International Survey of Secondary Thromboprophylaxis Practice Patterns in Pediatrics

Background/Aims: Despite the increase in clinicians identifying venous thromboembolism (VTE), we lack robust research to support clinical care guidelines. Although most children are at low risk for VTE recurrence, some have higher risks due to persistent prothrombotic risk factors. However, pediatric-specific guidance and expert consensus to recommend long-term anticoagulation in children is lacking. Understanding provider practices is a vital first step to addressing current limitations in pediatric guidelines for secondary thromboprophylaxis among such high-risk children. Methods: We performed an international survey of pediatric thrombosis physicians to approximate the number of children with persistent prothrombotic risk factors and characterize the contemporary practice patterns for the use of secondary thromboprophylaxis. Potential participants were identified using the membership registries of three of the primary pediatric thrombosis networks: Duration of Therapy for Thrombosis in children investigators, Children's Hospital Acquired Thrombosis consortium and the VENUS pediatric thrombosis subgroup. Surveys were disseminated December 2020 through January 2021 using Qualtrics (Provo, UT). Results: The survey was distributed electronically to 124 potential participants with 80 respondents. After exclusions, 61 complete surveys were evaluable. The majority of responders were from the United States, practicing more than 10 years at freestanding, academic pediatric hospitals with dedicated pediatric thrombosis programs. Providers were more likely to prescribe secondary thromboprophylaxis to adolescents and teenage patients as compared to infants and children. Respondents reported they were most likely to initiate chronic secondary thromboprophylaxis (therapeutic or low dose) in children with a potent thrombophilia (homozygous prothrombin or factor V Leiden mutations, protein C/S levels <20%, Antithrombin levels <30%), recurrent unprovoked VTE and in those with underlying inflammatory disorders (i.e., inflammatory bowel disease, systemic lupus erythematosus, sickle cell disease) and/or chronic indwelling central venous catheters. Conclusion: Our results show variation in practice patterns but less so in areas where we have more definitive guidelines. These findings highlight the need for a multi-center prospective cohort study to determine the impact of various risk factors on recurrence rates. This will inform the design of ultimate interventional studies aimed at safely decreasing the risk of recurrent VTE in children who have persistent prothrombotic risk factors upon completion of a conventional course of anticoagulation for provoked VTE. Disclosures Lebensburger: Novartis: Consultancy; Bio Products Laboratory: Consultancy. Goldenberg: Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

Deep vein thrombosis and pulmonary embolism in pediatric COVID-19

Thrombotic complications of SARS-CoV-2 have been increasingly recognized as an important component of COVID-19 in adults; however, they have been less evident in children. We report a case of a teenager with positive SARS‐CoV‐2 RT–PCR and underlying prothrombotic risk factors, including aromatase inhibitor therapy, who developed deep vein thrombosis resulting in pulmonary embolism. Laboratory tests revealed deranged coagulation parameters (high D-dimers and Factor VIII and low antithrombin). The patient required intensive care and was managed with anticoagulants, dexamethasone and antithrombin concentrate. Clinical condition and hemostatic profile gradually improved. A review of the available literature for similar cases is presented.

Approach to the Evaluation and Treatment of Venous Thromboembolism in Pregnancy

Thrombosis in pregnancy is a major cause of maternal and fetal morbidity and mortality. Risk stratification of venous thromboembolism (VTE) during pregnancy is complex. The hypercoagulability observed in pregnant women can reduce bleeding during childbirth, but may cause thrombosis especially in the presence of additional prothrombotic risk factors such as antiphospholipid antibodies or genetic thrombophilic defects. The availability of large datasets allows for the identification of additional independent risk factors, including assisted reproductive technologies (ARTs), endometriosis, and recurrent pregnancy loss. Data on the risk of VTE linked to COVID-19 in pregnant women are very limited, but suggest that infected pregnant women have an increased risk of VTE. Current guidelines on the prevention and treatment of VTE in pregnancy are based on available, albeit limited, data and mainly present expert opinion. Low-molecular-weight heparins (LMWHs) are the mainstay of anticoagulation to be employed during pregnancy. Administration of LMWH for VTE treatment in pregnancy should be based on the personalized approach, taking into account a weight-based adjusted scheme. During gestation, due to physiological changes, in women at high risk of VTE, monitoring of anti-Xa activity is performed to ensure adequate LMWH dosing. As for the treatment duration for pregnant women with acute VTE, guidelines suggest that anticoagulation should be continued for at least 6 weeks postpartum for a minimum total duration of therapy of 3 months.

Deep neonatal Cerebral Sinovenous Thrombosis: an interesting case report with anticoagulant treatment without risk factors

Cerebral sinovenous thrombosis (CSVT) is an uncommon neurological disease in newborns. Literature data report the association between prothrombotic risk factors and CSVT. This correlation can help the clinician make an earlier diagnosis of this subtle disease. Herein, we describe a severe neonatal CSVT in the absence of significant risk factors.

Incidence and Potential Risk Factors of Catheter Associated Thrombosis in Solid Tumors

PurposeCentral venous catheters (CVCs) have become common practice in oncology. Besides their benefits, as an invasive procedure, several complications are associated with them. Catheter associated thrombosis (CAT) is one of the most relevant due to their impact in quality of life and mortality, but the prothrombotic risk factors implied have been poorly assessed. The aim of the study is to evaluate the incidence of upper extremity deep vein thrombosis (UEDVT) associated to catheter use in patients with solid tumors. Secondary endpoints are to describe the population using CVCs and to evaluate potential risk factors of CAT. MethodsPatients diagnosed of solid tumors assisted at a tertiary level hospital between 2016 and 2019, and using CVCs were included.Results455 patients were enrolled. The incidence of CAT was 5.49% (25) in the whole population. 5.05% (23) was associated with PICC while 0.44% (2) was due to PORT use. Among the factors included in the univariate and multivariate regression models, age ≥50 years and PORT use were identified as protective factors related to the development of CAT.ConclusionCVCs remains a safe approach for the delivering of treatments in patients with solid tumors. Age ≤50 and use of PICC are risk factors for developing CAT. Larger prospective studies are needed to identify additional risk factors of CAT.

The ACUTE ISCHEMIC STROKE INDUCED BY COVID-19 DISEASE- A CASE REPORT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the agent of Coronavirus disease 2019 (COVID-19), may attack the central nervous system in addition to the respiratory system because of its neuro-invasive features. Increased inflammation, immobilization, hypoxia, and disseminated intravascular coagulation may predispose to the cerebrovascular diseases. A 73 years old man presenting to the emergency service with complaints of dyspnea, cough, and high fever was admitted to the hospital after being diagnosed as having COVID-19 upon findings of ground-glass densities and mild parenchymal involvement which was more prominent in the mid- and lower lobes of the lungs on his computerized tomography scan. His treatment was started with chloroquine, azithromycin, ceftriaxone and enoxaparin. On the neurological exam performed for symptoms of dizziness, imbalance, speech disorder and deviation of angle of mouth; he was conscious, cooperating, oriented limitedly and the right nasolabial groove was indistinct and he had dysarthria and ataxia. Acetyl salicylic acid was added to the treatment because cerebral diffusion magnetic resonance imaging revealed limited diffusion consistent with acute ischemia on the right posterolateral area of the bulbus. The patient whose respiratory distress worsened and who was admitted to the intensive care unit developed cardiac and respiratory arrest and he died despite all efforts of resuscitation. It should be kept in mind that the elderly patients with Covid-19 with prothrombotic risk factors are also at risk for cerebrovascular disease in addition to the infectious symptoms. In this case report, a patient infected with SARS-CoV-2 and diagnosed as acute ischemic stroke with anamnesis, clinical and radiological findings is presented.

Increased Frequency of Thromboses Among Patients with Philadelphia (Ph) Negative Myeloproliferative Neoplasms in New Mexico: The Role of Prothrombotic Risk Factors

Introduction Thromboses are a common complication in patients with myeloproliferative neoplasms (MPN) and are reported to occur at a rate of 15- 20% at sea level. In the MPN-Thromboses spectrum which includes both arterial and venous thrombosis, cardiovascular disease (CVD) is noted to be the most common thrombotic event. JAK2 V617F is reported to be the most common driver mutation in MPNs and is associated with increased risk of thromboses. CALR and MPL are other mutations whose contribution to the thrombotic phenotype is not known. Chronic hypoxia from living in moderate or high altitude is reported to be an independent prothrombotic risk factor. The average elevation of New Mexico is 5,700 feet (1,740 meters) above sea level. The goal of this study is to evaluate the frequency of thromboses and prothrombotic risk factors in patients with MPN in patients in this distinct population. Methods We reviewed 134 patients, who were diagnosed with MPN in University of New Mexico Comprehensive Cancer Center between 2001 to 2019. A retrospective chart review was conducted to identify demographics, clinical and molecular risk factors for both arterial and venous thromboses. The mutation analyses for Janus Kinase 2 (JAK2), myeloproliferative leukemia (MPL) gene and calreticulin (CALR) gene were performed by polymerase chain reaction (PCR). Contingency table and logistic regression methods were applied to analyze and compare the distribution of the prothrombotic risk factors between the patients with and without thrombosis. Results In this study, 62 patients (47%) were diagnosed with ET, 47 patients (35%) with PV, and 22 patients (17%) with primary myelofibrosis (PMF). Seventy-five patients (56%) were females. Mean age at diagnosis was 62 years. 102 patients (77%) were living in the Albuquerque metropolitan area with an average elevation of 5312 feet above sea level and others were in areas with an elevation of 6000 feet or higher in New Mexico. Forty-four patients (33%) experienced either arterial (29) or venous thromboses (11) or both (4). A significant percentage (70.4%) of thrombotic events were either ischemic stroke or myocardial infarction. The patients with thromboses were predominantly males (21/36, 57%) while most patients without thromboses were females (56/90, 62%) with p=0.003. Twenty-one (53%) patients with thromboses had ET; however, a higher proportion of patients with PV (20/47, 42.5%) developed thromboses compared to ET or PMF (32.2% and 9% respectively). Also, a significant number of patients (32/44, 76%) with thromboses have JAK2 mutations while only 4 patients (9%) have CALR gene mutation. Although not statistically significant, CALR mutation was associated with lesser thrombotic events than other MPN patients. In univariate logistic regression analysis, PV and ET were significantly associated with increased thrombotic events. Patients with PV showed a 7.7-fold increase and patients with ET have a 5.1-fold increase in odds for thrombosis compared to patients with PMF (p=0.0365). Female gender was associated with decreased thrombotic risk with an odds ratio of 0.46 (p=0.0387). There was no significant difference between patients with and without thromboses, regarding other clinical characteristics such as age, previous aspirin use, leukocytosis, diabetes, hypertension, hyperlipidemia, obesity, and smoking. Conclusion An increased frequency of thromboses was observed among patients with Ph negative MPN in New Mexico which is significantly higher than previously reported studies. This strongly suggests the role of mild to moderate hypoxia as a contributing prothrombotic risk factor for MPN. The role of chronic hypoxia and its influence in thrombotic events in MPN need to be further evaluated in prospective studies. The decreased risk of thrombosis in females and patients harboring CALR mutations compared to other common mutations was consistent with other published studies. JAK2 mutation was not associated with an increased risk of thrombosis. Other genetic factors in this population were not evaluated in this study. Disclosures Arana Yi: Jazz Pharmaceuticals: Other: Advisory Board.