Publications by authors named "Nathan T Connell"

48 Publications

To aPTT or not to aPTT: Evaluating the optimal monitoring strategy for unfractionated heparin.

Thromb Res 2021 Nov 22. Epub 2021 Nov 22.

Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, United States of America.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.11.012DOI Listing
November 2021

Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature.

Blood Adv 2021 Oct 21. Epub 2021 Oct 21.

McMaster University, Canada.

Von Willebrand disease, (VWD) disproportionately affects women due to potential issues with heavy menstrual bleeding (HMB), delivery complications, and postpartum hemorrhage (PPH). To systematically synthesize the evidence regarding first line management of HMB, treatment of women requiring/desiring neuraxial analgesia, and management of PPH. We searched Medline and EMBASE through October 2019 for randomized trials, comparative observational studies, and case series comparing the effects of desmopressin, hormonal therapy, and tranexamic acid (TXA) on HMB, comparing different von Willebrand factor (VWF) levels in women with VWD undergoing labor and receiving neuraxial anesthesia and the effects of TXA on PPH We conducted duplicate study selection, data abstraction, and appraisal of risk of bias. Whenever possible, we conducted meta-analyses. We assessed the quality of the evidence using the GRADE approach. We included 1 randomized trial, 3 comparative observational studies and 10 case series. Moderate certainty evidence showed that desmopressin results in a smaller reduction of menstrual blood loss (difference in mean change from baseline, 41.6 [95% CI, 16.6 to 63.6] points in pictorial blood assessment chart score as compared to TXA. There was very low certainty evidence about how first line treatments compare against each other, the effects of different VWF levels in women receiving neuraxial anesthesia, and the effects of TXA administration postpartum. Most of the evidence relevant to the gynecologic and obstetric management of women with VWD addressed by most guidelines is very low quality. Future studies addressing research priorities will be key when updating such guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021005589DOI Listing
October 2021

Surgical management of patients with von Willebrand Disease: summary of 2 systematic reviews of the literature.

Blood Adv 2021 Oct 15. Epub 2021 Oct 15.

Department of Health Research Methods, Evidence and Impact, McMaster University, Canada.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD undergoing surgeries is crucial to prevent bleeding complications. To systematically summarize the evidence on the management of patients with VWD undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE through October 2019 for randomized clinical trials (RCTs), comparative observational studies and case series comparing maintaining factor VIII levels or VWF levels >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and options for perioperative management of patients undergoing minor surgery. Two authors screened, abstracted data, and assessed the risk of bias. We conducted meta-analysis when possible. We evaluated the certainty of the evidence using the GRADE approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very low certainty evidence showed that maintaining factor VIII levels, or VWF levels > 0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74-100% of major surgeries. Low to very low certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in less bleeding complications after minor procedures compared to increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence to guide management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD undergoing surgical and invasive procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021005666DOI Listing
October 2021

Inherited Bleeding Disorders.

Authors:
Nathan T Connell

Hematol Oncol Clin North Am 2021 Dec 5;35(6):xiii-xiv. Epub 2021 Oct 5.

Brigham and Women's Hospital, Hematology Division, SR322, Boston, MA 02115, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hoc.2021.09.001DOI Listing
December 2021

Von Willebrand Factor Levels in The Diagnosis of Von Willebrand Disease: A Systematic Review and Meta-Analysis.

Blood Adv 2021 Oct 5. Epub 2021 Oct 5.

University of Kansas Medical Center, Kansas City, Kansas, United States.

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021005430DOI Listing
October 2021

Bleeding assessment tools in the diagnosis of VWD in adults and children: a systematic review and meta-analysis of test accuracy.

Blood Adv 2021 Dec;5(23):5023-5031

Department of Internal Medicine.

Von Willebrand disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. We systematically reviewed diagnostic test accuracy results of BATs to screen patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using the revised tool for the quality assessment of diagnostic accuracy studies and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval, 66-83) and 54% (29-77), respectively. Certainty of evidence varied from moderate to high. This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates, will influence patient management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021004368DOI Listing
December 2021

Use of Social Media in the Practice of Medicine.

Am J Med 2021 Sep 22. Epub 2021 Sep 22.

Frankel Cardiovascular Center and Michigan Program on Value Enhancement, University of Michigan Health System, Ann Arbor.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2021.08.030DOI Listing
September 2021

Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays.

Otolaryngol Head Neck Surg 2021 Aug 17:1945998211036339. Epub 2021 Aug 17.

School of Medicine, Indiana University, Indianapolis, Indiana, USA.

Objective: To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients.

Study Design: Retrospective cohort study.

Setting: Tertiary academic hospital.

Methods: Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average.

Results: Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW.

Conclusions: Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/01945998211036339DOI Listing
August 2021

Acquired von Willebrand Syndrome.

Hematol Oncol Clin North Am 2021 Dec 12;35(6):1103-1116. Epub 2021 Aug 12.

Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. Electronic address:

Acquired von Willebrand syndrome can occur in the setting of myeloproliferative neoplasms; plasma cell dyscrasias and other lymphoproliferative disorders; autoimmune conditions; and causes of increased shear forces, such as aortic stenosis or other structural heart disease and mechanical circulatory support. The depletion of von Willebrand factor, especially high-molecular-weight multimers, can lead to mucocutaneous bleeding and the formation of arteriovenous malformations, particularly in the gastrointestinal tract. Management focuses on correction of the underlying cause when possible, but may include intravenous immunoglobulins, von Willebrand factor concentrate, rituximab, or antiangiogenic therapy depending on the clinical context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hoc.2021.07.005DOI Listing
December 2021

Management of therapeutic unfractionated heparin in COVID-19 patients: A retrospective cohort study.

Res Pract Thromb Haemost 2021 May 7;5(4):e12521. Epub 2021 May 7.

Harvard Medical School Boston MA USA.

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). Given this benefit, it is important to evaluate response to therapeutic anticoagulation in this population.

Objectives: The aim of this study was to assess therapeutic UFH infusions and associated bleeding risk in patients with COVID-19.

Patients/methods: This retrospective cohort study includes patients at Brigham and Women's Hospital, Boston, Massachusetts, receiving weight-based nursing-nomogram titrated UFH infusion during a 10-week surge in COVID-19 hospitalizations. Of 358 patients on therapeutic UFH during this interval, 97 (27.1%) had confirmed COVID-19. Patient characteristics, laboratory values, and information regarding UFH infusion and bleeding events were obtained from the electronic medical record.

Results: Patients who were COVID-19 positive had fewer therapeutic activatrd partial thromboplastin times (aPTTs) compared to COVID-19-negative patients (median rate, 40.0% vs 53.1%;  < .0005). Both major and clinically relevant nonmajor bleeding were increased in COVID-19-positive patients, with major bleeding observed in 10.3% (95% confidence interval [CI], 5.7%-17.9%) of patients who were COVID-19 positive and 3.1% (95% CI, 1.6%-5.9%) of patients who were COVID-19 negative (< .005). In logistic regression, bleeding events were associated with receiving UFH for longer than 7 days, but not platelet count, coagulation, or inflammatory measurements.

Conclusions: Our data indicate a higher incidence of bleeding complications in patients with COVID-19 receiving weight-based nursing-nomogram titrated UFH infusions despite a higher prevalence of subtherapeutic aPTTs in this population. These data underscore the need for prospective studies aimed at improving the quality and safety of therapeutic anticoagulation in patients with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rth2.12521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114028PMC
May 2021

Oxaliplatin hypersensitivity complicated by thrombocytopenia during desensitization.

Ann Allergy Asthma Immunol 2021 08 7;127(2):267-269. Epub 2021 May 7.

Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2021.04.032DOI Listing
August 2021

ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease.

Blood Adv 2021 01;5(1):280-300

Outcomes and Implementation Research Unit, Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.

Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder known in humans. Accurate and timely diagnosis presents numerous challenges.

Objective: These evidence-based guidelines of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and other health care professionals in their decisions about VWD diagnosis.

Methods: ASH, ISTH, NHF, and WFH established a multidisciplinary guideline panel that included 4 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Outcomes and Implementation Research Unit at the University of Kansas Medical Center (KUMC) supported the guideline-development process, including performing or updating systematic evidence reviews up to 8 January 2020. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subsequently subject to public comment.

Results: The panel agreed on 11 recommendations.

Conclusions: Key recommendations of these guidelines include the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. Future critical research priorities are also identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020003265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805340PMC
January 2021

ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease.

Blood Adv 2021 01;5(1):301-325

Outcomes and Implementation Research Unit, Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients.

Objective: These evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and health care professionals in their decisions about management of VWD.

Methods: ASH, ISTH, NHF, and WFH formed a multidisciplinary guideline panel. Three patient representatives were included. The panel was balanced to minimize potential bias from conflicts of interest. The University of Kansas Outcomes and Implementation Research Unit and the McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing and updating systematic evidence reviews (through November 2019). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients. The panel used the GRADE approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 12 recommendations and outlined future research priorities.

Conclusions: These guidelines make key recommendations regarding prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of neuraxial anesthesia during labor and delivery, and management in the postpartum setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020003264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805326PMC
January 2021

Clinical Significance of CBC and WBC Morphology in the Diagnosis and Clinical Course of COVID-19 Infection.

Am J Clin Pathol 2021 Feb;155(3):364-375

Department of Pathology, Brigham and Women's Hospital, Boston, MA.

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 (51 intensive care unit [ICU] and 39 non-ICU) patients and 30 COVID-19-negative ICU patients. We collected CBC parameters (both standard and research) and PB morphologic findings, which were independently scored by two hematopathologists.

Results: All patients with COVID-19 demonstrated striking numeric and morphologic WBC changes, which were different between mild and severe disease states. More severe disease was associated with significant neutrophilia and lymphopenia, which was intensified in critically ill patients. Abnormal WBC morphology, most pronounced in monocytes and lymphocytes, was associated with more mild disease; the changes were lost with disease progression. Between COVID-19-positive and COVID-19-negative ICU patients, significant differences in morphology-associated research parameters were indicative of changes due to the severe acute respiratory syndrome coronavirus 2 virus, including higher RNA content in monocytes, lower RNA content in lymphocytes, and smaller hypogranular neutrophils.

Conclusions: Hospitalized patients with COVID-19 should undergo a comprehensive daily CBC with manual WBC differential to monitor for numerical and morphologic changes predictive of poor outcome and signs of disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqaa231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799218PMC
February 2021

Pregnancy outcomes, risk factors, and cell count trends in pregnant women with essential thrombocythemia.

Leuk Res 2020 11 29;98:106459. Epub 2020 Sep 29.

Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. Electronic address:

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 correlated with outcomes using logistic modeling. The overall live birth rate was 69 %. 48.7 % of all women experienced a pregnancy complication, the most common being spontaneous abortion, which occurred in 26 % of all pregnancies. Maternal thrombosis and hemorrhage rates were 2.5 % and 5.8 %. On multivariable analysis, aspirin use (OR 0.29, p = 0.014, 90 % CI 0.118-0.658) and history of prior pregnancy loss (OR 3.86, p = 0.011, CI 1.49-9.15) were associated with decreased and increased pregnancy complications, respectively. A Markov model was used to analyze the probability of a future pregnancy complication based on initial pregnancy outcome. An ET woman who suffers a pregnancy complication has a 0.594 probability of a subsequent pregnancy complication, compared to a 0.367 probability if she didn't suffer a complication. However, despite this elevated risk, overall prognosis is good, with a >50 % probability of a successful pregnancy by the third attempt. Platelet counts decreased by 43 % in ET during pregnancy, with nadir at delivery and prompt recovery in the postpartum period. Women with larger declines in gestational platelet counts were less likely to suffer complications (p = 0.083). Our study provides important guidance to physicians treating ET women during pregnancy, including counseling information regarding risk assessment and expected trajectory of platelet levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2020.106459DOI Listing
November 2020

Systems-based hematology: highlighting successes and next steps.

Blood Adv 2020 09;4(18):4574-4583

Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020002947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509880PMC
September 2020

Venous thromboembolism in the hormonal milieu.

Curr Opin Hematol 2020 09;27(5):327-332

Hematology Division, Department of Medicine, Brigham and Women's Hospital.

Purpose Of Review: Hormonal therapy is administered for multiple indications including contraception, alleviation of menopausal symptoms, hypogonadism, and more recently, gender-affirming care. Data suggest varying degrees of increased risk for venous thromboembolism (VTE).

Recent Findings: While oral progestin only methods do not appear to increase the risk of VTE, an association was seen with injection progestin contraception. Combined oral contraception with low-dose ethinyl estradiol and most types of progestin increased the risk of VTE compared with levonorgestrel-containing oral therapies. While transdermal hormonal contraception has been previously associated with increased VTE, a recently approved levonorgestrel and ethinyl estradiol transdermal patch reported low rates (<0.2%) in a large single-arm open-label study. Women receiving postmenopausal HRT experienced an increased risk of VTE in a dose-dependent manner when using oral hormonal therapy while nonoral methods, such as topical estrogen, did not appear to increase the risk of VTE. Some studies suggest no increased risk of VTE with testosterone therapy, however, a recent case-crossover study suggested higher VTE risk in men on testosterone, particularly men less than age 65 without hypogonadism. Route of administration had no effect on VTE rates. The estimated incidence rate of VTE risk in transgender women receiving estrogen therapy is 2.3 per 1000 person years, but may be imprecise due to heterogeneity in studies included in published meta-analyses. Surgical risk estimates are primarily indirect data drawn from cisgender patients receiving hormone therapy in the perioperative setting.

Summary: Hormonal therapy affects VTE risk to varying degrees dependent on specific type of hormone, formulation, and occasionally route of delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOH.0000000000000599DOI Listing
September 2020

VTE in ICU Patients With COVID-19.

Chest 2020 11 22;158(5):2130-2135. Epub 2020 Jul 22.

Department of Medicine, Hematology Division, Brigham and Women's Hospital, Boston, MA; Hematology Department, Dana-Farber Cancer Institute, Boston, MA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674987PMC
November 2020

Coagulopathy of COVID-19 and antiphospholipid antibodies.

J Thromb Haemost 2020 May 7. Epub 2020 May 7.

Brigham and Women's Hospital, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267637PMC
May 2020

Taken the wrong way, a complement becomes catastrophic.

Authors:
Nathan T Connell

Blood 2020 01;135(4):233-234

Brigham and Women's Hospital.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019004337DOI Listing
January 2020

An international survey to inform priorities for new guidelines on von Willebrand disease.

Haemophilia 2020 Jan 26;26(1):106-116. Epub 2019 Nov 26.

Outcomes and Implementation Research Unit, Department of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS, USA.

Introduction: von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative or qualitative dysfunction of von Willebrand factor. Clinicians, patients and other stakeholders have many questions about the diagnosis and management of the disease.

Aim: To identify topics of highest importance to stakeholders that could be addressed by guidelines to be developed by the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF) and the World Federation of Hemophilia (WFH).

Methods: A survey to determine and prioritize topics to be addressed in the collaborative development of guidelines for VWD was distributed to international stakeholders including patients, caregivers and healthcare providers (HCPs). Representatives of the four organizations coordinated the distribution strategy. The survey focused on both diagnosis and management of VWD, soliciting 7-point Likert-scale responses and open-ended comments, in English, French and Spanish. We conducted descriptive analysis with comparison of results by stakeholder type, gender and countries' income classification for the rating questions and qualitative conventional content data analysis for the open-ended responses.

Results: A total of 601 participants responded to the survey (49% patients/caregivers and 51% healthcare providers). The highest priority topics identified were diagnostic criteria/classification, bleeding assessment tools and treatment options for women and surgical patients. In contrast, screening for anaemia and differentiating plasma-derived therapy versus recombinant therapies received lower ratings.

Conclusion: This survey highlighted areas of importance to a diverse representation of stakeholders in the diagnosis and management of VWD, providing a framework for future guideline development and implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hae.13881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041556PMC
January 2020

Associations between hematology/oncology fellows' training and mentorship experiences and hematology-only career plans.

Blood Adv 2019 11;3(21):3278-3286

Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.

As the adult hematology and oncology fellowship training pathways have merged in the United States and concerns have arisen about the aging of practicing hematologists, the American Society of Hematology and hematology education leaders are looking to improve their understanding of the factors that contribute to fellows' plans to enter hematology-only careers. With the support of the American Society of Hematology, we collected and analyzed data from a survey of hematology/oncology fellows (n = 626) to examine the relationship between training and mentorship experiences and fellows' plans to enter hematology-only careers. Fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans. After controlling for prior interest in hematology and demographic characteristics, exposure to hematology patients in medical school and fellowship, hematology research experiences, and hematology mentorship (research collaboration and career coaching) were positively and significantly associated with hematology-only career plans. These findings suggest that increasing opportunities for exposure to hematology patients, research opportunities and mentors throughout training could be helpful in building a strong pipeline of potential hematologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019000569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855099PMC
November 2019

Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria.

Ther Adv Hematol 2019 10;10:2040620719874728. Epub 2019 Sep 10.

Hematology Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. Until recently, the complement inhibitor, eculizumab, was the only United States Food and Drug Administration (US FDA)-approved therapy for the treatment of PNH. Although effective, eculizumab requires a frequent dosing schedule that can be burdensome for some patients and increases the risk of breakthrough intravascular hemolysis. Ravulizumab, an eculizumab-like monoclonal antibody engineered to have a longer half-life, is intended to provide the same benefits as eculizumab but with a more convenient and effective dosing schedule. In two recently published phase III non-inferiority trials, ravulizumab was found to be non-inferior to eculizumab both in efficacy and safety for the treatment of patients with PNH. Based on these results, ravulizumab was approved by the US FDA on 21 December 2018 and is currently under regulatory review in both the European Union and Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2040620719874728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737867PMC
September 2019

Cost-effectiveness of edoxaban versus dalteparin for the treatment of cancer-associated thrombosis.

J Thromb Thrombolysis 2019 Oct;48(3):382-386

Hematology Division, Brigham and Women's Hospital, 75 Francis Street, SR322, Boston, MA, 02115, USA.

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-019-01903-zDOI Listing
October 2019

Andexanet Alfa (Andexxa) Formulary Review.

Crit Pathw Cardiol 2019 06;18(2):66-71

Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Andexanet alfa, a recombinant modified human "decoy" factor Xa (FXa) protein, is the first and only available antidote approved by the Food and Drug Administration to manage life-threatening or uncontrolled bleeding associated with the anti-Xa agents. It binds to direct and indirect anti-Xa oral anticoagulants with high specificity to reverse their inhibitory effects and restore the activity of FXa. Andexanet alfa is administered via two different dosing regimens, standard and high dose, based on the specific FXa inhibitor, dose, and time since the patient's last dose of FXa inhibitor. The approval for andexanet alfa is supported by data from two phase 3 studies (ANNEXA-A, ANNEXA-R) and preliminary data from the phase 3b/4 ANNEXA-4 trial. The first study found that andexanet alfa rapidly reduced anti-Xa activity by 92%-94% in healthy volunteers taking apixaban or rivaroxaban. The ANNEXA-4 study found that the median anti-Xa activity decreased by 89%-93% in patients with major bleeding taking apixaban or rivaroxaban. However, thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up in ANNEXA-4. Additionally, only 40% of patients had restarted anticoagulation and, in this group, the rate of thrombotic events was 12%. Four patients had a thrombotic event within 3 days after andexanet alfa treatment. The wholesale acquisition cost of the standard dose regimen is $24,750, and the high-dose regimen is $49,500. The estimated annual drug budget of treating 10-100 patients ranges from $248K to $495M. Effective October 1, 2018, Medicare will provide an add-on payment for andexanet alfa of up to $14,063 per qualifying case to Inpatient Prospective Payment System-participating acute care hospitals. In this formulary review for a health system's pharmacy and therapeutics committee, andexanet alfa clinical trials and medication package insert were summarized and, after consulting with clinical experts from our institutions, practical recommendations for use were generated to ensure appropriate and safe use of this agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HPC.0000000000000177DOI Listing
June 2019

Plasmacytoma presenting as jugular foramen tumor in a young woman with multiple myeloma.

Am J Hematol 2019 06 11;94(6):728-732. Epub 2019 Apr 11.

Department of Medicine, Harvard Medical School, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25477DOI Listing
June 2019

Fostamatinib for the treatment of chronic immune thrombocytopenia.

Blood 2019 05 25;133(19):2027-2030. Epub 2019 Feb 25.

Hematology Division, Brigham and Women's Hospital, Boston, MA; and.

Fostamatinib is a spleen tyrosine kinase inhibitor recently approved for the treatment of chronic immune thrombocytopenia (ITP) in patients without adequate response to at least 1 prior line of therapy. This article reviews fostmatinib's mechanism of action and its clinical safety and efficacy in 2 industry-sponsored multicenter phase 3 randomized controlled trials in North America, Australia, and Europe (FIT1 and FIT2). Cost comparisons are discussed as well as the role of fostamatinib in relation to other options for chronic ITP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2018-11-852491DOI Listing
May 2019

Ravulizumab: a complementary option for PNH.

Authors:
Nathan T Connell

Blood 2019 02;133(6):503-504

Harvard Medical School.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2018-12-891499DOI Listing
February 2019
-->