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Collection of hematopoietic progenitor cell products [HPC(A)] is deferred if the donor is symptomatic and tests positive for Covid-19. However, donor questionnaires are subjective and may miss minimally symptomatic donors. Alternatively, myalgia associated with Covid-19 infection can be falsely dismissed as an adverse effect of granulocyte stimulating factor (Filgrastim) administered prior to product collection. The likelihood of donors with an underlying acute but minimally symptomatic infection undergoing successful product collection is significant. In these circumstances, it is less known whether Covid-19 infection results in product viremia or alters the clinical outcome of transplant. We aimed to evaluate the above question by studying a donor whose product was collected during acute Covid-19 infection. Aliquots of the product tested negative for SARS-CoV-2 RNA by reverse-transcriptase polymerase chain reaction assay (RT-PCR). Importantly, the donor received an autologous stem cell transplant using the product collected at the time of infection, and their case will be described in this report. We describe one of the very few reports of successful transplant of HPC(A) product collected during acute Covid-19 infection.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2 , Transplante Autólogo , Humanos , COVID-19/virologia , COVID-19/terapia , SARS-CoV-2/genética , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Feminino , Adulto , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/virologiaRESUMO
PURPOSE: Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD. PATIENTS AND METHODS: In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria. RESULTS: Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals. CONCLUSION: The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.
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Background: The treatment landscape for relapsed or refractory immune thrombocytopenia (ITP) after corticosteroids is complex. Objectives: We aimed to assess the efficacy of danazol in treating ITP and evaluate the safety and adverse events following its administration. Methods: We searched the databases PubMed, EMBASE, and ClinicalTrials.gov for all published studies assessing danazol's efficacy and safety in treating ITP. The retrieved studies were screened by title and abstract, followed by full-text screening based on the eligibility requirements. The quality assessment was performed using a set of questionnaires. The data were extracted on the descriptive characteristics of the studies and participants, drug dosage, efficacy measures, and adverse effects, and the data were synthesized. Results: A total of 17 studies consisting of 901 participants were included. The overall response rate is around 61% in this analysis. Among the participants, 315 (34.9%) were men. The age of participants ranged from 16 to 86 years. Danazol combined with other pharmacologic interventions, including all-trans-retinoic acid or glucocorticoids, generated better results. The most common side effects appear to be liver injury and elevation of liver enzymes, weight gain, oligomenorrhea, amenorrhea, and myalgia. Conclusion: Danazol at low-to-medium doses was well tolerated and succeeded in improving ITP. Danazol therapy may be helpful in the treatment of chronic ITP that is corticosteroid refractory and when corticosteroids or splenectomy (or both) is contraindicated. Danazol can be considered for further research and development in treating primary immune thrombocytopenia.
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Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.
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Mastocitose Sistêmica , Humanos , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/terapia , Gerenciamento Clínico , Oncologia/normas , Oncologia/métodosRESUMO
BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. RESULTS: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). CONCLUSION: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).
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Inibidores do Fator Xa , Hemorragia , Neoplasias , Pirazóis , Piridonas , Prevenção Secundária , Tromboembolia Venosa , Humanos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Hemorragia/induzido quimicamente , Idoso , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Resultado do Tratamento , Fatores de Tempo , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fatores de Risco , Esquema de MedicaçãoRESUMO
INTRODUCTION: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments. MATERIALS AND METHODS: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses. RESULTS: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16. DISCUSSION: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML. CLINICAL TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov ID: NCT03226418.
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Leucemia Mieloide Aguda , Qualidade de Vida , Humanos , Idoso , Leucemia Mieloide Aguda/tratamento farmacológico , Nível de Saúde , Comorbidade , CogniçãoRESUMO
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
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Danazol , Síndromes Mielodisplásicas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Danazol/efeitos adversos , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Transplante Homólogo , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante/efeitos adversosRESUMO
The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.
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Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Adulto , Humanos , Oncologia , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/terapia , Policitemia Vera/diagnóstico , Mielofibrose Primária/diagnóstico , Trombocitemia Essencial/diagnósticoRESUMO
Heparin-induced thrombocytopenia (HIT) is suspected much more often than it is confirmed. Technically simple platelet factor 4 (PF4)-polyanion enzyme-linked immunosorbent assays (ELISAs) are sensitive but nonspecific. In contrast, accurate functional tests such as the serotonin release assay, heparin-induced platelet activation assay, and PF4-dependent P-selectin expression assay require fresh platelets and have complex assay end points, limiting their availability to specialized reference laboratories. To enable broad deployment of functional testing, we sought to extend platelet viability significantly by optimizing storage conditions and developed a simple functional assay end point by measuring the release of a platelet α-granule protein, thrombospondin-1 (TSP1), in an ELISA format. Platelet cryopreservation conditions were optimized by freezing platelets at controlled cooling rates that preserve activatability. Several-month-old cryopreserved platelets were treated with PF4 or heparin and were evaluated for their ability to be activated by HIT and vaccine-induced immune thrombotic thrombocytopenia (VITT) antibodies in the TSP1 release assay (TRA). HIT and spontaneous HIT patient samples induced significantly higher TSP1 release using both PF4-treated (PF4-TRA) and heparin-treated cryopreserved platelets relative to samples from patients suspected of HIT who lacked platelet-activating antibodies. This latter group included several patients that tested strongly positive in PF4-polyanion ELISA but were not platelet-activating. Four VITT patient samples tested in the TRA activated PF4-treated, but not heparin-treated, cryopreserved platelets, consistent with recent data suggesting the requirement for PF4-treated platelets for VITT antibody detection. These findings have the potential to transform the testing paradigm in HIT and VITT, making decentralized, technically simple functional testing available for rapid and accurate in-hospital diagnosis.
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Anticorpos , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Anticorpos/análise , Anticoagulantes/efeitos adversos , Criopreservação , Heparina/efeitos adversos , Fator Plaquetário 4 , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/diagnóstico , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Vacinas/efeitos adversos , Ensaio de Imunoadsorção Enzimática , PlaquetasRESUMO
Introduction: Pegcetacoplan, a pegylated penta-decapeptide, targets complement C3 to control both intravascular and extravascular hemolysis. This systematic review aims to study the efficacy and safety of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH). Methods: We performed a comprehensive and systematic literature search for all studies on PubMed, Google Scholar, Cochrane Library, and clinicaltrials.gov. The studies were searched using keywords "paroxysmal nocturnal hemoglobinuria" or "PNH," "Pegcetacoplan" or "Empaveli." The primary outcomes included change in hemoglobin level, transfusion independence, absolute reticulocyte count, and lactate dehydrogenase (LDH) level after pegcetacoplan therapy. The safety outcomes included the proportion of deaths and adverse effects. Results: We included a total of three studies. The total number of patients with PNH was112. 59.83% were female. In the PADDOCK study and study by Hillmen et al., the average increase in hemoglobin was 3.68 g/L and 2.37 g/L, respectively. In the study by de Castro et al., the hemoglobin level increased from below the lower limit of normal and stayed in the normal range (11.1-15.9 g/L). Absolute reticulocyte count and LDH levels decreased in all patients receiving pegcetacoplan. In the study by de Castro et al., LDH level remained stable, and within <1.5× upper limit of normal, whereas in the study by Hillman, the mean change of LDH from baseline was -15 ± 43 U/L. Two of six, seven of 23, and seven of 41 patients reported adverse events in the study by de Castro et al., PADDOCK, and Hillmen et al., respectively. Conclusion: Pegcetacoplan effectively improves hemoglobin level and transfusion requirements in patients with PNH, including those unresponsive to eculizumab.
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Understanding the association between insurance status and survival in an evolving US healthcare system remains a challenge but is essential to address healthcare disparities. We utilized National Cancer Database to evaluate the effects of insurance type on one-month mortality and overall survival (OS) in patients with acute promyelocytic leukemia. Among patients <65 years, one-month mortality was worse for uninsured patients and patients with Medicare compared to patients with private insurance. OS was similar between patients with private insurance and uninsured patients but worse for patients with Medicare and Medicaid/other government insurance. In multivariate analysis, older age and greater comorbidity burden conferred worse OS. For patients ≥65 years, insurance type did not affect one-month mortality and OS. Older age, greater comorbidity burden, and treatment at non-academic centers conferred worse one-month mortality and OS. Our results highlight healthcare disparities based on insurance types for both younger and older patients.
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Leucemia Promielocítica Aguda , Medicare , Humanos , Estados Unidos/epidemiologia , Idoso , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/epidemiologia , Leucemia Promielocítica Aguda/terapia , Cobertura do Seguro , Pessoas sem Cobertura de Seguro de Saúde , Medicaid , Disparidades em Assistência à Saúde , Seguro SaúdeRESUMO
INTRODUCTION: Survival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection. MATERIALS AND METHODS: In a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach. RESULTS: Broad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0-9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). One-year overall survival was 66% (95% CI 60-87%). DISCUSSION: Our data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Idoso , Avaliação Geriátrica , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Medicina de Precisão , Fatores de Risco , Resultado do TratamentoRESUMO
Thrombosis with Thrombocytopenia Syndrome (TTS) or Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) had been reported in patients receiving the Ad26.COV2.S vaccination (Johnson & Johnson [J&J]/Janssen) vaccine. They frequently presented with cerebral venous sinus thrombosis (CVST), but venous or arterial thrombosis at other locations can be present. The majority of those affected are younger adult females. Therefore, after a brief pause from April 13-23, 2021, the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) recommended caution in using this vaccine in females under 50 years. Based on the reported 28 cases of TTS after this vaccination (data till April 21, 2021) by CDC, 22 were females (78%), and 6 were male. None of those males had CVST but had thrombosis at other locations. We report the first case of a young male with TTS and CVST following Ad26.COV2.S vaccine presented with severe headache and diagnosed with acute right transverse and sigmoid cerebral venous sinus thrombosis, multiple right-sided pulmonary emboli, and right hepatic vein thrombosis. He was treated with parenteral anticoagulation with argatroban and intravenous immune globulin with the improvement of his symptoms. A heparin-induced thrombocytopenia with thrombosis (HITT) like syndrome caused by the genesis of a platelet-activating autoantibody against platelet factor 4 (PF4) triggered by adenoviral vector-based COVID-19 vaccinations is understood to be the underlying pathophysiology. TTS with CVST should be considered when patients present with headaches, stroke-like neurological symptoms, thrombocytopenia, and symptom onset 6-15 days after Ad26.COV2.S vaccination.
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Chronic myelomonocytic leukemia (CMML) is a rare but distinct hematological neoplasm with overlapping features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). Individuals with CMML have persistent monocytosis and bone marrow dyspoiesis associated with various constitutional symptoms like fevers, unintentional weight loss, or night sweats. It is established that there is a strong association of CMML with preceding or coexisting autoimmune diseases and systemic inflammatory syndromes affecting around 20% of patients. Various molecular abnormalities like TET2, SRSF2, ASXL1, and RAS are reported in the pathogenesis of CMML, but no such mutations have been described to explain the strong association of autoimmune diseases and severe inflammatory phenotype seen in CMML. Germline mutation in SH2B adaptor protein 3 (SH2B3) had been reported before to affect a family with autoimmune disorders and acute lymphoblastic leukemia. In this report, we describe the first case of a female subject with many years of preceding history of multiple sclerosis before the diagnosis of CMML. We outline the evidence supporting the pathogenic role of SH2B3 p.E395K germline mutation, connecting the dots of association between autoimmune diseases and CMML genesis.
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Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT. Here we demonstrate that while Ad26.COV2.S-associated VITT patients are uniformly strongly positive in PF4-polyanion enzyme-linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4-dependent p-selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150 x 103 /µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4-polyanion ELISAs and functional assay are non-specific and detect all three conditions. Here, we report that a novel un-complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV-19, from both spontaneous HIT, HIT and commonly-encountered HIT-suspected patients who are PF4/polyanion ELISA-positive but negative in functional assays. In summary, Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.