Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies targeting platelet factor 4 (PF4) and heparin complex. A higher antibody titer is reflected in a higher optical density (OD) by enzyme-linked immunosorbent assay for heparin-PF4 antibodies. This single-institution retrospective study of 116 HIT patients examined the effect of heparin-PF4 OD on time to platelet recovery, vascular thrombosis, and in-hospital mortality. Patients were divided into 3 cohorts based on heparin-PF4 OD: cohort 1 had an OD ≥ 2 and ≤ 2.4, cohort 2 had an OD > 2.4 and ≤ 2.8, and cohort 3 had an OD > 2.8. A higher OD titer was associated with significantly increased time to platelet recovery when compared between cohorts 1 versus 2 (HR = 0.599, p = 0.0221) and 1 versus 3 (HR = 0.515, p = 0.0014), as well as an increased risk of thrombosis (79.4%-cohort 3 vs 53.8%-cohort 2 vs 46.1%-cohort 1, p = 0.04), but had no impact on mortality (2.62-alive vs 2.65-deceased, p = 0.7432). A higher OD titer can inform risk assessment and support decision-making in HIT patients; however, prospective studies are needed to further clarify the impact of heparin-PF4 OD on outcomes.

BACKGROUND: Addison\'s disease and X-linked adrenoleukodystrophy (X-ALD) (Addison\'s-only) are two diseases that need to be identified. Addison\'s disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison\'s-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison\'s disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD.
METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.
RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison\'s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison\'s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.
CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison\'s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison\'s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT.
METHODS: After institutional review board (IRB) approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. The demographic and clinical variables were collected as follows: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes.
RESULTS: 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either noncardiac, nonvascular surgery, or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing), and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K ( ± 104.6 K) within an average of 2.3 days and 364K ( ± 273.9 K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days.
CONCLUSIONS: Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.

This article presents a case of a multimorbid 63-year-old woman with chronic kidney disease and heparin-induced thrombocytopenia (HIT). Following the insertion of a central venous catheter, she developed phlegmasia cerulea dolens (PCD) in her left arm, a rare and severe complication of deep vein thrombosis (DVT). Given the severity of the case, adapting to anticoagulant contraindications or unavailability, management with catheter-directed thrombolysis and mechanical thrombectomy was made. It is concluded that catheter-directed thrombolysis and mechanical thrombectomy are valuable therapeutic alternatives in critical situations where treatment options are limited.

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality. Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.

UNASSIGNED: Fcγ-receptors (FcγR) are membrane receptors expressed on a variety of immune cells, specialized in recognition of the Fc part of immunoglobulin G (IgG) antibodies. FcγRIIA-dependent platelet activation in platelet factor 4 (PF4) antibody-related disorders have gained major attention, when these antibodies were identified as the cause of the adverse vaccination event termed vaccine-induced immune thrombocytopenia and thrombosis (VITT) during the COVID-19 vaccination campaign. With the recognition of anti-PF4 antibodies as cause for severe spontaneous and sometimes recurrent thromboses independent of vaccination, their clinical relevance extended far beyond heparin-induced thrombocytopenia (HIT) and VITT.
UNASSIGNED: Patients developing these disorders show life-threatening thromboses, and the outcome is highly dependent on effective treatment. This narrative literature review summarizes treatment options for HIT and VITT that are currently available for clinical application and provides the perspective toward new developments.
UNASSIGNED: Nearly all these novel approaches are based on in vitro, preclinical observations, or case reports with only limited implementation in clinical practice. The therapeutic potential of these approaches still needs to be proven in larger cohort studies to ensure treatment efficacy and long-term patient safety.

Heparin-induced thrombocytopenia (HIT) is rare, affecting fewer than 1 in 1500 hospital admissions. Despite the increasing adoption of new therapies in HIT, such as direct oral anticoagulants and pooled immunoglobulins, there is limited high-quality evidence to guide clinicians. Numerous uncommon presentations of HIT and HIT-like entities have recently been recognized, and a harmonized approach to their classification is required to study them better. We present the results of an international survey of opinions from experts and practitioners in the field of platelet immunology regarding the role of direct oral anticoagulants in HIT, novel definitions of subclassifications of HIT-like platelet factor 4 immune conditions (spontaneous autoimmune HIT, persistent autoimmune HIT, and treatment-refractory HIT), and the role for intravenous immunoglobulins in the treatment paradigm of HIT and these HIT-like conditions. From 102 survey responses, there was broad acceptance of rivaroxaban (74.5%) and apixaban (73.5%) even before platelet recovery, as well as for intravenous immunoglobulin in the management of spontaneous (85.6%), persistent (83.7%), and treatment-refractory HIT (87.4%). With this mandate for harmonizing terminologies and treatment approaches in special situations without robust clinical data owing to their rarity, we plan to conduct a robust survey, establish international consensus, and draft management guidelines for HIT and platelet factor 4 immune diseases in the near future.

BACKGROUND: Robust adverse drug event (ADE) reporting systems are crucial to monitor and identify drug safety signals, but the quantity and type of ADEs captured may vary by system characteristics.
OBJECTIVE: We compared ADEs reported in 2 different reporting systems in the same jurisdictions, the Patient Safety and Learning System-Adverse Drug Reaction (PSLS-ADR) and ActionADE, to understand report variation.
METHODS: This retrospective observational study analyzed reports entered into PSLS-ADR and ActionADE systems between December 1, 2019, and December 31, 2022. We conducted a comprehensive analysis including all events from both reporting systems to examine coverage and usage and understand the types of events captured in both systems. We calculated descriptive statistics for reporting facility type, patient demographics, serious events, and most reported drugs. We conducted a subanalysis focused on adverse drug reactions to enable direct comparisons between systems in terms of the volume and events reported. We stratified results by reporting system.
RESULTS: We performed the comprehensive analysis on 3248 ADE reports, of which 12.4% (375/3035) were reported in PSLS-ADR and 87.6% (2660/3035) were reported in ActionADE. Distribution of all events and serious events varied slightly between the 2 systems. Iohexol, gadobutrol, and empagliflozin were the most common culprit drugs (173/375, 46.2%) in PSLS-ADR, while hydrochlorothiazide, apixaban, and ramipril (308/2660, 11.6%) were common in ActionADE. We included 2728 reports in the subanalysis of adverse drug reactions, of which 12.9% (353/2728) were reported in PSLS-ADR and 86.4% (2357/2728) were reported in ActionADE. ActionADE captured 4- to 6-fold more comparable events than PSLS-ADR over this study\'s period.
CONCLUSIONS: User-friendly and robust reporting systems are vital for pharmacovigilance and patient safety. This study highlights substantial differences in ADE data that were generated by different reporting systems. Understanding system factors that lead to varying reporting patterns can enhance ADE monitoring and should be taken into account when evaluating drug safety signals.

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Vasculitis and HIT have different etiologies, although both involve autoimmune mechanisms. Treatment of vasculitis often requires the use of an anticoagulant such as heparin, which can lead to the development of HIT and subsequent life-threatening complications. The analysis covered patients hospitalized in the Department of Internal Medicine, Nephrology and Dialysis in the period from September 2020 to March 2023. After analyzing the data, we selected four patients in whom vasculitis treatment was complicated by HIT. These included two patients with ANCA vasculitis and two patients with anti-GBM disease. We also described similar cases reported in the literature.