American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing.

Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.

Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism: Results of an Expert Consensus Panel.

In clinical practice, direct oral anticoagulants (DOACs) are increasingly used for venous thromboembolism treatment and prevention. A substantial proportion of patients with venous thromboembolism are also obese. International guidance published in 2016 stated that DOACs could be used in standard doses in patients with obesity up to a body mass index (BMI) of 40 kg/m2, but should not be used in those with severe obesity (BMI >40 kg/m2) owing to limited supporting data at the time. Although updated guidance in 2021 removed this limitation, some health care providers still avoid DOACs even in patients with lower levels of obesity. Furthermore, there are still evidence gaps regarding treatment of severe obesity, the role of peak and trough DOAC levels in these patients, use of DOACs after bariatric surgery, and appropriateness of DOAC dose reduction in the setting of secondary venous thromboembolism prevention. This document describes proceedings and outcomes of a multidisciplinary panel convened to review these and other key issues regarding DOAC use for treatment or prevention of venous thromboembolism in individuals with obesity.

Portomesenteric Vein Thrombosis After Laparoscopic Sleeve Gastrectomy: A Single-Institution Report.

Laparoscopic sleeve gastrectomy (LSG) is an effective weight-loss operation. Portomesenteric vein thrombosis (PMVT) is an important complication of LSG. We identified four cases of PMVT after LSG at our institution in women aged 36-47 with BMIs ranging from 44-48 kg/m2. All presented 8-19 days postoperatively. Common symptoms were nausea, vomiting, and abdominal pain. Thrombotic risk factors were previous deep vein thrombosis and oral contraceptive use. Management included therapeutic anti-coagulation, directed thrombolysis, and surgery. Complications were readmission, bowel resection, and bleeding. Discharge recommendations ranged from 3-6 months of anticoagulation using various anticoagulants. No consensus was reached on post-treatment hypercoagulable work up or imaging. All cases required multi-disciplinary approach with Surgery, Interventional Radiology, and Hematology. As PMVT is a rare but potentially morbid complication of LSG, further development of tools that quantify preoperative thrombotic risk and clear guidance regarding use of anticoagulants are needed for prevention and treatment of PMVT following LSG.

Risk of recurrence in women with venous thromboembolism related to estrogen-containing contraceptives: Systematic review and meta-analysis.

BACKGROUND: The risk of recurrence after a venous thromboembolism (VTE) related to estrogen-containing contraceptives is a key driver to guide anticoagulant treatment decisions. OBJECTIVE: To estimate the incidence rate of recurrent VTE after discontinuation of anticoagulant treatment in women with a first episode of VTE related to estrogen-containing contraceptives. METHODS: Embase, MEDLINE, and the CENTRAL were searched from 1 January 2008 to 27 May 2021 for prospective and retrospective studies reporting on recurrence after a first VTE related to estrogen-containing contraceptives. Risk of bias was assessed using QUIPS tool. Recurrence rates per 100 patient-years were pooled using Knapp-Hartung random-effects meta-analysis. Incidence rates were reported separately based on study follow-up duration (≤1 year, 1-5 years, and >5 years) and for several subgroups. RESULTS: A total of 4,120 studies were identified, of which 14 were included. The pooled recurrence rate was 1.57 (95%-CI: 1.10-2.23; I2  = 82%) per 100 patient-years. Recurrence rates per 100 patient-years were 2.73 (95%-CI: 0.00-3643; I2  = 80%) for studies with ≤1 year follow-up, 1.35 (95%-CI: 0.68-2.68; I2  = 44%) for studies with 1-5 years follow-up, and 1.42 (95%-CI: 0.84-2.42; I2  = 78%) for studies with >5 years follow-up. CONCLUSION: Among women with VTE associated with estrogen-containing contraceptives, the risk of recurrence after stopping anticoagulation is low, which favors short-term anticoagulation. Large prospective studies on VTE recurrence rates and risk factors after stopping short-term anticoagulants are needed.

Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

Although direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and safety in patients with obesity. We reviewed available data for use of DOACs for VTE treatment and prevention in patients with obesity, including phase 3, phase 4, meta-analyses, and pharmacokinetic and pharmacodynamics studies. In addition, we reviewed available data regarding DOACs in bariatric surgery. We provide updated guidance recommendations on using DOACs in patients with obesity for treatment and prevention of VTE, as well as following bariatric surgery.

Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases.

Corticosteroids constitute a first-line therapy for adults and children suffering from nonmalignant immune-mediated hematologic diseases. However, high disease relapse rates during the tapering period or upon drug discontinuation result in long-term corticosteroid use that increases the risk of infection. This same concept applies to other immunosuppressive agents, such as antimetabolites, calcineurin inhibitors, and cyclophosphamide. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection. Screening and antimicrobial prophylaxis against tuberculosis, hepatitis B, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia (PJP) might be indicated in patients who are scheduled to be on high-dose corticosteroids for >4 weeks (>30 mg of prednisone-equivalent dose [PEQ]) or in patients chronically treated (≥8 weeks of continuous or intermittent corticosteroid use) with moderate doses (≥15 to <30 mg PEQ). Antimetabolites (azathioprine, mycophenolate) increase the risk of progressive multifocal leukoencephalopathy (PML); however, other opportunistic infections and viral reactivation have also been reported. In case of new onset of neurological symptoms, PML needs to be considered, and an urgent neurology consultation should be obtained. Cyclophosphamide-induced myelosuppression can lead to serious infections related to neutropenia. PJP prophylaxis should be considered with combination therapy of cyclophosphamide and corticosteroids until a PEQ dose ≤ 5 mg/d is reached. Data on infectious risk when cyclosporine is used in patients with nonmalignant hematologic diseases are lacking. Discontinuation of any immunosuppressive agent during an episode of infection is recommended. In all patients, adherence to an age-based immunization schedule is appropriate.

An Evidence-Based Algorithm for Determining Venous Thromboembolism Prophylaxis After Degenerative Spinal Surgery.

BACKGROUND: Although venous thromboembolism (VTE) is a potentially serious and life-threatening complication, there is no widely accepted protocol to guide VTE prophylaxis in adult degenerative spinal surgery, and pharmacologic overtreatment may result in hemorrhagic complications. Previously, we published the VTE Prophylaxis Risk/Benefit Score, an evidence-based algorithm that balances the risk and consequences of thrombotic versus hemorrhagic complications by taking consideration of patient-related risks, procedure-related risks, and the risk of neurological compromise to guide VTE prophylaxis. To objective of this study was to validate the VTE Prophylaxis Risk/Benefit Score. METHODS: From January 1, 2016, to December 31, 2017, VTE Prophylaxis Risk/Benefit Scores and corresponding prophylaxes were prospectively assigned. When indicated, chemoprophylaxis was dosed 24 to 36 hours postoperatively to allow for adequate surgical hemostasis. Patients were retrospectively evaluated for immediate and short-term complications. The Fisher exact test compared incidence of complications by VTE prophylaxis. Multinomial logistic regression modeled the probability of complication by prophylaxis type, demographics, and comorbidities. Significance was set at P < .05. RESULTS: Of the 266 patients who met inclusion criteria, 79.3% were given mechanical prophylaxis alone and 20.7% were given combined mechanical and chemical prophylaxis. Complications including VTE (0.38%), delayed wound healing or infection (2.26%), and hematoma (0.75%) were observed at rates similar to or lower than previously published studies with increased utilization of chemoprophylaxis. Use of chemoprophylaxis and continuation of perioperative aspirin were significantly associated with the development of a hemorrhagic complication. No patient developed persistent neurologic deficit from hematoma or pulmonary embolism. CONCLUSIONS: The VTE Prophylaxis Risk/Benefit Score comprehensively considers the risk of thrombotic, wound, and bleeding complications and is an effective tool for determining appropriate thromboprophylaxis in adult degenerative spinal surgery. LEVEL OF EVIDENCE: 3.

How I treat unexplained arterial thrombosis.

Most arterial thrombotic events have a clear atherosclerotic or cardioembolic etiology, but hematologists are frequently asked to assist in the diagnosis and management of a patient with a nonatherosclerotic and noncardioembolic arterial event, referred to here as an unexplained arterial thrombosis. Because there is an assorted list of factors that can precipitate an arterial event, we present a systematic diagnostic approach to ensure consideration of not only primary hypercoagulable disorders, but also pro-thrombotic medications or substances, vascular and anatomic abnormalities, and undiagnosed systemic disorders, such as malignancy and autoimmune diseases. We also review existing literature of the role of hypercoagulable disorders in arterial thrombosis and discuss our approach to thrombophilia workup in patients after an unexplained arterial event. We conclude with 3 representative cases to both illustrate the application of the outlined diagnostic schema and discuss common management considerations, specifically the selection of anticoagulation vs antiplatelet therapy for secondary prevention.

Preventing infectious complications when treating non-malignant immune-mediated hematologic disorders.

Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune-mediated non-malignant hematologic disorders, with infection being the most common non-hematological adverse event from these therapies. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection, including opportunistic infections. Screening and antimicrobial prophylaxis against tuberculosis, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia, are indicated in selected patients on steroids and with certain risk factors for infection. Rituximab is associated with hepatitis B virus reactivation. All patients planned to be started on rituximab should be screened for hepatitis B surface antigen and total core antibody, with antiviral prophylaxis given depending on test results. In eculizumab treated patients, immunization against meningococcal serogroups ACWY and B is recommended. In addition, some guidelines suggest antibiotic prophylaxis for the duration of eculizumab treatment. In splenectomized patients, counseling and immunization are cornerstones of infection prevention. Several federal and society guidelines about immunizations and prophylactic antimicrobial therapies for patients treated with various immunosuppressive agents exist and are summarized in this manuscript in a clinical-focused table. In addition, management suggestions are made where no formal guidelines exist.

Analysis of anticoagulation strategies for venous thromboembolism during severe thrombocytopenia in patients with hematologic malignancies: a retrospective cohort.

The safety and efficacy of anticoagulation for venous thromboembolism (VTE) at times of severe thrombocytopenia is unclear. In this retrospective study, we evaluated patients with hematologic malignancy and either (1) acute or chronic VTE on anticoagulation before platelet count dropped below 50 × 109/L or (2) acute VTE occurring while platelets were <50 × 109/L. In 78 eligible patients, the primary outcomes of time to recurrent VTE or clinically significant bleeding within 100 d were compared by management strategy. Bleeding occurred in 27% of patients receiving anticoagulation versus 3% when anticoagulation was held (IRR 10.1, 95% CI 1.5-432.6). Recurrent VTE occurred in 2% of patients receiving anticoagulation versus 15% when anticoagulation was held (IRR 0.17, 95% CI 0.0-1.51). Most bleeding occurred before day 31(11/13), but recurrent VTE mostly occurred after day 40 (5/6). Our findings suggest that temporarily withholding anticoagulation for VTE during severe thrombocytopenia in patients with hematologic malignancies might reduce adverse outcomes.

Initiating and Managing Patients with Venous Thromboembolism on Anticoagulant Drugs: A Practical Overview.

Several new oral anticoagulants have recently been approved for the treatment of venous thromboembolism (VTE). In this review, we discuss the currently approved drugs and the factors that influence the choice of anticoagulant in a given patient. Once anticoagulation is initiated, periodic monitoring of adequacy of anticoagulation may be necessary depending on the choice of anticoagulant and patient-related factors, such as renal function. Situations that may warrant need for monitoring and the tests available for this purpose are discussed. We review reversal of anticoagulation in urgent/emergent situations as well as perioperative anticoagulation interruption in the elective setting. The data on use of direct oral anticoagulants in patients with compromised renal function, obesity and bariatric surgery, and in the treatment of cancer-associated thrombosis are discussed. The review aims to provide the clinician with the essential information to allow effective and safe use of anticoagulants for the treatment of VTE.

Leukocytosis due to markedly elevated granulocyte-colony stimulating factor levels in a patient with endometrial cancer: Case report and literature review.

•Granulocyte-colony stimulating factor (GCSF) secretion by gynecologic tumors is rare.•Elevations in serum GCSF can be seen in the absence of tumor GSCF secretion.•Extreme leukocytosis is associated with autocrine tumor growth and poor prognosis.