Plasma P-selectin is an early marker of thromboembolism in COVID-19

Objectives: The aim of this study was to explore the association of the plasma levels of coagulation proteins with venous thromboembolic events (VTE) in COVID-19 and identify candidate early markers of VTE. Background(s): Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and immunothrombosis and have been intensively studied. Yet, a full understanding of the pathogenesis and factors that lead to COVID-19 associated coagulopathy is lacking. Previous studies investigated only small numbers of coagulation proteins together, and they were limited in their ability to adjust for confounders. Method(s): This study was a post-hoc analysis of a previously published dataset (Filbin et al., 2021). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020;13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained on days 0, 3, and 7 and assays were performed on two highly-multiplexed proteomic platforms, that in combination cover 1472 + 4776 proteins. We included 31 coagulation proteins in our analysis. Result(s): Nine coagulation proteins were differentially expressed in patients with thromboembolic events. In multivariable models, day 0 levels of P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity and other confounders (p=0.0025). P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone (AUROC = 0.834 vs. 0.783). Conclusion(s): Our results suggest that plasma P-selectin is a potential early biomarker for the risk stratification of VTE in COVID-19 disease. Our findings support the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19.Copyright © 2023

HEMORRHAGIC PLEURAL EFFUSION IN A PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA ON IBRUTINIB THERAPY

SESSION TITLE: Problems in the Pleura Case Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), approved for treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia (CLL). There is an association of increased risk of bleeding with ibrutinib due to platelet dysfunction caused by the medication. Bleeding is usually non-life threating such as subcutaneous or mucosal bleeding, epistaxis, and ecchymosis. But major bleeding has been reported such as intracranial hemorrhage and gastrointestinal hemorrhage. Thoracic complications from ibrutinib are rare. Below is a case report discussing a hemorrhagic pleural effusion thought to be caused by Ibrutinib. CASE PRESENTATION: Patient is a 78-year-old male initially diagnosed with CLL on flow cytometry showing a low-grade B cell lymphoproliferative process. Patient was monitored by Hematology and when kappa light chain numbers began to rise, a bone marrow biopsy was performed showing 90% infiltration of the marrow with lymphoid cells. Patient was started on Ibrutinib therapy and responded well to treatment. A year after starting therapy, patient presented to the emergency room with increased shortness of breath and fatigue. Patient was found to be COVID-19 positive and chest x-ray showed a large right sided pleural effusion. Thoracentesis was performed draining 1650cc of bloody fluid. Fluid studies revealed a lymphocytic effusion with RBC count 1,185375, WBC of 1751. Cultures and cytology were negative. On further history, patient was without recent trauma or surgery, CTA chest was negative for pulmonary embolism. QuantiFERON Gold test was negative, indicating low likelihood of tuberculosis. Patient was not on any antiplatelet or systemic anticoagulation medications. Ibrutinib therapy was held during hospitalization and pleural effusion did not reaccumulate. Patient passed away during hospital stay secondary to respiratory failure due to COVID-19. DISCUSSION: Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib predisposes to bleeding by inhibiting BTK and Tec, which play a role in the inhibitory signaling pathway of platelet collagen receptors such as glycoprotein VI (GP VI) and C-type lectin-like receptor 2 (CLEC-2). Our patient had no other risk factors for developing a hemorrhagic effusion. CLL itself can cause malignant effusions, one study found the incidence of malignant effusions among patients with CLL to be 9%, but the effusion was noted to be serous or serosanguinous and there was pleural involvement in all patients which was not the case in our patient. CONCLUSIONS: There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. It is important to realize bleeding complications related to ibrutinib therapy can occur. Reference #1: Shatzel JJ, Olson SR, Tao DL, McCarty OJT, Danilov AV, DeLoughery TG. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost. 2017;15(5):835-847. doi:10.1111/jth.13651 Reference #2: Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-2437. doi:10.1056/NEJMoa1509388 Reference #3: Paydas S. Management of adverse effects/toxicity of ibrutinib. Crit Rev Oncol Hematol. 2019;136:56-63. doi:10.1016/j.critrevonc.2019.02.001 DISCLOSURES: No relevant relationships by fatima ali No relevant relationships by Joan Wiley

SEVERE IRON DEFICIENCY ANAEMIA SECONDARY TO UTERINE FIBROIDS CAUSING CEREBRAL VENOUS SINUS THROMBOSIS

Background and aims: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke, contributing to less than 1%. We report an unusual case of severe iron deficiency anaemia (IDA) causing CVST in a young woman with menorrhagia. Methods: Case report: A 40-year-old female with underlying anaemia presented with headache, right leg numbness and expressive dysphasia. She experienced massive menstrual bleeding prior to the symptoms onset on background of uterine fibroids. There was no history of contraceptive pills consumption, massive blood transfusion, COVID-19 infection or vaccination. Systemic review was unremarkable. Results: Blood investigations revealed haemoglobin of 4.5g/dl, MCV 52.3fL, platelet 657x1////////09/L and low ferritin level. Coagulation profile, connective tissue disease, thrombophilia screening, serum homocysteine and HIV test were normal. Computed tomography (CT) of the head showed left temporoparietal lobe infarct and left dural venous sinus thrombosis. CT venography revealed CVST within the distal left transverse sinus and the vein of Labbe. Pelvic ultrasound showed multiple uterine fibroids. She was warfarinised and had iron and red cell transfusion. She agreed to take progesterone-only pill and interval hysterectomy after gynaecological review. Discussion: CVST in association with IDA is rare in adults and is more prevalent in men. In IDA, hypercoagulability and venous stasis play a vital role in thrombus formation. One study found that IDA in women caused arachidonic acid-induced platelet dysfunction causing menorrhagia which is reversible with iron repletion. Conclusion: IDA is a rare cause of CVST but should be considered in the context of relevant history and blood tests.

Cerebrovascular Manifestations of COVID-19 in Young Adults

Objective: The aim of this study was to characterize patients hospitalized with COVID-19 and cerebrovascular disease, with a focus on young patients diagnosed with CVST and ICH/SAH. Background: There have been many reported neurologic manifestations of coronavirus disease 2019 (COVID-19) including cerebrovascular events such as ischemic stroke, hemorrhagic stroke including intracerebral hemorrhage/subarachnoid hemorrhage (ICH/SAH) and central venous sinus thrombosis (CVST). However, there has not been much focus on this topic in young adults aged under 50. Design/Methods: Retrospective chart review was used to obtain parameters of patients hospitalized in Chicago area hospitals with COVID-19 and a neurologic diagnosis including acute ischemic stroke, subarachnoid hemorrhage, intracranial hemorrhage, and cerebral venous sinus thrombosis. Data including patients' comorbidities and disease course was entered into a secure database by representatives from 4 different tertiary care centers. Results: A total of 27 patients aged 18 to 50 were hospitalized in Chicago land tertiary care centers from March 30, 2020 to February 1, 2021 with cerebrovascular disease and concurrently tested positive for COVID-19. Of these patients, 2 were found to have venous sinus thrombosis. 9 patients had hemorrhagic strokes, of these, 4 patients with ICH were thought to have had spontaneous hemorrhages. 9 of 27 patients had no past medical history. Conclusions: This population had a large portion, 11 out of 27 patients, with non-ischemic cerebrovascular insults such as CVST, ICH, or SAH while concurrently infected with COVID-19. Unlike most classic patients who develop these conditions, our population did not have traditional risk factors such as smoking or hypertension. Systemic inflammation, hypoxia, platelet dysfunction, or hyper-coagulability due to COVID-19 are theorized as the cause of these cerebrovascular manifestations in the absence of traditional risk factors. Spontaneous cerebrovascular manifestations of COVID-19 continue to be investigated, particularly in younger patients without traditional risk factors.

Coronavirus disease-19 pneumonia: The impact of coagulopathy

The development of coagulopathy is emerging as one of the most significant poor prognostic features in coronavirus disease (COVID)-19 pneumopathy. D-dimer, a protein product of fibrin degradation, has been found elevated in the most severe cases and correlated to mortality. Potentially involved factors in the impairment of coagulation caused by viral infection include the dysregulated inflammatory response, platelet, and endothelial dysfunction with impaired fibrinolysis. Heparin is an anticoagulant molecule that also showed anti-inflammatory properties and a potential antiviral effect. The use of low-molecular-weight heparin could prevent thromboembolic complications in COVID-19 pneumopathy. However, the correct timing of prophylaxis according to the stage of COVID-19 disease and the appropriate therapeutic dosage to use in severe cases needs further researches.

A rare case of reactive arthritis secondary to COVID-19

Case report-IntroductionIn December 2019, the first cluster of Coronavirus disease 2019 (COVID-19) cases caused by the novel coronavirus SARS-CoV-2 was identified in Wuhan, China. The disease was declared a global pandemic on 11th March 2020. COVID-19 was initially thought to cause respiratory complications only, however several extra pulmonary manifestations of the infection have since emerged.We report a rare case of reactive arthritis (ReA), urticarial rash and angioedema in a young female secondary to COVID-19 infection. Rashes were recently added to the World Health Organisation (WHO) criteria for diagnosis of COVID-19 demonstrating their significance.Case report-Case descriptionA 31-year-old female doctor was admitted with acute swelling of her lips, dysphagia, and a widespread urticarial rash. Preceding this she had a one-week history of fever, cough, and constitutional symptoms of malaise and weight loss. Her symptoms had started at the end of April 2020 during the peak of the COVID-19 pandemic in the United Kingdom. Three days later she developed painful swelling of her wrists, elbows, knees, and hands. She reported no back or sacroiliac joint pain, enthesitis or any previous history of inflammatory joint pains. She had a history of platelet dysfunction and was treated with Desmopressin.Clinical examination revealed a widespread urticarial rash over her face, limbs, and trunk, with no nail abnormalities. She had active synovitis in her right wrist, elbow, and mild bilateral knee effusions. All other joints including spine and sacroiliac joints were normal. She had no dactylitis or enthesitis. Systemic examination was normal. Investigations revealed Hb 113 g/L, MCV 88.2 fL, Platelets 282 x 109/L, WCC 6.6 x 109/L and Lymphocytes of 0.63 x 109/L with normal neutrophil and eosinophil count. CRP was raised at 107mg/L. She had a negative autoimmune screen including ANA, ANCA, IgM-RF, anti-CCP antibodies and HLA B27. Plain radiographs of knees were normal. SARS CoV-2 PCR was positive following a nasal swab. Urine and blood cultures were negative. Treatment was commenced with intravenous hydrocortisone and antihistamines with resolution of her angioedema symptoms;however, her rash and arthritis persisted.The patient was diagnosed with Reactive Arthritis (ReA), urticarial rash and angioedema secondary to COVID-19 infection. Prednisolone 30mg daily was started, and within a week her arthritis and rash markedly improved. Prednisolone was tapered over six weeks. By her two-month clinic follow up, she reported no further joint swelling and was functioning normally.Case report-DiscussionThe most common complication of COVID-19 is Acute Respiratory Distress Syndrome (ARDS) however several other serious complications have been identified including cardiac injury, thromboembolic events, neurological abnormalities, and an aggravated inflammatory response causing a cytokine storm.ReA is a post infectious arthritis commonly seen following gastrointestinal or genitourinary infections and is yet to be recognised as a complication of this disease. ReA most commonly presents as an asymmetrical peripheral or axial spondyloarthropathy. The affected joints do not contain pathogen. More than half of ReA cases resolve spontaneously within six months without requiring long-term treatments.Up to 20% of patients with COVID-19 infection have been shown to develop cutaneous manifestations including erythematous rash, vesicular rash, acral ischaemia, rash with petechiae, and widespread urticaria. This has led to the recent addition of rashes to the World Health Organisation (WHO) Criteria for diagnosis of COVID-19 infection. Additionally, as COVID-19 has an incubation period of 14 days where patients can be asymptomatic, cutaneous manifestations may serve as an early indicator of infection, aiding in a more rapid diagnosis.Case report-Key learning pointsWe present a rare case of ReA secondary to COVID-19 infection, with complete resolution of symptoms following administration of oral glucocorticoids. A detailed history and examination of t e musculoskeletal system should be undertaken in all patients presenting with COVID-19. Urticarial rashes should be considered as an early symptom of COVID-19 infection as per the WHO criteria for diagnosis. Glucocorticoids can be considered in treating patients with this presentation, where traditional anti-inflammatory agents have been refractory or contraindicated.