Incidence Of Heparin-induced Thrombocytopenia Research Articles

Analysis of big data for heparin-induced thrombocytopenia: valuable information but also some doubts

Heparin-induced thrombocytopenia is a well-known complication of heparin treatment, but is now thought to be rare apart from in some patient subgroups, such as those who have undergone cardiac surgery and received large doses of unfractionated heparin. However, the incidence of heparin-induced thrombocytopenia in patients treated in hospital is not well defined, and varies widely across different patient populations. 1 Greinacher A Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med. 2015; 373: 252-261 Crossref PubMed Scopus (215) Google Scholar The use of low-molecular weight heparin (LMWH) and of direct oral anticoagulants in the prevention and treatment of venous thromboembolism might have contributed to the perception among many health-care practitioners that heparin-induced thrombocytopenia is no longer a major concern in clinical practice. Disease burden, complication rates, and health-care costs of heparin-induced thrombocytopenia in the USA: a population-based studyComplication rates for heparin-induced thrombocytopenia remain high and more effective preventive and treatment interventions are needed. Full-Text PDF

Incidence and Outcomes of Heparin-Induced Thrombocytopenia in Patients Undergoing Vascular Surgery

The National Inpatient Sample (NIS) from years 2010 through 2012 was utilized to determine the incidence, predictive risk factors, and outcomes of heparin-induced thrombocytopenia (HIT) in patients undergoing vascular surgery. Retrospective population-based study. Data from the National Inpatient Sample (NIS) (2011 through 2013) using specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes corresponding with vascular surgery. 425,379 hospital admissions in patients which underwent vascular surgery. Among these, 1,290 (0.31%) were diagnosed with HIT, and 17,765 (4.18%) were diagnosed with secondary thrombocytopenia. The incidence of HIT is 0.3% in the vascular surgery population. The highest incidence is observed in thoraco-subclavian and vein reconstruction procedures. This study indicated that liver disease, endocarditis, chronic renal failure, congestive heart failure, atrial fibrillation, obesity, and female sex are associated with a higher incidence of HIT in this population. In vascular surgery patients, HIT can increase mortality by 3-fold and lead to severe complications such as acute renal failure, venous embolism, pulmonary embolism, and respiratory failure. The incidence of HIT in the vascular surgery population is similar to previously reported incidence in cardiac surgery patients. In the vascular surgery population, mortality increases 3-fold in patients with HIT versus those without any thrombocytopenia. Understanding the associated risk factors and complications will allow clinicians to make informed decisions and anticipate HIT and associated complications in certain high-risk populations.

Incidence and Outcomes of Heparin-Induced Thrombocytopenia in Patients Undergoing Transcatheter Aortic Valve Replacement.

The main objective of this study was to investigate the incidence and magnitude of impact of heparin-induced thrombocytopenia (HIT) on outcomes of patients undergoing transcatheter aortic valve placement (TAVR). The impact of HIT on procedural outcomes after cardiac surgery has been described. We sought to investigate the incidence and outcomes of HIT after TAVR using the Nationwide Inpatient Sample (NIS) database. We identified patients who underwent TAVR from 2011 to 2014. The primary outcome was the effect of HIT on inpatient mortality. Secondary outcomes included perioperative thromboembolic complications and ensuing sequelae. We also examined the length of hospital stay and hospital cost. Hierarchical mixed-effects models tested the association between HIT and main outcomes, adjusted by patient- and hospital-level characteristics. Among 33,790 patients who underwent TAVR (46.1% women and 81.4 ± 8.5years old), the cumulative incidence of HIT was 0.49% (95% CI 0.4% to 0.6%). After adjusting for patient- and hospital-level characteristics, in-hospital mortality was significantly higher in the TAVR group with HIT (odds ratio [OR] 5.6, 95% CI 2.0 to 15.6, p= 0.001). Venous thrombosis/pulmonary embolism (OR 6.3, 95% CI 1.4 to 28.8, p= 0.01) and acute kidney injury (OR 6.1, 95% CI 2.8 to 13.1, p <0.001) were significantly associated with HIT. Patients who developed HIT also had a longer hospital stay (p <0.001) with the median hospital cost of 68,168 USD versus 50, 494 USD for the group without HIT (p <0.001). In conclusion, among patient who underwent TAVR, HIT was associated with higher risk ofin-hospital mortality, venous thrombosis/pulmonary embolism, acute kidney injury,prolonged hospital stay, and increased cost.

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use the accepted definition of HIT. This was defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained greater than 150 x 109/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, we required circulating antibodies associated with the syndrome to have been investigated through laboratory assays. Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author. In this update, we included three trials involving 1398 postoperative participants. Participants were submitted to general surgical procedures, minor and major, and the minimum mean age was 49 years. Pooled analysis showed a significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was consistently reduced comparing participants undergoing major surgical procedures exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The occurrence of HIT complicated by venous thromboembolism was significantly lower in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84); low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one participant who received UFH. There were no amputations or deaths documented. Although limited evidence is available, it appears that HIT induced by both types of heparins is common in people undergoing major surgical procedures (incidence greater than 1% and less than 10%). This updated review demonstrated low-quality evidence of a lower incidence of HIT, and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in people undergoing major surgical procedures was lower when treated with LMWH compared to UFH (low-quality evidence). The quality of the evidence was downgraded due to concerns about the risk of bias in the included studies and imprecision of the study results. These findings may support current clinical use of LMWH over UFH as front-line heparin therapy. However, our conclusions are limited and there was an unexpected paucity of RCTs including HIT as an outcome. To address the scarcity of clinically-relevant information on HIT, HIT must be included as a core harmful outcome in future RCTs of heparin.

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.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients.

BACKGROUND:Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery.METHODS:Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2–0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT).RESULTS:Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding.CONCLUSIONS:Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2–0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.

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.

Clinical analysis of heparin induced thrombocytopenia after liver transplantation in children

Objective To analyze the clinical features and the impact of heparin induced thrombocytopenia (HIT) after liver transplantation in children. Methods The clinical data of 64 patients who underwent liver transplantation from June 2006 to March 2015 in the Children's Hospital of Chongqing Medical University were retrospectively analyzed. The aims were to investigate the risks of HIT, and its impact on prognosis of liver transplantation. Results 64 patients were enrolled in this study. Five patients (5/41, 12.1%) progressed to develop HIT postoperatively in the unfractionated heparin (UFH) group. This group included 2 patients who were aged under 3 years (2/33, 6.1%) and 3 patients who were aged over 3 years (3/8, 37.5%). No patient progressed to develop HIT in the low molecular weight heparin (LMWH) group. For the perioperative mortality, 3 patients (3/5, 60%) died in the HIT group including 2 patients had hepatic artery thrombosis. Six patients (8/59, 13.6%) died in the Non-HIT group. Conclusions HIT was one of the death causes after liver transplantation in children. Children aged over 3 years had a higher incidence of HIT. Key words: Children; Liver transplantation; Heparin; Thrombocytopenia

Presentation, management and outcome of heparin-induced thrombocytopenia after valvular heart surgery

The use of heparin exposes patients to heparin-induced thrombocytopenia, which is a challenging issue for both diagnosis and patient management. We sought to describe the clinical presentation, management and outcome of a series of patients diagnosed with heparin-induced thrombocytopenia after heart valve surgery. All consecutive patients diagnosed with heparin-induced thrombocytopenia during the postoperative period of heart valve surgery over a 6-year period were prospectively enrolled in a single-centre registry. Clinical and biological data were collected. In-hospital and mid-term outcomes were assessed. Information regarding the occurrence of all medical events including death, recurrence of thromboembolic events and/or thrombocytopenia was collected. We identified 93 patients (incidence proportion = 2.8%). Most patients (82%) were asymptomatic with isolated thrombocytopenia at the time of diagnosis. The other main circumstance of diagnosis was the occurrence of thromboembolic events in 17 patients (6 strokes, 10 prosthetic valve thrombosis and 1 peripheral embolic event). The in-hospital mortality rate was 1%. No thrombolysis, interventional procedure or redo surgery was performed. Danaparoid sodium was used as heparin replacement therapy in most cases (96%) and leading to complete and uneventful thrombus resolution in all cases with only one possibly related major bleeding complication. During a mean follow-up of 36 ± 20 months, no patient presented recurrence of any heparin-induced thrombocytopenia-related complication. In this contemporary series of patients, heparin-induced thrombocytopenia incidence was low and isolated thrombocytopenia was the most frequent presentation. Conservative management with early diagnosis and substitutive anticoagulation therapy introduction was associated with a low rate of clinical events and a remarkably good outcome with a low mortality rate.

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.

The incidence of heparin-induced thrombocytopenia in patients treated with low molecular weight heparin for superficial vein thrombosis

BackgroundThe risk of heparin induced thrombocytopenia (HIT) associated with low molecular weight heparin (LMWH) for treatment of superficial vein thrombosis (SVT) is uncertain. As a result the necessity of platelet count monitoring is unclear in this setting. AimsTo assess the risk of HIT in outpatients treated with LMWH for SVT. MethodsIn a prospective single centre study we included all symptomatic outpatients in whom a real-time B-mode and color Doppler ultrasonography examination revealed SVT without DVT. Patients treated with vitamin K antagonists or fondaparinux were excluded. Patients received full dose enoxaparin for 1week followed by half therapeutic dose for 3weeks or parnaparin 8500UI aXa for 10days followed by 6400UI aXa once daily for 20days. Platelet count was performed on the day of diagnosis (D0) and 7 (D7), and 14 (D14) days afterward. Primary outcomes were the rate of thromboembolic events and of HIT during a 3-month follow-up. Results678 outpatients (age: 64.7±16.2years, male: 42.0%) were evaluated. During follow-up, 7 venous thrombo-embolic events were recorded (1.03% CI 95%: 0.50–2.11%), while no major bleeding was observed (0.0% CI 95%: 0.0–0.56%). Platelet count was 255±93×109/L at D0, 245±93×109/L at D7 (p=0.204 vs. D0) and 261±116×109/L at D14 (p=0.405 vs. D0). No fall in platelet count>50% and no case of HIT were recorded (HR 0.0% CI 95%: 0–0.56%). ConclusionsA 4-week LMWH treatment for SVT is associated with an incidence of HIT lower than 0.6% and platelet count monitoring may be omitted in this setting.

Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge.

Exposure to heparin is associated with a high incidence of immunization against platelet factor 4 (PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia (HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on anti-heparin/PF4 antibodies and HIT in transplant recipients a systematic PubMed literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.

Efficiency of Diagnosing HIT at a Large Academic Medical Center

Background: Thrombocytopenia during heparin administration is common in hospitalized patients, leading to frequent testing for heparin-induced thrombocytopenia (HIT). The 4T score, which is based on degree and timing of thrombocytopenia, and whether there are other explanations for thrombocytopenia or the presence of thrombosis, is a commonly used tool to assess the clinical probability of HIT prior to performing laboratory testing. Published guidelines recommend further testing with an anti-PF4/heparin enzyme immunoassay (EIA) and confirmation with the serotonin-release assay (SRA) when the pretest probability of HIT is intermediate or high. The diagnosis of HIT confers high morbidity and mortality; therefore it is crucial to establish a definitive diagnosis in patients with suspected HIT. However, empiric treatment with alternative non-heparin anticoagulants increases the cost of hospitalization and may cause unnecessary risks in patients with a false positive EIA. The purpose of our study was to evaluate the utilization of EIA and SRA at a large tertiary care center and to assess the agreement between the 4T score, the EIA, and the SRA.Methods: We retrospectively reviewed all EIAs performed in our special hematology laboratory and SRAs sent to a reference laboratory at our institution in patients with suspected HIT between July 2012 and June 2014. First we evaluated the 4T score in all patients in whom laboratory testing was requested and subsequently assessed the correlation between the 4T score and the EIA and SRA results. A 4T score of 6 to 8 was high and a 4T score of 4 to 5 was intermediate. A strong positive EIA was defined as an EIA with an optical density (OD) of ≥ 1.00 and a weak/indeterminate EIA had an OD of 0.40-0.99.Results: A total of 583 unique PF4 EIAs were requested during the study period (Figure 1). Of these, 472 (81%) and 77 (13%) were performed in patients with intermediate/ high probability and with low-probability of HIT, respectively and in 34 patients (6%) the EIA was requested without documentation of the 4T score. Of the 472 patients with an intermediate or high 4T score, 36 (8%) had an EIA with an OD ≥ 1.0. Of these 36 patients, 27 (75%) had SRA performed and were positive in 14 patients (52%). Twenty-three (5%) of the 472 patients had a weakly positive EIA and in 18 (78%) of them the SRA was sent and were all negative. Five of the 472 patients (1%) had a positive SRA in the setting of an intermediate or high 4T score and a negative or indeterminate/weakly positive EIA. The SRA was sent in 24 patients with low probability 4T score (0-3) and in 9 patients with no documented 4T score. Two of these 33 (6%) patients had a positive SRA. Overall, the incidence of HIT based on a 4T score of 4 to 8, a positive EIA and positive SRA was found in 16 (3.4%) of the 472 patients; 2 of these 16 patients (12.5%) had a indeterminate/weakly positive EIA. Of the 216 SRAs sent, 21 were positive (9.7%). Patients with a lower pre-test probability based on a low or intermediate 4T score and negative/weakly positive EIA accounted for 33% of HIT cases observed. Patients with an intermediate/high 4T and strong or weakly positive EIA accounted for the remaining 67%.Conclusions: The incidence of definitive HIT in our study was low. There was a poor correlation between the 4T score and SRA positivity and between the EIA and SRA results. The combination of an intermediate/high 4T score and a strong EIA confirmed the diagnosis of HIT in only half of the patients. These findings underscore the need for improved screening tools for HIT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Diagnostic dilemma of post bypass thrombocytopenia – A case report

Various causes are attributed to postoperative thrombocytopenia in a patient who has undergone cardiac bypass. The incidence of heparin-induced thrombocytopenia (HIT) in Indians is 5.6%. We present here 2 cases of postcoronary artery bypass graft surgery; both were presenting with >50% drop in platelets on day 5 of heparin injection, both had acute kidney injury, and one also had transaminitis. The detection of anti-heparin PF4 antibodies was performed by rapid ID Micro-gel typing system in both the cases and one was confirmed as HIT.Heparin/PF4 Antibody card test and heparin-induced platelet aggregation test (PAT) other was negative and was finally diagnosed as disseminated intravascular coagulation. Thus rapid diagnosis was reached and patients were managed accordingly, which is different in both conditions.

Heparin-induced thrombocytopenia in patients undergoing cardiac surgery

To investigate the incidence for heparin-induced thrombocytopenia (HIT) in patients undergoing cardiac surgery and to evaluate the risk factors for the generation of HIT-antibody. A total of 315 patients undergoing cardiac surgery in the Department of Cardiothoracic Surgery, Xiangya Hospital between December, 2013 and July, 2014 were enrolled for this study. Among them, 120, 154 and 41 were for surgery of congenital heart defect, valve and coronary artery bypass graft, respectively. There were 170 male patients and 69 patients were under 18 years old. Platelet counts, HIT-antibody and concentration of platelet factor 4 (PF4) were tested before and after the surgery. Diagnosis of HIT was based on "4Ts" (Pretest Clinical Scoring System). HIT was diagnosed in 11 patients (3.5%, 11/315). And thromboembolic events occurred in 2 of 11 patients with HIT. The positive ratio for HIT-antibody was 36.5% (115/315). The coronary artery disease patients had a higher incidence of HIT than that of either the valve disease or the congenital heart defect (17.1%, 7/41 versus 1.9%, 3/154 or 0.8%, 1/120; P<0.05). The congenital heart defect patients had a higher positive ratio for HIT-antibody than that of both the valve disease and the coronary artery disease. The valve disease patients had a higher positive ratio for HIT-antibody than that of the coronary artery disease (51.7%, 62/120 versus 30.5%, 47/154 versus 14.6%, 6/41; P<0.05). Major postoperative complications occurred more frequently in HIT patients (36.4%, 4/11 versus 10.5%, 32/304; P<0.05). Age was a risk factor for HIT (P=0.030, OR=1.083, 95% CI 1.008-1.163). Cardiopulmonary bypass (CPB) (P=0.037, OR=3.113, 95% CI 1.071-9.050) and age (P<0.001, OR=0.970, 95% CI 0.959-0.982) were risk factors for HIT-antibody. The incidence of HIT is low during cardiac surgery, but HIT is a highly risk factor for the major postoperative complications. More attentions should be paid to these severe complications and the risk factors for HIT.

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

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

Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars

Objective: This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs).Methods: Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 – 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers.Results: Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine’s loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share.Conclusions: Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

Attributable Healthcare Cost and Length of Hospital Stay Associated with Heparin-Induced Thrombocytopenia

Background: Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction associated with an increased length of hospital stay (LOS) and utilization of healthcare services and even more so if heparin-induced thrombotic thrombocytopenia (HITT) occurs. Objective: To determine the attributable healthcare cost and LOS of patients experiencing HIT compared with control subjects. Methods: A retrospective case-control study conducted in hospitalized patients with HIT and their control subjects from January 1to December 31, 2013. Of the 462 HIT assay performed, 29 HIT cases and 141 matched control subjects were evaluated. Healthcare costs elements attributed to HIT included laboratory tests, non-heparin anticoagulant, medical imaging, physician visits and LOS. The healthcare costs and LOS of cases, HIT and HITT, and control subjects were determined in US$, year 2013. Result: Compared to the control subjects, the attributable healthcare cost and LOS were $3159 and 8 days for HIT cases and $18256 and 19 days for HITT cases, respectively. The HITT cases incurred median healthcare costs of $22893 compared with $7799 (p<0.001) for HIT cases without complication. Conclusion: Heparin-induced thrombocytopenia is significantly associated with increased healthcare costs and an increased LOS. These findings suggest that using low-molecular-weight-heparin (LMWH) is one of the strategies aiming to reduce the incidence of HIT.

A Radiolabeled PF-4 Staph-a Binding Assay Proposed As a Solitary Method for Confirming Heparin Induced Thrombocytopenia

Introduction:Heparin induced thrombocytopenia (HIT) is present in over 30% of normal subjects receiving heparin and the incidence of HIT may even be higher in patients with occlusive atherosclerotic disease. Confirmatory laboratory assays can broadly be classified as functional which have high specificity and rely on activation of platelets by the platelet factor 4 (FP4)-heparin-IgG immune complex or as immune based assays that are relatively more sensitive. At the time when the clinician is evaluating heparin as a cause of thrombocytopenia the 4 ”T” criteria are helpful. However, after the episode of decreased platelets is resolved, an increase in the patient’s platelet count is critical for confirmation of the diagnosis.Methods: We developed a variation of a previously described technique (Newman Thromb Haemost 1998;80:292) and used clinical criteria as the standard for comparison to evaluate the assay. Radiolabeled 125-I-PF4 is incorporated into the immune complex of PF-4-heparin-immunoglobulin and the amount of radiolabeled immune complex is measured after binding to Staphylococcal A Protein Sepharose. Our working hypothesis is that since this assay has both immune and binding components it would have better specificity and sensitivity than the currently used assays and as a single assay be more cost effective. The hospitalized subjects medical record was reviewed to; measure a 4 “T” score, to determine if the patient’s platelet count increased after heparin was stopped, to record the results of the hospitals’ assays for HIT and to ascertain what other causes of thrombocytopenia might be possible.Results: To date we have evaluated 20 samples. True positives were observed in 3 hospital patients and 4 known positives that were a gift from the Blood Center of S.E. Wisconsin. 10 true negatives included 5 from hospital patients and 5 from thrombocytopenic patients who were not treated with heparin. 3 samples were negative in our assay, had a 4 ”T” score of 6 and 5 and NA and had increased platelet counts after heparin was stopped and were judged as false negatives. However, these samples had high relative binding to the Staph-A-Sepharose in the sample without the addition of heparin suggesting that either the sample already had enough heparin from the patient’s treatment to form immune complexes or as has been recently reported another negatively charged molecule formed a complex with PF-4.(Warkentin Blood;2014;123:3651) Concordance between the radiolabeled PF-4 assay and the commercial PF-4 hospital assay was observed in 10 of 11 patients.Conclusions:To date when judged using clinical criteria, the radiolabeled PF-4 assay correctly distinguished true positives and true negatives in 17 of the 20 samples. This is an ongoing study with the goal of studying another 30 patients before the ASH December meeting. The addition of clinical criteria including the 4 “T” score and the increase in platelet count after stopping heparin to a review of the patient’s acute care hospital record is helpful in evaluating the reliability of the radiolabeled PF-4 assay as a predictor of HIT. DisclosuresNo relevant conflicts of interest to declare.

Heparin-induced thrombocytopenia after ICD-lead flushing

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening prothrombotic complication following heparin administration. We describe a patient, known with idiopathic dilating cardiomyopathy, presenting nine days after a biventricular ICD implantation with dyspnoea and thrombocytopenia. Thirteen days after administration of a single heparin fl ush during ICD implantation, the patient developed venous thrombosis in two extremities and pulmonary embolism caused by HIT. HIT is the development of thrombocytopenia, caused by IgG antibodies against complexes of platelet factor 4 and heparin, leading to platelet aggregation. HIT may be accompanied by thrombosis in 20-50% of patients and untreated mortality rates are high. Once HIT is suspected, heparin should be replaced by an alternative anti-factor Xa or anti-factor II therapy. Regardless of the low incidence of HIT, because of the widespread use of heparin and the potentially life-threatening course of HIT, all physicians should be aware of it.