Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

The CoVID-TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID-19.

BACKGROUND: Hospitalized patients with COVID-19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well-known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID-19 is lacking. OBJECTIVES: To assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID-19. METHODS: Among patients with cancer in the COVID-19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID-19-associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap. RESULTS: From March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti-cancer therapy. A simplified RAM for VTE was derived and named CoVID-TE (Cancer subtype high to very-high risk by original Khorana score +1, VTE history +2, ICU admission +2, D-dimer elevation +1, recent systemic anti-cancer Therapy +1, and non-Hispanic Ethnicity +1). The RAM stratified patients into two cohorts (low-risk, 0-2 points, n = 1423 vs. high-risk, 3+ points, n = 1034) where VTE occurred in 4.1% low-risk and 11.3% high-risk patients (c statistic 0.67, 95% confidence interval 0.63-0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission. CONCLUSIONS: Hospitalized patients with cancer and COVID-19 have elevated thrombotic risks. The CoVID-TE RAM for VTE prediction may help real-time data-driven decisions in this vulnerable population.

Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions.

BACKGROUND: Vaccine induced immune mediated thrombocytopenia or VITT, is a recent and rare phenomenon of thrombosis with thrombocytopenia, frequently including cerebral venous thromboses (CVT), that has been described following vaccination with adenovirus vaccines ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2·S Johnson and Johnson (Janssen/J&J). The evaluation and management of suspected cases of CVT post COVID-19 vaccination are critical skills for a broad range of healthcare providers. METHODS: A collaborative comprehensive review of literature was conducted among a global group of expert neurologists and hematologists. FINDINGS: Strategies for rapid evaluation and treatment of the CVT in the context of possible VITT exist, including inflammatory marker measurements, PF4 assays, and non-heparin anticoagulation.

Laboratory assessment of the direct oral anticoagulants: who can benefit?

Direct oral anticoagulants (DOACs), apixaban, dabigatran, edoxaban, and rivaroxaban, are widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation as well as for prevention and treatment of venous thromboembolism. Although DOACs do not require routine laboratory monitoring of anticoagulant effect, there are special situations in which laboratory assessment may be warranted. Laboratory tests include quantitative assays, which measure plasma DOAC levels, and qualitative or semi-quantitative assays, which may be used to screen for the presence of clinically relevant DOAC levels. Indications for laboratory assessment include emergent indications (serious bleeding, urgent surgery, acute ischemic stroke with consideration of thrombolysis) and elective indications (extremes of bodyweight, renal hypo- or hyperfunction, liver disease, suspected drug-drug interactions, suspected gastrointestinal malabsorption). In general, quantitative assays that measure DOAC levels may be used for elective indications, whereas screening assays may be necessary for emergent indications if a quantitative assay with sufficiently rapid turnaround time is not available. Therapeutic ranges for DOACs have not been defined. In lieu of therapeutic ranges, data from pharmacokinetic studies may be used to determine whether a patient's plasma DOAC level falls within the expected range. If it does not, a change in therapy may be warranted. Depending on the clinical scenario, a change in therapy may involve adjustment of the DOAC dose, a change to a different DOAC, or a change to a different class of anticoagulant.

Hereditary Myelodysplastic Syndrome and Acute Myeloid Leukemia: Diagnosis, Questions, and Controversies.

PURPOSE OF REVIEW: To review the diagnosis of individuals with hereditary hematopoietic malignancies (HHMs) that predispose to myelodysplastic syndrome and acute myeloid leukemia, barriers to HHM diagnosis, and unaddressed questions and controversies within the HHM field. RECENT FINDINGS: Pathogenic germline mutations in approximately a dozen genes predispose to HHMs, and many more genes are likely to be involved. Many of these HHM genes have only been identified recently. HHM phenotypes are diverse, but may be categorized as "purely" myeloid syndromes, syndromes with abnormal platelet number/function, and HHMs with additional organ system involvement. A number of questions remain unanswered in this emerging field, including the ideal diagnostic approach for patients at risk for HHMs, the optimal surveillance of unaffected carriers, and how to personalize care for individuals with HHMs. The field of HHMs is evolving rapidly. Ongoing research in this area will eventually inform the care of patients with both somatic and hereditary cancer syndromes, but much work remains to be done.

Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.

PURPOSE OF REVIEW: To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis. RECENT FINDINGS: The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension. While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.