ABSTRACT
Introduction: Cases of de novo immune thrombocytopenia (ITP), including a fatality following SARS-CoV-2 vaccination in a previously healthy recipient, led to studying its impact in pre-existing ITP. Published reports are limited but suggest that most patients with ITP tolerate the COVID-19 vaccines well without frequent ITP exacerbations (Kuter, BJH, 2021). Data regarding risk factors for exacerbation and relationship of response to first dose to that of second dose are limited. Methods: Data for patients with pre-existing ITP were obtained via 3 sources. First, via a ten-center retrospective study of adults with ITP who received a SARS-CoV-2 vaccine between December 2020 and March 2021 and had a post-vaccination platelet count (n=117);9 centers were in the United States. Eighty-nine percent of patients received mRNA-based vaccines. The second and third sources of data were surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom ITP Support Association. A 'stable platelet count' was defined as a post-vaccination platelet count within 20% of the pre-vaccination level. ITP exacerbation was defined as any one or more of: platelet decrease ≥ 50% compared to pre-vaccination baseline, platelet decrease by >20% compared to prevaccination baseline with platelet nadir < 30x10 9/L, receipt of rescue therapy for ITP. Continuous variables were described as mean ±SD or median [interquartile range];categorical variables were described as n (%). Relative risks and 95% confidence interval were calculated to estimate strength of association. Results: Among 117 patients with pre-existing ITP from 10 centers who received a SARS-CoV-2 vaccine, mean age was 63±17 years, 62% were female, with median 12 [4-23] years since diagnosis of ITP;patients had received a median of 3 [2-4] prior medical treatments. Sixtynine patients were on ITP treatment at the time of vaccination (Table 1). There was an almost even distribution of platelet count response following each vaccine dose. In 109 patients with data for dose 1, platelet counts increased in 32 (29%), were stable in 43 (39%), and decreased in 34 (31%);in 70 patients following dose 2, platelet counts increased in 24 (34%), were stable in 25 (36%), and decreased in 21 (30%) (Figure 1). Nineteen (17%) patients experienced an ITP exacerbation following the first dose and 14 (20%) of 70 after a second dose. In total, fifteen patients received and responded to rescue treatments (n = 6 after dose 1, n = 8 after dose 2, n = 1 after both doses). Of 7 patients who received rescue treatment after dose 1, 5 received dose 2 and only 1/5 received rescue treatment again. Rescue consisted of increased dose of ongoing medication, steroids, IVIG, and rituximab. Splenectomized persons and those who received 5 or more prior lines of medical therapy were at highest risk of ITP exacerbation. Only 1 of 47 patients who had neither undergone splenectomy nor received 5 or more lines of therapy developed ITP exacerbation after dose 1. There were 14 patients offtreatment at the time of dose 1 and 7 patients at time of dose 2;1 patient in each group developed ITP exacerbation with both these having had normal counts prior to vaccination and having undergone splenectomy. In 43 patients whose platelet counts were stable or increased after dose 1 and received dose 2, only 6 (14%) had platelet decreases to <50 x10 9/L after dose 2. Age, gender, vaccine type, and concurrent autoimmune disease did not impact post-vaccine platelet counts. In surveys of 57 PDSA and 43 U.K. ITP patients, similar rates of platelet change were seen (33% of participants reported decreased platelet count in both surveys) and prior splenectomy was significantly associated with worsened thrombocytopenia in each. Conclusions: Thrombocytopenia may worsen in pre-existing ITP post-SARS-CoV2-vaccination but when ITP exacerbation occurred, it responded well to rescue treatment. No serious bleeding events were noted. Rescue treatment was needed in 13% of patients. Proactive vaccination surveillance of patien s with known ITP, especially those post-splenectomy and with more refractory disease, is indicated. These findings should encourage patients with ITP to not only be vaccinated, but to receive the second dose when applicable to ensure optimal immunization. Rituximab interferes with vaccination response and ideally would be held until a minimum of 2 weeks after completion of vaccination.
ABSTRACT
[Formula presented] Background: Coronavirus disease-2019 (COVID-19) is an inflammatory, multisystem infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) and is associated with increased risk of thrombosis, particularly among critically ill patients. The myeloproliferative neoplasms (MPNs) include Philadelphia chromosome-negative (Ph-negative) MPNs polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), and Philadelphia-chromosome positive chronic myeloid leukemia (CML). Patients with MPNs, especially PH-negative, have increased risk of thrombotic complications. Given the increased propensity of thrombosis and prognostic significance of thrombosis in both COVID and MPNs, defining the risk of thrombotic complications in this patient population compared to the general population is important. Methods: Using an institutional database within the Mass General Brigham integrated health network, we retrospectively analyzed 63 consecutive patients with MPN who were ≥ 18 years old and tested positive for SARS-COV-2 infection based on polymerase chain reaction (PCR) testing from March 1, 2020 to January 1, 2021. We compared patients admitted to the hospital in our “MPN cohort” with patients admitted to the hospital from a separate COVID-19 (non-MPN cohort) Mass General Brigham registry of 1114 consecutive patients who tested positive for SARS-COV-2 infection based on PCR testing from March 13, 2020 to April 3, 2020. Care was taken to ensure the cohorts were mutually exclusive. The 90-day primary outcome for MPN cohort was a composite of all-cause death, any thrombosis (composite of arterial and venous thromboembolism [VTE]), International Society on Thrombosis and Haemostasis (ISTH) defined major and clinically relevant non-major bleeding. To identify risk factors for primary outcome in MPN cohort we used a multivariable logistic regression using age, sex, hospital admission status, MPN type, cytoreduction for MPN, hypertension, smoking status, baseline anticoagulation (AC), prior thrombosis (stroke, myocardial infarction or VTE) as co-variables. The 90-day outcomes of interest in our MPN vs non-MPN cohort analysis were any thrombosis, death, ISTH major and clinically relevant non-major bleeding and readmission for any reason. To assess impact of MPN status in hospitalized patients in our MPN vs non-MPN comparison, we used a multivariable logistic regression using age, sex, race, Hispanic ethnicity, ICU admission, treatment with steroids and/or Remdesivir, baseline AC and aspirin use, prior thrombosis (stroke, myocardial infarction or VTE), diabetes, heart failure, admission hematocrit, platelet count and D-dimer as co-variables. Continuous variables were compared using student t-test and categorical variables were compared using Fischer's Exact Test with a p value of < 0.05 considered significant. Results: Of the 63 patients with MPN (23 with PV, 17 ET, 4 PMF, 15 CML, 4 other), 27 (43%) were admitted to the hospital for COVID-19 and 5 (8%) required ICU admission. The mean age of all MPN patients was 66, 84% were White, 8% Black and 10% Hispanic. Primary 90-day outcome occurred in 12 (19%) of MPN patients. In multivariable analysis, only admission to hospital was associated with increased odds of composite (aOR 21.11, 95% CI 2.38 - 546.40), Figure 1A. In patients with (n = 27) and without MPN (n = 399) who were admitted to the hospital, patients with MPN were older (mean age 70 vs 61, p = 0.0076), more likely to be White (89% vs 54%, p = 0.0004) and less likely to be Hispanic (7% vs 29%, p = 0.0158), less likely to be admitted to the ICU (19% vs 43%, p = 0.0138), and more likely to be treated with corticosteroids (30% vs 14%, p = 0.025) or remdesivir (41% vs 13%, p < 0.0001). After multivariable logistic regression, diagnosis of MPN was significantly associated with increased odds of thrombosis (aOR 5.38, 95% CI 1.15-25.38) and readmission (aOR 6.28, 95% CI 1.60-24.88), but not bleeding (aOR 3.51, 95% CI 0.62-18.87) or death (aOR 4.29, 95% CI 0.95-18.9 ), Figure 1B. Conclusions: Thrombotic complications are common in patients with MPN and COVID-19, particularly if hospitalized for COVID-19. After multivariable analysis, MPN patients admitted for COVID-19 had a significantly increased risk of thrombotic complications compared with non-MPN patients. [Formula presented] Disclosures: Al-Samkari: Dova/Sobi: Consultancy, Research Funding;Novartis: Consultancy;Argenx: Consultancy;Rigel: Consultancy;Amgen: Research Funding;Agios: Consultancy, Research Funding;Moderna: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding;BMS: Consultancy, Research Funding;Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees;Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fathi: Agios/Servier: Consultancy, Other: Clinical Trial Support;BMS: Consultancy, Other: Clinical Trial Support;AbbVie: Consultancy, Other: Clinical Trial Support;Pfizer: Consultancy;Trillium: Consultancy;Kura: Consultancy;Blueprint Medicines Corporation: Consultancy;Genentech: Consultancy;Novartis: Consultancy;Trovagene: Consultancy;Daiichi Sankyo: Consultancy;Novartis: Consultancy;Morphosys: Consultancy;Kite: Consultancy;Foghorn: Consultancy;Takeda: Consultancy;Amgen: Consultancy;Seattle Genetics: Consultancy;NewLink Genetics: Consultancy;Forty Seven: Consultancy;Ipsen: Consultancy. Goldhaber: Bayer: Consultancy, Research Funding;Boehringer-Ingelheim: Consultancy, Research Funding;BMS: Research Funding;Boston Scientific BTG EKOS: Research Funding;Daiichi: Research Funding;Janssen: Research Funding;Pfizer: Consultancy, Research Funding;Agile: Consultancy. Piazza: Portola: Research Funding;Bayer: Research Funding;Amgen: Research Funding;BMS: Research Funding;Janssen: Research Funding;BSC: Research Funding. Hobbs: Celgene/Bristol Myers Squibb: Consultancy;Novartis: Consultancy;Merck: Research Funding;Constellation Pharmaceuticals: Consultancy, Research Funding;Bayer: Research Funding;Incyte Corporation: Research Funding;AbbVie.: Consultancy.
ABSTRACT
Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Aims: To examine incidence of radiographically-confirmed venous thromboembolism (VTE) and major bleeding in a large nationally-representative U.S. cohort and assess whether therapeutic anticoagulation affects survival. Methods: In a 67-center cohort study of 3239 critically ill adults with COVID-19, we examined incidence of VTE and major bleeding within 14 days following intensive care unit (ICU) admission. We identified predictors of VTE using multivariable logistic regression. To estimate the effect of therapeutic anticoagulation on 28-day mortality, we emulated a target trial in which critically ill patients with COVID-19 were assigned to receive or not receive therapeutic anticoagulation in the first two days of ICU admission (FIGURE 1). We adjusted for confounding using a Cox model with inverse probability weighting. Results: Patients' median age was 61 years (IQR, 53-71) and 2088 (64.5%) were male. 204 patients (6.3%) developed VTE, and 90 (2.8%) had a major bleeding event. Independent predictors of VTE were male sex (odds ratio [OR], 1.70;95% CI, 1.05-2.77), severe obesity (OR 2.08;95% CI, 1.17-3.70 for body mass index ≥ 40.0 versus < 30 kg/m2), and higher D-dimer on ICU day 1 (OR 4.20;95% CI, 2.17-8.14 for > 10,000 versus ≤0 ng/ml). Among 2809 patients included in the target trial emulation, 384 (11.9%) received therapeutic anticoagulation in the first two days of ICU admission. In the primary analysis, during a median follow-up of 27 days, patients receiving therapeutic anticoagulation had a similar risk of death asthose who did not (hazard ratio, 1.12;95% CI, 0.92 to 1.35), FIGURE 2A. Results were similar in subgroup analyses, FIGURE 2B. Conclusions: Among 3239 critically ill adults with COVID-19, the 14-day incidence of VTE and major bleeding were 6.3% and 2.8%. Receipt of therapeutic anticoagulation early after ICU admission did not affect survival.