Guidance for the treatment of deep vein thrombosis and pulmonary embolism

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

Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC). A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes

Duplex ultrasound screening for deep vein thrombosis in asymptomatic trauma patients: A survey of individual trauma surgeon opinions and current trauma center practices

Background: Many national agencies have suggested that deep vein thrombosis (DVT) rates measure quality of hospital care. However, none provide recommendations for standardized screening. If screening practices vary among clinicians or hospitals, DVT rates could be biased-centers which perform more duplex ultrasounds report more DVTs. We hypothesized that trauma surgeons have varying opinions regarding duplex ultrasound screening for DVT in asymptomatic trauma patients, which result in varying practice patterns. Methods: We conducted two web-based surveys regarding the use of duplex ultrasound screening for DVT in asymptomatic trauma patients. The first (individual provider level) surveyed members of two national trauma surgery organizations (American Association for the Surgery of Trauma and Eastern Association for the Surgery of Trauma). The second (trauma center level) surveyed practice patterns of National Trauma Data Bank hospitals. Results: Three hundred seventeen individual surgeons completed surveys. There was wide variation in individual opinions regarding DVT screening in asymptomatic trauma patients (53% agree, 36% disagree, and 11% neither agree nor disagree). Two hundred thirteen National Trauma Data Bank hospitals completed surveys of which 28% (n=60) have a written guideline regarding DVT screening in asymptomatic trauma patients. The proportion of centers with a written protocol varied significantly by trauma center level (p\u3c0.001) but not by teaching status. Opinions and practice patterns suggest that screening should start early and be performed weekly. The main risk factors used to suggest DVT screening are spinal cord injury and pelvic fracture. Conclusions: There are wide variations in trauma surgeons\u27 opinions and trauma centers\u27 practices regarding duplex ultrasound screening for DVT in asymptomatic trauma patients. This variability combined with the fact that performing more duplex ultrasounds finds more DVTs may influence reported DVT rates. DVT rates alone are biased and not reflective of true quality of trauma car

The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents

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 inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19

Case Report Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient's plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered

Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered

Inferior vena cava filters in the management of cancer-associated venous thromboembolism: a systematic review

This study systematically reviews outcomes after inferior vena cava (IVC) filtration in cancer-associated venous thromboembolism (VTE). A comprehensive review of the English language literature was performed using MEDLINE, COCHRANE library, Embase and CINAHL on outcomes (i.e., pulmonary embolism, recurrent DVT, postphlebitic syndrome and survival) following IVC filtration in cancer-associated VTE. Fourteen studies with 2,154 cancer patients receiving IVC filters post-VTE were included. All were observational studies. The mean duration of followup was 0.7–38 months and mean patient age was 56.8– 68 years. Among study participants, 47–87% had stage 3 or 4 cancers. Of the 47–93% of filters inserted for contraindications to anticoagulation (AC), 10–33% were placed for relative contraindications. Recurrent PE was seen in 0–6%, fatal PE in 0–4.5%, recurrent DVT in 0–18.2%, postphlebitic syndrome (PPS) in 0–2.7%, and IVC thrombosis (ICVT) in 3% of cancer patients. Median survival post-filter insertion was 2–10 months. Evidence supporting the utility of IVC filter insertion in cancer-associated VTE is limited to observational studies only. Preliminary data demonstrate similar safety and efficacy of filters in cancer and noncancer populations. The combination of filters and anticoagulation is no more effective than either modality alone. Retrievable filters are an attractive option for prevention of VTE in the presence of temporary risk factors or temporary contraindications to anticoagulation in patients who have a reasonable life expectancy, but there is no evidence to support their preferential use in patients with advanced malignancy