ABSTRACT
ABSTRACT: Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.
Subject(s)
Anticoagulants , Platelet Aggregation Inhibitors , Thromboembolism , Humans , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Thromboembolism/drug therapy , Thromboembolism/etiology , Male , Female , Aged , Middle Aged , Risk Factors , Venous Thrombosis/drug therapy , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiologySubject(s)
Autoantibodies , Platelet Factor 4 , Purpura, Thrombocytopenic, Idiopathic , Humans , Adenoviridae , Antibodies, Viral/blood , Autoantibodies/blood , Autoantibodies/immunology , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , ChAdOx1 nCoV-19/adverse effects , ChAdOx1 nCoV-19/immunology , Ad26COVS1/adverse effects , Ad26COVS1/immunology , Adenovirus Infections, Human/complications , Adenovirus Infections, Human/immunology , Adenovirus Infections, Human/virologyABSTRACT
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.
Subject(s)
Thrombosis/diagnosis , Thrombosis/therapy , Adult , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Disease Management , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Thrombosis/blood , Thrombosis/etiologyABSTRACT
Livedoid vasculopathy (LV) is a rare thrombotic vasculopathy of the dermis characterized by painful, relapsing ulcers over the lower extremities. Diagnosis is challenging due to the overlap in clinical appearance and nomenclature with other skin disorders. Treatment selection is complicated by poor understanding of the pathogenesis of LV and lack of robust clinical trials evaluating therapy efficacy. The terminology and pathophysiology of LV are reviewed here, along with its epidemiology, clinical and histologic features, and treatment options. A diagnostic pathway is suggested to guide providers in evaluating for comorbidities, referring to appropriate specialists, and choosing from the available classes of therapy.
ABSTRACT
BACKGROUND: Thrombosis of the left internal jugular vein in an astronaut aboard the International Space Station was recently described, incidentally discovered during a research study of blood flow in neck veins in microgravity. Given this event, and the high incidence of flow abnormalities, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thrombosis. METHODS: Duplex ultrasound of the bilateral internal jugular veins was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory maneuvers were performed. Images were analyzed for thrombosis and certain hemodynamic characteristics, including peak velocity and degree of echogenicity. RESULTS: Eleven astronauts were evaluated with matching terrestrial and in-flight ultrasounds. No thrombosis was detected. Compared to terrestrial ultrasound measurements, in-flight peak velocity was reduced and lowest in the left. Six of 11 astronauts had mild-moderate echogenicity in the left internal jugular vein during spaceflight, but none had more than mild echogenicity in the right internal jugular vein. Two astronauts developed retrograde blood flow in the left internal jugular vein. CONCLUSION: Abnormal flow characteristics in microgravity, most prominent in the left internal jugular vein, may signal an increased risk for thrombus formation in some individuals.
Subject(s)
Space Flight , Thrombosis , Venous Thrombosis , Weightlessness , Astronauts , Humans , Jugular Veins/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Weightlessness/adverse effectsSubject(s)
Adenoviridae Infections , Adenovirus Vaccines , Thrombocytopenia , Thrombosis , Humans , Adenoviridae , Adenoviridae Infections/complications , Antibodies , Thrombocytopenia/etiology , Thrombosis/etiology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/etiology , Adenovirus Vaccines/adverse effectsABSTRACT
BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).
Subject(s)
Anticoagulants/therapeutic use , Postthrombotic Syndrome/prevention & control , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Venous Thrombosis/drug therapy , Adult , Anticoagulants/adverse effects , Catheterization, Peripheral , Female , Hemorrhage/etiology , Humans , Incidence , Intention to Treat Analysis , Male , Middle Aged , Postthrombotic Syndrome/epidemiology , Postthrombotic Syndrome/etiology , Recombinant Proteins/therapeutic use , Risk Factors , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Venous Thrombosis/complicationsABSTRACT
It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-ß2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions â¼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P = .09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P = .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P = .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.
Subject(s)
Antibodies, Antiphospholipid/immunology , Venous Thromboembolism/etiology , Adolescent , Adult , Aged , Autoantibodies/immunology , Blood Coagulation , Blood Coagulation Tests , Female , Fibrin Fibrinogen Degradation Products , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Risk Factors , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Young AdultABSTRACT
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.
Subject(s)
Hematologic Diseases/drug therapy , Infection Control , Opportunistic Infections/prevention & control , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Anti-Infective Agents/therapeutic use , Antibiotic Prophylaxis , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Counseling , Hematologic Diseases/complications , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Opportunistic Infections/etiology , Patient Education as Topic , Practice Guidelines as Topic , Rituximab/adverse effects , Rituximab/therapeutic use , Splenectomy/adverse effects , Vaccination , Virus ActivationSubject(s)
Aerospace Medicine , Anticoagulants/therapeutic use , Jugular Veins/diagnostic imaging , Space Flight , Venous Thrombosis , Weightlessness/adverse effects , Drug Administration Schedule , Enoxaparin/therapeutic use , Humans , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Telemedicine , Ultrasonography , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Venous Thrombosis/etiologyABSTRACT
Direct Oral Anticoagulants (DOACs) require specific dosing and monitoring to ensure safe and appropriate use. The purpose of this evaluation was to identify patient- and process-related factors that correlate with increased risk of inappropriate prescribing of DOACs. A retrospective chart review was conducted in three outpatient clinics within an academic medical center to identify patients started on DOAC therapy and evaluate the appropriateness of DOAC initiation. Data collected included patient demographics, DOAC medication initiated, dose, indication, baseline laboratory values, concomitant medications, type and specialty of prescriber, and initiation setting. Appropriateness of initial dose was assessed and data were analyzed in order to identify factors correlating with inappropriate use. One-hundred sixty-seven patients initiated on a DOAC were identified. Most patients were prescribed anticoagulation for atrial fibrillation (74.9 %) and most commonly prescribed rivaroxaban (62.9 %). An inappropriate dose was prescribed in 24 (14.4 %) patients. Female patients and patients over 75 years were more likely to be prescribed an inappropriate initial dose. Baseline evaluation of blood counts and organ function were often not performed: hemoglobin values had not been drawn within the month prior to initiation in 28.7 % of patients, serum creatinine in 22.8 %, alanine transaminase in 52.1 %, and total bilirubin in 64.1 %. Lack of baseline labs was more pronounced in patients initiated on a DOAC in the outpatient setting. Dosing and baseline lab collection for DOAC initiation were suboptimal in all settings analyzed. Targeted interventions are needed to ensure the safe and appropriate use of DOAC therapy.
Subject(s)
Anticoagulants/administration & dosage , Medication Errors , Practice Patterns, Physicians'/standards , Administration, Oral , Aged , Aged, 80 and over , Antithrombins/administration & dosage , Factor Xa Inhibitors/administration & dosage , Female , Humans , Male , Medication Errors/statistics & numerical data , Medication Errors/trends , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.
Subject(s)
Factor V/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Prothrombin/genetics , Thrombophilia/epidemiology , Thrombophilia/genetics , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Alleles , Blood Coagulation , Blood Coagulation Tests , Child , Female , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Pregnancy , Risk , Thrombophilia/diagnosis , Thrombophilia/mortality , Young AdultABSTRACT
PURPOSE OF REVIEW: The purpose is to provide an update on management strategies for uterine fibroids in the setting of venous thromboembolism (VTE). RECENT FINDINGS: Uterine fibroids and VTE are independently associated with morbidity and increasing healthcare costs. Women with large uterine fibroids have a higher likelihood of VTE. Current strategies for stratifying patients with VTE take into account the nature of the VTE (i.e., truly provoked or unprovoked) and many patients may only require short-term anticoagulation. In those patients with risk factors for recurrent VTE, longer term anticoagulation may be required. SUMMARY: In women with large uterine fibroids, the likelihood of concurrent VTE increases. Peri and postoperative management should be determined based on patient-specific risk stratification, with the majority of patients requiring short-term anticoagulation. Further risk stratification may be required for patients with essentially an unprovoked VTE, and consultation with a thrombosis specialist is recommended.
Subject(s)
Anticoagulants/therapeutic use , Leiomyoma , Preoperative Care/methods , Venous Thromboembolism , Comorbidity , Guidelines as Topic , Humans , Leiomyoma/complications , Leiomyoma/surgery , Risk Assessment , Risk Factors , Time Factors , Venous Thromboembolism/drug therapy , Venous Thromboembolism/surgeryABSTRACT
This guidance document focuses on the diagnosis and treatment of venous thromboembolism (VTE). Efficient, cost effective diagnosis of VTE is facilitated by combining medical history and physical examination with pre-test probability models, D dimer testing and selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging can be used to tailor therapy to disease severity. Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs). DOACs are as effective as conventional therapy with LMWH and vitamin K antagonists. Thrombolytic therapy is reserved for massive pulmonary embolism (PE) or extensive deep vein thrombosis (DVT). Inferior vena cava filters are reserved for patients with acute VTE and contraindications to anticoagulation. Retrievable filters are strongly preferred. The possibility of thoracic outlet syndrome and May-Thurner syndrome should be considered in patients with subclavian/axillary and left common iliac vein DVT, respectively in absence of identifiable triggers. The optimal duration of therapy is dictated by the presence of modifiable thrombotic risk factors. Long term anticoagulation should be considered in patients with unprovoked VTE as well as persistent prothrombotic risk factors such as cancer. Short-term therapy is sufficient for most patients with VTE associated with transient situational triggers such as major surgery. Biomarkers such as D dimer and risk assessment models such the Vienna risk prediction model offer the potential to customize VTE therapy for the individual patient. Insufficient data exist to support the integration of bleeding risk models into duration of therapy planning.