group were: 15.8% in Negative HIT-Ab group (62/412), 48.9% in Weak-positiveHIT-Ab group (22/45), 75.0% in Moderate-positive HIT-Ab group (9/12), and100% in Strong-positive HIT-Ab group (3/3) (P<0.00) . When HIT-Ab≥1.0 U/ml, the specificity for diagnosing new thrombus was 93.0%, the sensitivity was 34.2%, the negative predictive value (NPV) was 84.2%, and the positive predictive value (PPV) was 56.5%. The diagnostic rates of HIT in each group were: negative 0% (0/412), weak-positive 62.2% (28/45), moderate-positive (12/12) and strong-positive (3/3) were 100%. When HIT-Ab ≥ 1.0 U/ml, the specificity for HIT diagnosis was 96.0%, the sensitivity was 100%, NPV was 100%, and PPV was 71.5%. Conclusions In suspected HIT patients, the incidence of new thrombosis increases with the elevated HIT-Ab level. HIT-Ab detection can be used as a crucial tool for new thrombosis prediction and HIT diagnosis in suspected HIT patients. Clinicians can develop treatment strategies based on HIT-Ab levels. Key words: Thrombocytopenia; Autoantibodies; Heparin; Venous thrombosis; Forecasting

Anticoagulation of a Percutaneous Left Ventricular Assist Device Using a Low-Dose Heparin Purge Solution Protocol: A Case Series

Background Impella CP® is a percutaneous left ventricular assist device that requires a heparin–dextrose purge solution. The manufacturer recommends heparin 50 units/mL, but supratherapeutic anticoagulation has been observed with this concentration. Objective The purpose of this evaluation was to observe the efficacy and safety of a low-dose heparin-based purge solution (25 units/mL in dextrose 20%). The primary outcome evaluated percentage of activated clotting times (ACTs) below therapeutic range. Secondary objectives included evaluating the incidence of device thrombosis and rate of heparin-induced thrombocytopenia (HIT). Platelet trends were characterized. Methods A single-site retrospective review was conducted for all adults with the Impella CP from January 2015 to December 2017. Results A total of 18 patients were included. The percentage of ACT readings within goal of 160 to 200 seconds was 49%, and 38% of readings were subtherapeutic. Per BARC bleeding criteria, 22% (n = 4) patients experienced class IIIa bleeding and 39% (n = 7) experienced class II bleeding. Though 4 (22%) patients were tested for HIT, no patients were positive. Patients showed universal reductions in platelet counts. Conclusions The use of a low-dose anticoagulation protocol of heparin 25 units/mL in dextrose 20% as needed warrants further evaluation.

Cost reduction associated with heparin-induced thrombocytopenia panel ordering for enoxaparin versus heparin for prophylactic and therapeutic use: A retrospective analysis in a community hospital setting.

Background:Most hospitals still use unfractionated heparin (UFH) as the primary agent for venous thromboembolism (VTE) prophylaxis in the hospital setting due to ease of use and insignificant cost. However, the risk of heparin-induced thrombocytopenia (HIT) has led some groups to favor other options for therapeutic and prophylactic anticoagulation. This is particularly relevant in light of recent data demonstrating a lower rate of HIT in patients receiving enoxaparin compared with UFH. This study examines the cost-effectiveness of enoxaparin, compared to UFH for prophylactic and therapeutic usage in hospitals.Methods:We conducted a retrospective chart review of patients who underwent HIT panel testing at the Inspira Health Network, Vineland campus (an approximately 262-bedded 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 UFH and enoxaparin for the specified time period were collected from the hospital pharmacy database for evaluation, as were records of HIT panels. The information was analyzed to determine the frequency of HIT panel testing orders for patients receiving UFH versus those receiving enoxaparin. Annual cost-savings for the hospital were extrapolated using the comparative incidence of HIT panels and associated costs, including increased length of stay, hematology/oncology consultation, use of an alternative anticoagulant, critical bleeding requiring transfusion, and complications of HIT-associated thrombosis. These variables were multiplied by the incidence rate for each specified drug and usage to determine the daily cost for each drug.Results:The 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). When the data were stratified to examine prophylactic and therapeutic anticoagulation, there was a marked difference in the frequency of HIT testing. The rate ratio of HIT panel orders for patients receiving therapeutic enoxaparin rather than intravenous (IV) UFH was 0.118 (0.006, 0.625). These numbers were used to extrapolate the total daily cost of enoxaparin compared with IV UFH; therapeutic enoxaparin cost $30.66, while IV UFH cost $162.30. IV UFH use was associated with a higher incidence rate of HIT panel orders, and consequently a higher daily cost due to the likelihood of increased length of stay, use of alternative anticoagulation, bleeding requiring transfusion, and request for expert consultation.Conclusion:In this study, the use of enoxaparin was associated with a significant cost-saving over IV UFH when used for therapeutic anticoagulation, but this cost saving was not observed for prophylactic anticoagulation.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study.

In recent years, US hospitals have switched from use of unfractionated heparin to use of low-molecular-weight heparin, which is associated with lower risk of heparin-induced thrombocytopenia (HIT). In the study reported here, we retrospectively searched the Nationwide Inpatient Sample (NIS) for patients who were at least 18 years old and received a diagnosis of HIT between 2009 and 2011. Our goal was to get an updated perspective on the incidence and economic impact of HIT. We calculated the incidence of HIT overall and in subgroups of patients who underwent cardiac, vascular, or orthopedic surgery. We compared characteristics of patients with and without HIT and compared characteristics of patients with HIT with thrombosis (HITT) and HIT patients without thrombosis. Of 98,636,364 hospitalizations, 72,515 (0.07%) involved HIT. Arterial and venous thromboses were identified in 24,880 (34.3%) of HIT cases. Men were slightly more likely to have a HIT diagnosis (50.1%), but women had higher rates of HIT after cardiac surgery (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26-1.58) and vascular surgery (OR, 1.42; 95% CI, 1.29-1.57). Rates of HIT were 0.53% (95% CI, 0.51%-0.54%) after cardiac surgery, 0.28% (95% CI, 0.28%-0.29%) after vascular surgery, and 0.05% (95% CI, 0.05%-0.06%) after orthopedic surgery. HIT and HITT cases were significantly (P ⟨ 0.001) more likely than non-HIT cases to be fatal (9.63% and 12.28% vs 2.19%), and they had significantly higher costs and longer inpatient stays. HIT and especially HITT are associated with increased mortality, costs, and length of stay. Journal of Hospital Medicine 2017;12:94-97.

Use of "Big Data" to Define Disease Burden, Complication Rates and Healthcare Costs in Patients with Heparin Induced Thrombocytopenia (HIT)

Background: HIT is a life-threatening complication that occurs in a subset of heparin-treated patients. To our knowledge, a large population-based estimate of HIT disease burden, complication rates and economic cost has not been reported previously. Based on small studies, wide variations in the incidence of HIT has been observed in some patient populations. For example, among patients undergoing knee and hip arthroplasties, rates of HIT were reported to be less than 0.5% in some studies, but others, including a recent study suggest a much higher risk (Blood. 2016 25;127(8):1036-43). Similarly, rates of HIT reported in patients undergoing hemodialysis are highly variable, with some reporting an incidence as high as 3.9% (AJKD 1996; 28(1):82-5). To better address these discrepant findings and to benchmark disease burden and complication rates, we performed an analysis of the Nationwide Inpatient Sample (NIS).Methods: The NIS is a large inpatient healthcare database in the US. Unweighted, it contains data from >7 million hospital stays each year and weighted, it estimates >35 million hospitalizations. Full-year HIT data was available for 2009-2013, and this study period was queried to identify patients >18 years of age with a discharge diagnosis of HIT. Survey weighted domain analysis was conducted to estimate the incidence of HIT. HIT rates were also estimated in patients who underwent specific procedures (coronary artery bypass grafting [CABG, a known "high" risk setting for HIT development], hip and knee replacement, and dialysis. Incidence of thrombosis, bleeding, in-hospital mortality, and length and cost of hospitalization were also calculated. Outcomes in HIT patients were compared to those without HIT using ANOVA and Chi-squared test for continuous and categorical variables, respectively.Results: The annual HIT burden averaged ~22,000 annually over the study period with no change over that time frame (Fig 1A, p=0.1). The incidence of HIT was highest in patients undergoing CABG at 0.51%, followed closely by dialysis at 0.43% (Fig 1B). HIT rates were low in knee and hip arthroplasty at 0.02% each, even lower than the 0.07% overall rate of HIT for all patients (Fig 1B). The incidence of thrombosis was high in HIT (Fig 1B) with venous thrombosis being the most common type (17.9%), followed by pulmonary embolism (8.3%) and arterial thrombosis (2.3%) (Fig 1C), consistent with the relative incidence reported in the published literature. Rates of major bleeding in HIT is estimated to be 10-20% with direct thrombin inhibitor therapy. Our analysis yielded much lower major bleeding rates of 2.5% and 0.7% for gastrointestinal and intracranial bleeding, respectively (Fig 1D). In-hospital mortality in HIT was 9.5%, almost five times higher than in patients without HIT (Fig 1E). Notably, the length of hospitalization and cost of care were approximately 3x higher in patients with HIT compared to those without (Fig 1E & 1F).Conclusions: Surprisingly, HIT disease burden was large and unchanged during the study period averaging >20,000 cases annually. A recent study suggests that an "avoid unfractionated heparin" protocol can significantly decrease the incidence of HIT (Blood. 2016; 127(16):1954-9). Large scale interventions of this type may be needed to tackle this common disorder. Our data also suggests that rate of HIT in knee and hip arthroplasty are low, while in patients undergoing dialysis it is more common than generally believed. We found that thrombosis, a serious complication of HIT is a very common finding, but major bleeding rates were low. HIT also resulted in a disproportionate utilization of resources with costs per patient of ~ $150,000. There are important limitations with use of data from the NIS, where missing/miscoded information are concerns. Additionally, the NIS has no information on drug use. For example, HIT incidence in CABG includes all patients who underwent the procedure whether or not heparin exposure occurred (both off- and on-pump). In addition, rates of thrombosis may be overestimates as heparin may have been used to treat thrombosis in some patients and caused HIT with isolated thrombocytopenia. Despite these shortcomings, in addition to disease benchmarking, this information may aid healthcare providers and public health professionals plan and implement broad preventative and therapeutic interventions to tackle this dangerous yet common disease. [Display omitted] DisclosuresPadmanabhan:Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591; Fenwal (Fresenius Kabi): Research Funding; Terumo BCT: Consultancy, Honoraria; Mallinckrodt Pharmaceuticals: Consultancy, Honoraria; LEK Consulting: Consultancy, Honoraria; Schlesinger & Associates: Consultancy, Honoraria.

Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit.

The obese state has been linked to several immune-mediated conditions. Our objective was to examine the association of body mass index (BMI) with the diagnosis of heparin-induced thrombocytopenia (HIT). Prospectively collected data on patients in the surgical and cardiac intensive care unit suspected of having HIT between January 2007 and August 2014 were analyzed. Patients were categorized into five discrete BMI (kg/m) groups and compared. Data collected included Warkentin 4-T scores, antiplatelet factor 4 (anti-PF4OD) values, serotonin release assay values, and thromboembolic diseases. HIT positivity was defined as serotonin release assay value greater than 20%. Of 304 patients meeting inclusion criteria, mean (SD) age was 62.1 (16.5) years, 59% were male, and mean (SD) BMI was 27 (6) kg/m. Thirty-six (12%) were positive for HIT. Incidence of HIT increased progressively with BMI (0%, 8%, 11%, 19%, 36%; p < 0.001). Compared with patients with normal BMI, patients with a BMI of 30 kg/m to 39.9 kg/m had a 200% increase in the odds for HIT (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.20-7.54; p = 0.019), while patients with a BMI of 40 kg/m or greater had a 600% increase (OR, 6.98; 95% CI, 1.59-28.2; p = 0.012). After regression analysis, BMI remained an independent predictor of the development of HIT (adjusted OR per kg/m, 1.08; 95% CI, 1.02-1.14; p = 0.010). Anti-PF4OD values greater than or equal to 2.0 also increased with BMI (p < 0.001). In-hospital mortality increased significantly with BMI above normal (p = 0.026). Warkentin 4-T scores, deep venous thrombosis, pulmonary embolism, and stroke incidence did not correlate with changes in BMI. Increasing BMI seems to be strongly associated with increased rates of HIT in intensive care unit patients. Obesity is an important new clinical variable for estimating the pretest probability of HIT, and patient "thickness" could be considered a fifth "T" of the 4-T scoring system. Additional biochemical work is indicated to decipher the role of obesity in this immune-mediated condition. Prognostic/epidemiologic study, level III.

Medical and Economic Burden of Heparin-Induced Thrombocytopenia: Data from the National Inpatient Sample 2009-2011

▪BackgroundAlthough generally safe, heparin use can trigger an immune response in which platelet factor 4-heparin complexes set off an antibody-mediated cascade that can result in heparin-induced thrombocytopenia (HIT). Although older studies report incidences as high as 5% in high-risk subgroups of surgical patients, recent studies report a much lower incidence (0.02% of hospital admissions and <0.1-0.4% among patients exposed to heparin). As hospitals transition to the less immunogenic low molecular weight heparins, reassessment of the overall national burden of HIT would help inform needs for monitoring strategies for this potentially fatal complication of anticoagulation.MethodsWe used the 2009-2011 National Inpatient Sample database to identify patients aged ≥18 years with primary and secondary diagnoses of HIT (International Classification of Diseases, 9th Revision, Clinical-Modification [ICD-9-CM] code 289.84). We derived the prevalence rate of HIT overall as well as among subgroup of patients undergoing 3 types of surgeries (cardiac, vascular and orthopedic surgeries). We compared characteristics of patients diagnosed with versus without HIT, and HIT with thrombosis (HITT) versus those without thrombosis. Statistical analysis was performed using Stata 13.1, which accounted for the complex survey design and clustering. We used a 2-sided p- value of <0.05 to determine statistical significance.ResultsWe identified 72,515 cases of HIT among a total of 98,636,364 hospitalizations (0.07%). Arterial and venous thromboses were identified in 24,880 (34.3%) of cases with HIT. Males were slightly more likely to be diagnosed with HIT (50.12% vs. 49.88%, odds ratio, OR 1.48, 95% CI: 1.46-1.51), but females had higher rates of post-cardiac and vascular surgery-associated HIT (OR: 1.41, 95% confidence interval, CI: 1.26-1.58, p<0.001 and OR 1.42, 95% CI: 1.29-1.57, p<0.001 respectively). Prevalence rates of HIT among cardiac, vascular and orthopedic surgeries were 0.53% (95% CI: 0.51-0.54%), 0.28% (95% CI: 0.28-0.29%) and 0.05% (95% CI: 0.05-0.06%) respectively. Patients with HIT and HITT were significantly more likely to be fatal than cases without diagnosed HIT (9.63% and 12.28% versus 2.19% respectively, p<0.001), and have significantly higher costs ($137401 and $179735 versus $35905) and length of stay (14.07 and 16.51 days versus 4.76 days).ConclusionAlthough rates of HIT appear lower in the modern era of widespread low molecular weight heparin use, patients undergoing cardiac and vascular surgeries remain at significant risk. Even in recent years, one-third of patients with HIT develop thrombosis, which significantly increases mortality, cost and length of stay. Strategies to monitor and mitigate that risk in high-risk patients appear to be warranted.Table 1In-hospital mortality, mean LOS and Mean hospital charges for patients with heparin induced thrombocytopenia (HIT) and HIT with thrombosis (HITT)No HITHITPHIT without thrombosisHITTPIn-hospital mortality2.19%9.63% (OR 4.75, 95% CI 4.45-5.08)<0.0018.24%12.28% (OR 1.56, 95% CI 1.40-1.74)<0.001Mean LOS (days)4.76 (95% CI 4.71-4.82)14.07 (95% CI 13.67-14.48)<0.00112.80 (95% CI 12.38-13.23)16.51 (95% CI 15.96-17.06)<0.001Mean total hospital charge (USD)35905 (95% CI 34626- 37185)137401 (95% CI 129369-145433)<0.001115456 (95% CI 108251-122661)179735 (95% CI 168582-190889)<0.001HIT= Heparin induced thrombocytopenia; HITT= Heparin induced thrombocytopenia with thrombosis; LOS=Length of stay; USD=US Dollars. DisclosuresNo relevant conflicts of interest to declare.

The frequency of heparin-induced thrombocytopenia in Taiwanese patients undergoing cardiopulmonary bypass surgery

There are few studies on heparin-induced thrombocytopenia (HIT) reported from Taiwan and Asian countries. We conducted a prospective study to investigate the frequency of HIT in patients undergoing cardiopulmonary bypass surgeries. A cohort of 54 patients was enrolled from January 01, 2010 to October 31, 2011. Patients' clinical information was obtained for 4T score classification. Plasma (2-4mL) was also collected before surgery and on Days 5 and 10 following heparin administration during the bypass procedure. This was tested for anti-heparin/PF4 antibodies and functional assay using flow cytometry (FC). The mean platelet count for this cohort followed the expected pattern in the postoperative setting. Seven of the 54 (13%) patients had positive antibodies assays before bypass surgery. This increased to 32% on Day 5 and was markedly elevated to 63% on Day 10 after surgery. Only one of the 54 patients (1.8%) was found to have both positive antibody assay and platelet activation, but no clinical HIT/thrombosis developed. Our study is the first report on the rates of HIT in the setting of cardiopulmonary bypass surgery in Taiwan and demonstrated no clinical HIT occurrence, despite the high frequency of HIT antibody in our cohort.

More is Less: Extended Enoxaparin After Surgery for Inflammatory Bowel Disease - A Cost-based Decision-Analysis

Inflammatory Bowel Disease (IBD) patients undergoing colorectal surgery are at an increased risk of Venous Thromboembolism (VTE), particularly beyond 10 days post-op. Optimal VTE prophylaxis, however, is not well defined in this population. In cancer patients undergoing abdominopelvic surgery, several randomized trials suggested that extended therapy with enoxaparin was a more effective treatment strategy, while several decision analyses suggested subcutaneous heparin may result in more cost minimization. These previous studies were performed prior to the availability of generic enoxaparin and failed to incorporate rates of patient compliance. Thus we aimed to construct a cost minimization decision analysis which included these important factors in a population known to be at high-risk for VTE. We constructed a cost minimization decision model to evaluate four strategies for management of postoperative VTE risk after surgery for IBD: (1) inpatient subcutaneous heparin (SQH) 5000 units TID × 10 days; (2) inpatient enoxaparin 40 mg daily × 10 days; (3) SQH 5000 units TID × 30 total days (10 inpatient, 20 outpatient days); (4) enoxaparin 40 mg daily × 30 total days (10 inpatient, 20 outpatient days). Our model made the following assumptions: (1) no prior history of VTE; (2) only major bleeding required intervention; (3) 90% of major bleeds were treated medically with transfusion of 2 units PRBC and 10% required reoperation; (4) heparin-induced thrombocytopenia (HIT) occurred within the first 10 days of exposure. Rates of inpatient and outpatient VTE, adherence to outpatient treatment, and strategy specific complications including HIT and major bleeding for each strategy, were obtained from published literature and modeled. Costs (in US dollars), including costs of strategy specific complications, were based on published literature, institutional charges and average wholesale pricing. Sensitivity analyses were performed to account for uncertainty in estimates. In this model, extended duration prophylaxis with enoxaparin was associated with the greatest cost minimization with an estimated cost of $2,585, compared to extended SQH which cost $2,768. Inpatient-only prophylaxis with enoxaparin and SQH cost $2,944 and $3,267, respectively. Our model was sensitive to rates of VTE (Figure 1), rates of HIT, and drug costs (Figure 2). Sensitivity analysis revealed that the extended SQH strategy was associated with the most cost minimization when VTE rates with enoxaparin were >6.5% (vs. 5.7% in the base case) and costs of outpatient enoxaparin were >$712 (vs. $528 in the base case). SQH was also associated with the most cost minimization if patient adherence rates were >85% (vs. 65% in the base case). Our model, in contrast to previously published cancer surgery literature, suggests that in IBD patients extended duration prophylaxis with enoxaparin for a total of 30 days post-operatively would result in the greatest costminimization. This may be in part due to the availability of generic enoxaparin, reduced risk of HIT, and increased adherence with outpatient enoxaparin resulting in greater VTE prevention relative to SQH.

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Introduction: Heparin Induced Thrombocytopenia (HIT) in critically ill patients remains associated with increased morbidity and mortality. Yet, the burden of this disease in the intensive care unit (ICU) remains poorly understood. We sought to clarify the incidence of HIT in ICU patients. Hypothesis: HIT occurs infrequently in non-cardiac surgery ICU patients. Methods: We performed a prospective observational study in consecutive ICU patients who underwent HIT antibody testing (August 2009 – March 2012). The decision to pursue HIT diagnostically was left to the primary team. The enzyme immunoassay served as the initial screening test for HIT and by convention an optical density > 0.4 defined a positive test. The final diagnosis of HIT was confirmed by a serotonin release assay (SRA) which was performed in a central lab in all subjects. The incidence of HIT represented our primary endpoint. We then compared rates of HIT in various patient populations. Results: The cohort consisted of 218 subjects (mean age: 62.5 +/- 17.1; male gender: 56.0%). An SRA was positive and the diagnosis of HIT confirmed in 3.2% of patients tested. Physicians were more likely to order HIT in the surgical (SICU) compared to the medical service (67.5% vs 32.5%). HIT was diagnosed in 1.1% of the medical ICU patients tested vs 4.7% of the surgical ICU patients (p=0.17). Among the surgical population diagnosed with HIT, 83.3% had undergone cardiovascular surgery prior to the development of HIT. Coronary artery bypass grafting (CABG) was the most common cardiovascular surgery that predisposed to HIT (49.6%). In all non-cardiac surgery ICU patients, HIT occurred in 0.00%. Conclusions: HIT remains rare in the ICU, particularly in the general medical-surgical ICU patient population. The highest burden of this disease in the ICU is associated with those who undergo cardiovascular surgery. More importantly, patients who undergo CABG have higher risk than other general surgical ICU patients. Given the low prevalence of HIT in the non-cardiac ICU patient population, testing for HIT should only be pursued if the pre-test probability for HIT is high.

Evaluation of Prophylactic Anticoagulation, Deep Venous Thrombosis, and Heparin-Induced Thrombocytopenia in 21 Burn Centers in Germany, Austria, and Switzerland

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in intensive care settings. The timely diagnosis and management of HIT are challenging, and the incidences of HIT and deep venous thrombosis (DVT) may be related to prophylactic anticoagulation standards in burn units. We therefore evaluated, using a questionnaire, prophylactic anticoagulation, HIT management, and incidences of DVT and HIT in burn centers located in the German-speaking part of Europe. In the 21 responding burn centers, 1611 patients were treated and the overall incidences for clinically overt DVT and HIT in 2008 were 1.1% and 1.4%, respectively. Burn centers using low molecular weight heparin (LMWH) subcutaneous for all patients had a low rate of DVT (0.9%) and significantly lower rates of HIT (0.2%) relative to all other centers (P < 0.05). The highest rates of HIT (2.7%) and DVT (3.8%) were found in burn centers administering unfractionated heparin intravenous. While current HIT guidelines do not specify the administration of unfractionated heparin or LMWH for burn patients, these data warrant controlled prospective studies to confirm the advantage of LMWH administration in burn patients.

Overdiagnosis of Heparin-Induced Thrombocytopenia in Surgical ICU Patients

Heparin use in surgical patients places them at increased risk for developing heparin-induced thrombocytopenia (HIT). The false positive rate of HIT using the current standard criteria is unknown in surgical ICU patients, who often have confounding factors that cause thrombocytopenia. Surgical ICU patients, admitted over a 2-year period with a positive screening test for HIT (platelet factor [PF] 4 ≥ 0.4 optical density [OD]), were reviewed retrospectively at a single institution. Correlation of the Warkentin 4-T score and commercial heparin PF4 ELISA with serotonin releasing assay (SRA) was performed. Logistic regression was used to determine independent risk factors associated with the development of HIT. PF4 tests were requested in 643 patients based on a clinical suspicion of HIT. Of these, 104 patients had a PF4 result, an SRA value (%), and a 4-T score available. Twenty patients (19%) had true positive HIT, defined as a positive PF4 and positive SRA (SRA ≥ 20%). Eighty-four patients (81%) were false positive, defined as a positive PF4 and negative SRA. Five of 58 patients with Warkentin score of 0 to 3, and 6 of 14 patients with Warkentin score of 6 to 8 were HIT positive by SRA. In surgical ICU patients, clinical suspicion for HIT necessitates PF4 and SRA analysis. Testing for HIT or treatment with a direct thrombin inhibitor should not depend on the Warkentin 4-T score alone. Although a PF4 ≥ 0.4 OD is considered a positive screening test for HIT, a PF4 ≥ 2.0 OD is preferable in surgical ICU patients.

High Rates of Venous Thromboembolism Prophylaxis Did Not Increase the Incidence of Heparin-Induced Thrombocytopenia

Venous thromboembolism (VTE) prophlaxis is recommended for most hospitalized patients. At a 505-bed urban academic medical center, the rate of VTE prophylaxis recently increased from 50%-55% to > 95% of eligible patients. Heparin-induced thrombocytopenia (HIT) is a potentially devastating, but rare, reaction to medications commonly used for VTE prophylaxis. Patients were identified who were tested for HIT, treated with direct thrombin inhibitors (DTIs), or received International Classification of Diseases, 9th Revision codes consistent with HIT ("suspected HIT") from January 2005 through April 2008. Two physicians classified each patient as having confirmed, possible, or excluded HIT on the basis of laboratory testing, final diagnosis, and clinical course. The rate of suspected and confirmed HIT during the latter two years was compared to rates during the first (reference) year of the project. Some 430 unique patients had received HIT testing or DTI therapy for possible HIT. Thirteen cases of confirmed HIT were identified, of which 7 were due to treatment at the institution and 2 occurred while on VTE prophylaxis. HIT was confirmed in 0.02% of hospital admissions and only 3% of patients initially tested or treated for HIT. Rates of suspected and confirmed HIT did not change during the study period (Risk Ratios [95% confidence intervals] 0.976 [0.77-1.23] and 1.09 [0.39-2.99]). Optimizing the VTE prophylaxis rate to > 95% of eligible patients at a single academic institution did not cause an increase in the rate of HIT. Concerns about HIT should not limit implementation ofVTE prophylaxis protocols. HIT surveillance in patients on VTE prophylaxis may have a very low yield.

Clinical observation of heparin-induced thrombocytopenia

To explore the treatment of heparin-induced thrombocytopenia (HIT) in venous thromboembolism. A total of 202 patients with venous thromboembolism without anticoagulation contraindications were enrolled. All of them were treated with low molecular weight heparin (LMWH) and/or unfractionated heparin (UFH). The peripheral blood cells were examined regularly. HIT occurred in 6 patients. And argatroban was used to treat HIT. The overall incidence rate of HIT in this study was 2.97%. The time of occurrence of HIT was about Days 3 - 9 after using heparin. The platelet recovered to the basic level at Days 3 - 7 after withdrawing heparin and initiating argatroban. The count of platelet should be measured in the patients receiving regular LMWH and/or UFH therapy. And the above regimen should be discontinued timely when the platelet count declined progressively by over 50%. Argatroban was effective.

Low-molecular weight heparin for deep vein thrombosis prophylaxis in hospitalized medical patients: results from a cost-effectiveness analysis

Multiple options exist for the prevention of deep vein thrombosis (DVT) in medical inpatients. We sought to determine the cost-effectiveness of low-molecular-weight heparin (LMWH) relative to unfractionated heparin (UFH) for DVT prevention in this setting. We conducted a cost-effectiveness analysis from the perspective of a third-party payer employing a decision model and literature-based estimates for inputs. In the base-case analysis, LMWH had little impact on the rate of DVT. Despite higher acquisition costs, however, LMWHs resulted in net savings. Routine use of LMWH saves approximately US$89 per patient. The lower rate of heparin-induced thrombocytopenia (HIT) with LMWH accounted for this differential. Univariate sensitivity analysis revealed the model was moderately sensitive to the odds ratio of HIT with LMWH and the cost of HIT. Multivariate sensitivity analysis confirmed the LMWH approach dominated financially. 'Worst-case' scenario modeling, where LMWH actually increased the risk for DVT, had little effect on the rate of HIT, and was substantially more costly than UFH, still demonstrated that LMWHs were economically superior. Monte-Carlo simulation indicated the 95% confidence interval around the estimate for savings with LMWH ranged from US$7 to US$373. We conclude that, despite their higher cost, LMWHs for thromboprophylaxis in medical patients result in savings.