Heparin-induced Thrombocytopenia Research Articles

Heparin-Induced Thrombocytopenia

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia

BackgroundVaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin. ObjectivesWe assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context. MethodsThe ability of F(ab′)2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4. ResultsA strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition. ConclusionA simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia using Two Combined Automated Rapid Immunoassays.

Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder caused by antibodies against platelet factor 4 (PF4) and heparin complexes. Rapid immunoassays (IAs) for detection of these antibodies mark a milestone in HIT diagnosis, despite a higher false-positive rate compared with functional platelet-activation assays. However, combining different rapid IAs may help to improve their diagnostic specificity. Here, we compared the individual performance of the latex immunoturbidimetric assay (LIA; HemosIL HIT-Ab [PF4-H]; sensitivity 91.7%, specificity 68.4%) and chemiluminescence immunoassay (CLIA; HemosIL AcuStarHIT-Ab [PF4-H]; sensitivity 92.4%, specificity 85.8%) with their combined performance using two unique diagnostic algorithms in a single prospective cohort of suspected HIT patients. Using the simultaneous algorithm adapted from Warkentin et al, the combined LIA-CLIA had a sensitivity of 99.0% and specificity of 64.3%. The sequential algorithm adapted from Rittener-Ruff et al was applied in two theoretical scenarios to reflect real-world circumstances in diagnostic laboratories where access to clinical information is limited: (1) assuming all patients had an intermediate 4Ts score and (2) assuming all patients had a high 4Ts score. This algorithm correctly predicted HIT in 94.5% (high 4Ts) and 96.0% (intermediate 4Ts) and excluded HIT in 82.6% (high 4Ts) and 80.1% (intermediate 4Ts) of patients in either scenario, respectively. Although both combined algorithms improved diagnostic performance of individual IAs, the simultaneous algorithm showed fewer false predictions (7.9%) than the sequential algorithm (intermediate 4Ts: 37.6% and high 4Ts: 41.5%) and proved more practical as it does not rely on physician evaluations. Our findings highlight the importance of accounting for clinician and interlaboratory variability when evaluating diagnostic tests for HIT.

C-reactive protein level at admission is associated with increased mortality in critically ill cardiac patients with heparin-induced thrombocytopenia

Abstract Funding Acknowledgements None. Introduction Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated disorder related to the use of unfractionated heparin or low-molecular weight heparin. As heparin is commonly used in critically ill cardiac patients, HIT consititute a relevant clinical issue in the intensive cardiac care unit. Despite this, there isn't any known factor that could predict mortality in acute cardiac patients with heparin-induced thrombocytopenia. Purpose The purpose of our study was to verify if any clinical or laboratory factor could predict mortality in critically ill cardiac patients with heparin-induced thrombocytopenia. Methods We retrospectively collected data of all patients with HIT who were hospitalized in our intensive cardiac care unit in 2016-2023. We had used functionalized latex immunoassay to confirm the diagnosis of HIT. We performed statistical analysis including clinical and laboratory variables to find any predictor of mortality in critically ill cardiac patients with HIT. Results Among 22 483 patients hospitalized in 2016-2023 in our department of cardiology 12 were diagnosed with HIT. 4 of them died during index hospitalization and 8 survived. Among clinical and laboratory characteristics only C-reactive protein level at admission was associated with increased mortality in acute caridac patients with HIT. Non-survivors had higher CRP levels at admission as compared to survivors, 190 [125-247] mg/l vs. 22 [9-71] mg/l respectively (p = 0,03). Conclusions C-reactive protein level at admission is associated with increased mortality in critically ill cardiac patients with HIT. Initial underlying systemic inflammatory response may constitute the precipitating factor of unfavorouble outcome in acute cardiac patients with heparin-induced thrombocytopenia. Further studies are necessary to confirm these findings.

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: an international survey of the ACVC Association of the ESC joint with EuroELSO

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background/introduction Bleeding and thrombotic complications impair the outcomes of patients on percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps such as the Impella™. Very recent MCS-trials still show a 23.9% moderate/major bleeding incidence during V-A ECMO. Antithrombotic practices are an important determinant of the meticulous coagulopathic risk management, but guidelines here are non-existing. Purpose Providing an overview of the current European practices in antithrombotic management in adults on pMCS is a first but crucial step to design trials, standardize practice and improve outcome. Methods This online cross-sectional survey was distributed via a digital newsletter and social media platforms through the Association of Acute Cardiovascular Care (ACVC) and the European Extracorporeal Life Support Organization (EuroELSO). The survey was accessible between 17.04 and 23.05.2023. The target population were European clinicians involved in adult critical care and pMCS-management. Results We included responses from 105 different units from 26 European countries. 72.4% Of the European responders have an institutional anticoagulation protocol installed. Unfractionated heparin is the predominantly used anticoagulant (Impella™: 97.0% and V-A ECMO: 96.1%). Argatroban is the preferred alternative in case of heparin-induced thrombocytopenia (Impella™: 52.3% and V-A ECMO: 50.7%). 10.8% And 14.5% of the anticoagulation protocols rely on anti-factor-Xa assay with activated partial thromboplastin time (APTT) in parallel for Impella™ and V-A ECMO, respectively. Up to 43.1% (Impella™) and 32.9% (V-A ECMO) of the European respondents rely on a monitoring strategy with APTT alone. Anticoagulant targets for heparin vary significantly between institutions. 54.0% And 42.7% of the European survey participants administer dual antiplatelet therapy (DAPT) during Impella™ and V-A ECMO support after acute coronary syndrome without percutaneous coronary intervention (PCI), increasing to 93.7% and 84.0% after recent PCI, respectively. Typical thresholds for transfusion or administration of blood products without acute bleeding also vary substantially and are frequently not predefined. Conclusion Large heterogeneity in antithrombotic practices is observed across Europe. Consequently, device-associated coagulopathic complications may largely vary due to non-standardized management and heterogeneity between institutions. This survey underpins the importance of urgent prospective trials investigating important basic questions concerning antithrombotic therapy during pMCS (anticoagulation targets, monitoring strategy, concomitant use of DAPT among others).

Heparin-induced thrombocytopenia after cardiac surgery. A single-center, retrospective cohort study

BackgroundCardiac surgery is a high-risk setting for heparin-induced thrombocytopenia (HIT). However, large differences in its incidence, rate of thrombotic complications, and mortality have been reported in this context. Few studies address the pharmacologic management of HIT specifically in this setting. ObjectivesTo describe the incidence, outcomes, and management of patients with HIT in our cohort and to compare them with patients presenting platelet factor 4/heparin antibodies but without platelet-activating capacity. MethodsA retrospective observational study was conducted over a period of 10 years and 6 months on 13,178 cardiac operations in a single high-volume cardiac surgery center. ResultsHIT was diagnosed in 0.22% of patients. HIT with associated thromboembolic complications occurred in 0.04% of cases. Two deaths at 30 days were registered, both in patients with associated thrombosis. The 4T score showed a 99.9% negative predictive value. The immunoglobulin G-specific chemiluminescence test positivity rate was highly predictive of HIT. Warfarin was often started early after surgery, and although it was rarely stopped when the diagnosis of HIT was made, no new thromboembolic complications subsequently occurred. Thrombocytopenia appeared to be a poor prognostic sign, whatever the cause. ConclusionAlthough rare, HIT is characterized by high mortality in this setting, especially if thrombotic complications occur. Large multicentric studies or an international registry should be created to enhance the scientific evidence on HIT diagnosis and management in this context.

Antibodies against Platelet Glycoproteins in Clinically Suspected VITT Patients.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following COVID-19 vaccination, marked by thrombocytopenia and thrombosis. Analogous to heparin-induced thrombocytopenia (HIT), VITT shares similarities in anti-platelet factor 4 (PF4) IgG-mediated platelet activation via the FcγRIIa. To investigate the involvement of platelet-antibodies in VITT, we analyzed the presence of platelet-antibodies directed against glycoproteins (GP)IIb/IIIa, GPV and GPIb/IX in the serum of 232 clinically suspected VITT patients determined based on (suspicion of) occurrence of thrombocytopenia and/or thrombosis in relation to COVID-19 vaccination. We found that 19% of clinically suspected VITT patients tested positive for anti-platelet GPs: 39%, 32% and 86% patients tested positive for GPIIb/IIIa, GPV and GPIb/IX, respectively. No HIT-like VITT patients (with thrombocytopenia and thrombosis) tested positive for platelet-antibodies. Therefore, it seems unlikely that platelet-antibodies play a role in HIT-like anti-PF4-mediated VITT. Platelet-antibodies were predominantly associated with the occurrence of thrombocytopenia. We found no association between the type of vaccination (adenoviral vector vaccine versus mRNA vaccine) or different vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S, mRNA-1273, BTN162b2) and the development of platelet-antibodies. It is essential to conduct more research on the pathophysiology of VITT, to improve diagnostic approaches and identify preventive and therapeutic strategies.

AB162. SOH24AB_095. Heparin-induced thrombocytopenia complicating orthopaedic surgery: a challenging case in an elderly patient

AB162. SOH24AB_095. Heparin-induced thrombocytopenia complicating orthopaedic surgery: a challenging case in an elderly patient

How We Interpret Thrombosis with Thrombocytopenia Syndrome?

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Electronic alerts to improve management of heparin-induced thrombocytopenia

BackgroundHeparin-induced thrombocytopenia (HIT) is a difficult clinicopathologic diagnosis to make and to treat. Delays in identification and appropriate treatment can lead to increased morbidity and mortality. ObjectivesTo use electronic health alert interventions to improve provider diagnosis and management of heparin-induced thrombocytopenia through guideline-based, accurate care delivery. MethodsThis quality improvement initiative developed 3 electronic health record-based interventions at our 750-bed academic medical center to improve the initial management of suspected HIT between 2018 and 2021: 1. an interruptive alert to recommend discontinuation of active heparin products when signing a heparin-platelet factor 4 test (PF4) order, 2. integrated 4T score calculation in the heparin-PF4 test order, and 3. interruptive alert suggesting not to order heparin-PF4 tests when the 4T score is <4. Changes in practice were assessed over defined time periods pre and post each intervention. ResultsIntervention 1 resulted in heparin discontinuation in more patients, with 65% (191 heparin orders/293 heparin-PF4 enzyme-linked immunosorbent assay tests) of cases continuing heparin prealert and only 54% (127 heparin orders/235 heparin-PF4 enzyme-linked immunosorbent assay tests) postinterruptive alert (95% CI 2.3-19.9; P = .015). Intervention 2 increased appropriate heparin-PF4 test ordering from 40.4% (110/272) preintervention to 79.1% (246/311) (95% CI 30.9-46.4; P < .00001) postintervention, with inappropriate PF4 ordering defined as testing when 4T score was <4. Intervention 3 did not lead to reduction in heparin-PF4 testing in the control group (96 inappropriate orders/402 total orders, 24%) compared to the randomized alert group (56 inappropriate orders/298 total orders; 19%) (95% CI −1.2 to 11.5; P = .13). ConclusionImplementation of unique electronic health record interventions, including both diagnostic and management interventions, led to improved guideline-based, accurate care delivery with 4T score calculation and cessation of heparin for patients with suspected HIT.

Limb Ischemic Necrosis Secondary to Microvascular Thrombosis: A Brief Historical Review.

Ischemic limb injury can be broadly classified into arterial (absent pulses) and venous/microvascular (detectable pulses); the latter can be divided into two overlapping disorders-venous limb gangrene (VLG) and symmetrical peripheral gangrene (SPG). Both VLG and SPG feature predominant acral (distal) extremity ischemic necrosis, although in some instances, concomitant nonacral ischemia/skin necrosis occurs. Historically, for coagulopathic disorders with prominent nonacral ischemic necrosis, clinician-scientists implicated depletion of natural anticoagulants, especially involving the protein C (PC) system. This historical review traces the recognition of natural anticoagulant depletion as a key feature of nonacral ischemic syndromes, such as classic warfarin-induced skin necrosis, neonatal purpura fulminans (PF), and meningococcemia-associated PF. However, only after several decades was it recognized that natural anticoagulant depletion is also a key feature of predominantly acral ischemic microthrombosis syndromes-VLG and SPG-even when accompanying nonacral thrombosis is not present. These acquired acral limb ischemic syndromes typically involve the triad of (a) disseminated intravascular coagulation, (b) natural anticoagulant depletion, and (c) a localizing explanation for microthrombosis occurring in one or more limbs, either deep vein thrombosis (helping to explain VLG) or circulatory shock (helping to explain SPG). In most cases of VLG or SPG there are one or more events that exacerbate natural anticoagulant depletion, such as warfarin therapy (e.g., warfarin-associated VLG complicating heparin-induced thrombocytopenia or cancer hypercoagulability) or acute ischemic hepatitis ("shock liver") as a proximate factor predisposing to severe depletion of hepatically synthesized natural anticoagulants (PC, antithrombin) in the setting of circulatory shock.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

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.

Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia

ObjectivesHeparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. Materials and methodsHere we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. ResultsBivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. ConclusionsHeparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

114 Burn Specific VTE Prophylaxis: Higher Enoxaparin Dose and Anti-Xa Adjustments Is Safe and Potentially Beneficial

Abstract Introduction Burn and trauma patients are at high risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolus (PE). VTE prophylaxis guidelines for trauma patients recommends a higher standard dose of enoxaparin and anti-Xa level adjustments in select patients; however, no guidelines specific to burn patients exist. We hypothesize that higher standard doses of enoxaparin and anti-Xa level adjustments will be safe and effective at reducing VTE complications in burn patients. Methods This retrospective review included patients admitted to a regional burn center six months prior to and after the initiation of a VTE prophylaxis quality improvement protocol. The protocol doubled the standard dose of enoxaparin, 40 mg daily to 40 mg twice a day, for all burn patients who were &amp;gt; 50 kg and had creatinine clearance &amp;gt; 60mg/dl. Peak anti-Xa level monitoring was indicated if a high-risk factor (TBSA ≥20%, inhalation injury, burn shock, BMI ≥40) was present. Patients on therapeutic anticoagulation or anti-platelet therapy, had a history of chronic kidney disease, decompensated cirrhosis, coagulation disorder, heparin induced thrombocytopenia (HIT), or were admitted for polytrauma were excluded. Efficacy was evaluated by rates of VTE within 31 days of discharge. Safety was evaluated by bleeding complications, including estimated blood loss (EBL), number of transfusions and gastrointestinal (GI) bleeding events. Differences between groups were compared using a two-sample t-test or Wilcoxon rank-sum test. A p-value of &amp;lt; 0.05 signified statistical significance. Results The pre-protocol group included 217 patients and the post-protocol group included 207 patients. There were no significant differences in age (45 vs 44 years), BMI (27 vs 26.4 kg/m2), TBSA (5.9 vs 5.3%), IHI (4.6 vs 7%), number of procedures (3 vs 3), mortality (4.1 vs 3%), or ICU length of stay (1.9 vs 1.6 days) between groups. No significant difference in EBL (50 vs 25 cc), number of transfusions (3.3 vs 2.4 units), or GI bleeding events (1 vs 1) was noted between groups, and no patient developed thrombocytopenia or HIT. There were 5 patients (2.3%) with a VTE within 31 days of discharge in the pre-protocol group compared to 1 patient (0.4%) in the post-protocol group (p=0.19). There was not enough power to determine statistically significant VTE prevention. Conclusions A lack of VTE prophylaxis recommendations for burn patients leads to variability in protocols among burn centers. These protocols are infrequently studied. This protocol, which doubled the standard dose of enoxaparin and adjusted based on anti-Xa levels for high-risk patients, was safe. Efficacy and applicability to other centers needs further elucidation. Applicability of Research to Practice Enoxaparin 40mg twice a day with anti-Xa level adjustments is safe and a promising strategy to reduce the rates of VTE in the burn population without increasing bleeding complications.

Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID-19 vaccination. VITT pathophysiology is not fully unravelled but shows similarities to heparin-induced thrombocytopenia (HIT). HIT is characterized by the presence of antibodies against platelet factor 4 (PF4)/heparin complex, which can activate platelets in an FcγRIIa-dependent manner, whereas IgG-antibodies directed against PF4 play an important role in VITT. We characterized all clinically suspected VITT cases in the Netherlands from a diagnostic perspective and hypothesized that patients who developed both thrombocytopenia and thrombosis display underlying mechanisms similar to those in HIT. We conducted an anti-PF4 ELISA and a functional PF4-induced platelet activation assay (PIPAA) with and without blocking the platelet-FcγRIIa and found positivity in both tests, suggesting VITT with mechanisms similar to those in VITT. We identified 65 patients with both thrombocytopenia and thrombosis among 275 clinically suspected VITT cases. Of these 65 patients, 14 (22%) tested positive for anti-PF4 and PF4-dependent platelet activation. The essential role of platelet-FcγRIIa in VITT with mechanisms similar to those in HIT was evident, as platelet activation was inhibited by an FcγRIIa-blocking antibody in all 14 patients. Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcɣRIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology ('non-HIT like') leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.

Characterization of the Benefits and Risks of Therapeutic Anticoagulation in Patients Admitted with Severe COVID-19 (CRITAC).

Severe COVID-19 is associated with increased rates of thrombotic complications. Recent provincial recommendations in British Columbia have suggested providing thromboprophylaxis with therapeutic anticoagulation for hospital inpatients with severe COVID-19 who do not have a high risk of bleeding. To characterize the rates of major bleeding, thrombotic events, complications from COVID-19, and adverse effects among patients with severe COVID-19 treated with therapeutic anticoagulation. This retrospective chart review involved patients with laboratory-confirmed COVID-19 who were admitted to 3 sites within a local health authority between April 1 and December 31, 2021, and received therapeutic anticoagulation for thromboprophylaxis. After screening of 1036 patients, 72 patients were included in the study. The mean age of participants was 54 years, 63% (n = 45) were male, and 92% (n = 66) were receiving supplemental oxygen by nasal prongs on admission. The primary outcome, major bleeding, was experienced by 1 patient (1%). Increasing oxygen requirements resulting in progression to high-flow nasal cannula occurred in 11 patients (15%), and 5 patients (7%) required admission to the intensive care unit. One patient (1%) experienced a thrombotic event, and 1 patient (1%) had a minor bleed. The mean duration of hospitalization was 10 (standard deviation 10.8) days. One death occurred during the study period, and no cases of heparin-induced thrombocytopenia were observed. In this study of hospital inpatients with severe COVID-19 who were deemed to be at low risk of bleeding and who received therapeutic anticoagulation, there were low rates of both major bleeding and thrombotic events.

Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia

AbstractNew analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n = 32; HIT ruled out, n = 38; and positive heparin/platelet factor 4 [H/PF4] antibodies, n = 28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using enzyme-linked immunosorbent assay (ELISA) in above mentioned patients and an additional second data set (n = 49). HIT was defined as a positive heparin-induced platelet activation assay (washed platelet assay). Among 98 patients of the primary data set, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive H/PF4 antibodies, and 3 in patients without HIT. The median optical density of a polyspecific H/PF4 ELISA were 3.0, 0.9, and 0.3. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver operating characteristic curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.

Heparin-induced Thrombocytopenia with Thrombosis in COVID-19 versus Vaccine-induced Immune Thrombocytopenia and Thrombosis in the United Kingdom.

Heparin-induced Thrombocytopenia with Thrombosis in COVID-19 versus Vaccine-induced Immune Thrombocytopenia and Thrombosis in the United Kingdom.