COVID-19 and thrombosis: searching for evidence

Early in the pandemic, COVID-19-related increases in rates of venous and arterial thromboembolism were seen. Many observational studies suggested a benefit of prophylactic anticoagulation for hospitalized patients using various dosing strategies. Randomized trials were initiated to compare the efficacy of these different options in acutely ill and critically ill inpatients as the concept of immune-mediated inflammatory microthrombosis emerged. We present a case-based review of how we approach thromboembolic prophylaxis in COVID-19 and briefly discuss the epidemiology, the pathophysiology, and the rare occurrence of vaccine-induced thrombotic thrombocytopenia

An Unusual Complication of Metastatic Colorectal Cancer: Port-Site Hematoma as the First Sign of Bone Marrow Involvement and Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is a life-threatening condition marked by a spectrum of thrombosis due to activation of procoagulant factors and bleeding due to eventual consumption of these factors. DIC invariably occurs secondary to an underlying condition, including infection, inflammatory conditions, trauma, and malignancies. Treatment of DIC primarily involves treatment of the underlying cause.1 Bone marrow invasion occurs when tumor cells infiltrate the hematopoietic marrow space, displacing progenitor cells and causing cytopenias. This process is distinct from bone metastases, where malignant cells spread to the cortical or trabecular bone, typically causing bone pain, pathologic fractures, or hypercalcemia. Disseminated carcinomatosis of the bone marrow (DCBM) is a particularly severe form of marrow involvement, characterized by widespread and uniform infiltration that can result in profound cytopenias, marrow failure, and DIC.2,3 Cancers most commonly associated with bone marrow invasion include prostate, lung, breast, and gastric malignancies. While gastric cancer rarely metastasizes to bone, it is frequently cited as a malignancy associated with marrow infiltration. In contrast, metastatic colorectal cancer rarely presents with DCBM leading to DIC.4,5 We present a case of a patient with metastatic colon cancer who developed acute anemia due to a large port-site hematoma. Further investigation revealed DCBM, rising carcinoembryonic antigen (CEA) levels, and DIC. In this case report, we outline the clinical course and management of this patient. Additionally, we review published cases of this rare pathology, providing insights into its presentation and clinical implications

Perioperative Outcomes of Patients with Bleeding Disorders Undergoing Major Surgery at an Academic Hemophilia Treatment Center

Persons with bleeding disorders (PwBD) are at high risk for bleeding with invasive procedures. However, the risk of bleeding in PwBD undergoing major surgery and outcomes of patients managed perioperatively at a hemophilia treatment center (HTC) are not well described. We performed a retrospective review of surgical outcomes among PwBD undergoing major surgery between January 1st, 2017 and December 31st, 2019 at the Cardeza Foundation Hemophilia and Thrombosis Center in Philadelphia, PA. The primary outcome was postoperative bleeding, assessed according to the ISTH-SSC\u27s 2010 definition. Secondary outcomes included use of unplanned postoperative hemostatic therapy, LOS, and 30-day readmission rate. Results were compared to non-PwBD population from a surgical database, matched for surgery, age, and sex. During the study period, 50 PwBD underwent 63 major surgeries. The most common diagnoses were VWD (64%) and hemophilia A (20.0%). The most common surgical procedure category was orthopedic (33.3%), predominantly arthroplasties. Postoperatively,4.8% of procedures were complicated by major bleeding and 1.6% by non-major bleeding. The mean LOS was 1.65 days, and 30-day readmission rate was 1.6%. In comparison to matched, non-PwBD patients in a national surgical database undergoing the same procedures, study patients had a similar rate of bleeding complications per procedure (5.0% vs 1.04

At the Leading Edge of Change: Creation of the Housestaff Quality and Safety Leadership Council

Background: The ACGME Clinical Learning Environment Review (CLER) is driving a national re-evaluation of the engagement and alignment of housestaff in institutional Quality and Safety. In 2008, the concept of a housestaff quality and safety committee was born, as a means of driving practice change Our CLER data suggested that we need a similar councilhttps://jdc.jefferson.edu/patientsafetyposters/1004/thumbnail.jp

Getting Engaged: Efforts to Increase Housestaff Event Reporting

Background: Residents traditionally are under-engaged in event reporting through institutional channels. The ACGME Clinical Learning Environment Review prioritizes this issue, and is establishing national benchmarks. In 2015 the Housestaff Quality and Safety Leadership Council selected Increasing Error Reporting as their clinical quality initiative.https://jdc.jefferson.edu/patientsafetyposters/1010/thumbnail.jp

The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling. This report briefly reviews our current understanding of cGVHD pathophysiology and reviews clinical and preclinical trials with B cell-targeted agents

Inpatient Inherited Thrombophilia Testing at an Academic Health Center: High Cost, Low Value

Testing for inherited thrombophilias following venous and arterial thrombotic events remains controversial. These conditions are associated with an increased risk of initial and recurrent venous thromboembolism (VTE) and, in some cases, arterial events such as strokes and myocardial infarctions. However, testing for them in unselected patients with thrombotic events is not associated with lower recurrence rates, and other risk factors may be more clinically useful for determining whether and for how long to anticoagulate. Further, these tests are expensive and in the setting of an acute thrombosis, many may result in false positives. As such, the American Society of Hematology and American Society for Clinical Pathology recommended in their Choosing Wisely campaigns to not test for inherited thrombophilias after a provoked VTE or in the acute setting, respectively. The AHA/ASA determined that the utility of thrombophilia screening in stroke patients was unknown in its 2014 guidelines. This single institution, retrospective study reviewed all instances of inpatient inherited thrombophilia testing in 2019 at Thomas Jefferson University Hospitals, including its 3 primary hospitals in Philadelphia, PA. Tests included those to evaluate the following conditions: Factor V Leiden (FVL); prothrombin G20210A mutation; Protein C, S, and antithrombin deficiency; hyperhomocysteinemia; and plasminogen activator inhibitor-1 (PAI-1) elevation. The study included 231 patients, among whom a total of 872 tests were sent. Tests sent for non-thrombotic indications, such as homocysteine for B12 or folate deficiency, or in patients with a known deficiency were excluded. Median age of the patients was 50.8 years (IQR 38-63) and 129 (55.8%) were female. Diagnoses for which testing was sent and predisposing risk factors are summarized in Table 1. Arterial events were most common (54.5%), followed by VTE (26.0%). 14.7% of patients had no documented thrombosis, ischemic event, or pregnancy complication. Arterial events primarily included stroke/TIA (74.6%), and 76.7% of patients had at least one documented risk factor for these conditions. VTE was associated with a major transient risk factor or cancer in 32.8% of patients. Among all inherited thrombophilia tests sent, the most common were for the evaluation of FVL (20.9%), hyperhomocysteinemia (17.0%), Protein S deficiency (16.5%), prothrombin G20210A mutation (15.1%), Protein C deficiency (14.8%), and antithrombin deficiency (14.3%) (Table 2). Overall, 83.3% of tests were normal. Tests that were most frequently abnormal included MTHFR mutation (76.0%), antithrombin (36.0%), Protein C antigen (40.0%), PAI-1 (33.3%), and total Protein S (22.2%). Given our lab's references ranges, values for antithrombin, and Protein C antigen and function, and total Protein S that fell below normal but &amp;gt;60% were deemed "borderline positive." The likelihood of an abnormal result was not significantly different in cases of unprovoked VTE or arterial event without a risk factor, compared to those with risk factors. All charts were reviewed, including both inpatient and outpatient notes, to determine short- and long-term clinical decision-making. Importantly, among all positive tests, clinical management was not definitively changed in response to the test result in a single case. In two patients, it was unclear whether anticoagulation was continued based upon the test result. Both patients had heterozygous FVL mutations. Most positive results were deemed by the treating clinicians to be due to the acute thrombotic episode. Last, the hospital's chargemaster was queried, showing that these tests were associated with $398,912 in total charges. This single-institution retrospective study of inpatient inherited thrombophilia tests reveals the limited benefit of thrombophilia testing in the acute setting. Arterial ischemic/thrombotic events were the most common indication for testing, yet over 3/4 of patients had at least one risk factor. Nearly a third of patients with VTE had a major provoking factor, patients in whom thrombophilia testing is not recommended. While nearly 17% of tests returned abnormal, not one was associated with a clear change in clinical management. Despite limited clinical utility, costs of these tests are high. These data justify education and pathway implementation aimed at decreasing inpatient utilization of thrombophilia tests. Disclosures No relevant conflicts of interest to declare. </jats:sec

A Multidisciplinary Approach to Eliminating Overuse of Inpatient Inherited Thrombophilia Tests

This project sought to address the overutilization of inherited thrombophilia testing in the hospital after a blood clot or stroke. At Jefferson Health’s three urban hospitals, these tests were frequently ordered, with charges of nearly $400,000 in 2019, yet no patients with a positive test had their clinical management definitively changed as a result. The project’s aim was to decrease test utilization at these hospitals by 75% by the end of 2020. Interventions were carried out in cycles and included a series of educational sessions and sharing of practice-level data, targeted at the highest utilizers

The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling. This report briefly reviews our current understanding of cGVHD pathophysiology and reviews clinical and preclinical trials with B cell-targeted agents

Abstract TMP59: Low Value Of Inherited Thrombophilia Testing Among Patients With Stroke Or Transient Ischemic Attack: A Single-institution Study

Background/Purpose: Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and in many cases does not change clinical management. We sought to determine the value of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. Methods: We retrospectively analyzed a database comprising patients who were admitted for acute ischemic stroke or TIA in 2019 at Thomas Jefferson University Hospitals in Philadelphia, PA and had inherited thrombophilia testing performed during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. Results: The study included 102 patients (median age 49.0 years, 53.9% female) who presented with acute ischemic stroke or TIA (including branch and central retinal artery occlusions) and underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 406 tests were ordered, among which 14.0% resulted abnormal, and 41.2% of patients had at least one abnormal test. Patients without stroke risk factors were more likely to have an abnormal result (60.0% vs 35.1%, P = .028). However, 40% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. Considering only definitively positive results, there was no significant difference in the likelihood of a positive test in patients with vs without stroke risk factors (32.0% vs 26.0%, P = .557) or those under vs over age 50 years (30.2% vs 24.5%, P = .519). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $182,994 USD. Conclusions: Inpatient inherited thrombophilia testing immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of false positive results and was expensive. Positive results did not change clinical management in a single case. </jats:p