Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter, retrospective study described the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically-confirmed VTE rate was 4.8% (95% CI, 2.9-7.3%) and the overall thrombotic complication rate was 9.5% (6.8-12.8%). The overall and major bleeding rates were 4.8% (2.9-7.3%) and 2.3% (1.0-4.2%). In the critically ill, radiographically-confirmed VTE and major bleeding rates were 7.6% (3.9-13.3%) and 5.6% (2.4-10.7%). Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization [D-dimer >2,500 ng/mL, adjusted OR for thrombosis, 6.79 (2.39-19.30), adjusted OR for bleeding, 3.56 (1.01-12.66)], critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450×109/L [adjusted OR, 3.56 (1.27-9.97)], C-reactive protein (CRP) >100 mg/L [adjusted OR, 2.71 (1.26-5.86)], and erythrocyte sedimentation rate >40 mm/h [adjusted OR, 2.64 (1.07-6.51)]. ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than those without. DIC, clinically-relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immune-mediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger). Clinical and laboratory manifestations include fever, splenomegaly, neurologic dysfunction, coagulopathy, liver dysfunction, cytopenias, hypertriglyceridemia, hyperferritinemia, hemophagocytosis, and diminished NK cell activity. It is treated with immune suppressants, etoposide, and allogeneic hematopoietic stem cell transplantation; more than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management. Newer agents directed at subduing the uncontrolled immune response in a targeted fashion offer promise in this highly morbid disease.
for the STOP-COVID investigators † Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 .Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used.Setting: 67 hospitals in the United States.Participants: Adults with COVID-19 admitted to a participating ICU.Measurements: Time to death, censored at hospital discharge, or date of last follow-up.Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]).Limitation: Observational design. Conclusion:Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation.
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered via a multidisciplinary approach with appropriate diagnosis, screening and local and/or systemic management of lesions. Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.
Blood groups are inherited traits that vary across populations, likely due to both founder effects and natural selection. A link between blood groups and susceptibility to infectious disease has been well‐described, with notable examples being H. Pylori and Plasmodium falciparum infection. Blood group antigens may influence disease susceptibility by several mechanisms, including serving as receptors or decoys for infectious organisms and modifying immune response in the form of anti‐ABO antibodies.
Cases of de novo immune thrombocytopenia (ITP) - including a fatality - following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in pre-existing ITP. In this study, four data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a ten-center retrospective study of adults with pre-existing ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA, United States) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] x109/L approximately 1-week post-vaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 109 patients with pre-existing ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30x109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK ITP patients, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in pre-existing ITP or be identified de novo post-SARS-CoV2-vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those post-splenectomy and with more refractory disease, is indicated.
Clinically significant bleeding can occur as a consequence of surgery, trauma, obstetric complications, anticoagulation, and a wide variety of disorders of hemostasis. As the causes of bleeding are diverse and not always immediately apparent, the availability of a safe, effective, and non-specific hemostatic agent is vital in a wide range of clinical settings, with antifibrinolytic agents often utilized for this purpose. Tranexamic acid (TXA) is one of the most commonly used and widely researched antifibrinolytic agents; its role in postpartum hemorrhage, menorrhagia, trauma-associated hemorrhage, and surgical bleeding has been well defined. However, the utility of TXA goes beyond these common indications, with accumulating data suggesting its ability to reduce bleeding and improve clinical outcomes in the face of many different hemostatic challenges, without a clear increase in thrombotic risk. Herein, we review the literature and provide practical suggestions for clinical use of TXA across a broad spectrum of bleeding disorders.
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