Asymptomatic Pulmonary Embolism Research Articles

Upper extremity deep venous thrombosis prevalence in the NHS Grampian Medical Ambulatory clinic: diagnostic, therapeutic, and prognostic considerations in oncology patients

IntroductionWhilst upper extremity deep vein thromboses (UEDVT) account for approximately 5 to 10% of all cases of DVT, rigorous guidelines regarding diagnosis and management of presenting patients remain to be developed. The association of UEDVT with concurrent asymptomatic pulmonary embolism as well as the first presentation of malignancy deems essential rigorous research and clinical guideline development to ensure optimal patient care.MethodsThis retrospective audit study is the first to provide estimates of UEDVT prevalence in the North-East Deanery main hospital centre, Aberdeen Royal Infirmary (ARI).ResultsOf the 605 patients attending the ARI Ambulatory Emergency Care (AEC) clinic with clinical suspicion of UEDVT, 38 (6.2%) had a confirmatory diagnosis. Underlying malignancy, presence of PICC line, and cardiovascular co-morbidities were identified as common confounding factors. Subclavian vein with concurrent extension to primarily the cephalic vein thrombosis was identified as the most commonly thrombosed venous territories. Importantly, oncology patients were found to have poorer survival outcomes following an UEDVT, in comparison to patients with other significant co-morbidities (cardiovascular, chronic renal disease, inflammatory bowel disease): HR 5.814 (95%CI 1.15, 29.25), p 0.012. Lastly, genetic associations were drawn between patient genetic status as tested for other co-morbidities and prothrombotic cellular cascades, suggesting rigorous VTE assessment in patients identified with congenital or acquired mutations, namely, in CALR, JAK, MSH 2/6, MYC, and FXN.ConclusionsOverall, this study offers the first report of UEDVT presentations in the UK with no restrictions of patient performance status or underlying co-morbidities and provides a rounded clinical picture of patient characteristics, diagnosis, management, and prognostic associations in view of rigorous guideline development.

Tocilizumab in SARS-COVID19 following postoperative laparoscopic transhiatal esophagectomy for the adenocarcinoma of esophagogastric tumor: A case report.

Introduction and importanceEsophagectomy for esophageal cancer is one of the most challenging surgical procedures, with high rates of morbidity, especially from respiratory complications. SARS-COVID19 represents a health threat nowadays. Peri-operative SARS-COVID19 infection after esophagectomy might negatively affect the postoperative outcomes. The use of tocilizumab as an alternative to reduce the inflammatory response in SARS-COVID19 is an option that has not been described in the literature after esophagectomy.Case presentationA SARS-COVID19-vaccinated (CORONAVAC) 73-year-old man with pulmonary emphysema, coronary artery disease, previous asymptomatic pulmonary embolism, and adenocarcinoma of the esophagogastric junction tumor was submitted to laparoscopic transhiatal esophagectomy (ypT2N0M0) after perioperative neoadjuvant chemotherapy. He was also infected with SARS-COVID19, confirmed by PCR test at the 14th postoperative day. During follow-up, mild hypoxemia persisted without evidence of infection except for SARS-COVID19, and a high-flow cannula was required to maintain oxygenation. Tocilizumab was administered following high parameters of a high-flow cannula, and invasive mechanical ventilation was avoided.DiscussionBesides of the risk of secondary infection, after administration of tocilizumab, the parameters of oxygen supplementation were systematically reduced, and he stayed in the ICU for seven days. He was discharged from the ward six days later. He developed late cervical anastomotic leakage, which was treated with conservative therapy.ConclusionAlthough the patient had high-risk comorbidities, esophagectomy, and SARS-COVID19 infection, the use of tocilizumab was safe and improved the pulmonary recovery.

Renal Vein Thrombosis and Pulmonary Embolism Secondary to Vaccine-induced Thrombotic Thrombocytopenia (VITT).

The Medicines and Healthcare products Regulatory Agency (MHRA) of the UK has approved the use of three vaccines to combat COVID-19 (SARS-CoV-2). There have been rare reports of thrombosis after vaccination with the AstraZeneca vaccine. We present three cases of vaccine-induced thrombotic thrombocytopenia (VITT) in one UK district general hospital following administration of this vaccine. Two of the patients had asymptomatic pulmonary emboli, while the other is the first known case of both renal vein thrombosis and pulmonary embolism.LEARNING POINTSVaccine-induced thrombotic thrombocytopenia (VITT) can be associated with unusual and multiple sites of thrombosis.Clinicians should have a low threshold for requesting anti-PF4 antibody tests and imaging (especially pulmonary imaging) in thrombocytopenic patients after administration of the AstraZeneca vaccine.We describe a localised cluster of VITT despite its rarity according to current statistics, highlighting the need for an efficient data collection system to ensure the incidence of VITT is accurately reported.

Prevalence of Symptomatic Venous Thromboembolism in Patients with Malignant Bone and Soft Tissue Tumors Undergo Surgery without Chemoprophylaxis

Background: The prevalence and risk factors of venous thromboembolism (VTE) in malignant bone and soft tissue tumor patients that undergo surgery is reported in many studies. However, there is lack of studies on the patients without chemoprophylaxis. Objective: To evaluate the prevalence and risk factors for VTE after surgery in malignant bone and soft tissue tumor patients without chemoprophylaxis Materials and Methods: A retrospective medical chart review identified 260 cases of malignant bone and soft tissue tumor operated between 2008 and 2017. Official diagnostic reports were reviewed from the Picture Archiving and Communication System (PACs). The incidence of VTE and its risk factors were assessed using Chi-square test, t-test, and binary logistic regression. Results: The overall prevalence of symptomatic VTE was 0.8% (2/260 patients), all of which had PE. No fatal VTE was detected. Asymptomatic pulmonary embolism (PE) was identified in two patients (0.8%) Mean follow up interval of the available data was 9.5 (3 to 36) months. No significant risk factor was found. Conclusion: The authors found that patients with malignant bone and soft tissue tumors that underwent surgery without chemoprophylaxis in the authors’ center had lower prevalence of VTE when compared to most previous studies whose patient received chemoprophylaxis. Keywords: Venous thromboembolism, Sarcoma, Cancer, Deep vein thrombosis, Pulmonary embolism, Thromboprophylaxis, Chemoprophylaxis

Safety and efficacy of cement augmentation with fenestrated pedicle screws for tumor-related spinal instability

Achieving rigid spinal fixation can be challenging in patients with cancer-related instability, as factors such as osteopenia, radiation, and immunosuppression adversely affect bone quality. Augmenting pedicle screws with cement is a strategy to overcome construct failure. This study aimed to assess the safety and efficacy of cement augmentation with fenestrated pedicle screws in patients undergoing posterior, open thoracolumbar surgery for spinal metastases. A retrospective review was performed for patients who underwent surgery for cancer-related spine instability from 2016 to 2019 at the Massachusetts General Hospital. Patient demographics, surgical details, radiographic characteristics, patterns of cement extravasation, complications, and prospectively collected Patient-Reported Outcomes Measurement Information System Pain Interference and Pain Intensity scores were analyzed using descriptive statistics. Logistic regression was performed to determine factors associated with cement extravasation. Sixty-nine patients underwent open posterior surgery with a total of 502 cement-augmented screws (mean 7.8 screws per construct). The median follow-up period for those who survived past 90 days was 25.3 months (IQR 10.8-34.6 months). Thirteen patients (18.8%) either died within 90 days or were lost to follow-up. Postoperative CT was performed to assess the instrumentation and patterns of cement extravasation. There was no screw loosening, pullout, or failure. The rate of cement extravasation was 28.9% (145/502), most commonly through the segmental veins (77/145, 53.1%). Screws breaching the lateral border of the pedicle but with fenestrations within the vertebral body were associated with a higher risk of leakage through the segmental veins compared with screws without any breach (OR 8.77, 95% CI 2.84-29.79; p < 0.001). Cement extravasation did not cause symptoms except in 1 patient who developed a symptomatic thoracic radiculopathy requiring decompression. There was 1 case of asymptomatic pulmonary cement embolism. Patients experienced significant pain improvement at the 3-month follow-up, with decreases in Pain Interference (mean change 15.8, 95% CI 14.5-17.1; p < 0.001) and Pain Intensity (mean change 28.5, 95% CI 26.7-30.4; p < 0.001). Cement augmentation through fenestrated pedicle screws is a safe and effective option for spine stabilization in the cancer population. The risk of clinically significant adverse events from cement extravasation is very low.

Risk Factors and Outcomes for Preoperative Asymptomatic Pulmonary Embolism in Patients Aged 60 Years and Over with Hip Fracture.

ObjectiveTo investigate the risk factors for, and outcomes of, preoperative asymptomatic pulmonary embolism (PE) in patients ≥60 years old following delayed operation for hip fracture.MethodsFrom March 2017 to December 2018, 90 patients aged ≥60 years with hip fracture who suffered a delay in surgery were recruited to this prospective study following admission to our hospital. Computed tomography pulmonary angiography (CTPA) was used to detect preoperative asymptomatic PE and calculated its incidence. Time from injury to admission, baseline characteristics, medical comorbidities, and blood biomarker levels were evaluated as potential risk factors. Logistic regression analysis was used to identify risk factors. Mortality and major bleeding events were recorded and compared between individuals with PE and without. Data were analyzed by t‐test, Mann–Whitney U test, χ 2 test, Fisher's exact test, and logistic regression analysis.ResultsThe incidence of preoperative asymptomatic PE was 18.9% (17/90 patients). In the univariate analysis, the risk factors for preoperative asymptomatic PE were male sex, hypertension, cerebrovascular accident, smoking, plasma D‐dimer level, potassium level, urea level, creatinine level, and cysteine level. Multivariate logistic regression analysis showed that the risk of preoperative asymptomatic PE was higher in patients with hypertension (odds ratio [OR] = 10.048; 95% confidence interval [CI], 1.118–90.333), cerebrovascular accident (OR = 20.135; 95% CI, 1.875–216.164), smoking (OR = 48.741; 95% CI, 4.155–571.788), high plasma D‐dimer levels (OR = 1.200; 95% CI, 1.062–157.300), and high plasma potassium levels (OR = 12.928; 95% CI, 1.062–157.300). All patients were followed up for 21.0 months (range, 2 to 36 months). Mortality within the first year postoperatively was higher in patients with PE (29.41% vs 9.59%, P = 0.046).ConclusionsIn view of the high incidence of preoperative asymptomatic PE and the inferior prognosis in individuals with PE, routine CTPA examination for preoperative asymptomatic PE could be useful for patients aged ≥60 years with hip fracture for whom surgery is delayed.

Prognostic Significance of Asymptomatic Pulmonary Embolism on Routine Ventilation-Perfusion Scans after Lung Transplantation

<h3>Purpose</h3> Asymptomatic pulmonary embolism (PE) is a challenging clinical entity with unclear treatment implications. This is also true of PE detected on routine studies after lung transplant were clot may be donor derived. Our program performs routine ventilation-perfusion (VQ) scans at 3-months post-transplant to establish baseline airway and vascular function but in some cases, these are positive for PE. We hypothesized that asymptomatic PE in this context would carry a benign prognosis irrespective of therapy. <h3>Methods</h3> We studied VQ scans obtained routinely at 3-months post-transplant from double lung transplant recipients in our program between 2004-2016. The risk group was patients whose studies were interpreted as high probability for PE. We used chi square testing for the relationship between PE with 1-year survival. We also used Kaplan Meier analysis with log rank testing and t-tests for the association with overall survival and peak forced expiratory volume in 1 second (FEV1) percent predicted. <h3>Results</h3> 373 patients met inclusion criteria, of whom 35 (9%) had VQ scans interpreted as high probability for PE. The PE group were less likely to have had severe primary graft dysfunction (3% vs. 19%; p=0.03) but were otherwise similar to patients without PE. 7 patients in the PE group (20%) were treated with therapeutic anticoagulation and the remainder treated expectantly. Patients with PE had similar 1-year survival (100% vs. 98%, p=1.00), overall survival (log rank p=0.90) and peak FEV1% predicted (94% [SD 20%] vs. 92% [SD 21%]; p=0.58). We observed no differences between treated and untreated PE. <h3>Conclusion</h3> Asymptomatic PE diagnosed on routine post-transplant VQ scan was not associated with a difference in survival or lung function, irrespective of therapy. This may suggest these changes are donor derived and not reflective of recipient hypercoagulability.

Determination of the value of albumin, anti-thrombin III, fibrinogen and D-dimer factors in the diagnosis of asymptomatic pulmonary embolism in patients with nephrotic syndrome.

Thromboembolism is one of the most important and dangerous complications of nephrotic syndrome. This study aimed to determine the value of albumin, anti-thrombin III, fibrinogen and D-dimer factors in the prediction of asymptomatic pulmonary embolism in patients with nephrotic syndrome in non-remission period. Plasma levels of albumin, anti-thrombin III, fibrinogen and D-dimer were assessed in 30 nephrotic children in non-remission period (including new case-patient or relapse period), and the results were compared with chest X-ray and lung perfusion scintigraphy (Q scan). The mean age of patients was 6.22 ± 3.5 years (range 2-12 years). Of patients, 23.3% had abnormal findings in perfusion scan suggestive of pulmonary emboli despite absence of any respiratory manifestations. Median plasma albumin and anti-thrombin III levels in patients with asymptomatic pulmonary embolism were lower than in patients without pulmonary embolism. Also, median fibrinogen and D-dimer levels in patients with asymptomatic pulmonary embolism were higher than in patients without pulmonary embolism, with no statistically significant differences between sex, age, hemoglobin and hematocrit of patients and lung perfusion scan results. Patients with abnormal blood levels of albumin (< 3.5 g/dl), anti-thrombin III (< 80 ml/dl), fibrinogen (> 400 ml/dl) and D-dimer (> 0.5 μg/dl) underwent CXR/Q scan and were treated with heparin if there was pulmonary embolism.

Is routine screening for silent pulmonary embolism justified in patients with deep vein thrombosis?

The incidence of asymptomatic pulmonary embolism (PE) exceeds 70% in patients with deep venous thrombosis (DVT), even in cases of distal deep vein thrombosis. We report the case of a patient with a diagnosis of DVT in the lower left limb associated with asymptomatic PE who presented late symptoms due to this same PE. The absence of acute symptoms and the late onset of symptoms could have provoked doubts about the most appropriate treatment, resulting in unnecessary interventions, if pulmonary embolism had not already been diagnosed with tomography. In the present case, we demonstrate that computed tomography angiography conducted at the time of DVT diagnosis accurately diagnosed PE and prevented any misinterpretation of recurrent DVT in a patient already being medicated, which could have been mistakenly interpreted as demonstrating failure of anticoagulant therapy. Such a situation could lead to unnecessary intervention to fit an inferior vena cava filter. We cannot suggest that a classic medical conduct should be reformulated simply on the basis of a case report. However, we would be remiss not to suggest that well-designed studies should be carried out in the future to assess the need for this examination in the acute phase.

Clinical characteristics and 3-month outcomes in cancer patients with incidental versus clinically suspected and confirmed pulmonary embolism.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared. We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PE versus those with clinically suspected and confirmed PE. The primary outcome was 90-day all-cause mortality. Secondary outcomes were PE-related mortality, symptomatic PE recurrences and major bleeding. From July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95% versus 90%) received low-molecular-weight heparin therapy. During the first 90 days, 598 patients died, including 42 from PE. Patients with incidental PE had a lower all-cause mortality rate than those with suspected and confirmed PE (11% versus 22%; OR 0.43, 95% CI 0.34-0.54). Results were consistent for PE-related mortality (0.3% versus 1.7%; OR 0.18, 95% CI 0.06-0.59). Multivariable analysis confirmed that patients with incidental PE were at lower risk of death (adjusted OR 0.43, 95% CI 0.34-0.56). Overall, 29 (0.9%) patients developed symptomatic PE recurrences, and 122 (3.8%) had major bleeding. There were no significant differences in PE recurrences (OR 0.62, 95% CI 0.25-1.54) or major bleeding (OR 0.78, 95% CI 0.51-1.18). Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.

LARGE SADDLE PULMONARY EMBOLUS IN AN ASYMPTOMATIC PATIENT

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary embolism (PE) represents a mechanical obstruction of one or more branches of the pulmonary vasculature, usually due to a blood clot. Saddle PE lodges at the bifurcation of the main pulmonary artery, often extending into the right and left main pulmonary arteries. Approximately 3 to 6 percent of patients with PE present with a saddle embolus. We report an atypical case of asymptomatic large saddle PE with normal right heart function. CASE PRESENTATION: A 47-year-old male with history of diabetes, OSA, hypertension, obesity and family history of Factor V Leiden mutation presented with 1-day history of progressively worsening left leg pain and swelling. He denied any fevers, chills, SOB, cough or palpitations, recent surgery, or long car rides. On physical examination, the patient was comfortable, alert and oriented, afebrile, respiratory rate 21/minute, saturating 97% on room air. Laboratory workup was insignificant. EKG showed sinus tachycardia. Venous scan of left lower extremity revealed subacute deep venous thrombosis (DVT) involving the left femoral and popliteal veins. CT pulmonary angiography (CTPA) revealed extensive bilateral pulmonary emboli with large saddle. 2D ECHO revealed normal left ventricle (LV) systolic function with ejection fraction >55% and normal right ventricle (RV) size and function. Patient was started on heparin drip and switched to Eliquis. He was discharged home in a stable condition. DISCUSSION: Saddle PE is a radiologic definition and refers to thrombus that straddles the bifurcation of the pulmonary artery trunk. Saddle PE is found in 2.6% to 5.4% of patients with PE.1,2 Patients with saddle PE presented more frequently with concurrent DVT on hospital admission (75%).3 The presenting symptoms are dyspnea (72%), syncope (43%). Our patient presented with progressive left leg swelling and pain with DVT and no respiratory symptoms. Alkinj et al in 20172 had reported that 18% of patients with saddle PE had normal RV systolic function. One third patients had hemodynamic instability fulfilling the definition of massive PE unlike in our patient. Our patient was hemodynamically stable and had normal RV function, the risk of bleeding outweighed the benefits of fibrinolytic therapy, therefore this patient was managed with conventional treatment. CONCLUSIONS: Despite looking sinister in appearance on imaging studies, patients with saddle pulmonary embolus may be nearly asymptomatic, hemodynamically stable and can be successfully managed with conventional treatment. Reference #1: Ryu JH, Pellikka PA, Froehling DA, Peters SG, Aughenbaugh GL.Saddle pulmonary embolism diagnosed by CT angiography: frequency,clinical features and outcome. Respir Med. 2007;101(7):1537-1542. Reference #2: Alkinj B, Pannu BS, Apala DR, Kotecha A, Kashyap R, Iyer VN. Saddle vs Nonsaddle Pulmonary Embolism: Clinical Presentation, Hemodynamics, Management, and Outcomes. Mayo Clin Proc. 2017;92(10):1511-1518. Reference #3: Girard P, Musset D, Parent F, Maitre S, Phlippoteau C, Simonneau G. High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism. Chest 1999;116:903-8. DISCLOSURES: No relevant relationships by Salil Avasthi, source=Web Response No relevant relationships by DEEPTI AVASTHI, source=Web Response No relevant relationships by Rathnavali Katragadda, source=Web Response No relevant relationships by Shanti Pittampalli, source=Web Response

Paget-Schroetter Syndrome with Asymptomatic Pulmonary Embolism in a Collegiate Baseball Pitcher

Paget-Schroetter Syndrome with Asymptomatic Pulmonary Embolism in a Collegiate Baseball Pitcher

Paget-Schroetter Syndrome with Asymptomatic Pulmonary Embolism in a Collegiate Baseball Pitcher

Introduction: An 18-year old baseball player with a history of chronic right arm swelling presented with a 1-day history of right arm soreness, swelling, and discoloration. The patient was found to have right upper extremity deep venous thrombosis (DVT) and bilateral lower lobe pulmonary emboli. The patient was diagnosed with Paget-Schroetter Syndrome (PSS), also known as effort thrombosis, which is a rare subset of thoracic outlet syndrome in which DVT of the upper extremity occurs resulting from repetitive microtrauma and compression of the subclavian vein. The patient was treated with …

Asymptomatic pulmonary embolism secondary to cement leakage after vertebroplasty

Asymptomatic pulmonary embolism secondary to cement leakage after vertebroplasty

Prostate Cancer-Associated Trousseau´S Syndrome Versus Asymptomatic Isolated Muscular Calf Vein Thrombosis as the Origin of Acute Submassive Pulmonary Embolism: A Case Report and Review of the Literature

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients. Cancer patients have a four to sevenfold increased risk of VTE compared with non-cancer patients and approximately 20% -30% of all VTE occurs in patients with cancer. Incidence of VTE varies with cancer type and is the highest among patients with metastatic-stage disease. Assessing risk of VTE in the patients with cancer and risk stratification tools as the Khorana score may predict VTE. The highest risk is associated with cancers of the pancreas, stomach, brain, and lung and some hematologic malignancies, whereas lower risks are associated with breast and prostate cancer. The incidence rate ratio (IRR) for prostate cancer is 3.25(2,56 - 4,13) and for pancreas 15.56 (10.50-23.0). We give a case report with a quite perplexing undertaking, where a submassive acute pulmonary embolism (PE) originated from an asymptomatic calf vein thrombosis or intertwined with the Trousseau´s syndrome. Essential Section: One of the authors (A.T) was unexpected faced with the diagnosis of poorly differentiated prostate cancer. There were no signs of the disease, the PSA level was normal. As a retired medical oncologist, he had to care for many patients with prostate cancer and had now to cope with this cancer. To make the matter worse he suffered after the radical prostatectomy a submassive asymptomatic pulmonary embolism. Clinically there were no signs if a deep venous thrombosis. The coincidence of both events without clinical signs of a thrombosis could be caused by the Trousseau´s syndrome. Prostasomes extracellular vesicles synthesizes by prostate cancer cells and secreted into body fluids are prothrombotic by virtue of the expression of polyphosphate-activated coagulation factor XII.

Asymptomatic Pulmonary Cement Embolism after Cement-Augmented Pedicle Screw Instrumentation: A Case Report

Asymptomatic Pulmonary Cement Embolism after Cement-Augmented Pedicle Screw Instrumentation: A Case Report

Abstract P5-11-06: Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine therapy

Abstract Background: TTC-352 is a selective human ER partial agonist (ShERPA) developed for treatment of ER+ breast cancer (BC). ShERPAs mimic the effects of estradiol (E2) in hormone-independent, endocrine-resistant BC cells, but since it has only partial agonist activity in ER+ cells, it could have an improved side effect profile. Thus, TTC-352 could be a promising option for endocrine-resistant BC. Methods: This is an open-label, accelerated dose escalation study with primary endpoint of maximum tolerated dose (MTD) that is evaluating up to five dose levels of TTC-352 in patients with ER+ endocrine-resistant metastatic BC (NCT03201913). The MTD of TTC-352 is determined using initial single-patient cohort escalations until grade 2 toxicity, then expansion to a modified-Fibonacci dose-escalation 3+3 design. The secondary objectives are: best response (BR), progression-free survival, overall survival, treatment tolerability, and pharmacokinetics (PK) of TTC-352. Patient population: patients with metastatic ER+ BC who received and progressed on at least two lines of endocrine therapy, with one that included a CDK4/CDK6 inhibitor, and with adequate hepatic, renal, and bone marrow function at screening. Results: This study completed enrollment of a total of 15 patients on June 5, 2019. Dose LevelTTC-352 Dose Level (mg)Number of SubjectsTwice-Daily (BID) DoseTotal Daily Dose115302230601360120141202401518036010 No dose limiting toxicity has been seen to date with any of the tested dose levels. There was one treatment-related grade 3 event of asymptomatic pulmonary embolism (30mg BID). The number and percentage (n, %) of patients with treatment-related grade 1 and grade 2 adverse events reported in two or more patients across all dose levels were diarrhea (9, 60), hot flush (4, 26), headache (3, 20), nausea (3, 20), abdominal pain (3, 20), rash (3, 20), blurred vision (2, 13) vomiting (2, 13), dizziness (2, 13), peripheral neuropathy (2, 13), breast pain (2, 13), uterine/vaginal hemorrhage (2, 13) and vaginal discharge (2, 13). BR in the 7 evaluable patients (patients with at least two 28-day cycles of treatment) showed that 3 patients had stable disease (SD) for 4, and 10 months, respectively; 1 patient continues study treatment with SD after 9 months; and 4 patients had progressive disease (PD) after completing two cycles of treatment. All 5 non-evaluable patients had PD prior to completing two cycles of treatment. PK: The intra- and inter-individual variability for AUC0-∞ hampered assessment of the relationship between dose and AUC0-∞., Half-life was 7.6-14.3 hrs. Trough TTC-352 plasma concentrations at steady-state (SS) remained well above the plasma concentrations associated with efficacy in animal models. PKC alpha expression in tumor tissue did not correlate with length of disease control with TTC-352 therapy, though the numbers are small and not all of the available specimens were metastatic. Conclusions: TTC 352 demonstrates manageable safety and early clinical evidence of antitumor activity in patients with BC progressing on endocrine therapy. Based upon SS TTC-352 plasma concentrations and tolerability, the 180mg BID dose is recommended for further testing. Citation Format: Ruth O'Regan, Randolph Hurley, Jasgit Sachdev, Jonathan Bleeker, Debra Tonetti, Gregory Thatcher, Robert Venuti, Arkadiusz Dudek. Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-06.

COT-18 TWO CASES OF GLIOBLASTOMA WITH ASYMPTOMATIC PULMONARY ARTERY EMBOLISM AND DEEP VEIN THROMBOSIS FROM ADMISSION TO HOSPITAL

Patients with malignant tumors are susceptible to concurrent venous thromboembolism. We report two cases of glioblastomas that showed asymptomatic pulmonary embolism and deep vein thrombosis on admission. The first case was a 77-year-old male. He was referred to our clinic for a tumor found in the left temporal lobe on computed tomography scan performed when he suffered pneumonia. On admission,he had a Karnofsky performance status (KPS) score of 50 and an elevated D-dimer level (16.46 μg/ml). Pulmonary embolism and deep vein thrombosis were noted on detailed examination. Direct oral anticoagulant (DOAC) therapy resulted in the disappearance of pulmonary embolism. On biopsy,the tumor was diagnosed as glioblastoma. The patient underwent radiation therapy in combination with chemotherapy. The second case was a 71-year-old female. She developed a disorder of consciousness and was admitted to a clinic. Brain magnetic resonance imaging (MRI) revealed a high T2 signal area in the left temporal lobe. The patient was initially diagnosed with encephalitis. Though the consciousness disorder improved quickly,she was referred to our clinic after a hyperintense area was observed on MRI. On admission,she had a KPS score of 100,and an elevated D-dimer level (7.59μg/ml),revealing pulmonary embolism and deep vein thrombosis. She was started on a DOAC and underwent surgical removal of the tumor via craniotomy. She was diagnosed with glioblastoma and underwent radiation therapy in combination with chemotherapy. Approximately 20% of the patients with glioblastomas suffer concurrent symptomatic venous thromboembolism. The incidence of venous thromboembolism is further elevated in patients with a poor KPS score or elderly people. Many patients with glioblastomas suffer asymptomatic venous thromboembolism. In this report,asymptomatic venous thromboembolism was noted in patients with a good KPS score. In glioblastoma patients,it is necessary to test for venous thromboembolism by measuring D-dimer levels before surgery.

Evaluation of a D-Dimer Protocol for Detection of Venous Thromboembolism

The use of venous duplex ultrasonography (VDU) for confirmation of deep venous thrombosis in neurosurgical patients is costly and requires experienced personnel. We evaluated a protocol using D-dimer levels to screen for venous thromboembolism (VTE), defined as deep venous thrombosis and asymptomatic pulmonary embolism. We used a retrospective bioinformatics analysis to identify neurosurgical inpatients who had undergone a protocol assessing the serum D-dimer levels and had undergone a VDU study to evaluate for the presence of VTE from March 2008 through July 2017. The clinical risk factors and D-dimer levels were evaluated for the prediction of VTE. In the 1918 patient encounters identified, the overall VTE detection rate was 28.7%. Using a receiver operating characteristic curve, an area under the curve of 0.58 was identified for all D-dimer values (P= 0.0001). A D-dimer level of ≥2.5 μg/mL on admission conferred a 30% greater relative risk of VTE (sensitivity, 0.43; specificity, 0.67; positive predictive value, 0.27; negative predictive value, 0.8). A D-dimer value of ≥3.5 μg/mL during hospitalization yielded a 28% greater relative risk of VTE (sensitivity, 0.73; specificity, 0.32; positive predictive value, 0.24; negative predictive value, 0.81). Multivariable logistic regression showed that age, male sex, length of stay, tumor or other neurological disease diagnosis, and D-dimer level ≥3.5 μg/mL during hospitalization were independent predictors of VTE. The D-dimer protocol was beneficial in identifying VTE in a heterogeneous group of neurosurgical patients by prompting VDU evaluation for patients with a D-dimer values of ≥3.5 μg/mL during hospitalization. Refinement of this screening model is necessary to improve the identification of VTE in a practical and cost-effective manner.

OC4. Abstract Title: Thrombus Stability Explains the Factor V Leiden Paradox: A Mouse Model

<h3>Background</h3> Factor V Leiden (FVL) is an inherited autosomal dominant condition that is identified in 20%-50% of patients with venous thromboembolic diseases and 5-8% of the population in Canada. People with FVL are often called hypercoagulable, and have a five-fold increase in the risk of venous thrombosis. There is a low prevalence of FVL among patients with fatal pulmonary embolism (PE) and a higher incidence of deep vein thrombosis (DVT) than PE in patients with FVL. This has been referred to as the FVL paradox in thrombosis. We wished to test whether FVL and normal patients are at the same risk of initial thrombus formation, expect FVL patients present with symptomatic DVT while normal patients do not present, because the small asymptomatic DVT in normal patients embolizes to become an asymptomatic PE. <h3>Aim</h3> Therefore, to explain why patients with FVL are more likely to present with a DVT rather than a PE we will study DVT stability in FVL mice using a modification of our previously published mouse model of venous thrombus stability. <h3>Methods</h3> Platelets were fluorescently labeled using CD41 fab fragments conjugated to an Alexa Fluor 488. DVT was induced using a ferric chloride saturated filter paper on the femoral vein of female mice. We chose conditions such that only a small thrombus developed in wild type (WT) mice, and then compared them to thrombi in FVL heterozygous (F5L/+) and FVL homozygous (F5L/L) mice. Intravital videomicroscopy recorded embolic events leaving the thrombus and the thrombus sizes every 10 minutes for 2 hours. Lungs were harvested sectioned and stained for presence of PE. <h3>Results</h3> Although thrombus size remained small in WT mice, it significantly increased over time in F5L/+ and F5L/L mice. The number of total and large embolic events, and the percent of thrombus that embolized was significantly decreased in F5L/+ and F5L/L mice compared to WT mice. Previously we have correlated increased large embolic events with increased PE burden. FVL mice had significantly reduced PE burden compared to WT mice. Mice with F5L had higher F1.2 levels than in WT, consistent with increased thrombin generation. <h3>Conclusion</h3> This suggests that in noncarriers (reflected by WT), a minor insult initially resulting in a small DVT tends to remain small and asymptomatic, due to the embolization. Alternatively, the same insult in people with FVL (reflected by F5L/L) leads to thrombus growth due to less embolization and thus development of symptomatic DVT, but no PE.