Jean Marie Connors

Brigham and Women's Hospital/Dana farber cancer Institute · Hematology Division

International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs) monotherapy for the initial and long-term treatment of cancer-associated thrombosis (CAT). Several new randomized controlled trials (RCTs) have recently reported additional results on t...

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a...

Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end‐organ failure, and possibly mortality in patients with coronavirus disease 2019 (COVID‐19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient...

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Importance Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism...

Direct-acting oral anticoagulant (DOAC) use has increased dramatically since their introduction because of the growing evidence of proven efficacy and enhanced safety compared with warfarin and the low-molecular-weight heparins in the general population. Unfortunately, there is a dearth of quality data regarding the safety and efficacy of the DOACs...

(Anesth Analg. 2021;133:1244–1250) Von Willebrand disease (vWD) affects 1% to 2% of the population and can complicate neuraxial anesthesia in obstetric patients. Currently, there are no clear guidelines for the pretreatment and timing of neuraxial anesthesia in pregnant patients with vWD. Previous reports suggest safe neuraxial anesthesia is attain...

Vaccines to combat SARS-CoV-2 infection and the COVID-19 pandemic were quickly developed due to significant and combined efforts by the scientific community, government agencies, and private sector pharmaceutical and biotechnology companies. Following vaccine development, which took less than a year to accomplish, randomized placebo controlled clin...

Testing for polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene is still a standard part of thrombophilia testing in many laboratories. However, it is clear that these polymorphisms are not risk factors for arterial or venous thrombosis and therefore should not be part of thrombophilia testing. Eliminating MTHFR from thrombophilia...

Background Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment–related bleeding, but the correlation of these risks with the cancer stage is unclear. Methods We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients...

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications,...

Background: In 2017, the Brigham and Women's Hospital Anticoagulation Management Service (BWH AMS) expanded services to patients on direct oral anticoagulants (DOACs). We have since updated our DOAC management plan and adjusted the workflow of our clinic. Objectives: This report describes how our DOAC management has evolved and describes key int...

Heatstroke is increasingly becoming a significant concern due to global warming. Systemic inflammation and coagulopathy are the two major factors that provoke life-threatening organ dysfunction in heatstroke. Dysregulated thermo-control induces cellular injury, damage-associated molecular patterns release, hyperinflammation, and hypercoagulation wi...

Importance The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective To quantify spatiotemporal variation in COVID-19 outc...

Background Four-factor prothrombin complex concentrate (4F-PCC) dosing is based on INR and actual body weight (ABW), with maximum doses not to exceed the dose used in patients weighing >100 kg (Kcentra PI). There are limited data comparing the efficacy of 4F-PCC between patients with low body weight ≤100 kg (LoWT) and high body weight >100 kg (HiWT...

Myeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis and bleeding. Vitamin K antagonists (VKAs) are the historic anticoagulant recommended for use in MPNs. Direct oral anticoagulants (DOACs) are being increasingly used in general and cancer populations. However, DOAC safety and efficacy in MPN patients remains un...

Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 M...

Introduction: International clinical practice guidelines (ITAC, ASCO, NCCN and ASH) have progressively endorsed direct factor Xa inhibitors (edoxaban, rivaroxaban and apixaban) as an alternative to monotherapy with low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients. The results from new randomiz...

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are at increased risk of arterial (ATE) and venous thromboembolism (VTE). There are no clear guidelines regarding selection of anticoagulation (AC) in MPN patients. Direct oral anticoagulants (DOACs...

Cardiovascular disease and cancer are the 2 leading causes of death worldwide. Emerging evidence suggests common mechanisms between cancer and cardiovascular disease, including atrial fibrillation and atherosclerosis. With advances in cancer therapies, screening, and diagnostics, cancer-specific survival and outcomes have improved. This increase in...

Background Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support (MCS), such as extracorporeal membrane oxygenation (ECMO) a...

Background Both andexanet alfa and 4F-PCC reversal strategies have been associated with thrombotic events. It remains unclear whether the risk is associated with the reversal agent or the lack of re-initiation of anticoagulation. Objective The aim of this study was to describe anticoagulant (AC) re-initiation patterns in patients presenting with m...

Peritoneovenous shunts (PVSs) are used to relieve ascites in cirrhosis. Disseminated intervascular coagulation (DIC) is a complication of PVSs requiring immediate PVS removal. We report a patient who developed new elevations of prothrombin time (PT) and activated partial thromboplastin time (aPTT) 6 hours after PVS placement, concerning for new‐ons...

Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in th...

Introduction Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the bleeding risk that accompanies systemic administration of higher alteplase doses. While studies suggest that alteplase given over 2 to 6 hours is safe and effective, few data exist to support alteplase sta...

Factor XI (FXI) deficiency (hemophilia C or Rosenthal disease) was first described in the 1950s in a multigenerational family experiencing bleeding related to surgery and dental procedures. Managing patients with FXI deficiency presents several challenges, including a lack of correlation of bleeding symptoms with FXI activity levels, the large volu...

Background Coronavirus disease 2019 (COVID-19) is associated with macro and micro thrombosis, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID-19, with preliminary r...

Heparin resistance is often invoked when the aPTT does not increase as expected in response to a given dose of heparin. In patients with Covid-19 and those with other acute infections, substantial discordance is often noted in the results of functional clot-based assays and chromogenic-based, anti-factor Xa assays and is caused by the elevated leve...

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We run a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as risk factor for bleeding or recurrence in patients treated with dal...

Cancer is a leading cause of venous thromboembolism (VTE), which contributes to significant morbidity and mortality in these patients. Increased thrombotic risk in cancer patients is modified by tumor-specific biology, disease-directed interventions, and individual comorbidities. Risk stratification for prophylaxis and treatment requires regular re...

Patients hospitalized for an acute medical illness remain at risk of developing venous thromboembolism (VTE) post-discharge. Betrixaban, an oral direct Factor Xa inhibitor, is approved for extended VTE thromboprophylaxis in acutely ill medical patients. The primary objective of this study was to evaluate patients re-admitted with VTE within 30 days...

Background: Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical features and outcomes of cancer patients with incidental or symptomatic VTE randomized in the Caravaggio study. Methods: The Caravaggio study compared apixaban versus dalte...

Vascular endothelial injury is a hallmark of acute infection at both the microvascular and macrovascular levels. The hallmark of SARS‐CoV‐2 infection is the current COVID‐19 clinical sequelae of the pathophysiologic responses of hypercoagulability and thromboinflammation associated with acute infection. The acute lung injury that initially occurs i...

Background Diagnosing heparin-induced thrombocytopenia (HIT) in patients with end-stage renal disease (ESRD) can be difficult, as they are frequently exposed to heparin and have multiple etiologies for thrombocytopenia. Objective To correlate 4T scores, IgG heparin–platelet factor 4 (PF4-heparin) ELISA results, and serotonin release assay (SRA) re...

Aims Over decades, Left Ventricular Assist Device (LVAD) technology has transitioned from less durable bulky pumps to smaller continuous-flow pumps which have substantially improved long-term outcomes and quality of life. Contemporary LVAD therapy is beleaguered by hemocompatibility related adverse events including thrombosis, stroke and bleeding....

Background: Patients hospitalized with severe acute respiratory syndrome coronavirus 2 infection are at risk for thrombotic complications necessitating use of therapeutic unfractionated heparin (UFH). Full-dose anticoagulation limits requirements for organ support interventions in moderately ill patients with coronavirus disease 2019 (COVID-19). G...

Background: Although Von Willebrand disease (vWD) is the most common heritable bleeding disorder, there are limited reports regarding the safety of neuraxial anesthesia in the obstetric population and no definitive guidelines specifying recommended pretreatment or therapies for patients with vWD. The aim of this study is to describe the anesthetic...

Andexanet alfa is a targeted reversal agent for apixaban and rivaroxaban for life-threatening or uncontrolled bleeding. There are few multicenter, real world studies that also include patients with off-label use who require emergent surgery. The objective was to describe hemostatic efficacy, thrombotic events, clinical applications, pharmaceutical...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare iss...

Introduction: Disseminated intravascular coagulation (DIC) has long been understood as a condition where both thrombotic and hemostatic abnormalities coexist. DIC is a difficult complication for clinicians to manage as it is due to multiple underlying complications of pathophysiologic abnormalities in diverse disease states. Ongoing research conti...

Background Venous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added risk of ICH in patients with brain metastases receiving therapeutic anticoagulation. Methods We performed a ma...

As a result of the coronavirus disease 2019 pandemic, the International Society on Thrombosis and Haemostasis (ISTH), like many societies around the world, canceled their in‐person hematology congress planned for Milan, Italy, in July 2020. As a result, the first virtual ISTH congress in the organisation’s 51‐year history was delivered, inviting fr...

Introduction The first patients with Coronavirus disease 2019 (COVID-19) emerged at the end of 2019. This novel viral infection demonstrated unique features that include prothrombotic clinical presentations. However, one year after the first occurrence, there remain many unanswered questions. We try to address some of the important queries in this...

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in o...

Patients on long-term anticoagulation combined with antiplatelet therapy have an increased risk of bleeding compared to patients on anticoagulation alone. The aim of this study was to evaluate the appropriateness of antiplatelet therapy in patients who are on long-term warfarin therapy and are managed by Brigham and Women’s Hospital Anticoagulation...

Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) are stem cell clonal neoplasms characterized by expansion of late myeloid cells. Thrombosis risk is elevated in MPNs and contributes significantly to morbidity and mortality. Current consensus guidelines make no spec...

Thromboembolic events contribute to morbidity and mortality in coronavirus disease 2019 (COVID-19). As a result, thromboprophylaxis using low-molecular-weight heparin (LMWH) is universally recommended for hospitalized patients based on multiple guidelines. However, ethnic differences with respect to thrombogenicity have been reported and the incide...

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiologic features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses and durations of therapy are being assessed in ongo...

Heart failure patients that require mechanical circulatory support with a ventricular assist device (VAD) are at a high risk of bleeding due to the underlying physiology of their disease, the physical presence of the VAD, and the requirement of antithrombotic therapy. The VAD pump itself can influence hematologic, inflammatory, and immunologic para...

Evaluation of bleeding risk prior to invasive procedures is important to minimize bleeding throughout the periprocedural period. A thorough bleeding assessment includes an evaluation of bleeding associated with the procedure in the presence and absence of anticoagulation, if applicable, and a patient assessment including personal and family history...

Disseminated intravascular coagulation (DIC) is a common and life-threatening complication in sepsis. Sepsis-associated DIC is recognized as the systemic activation in coagulation with suppressed fibrinolysis that leads to organ dysfunction in combination with systemic intravascular inflammation. In this process, thrombin contributes a key role in...

Background: The standard of care for stroke prevention in non-valvular atrial fibrillation (AF) is the use of direct oral anticoagulants (DOACs). However, many patients established on warfarin therapy have not been considered for a transition to a DOAC. Objectives: Assess the AF patient population of Brigham and Women's Hospital (BWH) Anticoagul...

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer-associated VTE is critical because an optimal thromboprophylaxis strategy is best...

Malignancy is a significant risk factor for venous thromboembolism (VTE). It is estimated that up to 20% of patients with cancer may develop VTE at some time in their cancer journey. Cancer-associated VTE can lead to hospitalizations, morbidity, delayed cancer treatment, and mortality. The optimal prevention and management of cancer-associated thro...

An outstanding group of medical oncologists, hematologists, cardiologists, and epidemiologists developed a series of manuscripts on management approaches for the prevention and treatment of cancer‐associated venous thromboembolism. This article introduces this multidisciplinary collaborative effort.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. Over the past 2 decades, enormous advances have been made in the management of CAT. The growing evidence base informing practice has led to the publication of a number of guidelines and guidance documents on the diagnosis and treatment of CAT. Th...

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient-specific and cancer-related factors that influence the approach to treatment. Historically, anticoagulant therapy with low-molecular-weight heparin (LMWH), give...

Objectives To investigate the clinical significance of numeric and morphologic peripheral blood (PB) changes in coronavirus disease 2019 (COVID-19)–positive patients in predicting the outcome, as well as to compare these changes between critically ill COVID-19–positive and COVID-19–negative patients. Methods The study included 90 COVID-19–positive...

Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially...

Background: COVID-19-associated coagulopathy (CAC) characterized by the elevated D-dimer without remarkable changes of other global coagulation markers is associated with various thrombotic complications and disease severity. The purpose of this review is to elucidate the pathophysiology of this unique coagulopathy. Methods: The authors performe...

Patients with acute leukemia frequently develop thrombocytopenia and hemostatic complications caused by coagulopathy. Coagulopathy complicates the management of these patients and can lead to significant morbidity and mortality. This guidance document aims to review and provide guidance on the management of hemostatic complications in adult patient...

Pregnancy in essential thrombocythemia (ET) is associated with increased risk of obstetric complications. We retrospectively evaluated risk factors in 121 pregnancies in 52 ET women seen at 3 affiliate hospitals. Univariable and multivariable analyses were performed at the α = 0.10 level. Cell counts were characterized throughout pregnancy and corr...

Venous thromboembolism (VTE) is a common complication in patients with cancer and portends a poor prognosis. Our understanding of the underlying pathophysiology of VTE in cancer has advanced since Trousseau first described hypercoagulability in patients with malignancy and Virchow described his famous triad of thrombosis formation. Malignancy itsel...

The management of cancer-associated thrombosis (CAT) is an evolving area. With the use of direct oral anticoagulants as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with venous thromboembolism. A personalized approach, matching the right drug to the right patient, based on drug propert...

Background: It remains unclear which patients with metastatic germ cell tumours (mGCTs) need prophylactic anticoagulation to prevent venous thromboembolic events (VTEs). Objective: To assess the risk and onset of VTEs stratified by risk factors. Design, setting, and participants: This multi-institutional retrospective dataset included mGCT pat...

SARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhib...