Thromboembolic Event

Article Author:
Sarosh Vaqar
Article Editor:
Matthew Graber
Updated:
10/30/2019 10:51:01 AM
PubMed Link:
Thromboembolic Event

Introduction

Thromboembolic events count among the most feared complications of hospitalizations. Venous thromboembolism (VTE) is the third leading cardiovascular diagnosis after a heart attack and stroke.[1] According to the American Heart Association, it affects between 300000 to 600000 people per year and bears a significant cost burden. VTE refers to the interrelated diagnoses of deep vein thrombosis (DVT) and pulmonary embolism (PE). Together with an individual predisposition to form vascular thrombi and with clinical scenarios that increase this propensity further, VTE poses a significant risk of added morbidity and mortality for a vast majority of the world’s population. Considerable research has been done to identify those at risk and to provide appropriate prevention where indicated. However, VTE remains a growing public health concern today, and much needs to take place to raise awareness amongst the public as well as healthcare providers.

Etiology

The predisposition to thromboembolic disease is multifactorial. Individual patient factors, current disease state, recent or planned surgical procedures, and underlying hematologic disorders, all add up to give a patient’s risk of VTE at that particular time. Patient-related factors include age over 40 years, obesity, the presence of varicose veins, and immobility. The use of oral-contraceptive medications and smoking increases the risk of VTE, as well.[2][3] Disease states that are generally known for increasing risk for VTE are malignancies, spinal cord injuries with paralysis, and nephrotic syndrome.[4][5] However, the presence of congestive heart failure,[6] inflammatory bowel disease,[7], and a recent myocardial infarction also confer a higher risk of VTE.[8] The presence of pelvic, hip, or long-bone fractures, along with orthopedic surgeries involving the hip and knee, all increase the risk of VTE as well. Hematologic disorders that lead to hypercoagulability include activated protein C resistance (factor V Leiden mutation), protein C or protein S deficiency, antithrombin III deficiency, presence of lupus anticoagulant, dysfibrinogenemia, prothrombin mutation, polycythemia vera, and paroxysmal nocturnal hemoglobinuria. The physiologic state of pregnancy also confers a higher risk of VTE. 

Multiple risk assessment models have now been developed to identify those at the highest risk of hospital-acquired VTE and to provide appropriate thromboprophylaxis for these patients. The Caprini model was the first quantitative VTE risk assessment model to be validated and have worldwide use. The Brigham and Women's Hospital Model (Kucher model), the Padua model, Roger’s model, the Intermountain model, the IMPROVE model, and the Premier model have since undergone development and validation.[9]

Epidemiology

Reviewing available literature reveals the global annual burden of VTE to be in millions of cases. The morbidity and mortality associated with these cases are significant, as well. In the United States alone, there are approximately 100000 to 300000 VTE-related deaths reported every year.[10] In Europe, this number rises to greater than 500000 deaths annually by most published reports. The most concerning fact about these numbers is that the majority of these cases are hospital-related or acquired. With 60% of VTE cases being hospital-acquired, VTE is the leading preventable cause of death in hospitalized patients.[11]

Pathophysiology

Venous thrombosis refers to the formation of a platelet and fibrin clot within the vascular lumen. Clinically significant thrombi are formed in vessels with large lumens such as the deep veins of the legs, pelvis, and arms. The clot can then propagate with proximal extension. Clinical symptoms of the thrombus are seen when the clot propagates enough to have obstruction of vascular flow. If the clot dislodges, it can then embolize to a distant site. The most common site of embolization for these clots is in the pulmonary vasculature. Obstruction to pulmonary vascular flow can cause impaired gas-exchange, alveolar edema, or even pulmonary alveolar necrosis. Chronic repetitive pulmonary embolization can lead to increased pulmonary vascular resistance and eventually, pulmonary hypertension. In the presence of cardiac abnormalities such as a patent foramen ovale or an atrial septal defect, paradoxical embolism of the clot into the systemic arterial vascular can occur.

History and Physical

With DVT, the patient presents with a complaint of unilateral limb pain. This pain may be accompanied by physical signs of swelling, warmth, and tenderness to touch. However, physical exam signs for the diagnosis of DVT are of low yield. 

With PE, the most common presenting complaint is that of dyspnea that is sudden in onset. Patients may also demonstrate pleuritic chest pain and cough, as well as hemoptysis in some cases. Massive pulmonary embolism presents with syncope and signs of hemodynamic compromise such as hypotension and shock. Physical examination of patients with PE may reveal hypoxia, tachycardia, and fever. Tachypnea, with a respiratory rate over 18/min, is the most common sign of PE. However, in general, physical exam findings for PE are variable and nondiagnostic. The presence of confounding factors such as sickle cell disease may complicate presentation even further. In these patients, PE usually presents with a chest infection. In the elderly, new-onset, atrial fibrillation may be the presenting symptom of a PE and requires exclusion in such cases. 

In patients with established PE, tachypnea (respiratory rate over 18/min) is the most common physical findings. The pulmonary exam may reveal rales in up to 50% of the cases with an accentuated second heart sound. Tachycardia (heart rate over 100/min) and fever are present in about 45% of the patients. Diaphoresis and an S3 or S4 gallop may be audible in about 30% of the patients. A pleural friction rub may be present in cases with pleuritic chest pain, which suggests a peripheral PE and is often associated with pulmonary necrosis.

Patients with chronic recurrent VTE syndromes may present with signs of pulmonary hypertension and cor pulmonale. Dyspnea will be the most common presenting complaint in these patients. The physical exam may reveal a palpable impulse over the second left intercostal space, a loud P2, a right ventricular S3 gallop, and a systolic murmur on inspiration at the left sternal border from tricuspid regurgitation. Hepatomegaly and dependent pitting edema may also occur. 

However, due to the poor sensitivity and specificity of clinical signs and symptoms for DVT and PE, clinical decision-making tools have been developed to identify those with a high pretest probability of VTE; this is possible using the Modified Well’s criteria. The patient suspected of having venous thromboembolism is given points for the presence of predisposing criteria. This includes 3 points for clinical signs or symptoms of DVT, 3 points if an alternative diagnosis less likely than PE, 1.5 points for heart rate 100 beats per minute or more, 1.5 points for immobilization (over 3 days) or surgery in the preceding 4 weeks, 1.5 points for a previous history of DVT or PE, and 1 point each for hemoptysis and active cancer in the last 6 months. Patients who score less than 2 points have low risk, a score of 2 to 6 points qualifies as moderate risk, and a score greater than 6 equates to high risk according to the original Well's criteria. The Modified Well's criteria simplified the probability using 4 points as the cut-off. Patients with greater than or equal to 4 points are considered to have PE as the probable cause of the presentation.[12] 

Patients who are suspected of having VTE but score low on the pre-test probability scoring can undergo assessment via the highly sensitive D-dimer assay due to its high negative predictive value. Those who are suspected of having VTE and have a high pretest probability of the disease should be evaluated using definitive testing.[13]

Evaluation

Definitive testing for VTE

Individuals that have a low pretest probability for VTE may be ruled out using a high sensitivity D-dimer assay.[13] The D-dimer assay has a high negative predictive value, but low sensitivity and thus should be used to rule out the disease. However, D-dimer assay cannot be used to diagnose VTE.

Pulmonary angiography has traditionally been the gold-standard for the diagnosis of PE; however, due to its invasive nature, it is no longer used on a routine basis. An elevated D-dimer, in suspected cases of PE, needs to be followed by a ventilation-perfusion (VQ) scan or a computed tomography pulmonary angiography (CTPA) to confirm the diagnosis of PE. Individuals with a moderate or high Modified Well’s score should be evaluated directly using CTPA, or a VQ scan if a CTPA is contraindicated.

In high pretest probability for DVT or an elevated D-dimer in cases suspected of having DVT, proximal or whole-leg ultrasonography should be used to confirm the diagnosis. Serial ultrasonography is an option if the initial ultrasonogram is negative, and suspicion for DVT remains high.[13] 

It is important to note that high sensitivity D-dimer assay is a marker of fibrinolysis and can appear elevated in pneumonia, cancer, sepsis, and recent surgery. It can also be elevated in patients with poor renal function and varies considerably with advanced age as well. An age-adjusted D-dimer cutoff value can be useful in patients with advanced age.[14] Patients suspected of having a PE but who are low risk may have the PERC rule applied to rule out PE. If they meet all criteria, a d-dimer is avoidable, and PE is ruled out on a clinical basis.

The American College of Radiology considers CTPA as the standard of care for the detection of PE. The advantage of this imaging modality, in addition to the diagnosis of the disease, is that it provides important additional information. The spiral (helical) CT scan may suggest an alternative diagnosis if present; this is an advantage when compared to pulmonary angiography or scintigraphy.[15]

The PERC rule

This rule was established to avoid excessive testing and to avoid the high frequency of false-positive readings in low-risk patients. Kline et al. developed this clinical tool in 2004 which identified the presence of age below 50 years, pulse less than 100 beats per minute, arterial oxygen saturation (SpO2) greater than 94 %, no unilateral leg swelling, no hemoptysis, no recent trauma or surgery, no prior PE or deep venous thrombosis (DVT) and no exogenous estrogen use as low risk factors for VTE, specifically PE. If a patient fulfills all these criteria, he is considered PERC-negative and is at low risk for PE. In this individual positive D-Dimer is likely to be a false-positive and should be avoided. Kline et al. reported that the prevalence of PE in these cases was 1.4 %. Two meta-analyses confirmed the benefits and safety of the PERC rule, with less than 1 % PE in PERC-negative patients after one year follow up.[16]

Additional studies

The use of other laboratory tests (such as arterial blood gas, troponin level, and serum brain-natriuretic peptide) or diagnostic studies (such as chest X-ray or electrocardiogram) is of low yield for the general population.

Arterial blood gas (ABG) may reveal hypoxemia, hypocapnia, and respiratory alkalosis, which has poor positive predictive value for the diagnosis of PE. In high-risk settings, however, such as a patient with post-operative respiratory distress, in whom other causes of dyspnea have been ruled out (such as infection and pulmonary edema), the low partial pressure of oxygen (PaO2) may have significant predictive value for PE. In the general population, the ABG derived hypoxemia has little predictive value for PE because other conditions are more likely to lower PaO2 in these cases than PE. 

Serum troponin levels may be elevated in patients with a moderate to large PE due to acute right ventricular myocardial stretch. However, troponin levels do not have a role in the diagnosis of PE and are not a recommended part of a routine diagnostic workup. In patients with established PE, however, elevated serum troponin levels may be associated with higher mortality.[17]

Brain natriuretic peptide (BNP) level is neither sensitive nor specific for PE. An elevated level of BNP, however, correlates with an increased risk of subsequent complications and increased mortality in patients with acute PE.

There is no specific role for electrocardiogram (ECG) in the evaluation of a patient with VTE / PE. The clinical utility of ECG lies in rule out acute myocardial infarction in a patient who presents with chest pain, dyspnea, and perhaps other signs of PE. The ECG in most PE cases is normal except for the presence of tachycardia and non-specific ST-T wave abnormalities. The classical findings of S1 Q3 T3 have poor specificity for PE. If significant right heart strain is present with acute cor pulmonale, the ECG may reveal tall, peaked P waves in lead II, a rightward axis deviation; right bundle-branch block; and an S1 Q3 T3 pattern; or atrial fibrillation. 

Echocardiography is indicated in cases of massive PE to evaluate for signs of right-heart strain. It allows visualization and dynamic evaluation of the right ventricle and aid in the assessment of pulmonary arterial pressures. Echocardiography in these cases provides a prognostic assessment, as increased mortality is associated with the presence of right ventricular dysfunction on echocardiography in these cases. Findings of right heart strain on echocardiography include right ventricular enlargement, right ventricular hypokinesis, leftward septal shift, and evidence of pulmonary hypertension. If the right ventricular dysfunction appears on echocardiography, the diagnosis of acute submassive or massive pulmonary embolism is confirmed. Although it may also provide useful information in the identification of alternative diagnoses, it is not a recommended part of a routine workup for PE. 

The American College of Radiology recommends chest radiography as a study for ruling out other causes of chest pain in patients with suspected pulmonary embolism. Chest radiographs, although abnormal in most cases, provide little diagnostic information for the disease. The classic findings of a wedge-shaped pulmonary infarct seen as a pleura-based triangular opacity pointing towards the hilus (also known as the Hampton hump) or decreased pulmonary vascularity (also known as the Westermark sign) seldom present.

Treatment / Management

Anticoagulation remains the primary treatment for VTE (DVT and PE). Thrombolytic therapy and intravenous filter placement are options reserved for specialized cases. In general, the use of direct-acting oral anticoagulants, such as apixaban, dabigatran, edoxaban, and rivaroxaban, is preferred over parenteral heparin and vitamin K antagonist therapy. Is it imperative to note that traditional vitamin K antagonists are not effective without concomitant parenteral heparin therapy for at least 5 to 7 days. Also, dabigatran and edoxaban have not yet had testing in acute VTE without previous parenteral heparin therapy. Apixaban and rivaroxaban are both United States Food and Drug Association (U.S. FDA) approved for monotherapy for acute VTE, including both acute DVT and acute PE episodes. 

The duration of therapy for the initial episode of VTE (DVT or PE) remains 3 to 6 months, except for patients with isolated distal DVT and a low risk of recurrence.[18] According to recommendations by the European Society of Cardiology, these patients can safely receive therapy with a short 4 to 6-week course of anticoagulation.[19] Alternative treatment for this group includes no anticoagulation and surveillance compression ultrasound. 

Patients without cancer should receive therapy with direct oral anticoagulants or warfarin. In obese patients who have treatment with low-molecular-weight heparin for the treatment of acute VTE, the American Society of Hematology recommends using their actual weight rather than a “capped” dose.[18] In cancer patients, low-molecular-weight heparin is the drug of choice for the treatment of acute VTE.[20]

In pregnant patients, low molecular-weight heparin is the drug of choice for initial and long-term treatment as well. The duration of treatment in the pregnant patient is at least 6 weeks post-partum with a minimum of 3 months of the total duration of treatment.[21] 

Vena cava filters should only be a consideration if there is a contraindication to anticoagulation. Due to the inferior efficacy of these filters in preventing thromboembolic events, experts recommend a periodic reassessment of these contraindications to anticoagulation.

Thrombolytic therapy is indicated for patients with massive PE causing hemodynamic instability. However, it is essential to note the absolute and relative contraindications for the use of thrombolytic treatment before its application. DVT cases with complete obstruction of blood flow with impending compartment syndrome should also merit consideration for thrombolytic therapy. 

Therapy for recurrent VTE is lifelong anticoagulation. 

Inpatient vs. Outpatient Treatment

Given the inherent risk of hospitalizations, current guidelines increasingly recommend outpatient therapy when possible. Almost all DVT cases can have diagnosis and treatment without hospitalization. For PE, clinical tools have been developed to identify those patients that are safely treatable as an outpatient. The Pulmonary Embolism Severity Index (PESI) predicts clinical severity for patients with PE using a patient's age, gender, history of malignancy, history of congestive heart failure or chronic lung disease, and patient's vital signs on presentation. Patients with a low PESI score can safely receive treatment for PE as an outpatient. A simplified version of the PESI score defines low-risk patients as those who are younger than 80 years and have no significant comorbidity with a pulse rate of less than 110/min, systolic blood pressure greater than 100 mm Hg, and oxygen saturation greater than 90% on room air on presentation. 

Differential Diagnosis

Localized symptoms of DVT can be similar to cellulitis, arterial insufficiency, lymphedema, and hematoma.

Patients with PE can have a varied presentation and a broad differential. Congestive heart failure, acute respiratory distress syndrome, pneumonia, and myocardial infarction are always on the differential for patients with PE. The evaluation of PE, therefore, must also include an assessment to rule out these conditions as well.

Prognosis

According to the literature, thromboembolic events represent the number one cause of hospital-acquired morbidity and mortality worldwide. The mortality rate is also dependent on underlying comorbidities. Patients admitted to the hospital for acute VTE, especially PE, with multiple comorbidities including heart failure and atrial fibrillation, can have an in-hospital mortality rate as high as 4.5% in the first 30 days.[22] In patients with active malignancy, this number has been reported to be as high as 10%.[23] A significant number of these patients present with clinically significant and hemodynamically unstable VTE. All-cause 30-day mortality in patients who present with unstable PE is reported as high as 14%.[24] The rate of recurrence also depends on the underlying patient characteristics and predisposing factors to VTE. According to a recent study, the 5-year incidence of recurrent VTE was 17.7% in patients with active cancer and 8.6% in those without cancer.[25] Due to the sheer number of VTE events worldwide on an annual basis and the statistics mentioned above in regards to its mortality and recurrence, an overhaul of thromboprophylaxis policies is necessary to consistently and accurately treat those at the highest risk of the disease. A subset of the population diagnosed with VTE remains at risk for recurrent VTE. Risk factors for VTE recurrence are similar to those required for the initial event and are not necessarily limited to disorders of anticoagulation. Validated and recommended risk prediction models to determine the risk of VTE recurrence include the Vienna model, the DASH score, and the HERDOO-2 model.

Complications

Long term complications of adequately treated VTE are few. The most commonly reported long-term complication is post-thrombotic syndrome in patients diagnosed with DVT, which characteristically presents as pain and swelling of the limb with chronic venous insufficiency.

Longterm sequelae of recurrent PE include pulmonary hypertension and cor pulmonale, as described above.

Bleeding

Bleeding remains the most pertinent and feared complication of the treatment of VTE. Patients with advanced age and underlying hepatic or renal dysfunction are at a higher risk of bleeding. Despite this risk, most guidelines recommend against routine use of laboratory monitoring in patients receiving the newer anticoagulants. For patients receiving vitamin K antagonist therapy and having INR levels monitored, who have a level above 4.5 but under 10 without clinically relevant bleeding, the recommendation is to hold the drug temporarily. Reversal therapy is not a recommendation in this scenario.

If, however, a patient develops life-threatening bleeding with vitamin K antagonist therapy, treatment with intravenous vitamin K along with four-factor prothrombin complex concentrates (PCC) transfusion is the recommended appraoch. For patients receiving newer oral anticoagulant therapy and a life-threatening bleed, transfusion of four-factor PCC transfusion, the clinician can trial recombinant factor Xa infusion or inactivated-zhzo infusion. In some cases where the risk of life-threatening bleeding is high, clinicians may prefer dabigatran of the newer oral anticoagulation agents as idarucizumab is now available for the reversal of this agent. It is important to note that the reocmmendation is for resumption of anticoagulation after a major bleeding episode within 90 days.

Heparin-Induced Thrombocytopenia

Immune-mediated heparin-induced thrombocytopenia (HIT) typically occurs 5 to 10 days after exposure to heparin; this clinically manifests as thrombosis with thrombocytopenia and can be life-threatening. If a patient on heparin therapy has a decline of 50% of more after exposure to heparin, then HIT merits consideration, and antibodies to platelet factor 4 should be checked to make the diagnosis. All heparin containing products should be stopped immediately and should not be given to the patient again. It is important to note that anti-platelet factor 4 is a highly sensitive assay and is used to rule out the disease. If this test is positive, the diagnosis of HIT should be confirmed using the serotonin release assay or the heparin-induced platelet aggregation assay. Treatment for HIT associated thrombosis includes argatroban, bivalirudin, danaparoid, fondaparinux, or a non–vitamin K antagonist oral anticoagulant (such as rivaroxaban). 

Warfarin-Induced Skin Necrosis

Warfarin induced skin necrosis is a rare complication of warfarin therapy and occurs in less than 0.1% of the population. Protein C deficiency is a risk factor for the development of this disorder. In patients with hereditary protein C deficiency, there is a rapid decrease in the concentration of protein C as compared to the other vitamin K-dependent procoagulant factors; this results in a temporary hypercoagulable state which can lead to thrombotic occlusions particularly of the microvasculature. These will clinically manifest as skin necrosis after initiation of warfarin therapy.

Deterrence and Patient Education

There is considerable evidence to support the decreased risk of VTE with appropriate prophylaxis. Considering that the majority of the cases of VTE are hospital-acquired, it provides a unique opportunity for thromboprophylaxis polices to be effectively instituted. Knowing that despite surviving an episode of VTE and anticoagulation, patients remain at risk for repeat episodes amplifies the magnitude of the problem. By some estimates, thromboprophylaxis can reduce VTE incidence by 30 to 65 percent, without a concomitant increase in complications of anticoagulation therapy.[26]

In medically ill patients at moderate-high risk for VTE, prophylaxis with low-molecular-weight heparin is recommended. Recent studies have shown however, that this risk extends beyond their hospitalization.[28] Betrixaban is an oral factor Xa inhibitor which was recently approved by the U.S Food and Drug Administration for extended VTE prophylaxis in adults hospitalized for acute medical illness.

POSTOPERATIVE PREVENTION

Given the higher incidence of VTE in patients undergoing orthopedic surgery, the American Academy of Orthopaedic Surgeons (AAOS) published specific guidelines for what is considered appropriate thromboprophylaxis. They recommend a variety of chemoprophylaxis choices for patients at different levels of risk and go on to state that even patients at elevated risk for major bleeding should receive VTE prophylaxis with aspirin or warfarin (with an INR goal below 2.0).[27] The recommended duration of this prophylaxis is for 7 to 10 days postoperatively. Specifically stated, they recommend that in patients planned for total hip or knee arthroplasty, they should receive VTE prophylaxis for a minimum of 10 to 14 days. This prophylaxis is possible through the use of low-molecular-weight heparin, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose vitamin K antagonist, or aspirin. Intermittent pneumatic compression devices are an option if there are contraindicaitons to anticoagulation therapy. In general, however, monotherapy with mechanical methods of VTE prophylaxis is not recommended. 

According to the American College of Chest Physicians (ACCP), hip fracture surgery, and total knee or hip arthroplasty pose a high risk for VTE. In these cases, mechanical (nonpharmacologic) and pharmacologic VTE prophylaxis is the recommended course. The recommended duration of VTE prophylaxis in patients undergoing orthopedic surgery is 10 to 14 days, according to the ACCP. In patients at low risk for bleeding, they recommend extended-duration postoperative prophylaxis of up to 35 days. Routine surveillance for VTE with ultrasonography is not a recommendation in patients undergoing orthopedic, general, abdominal-pelvic, or trauma surgery.

Pearls and Other Issues

AMERICAN SOCIETY OF HEMATOLOGY (ASH) CLINICAL PRACTICE GUIDELINES ON VENOUS THROMBOEMBOLISM

Below is a summary of the salient points from the latest clinical practice guidelines published by ASH on the diagnosis and management of VTE.

  • In patients with low pretest probability for VTE, the initial test to obtain is a D-dimer.
    • A ventilation-perfusion scan or a CTPA should follow this test if the results are positive, while negative test rules out VTE. 
  • In patients with low pretest probability for PE who present to an emergency department, PERC rule may be used to determine whether D-dimer testing is needed.
  • A positive D-dimer alone cannot be used to make the diagnosis and must be followed up with additional testing. 
  • In patients with low pretest probability under evaluation for possible recurrent VTE, D-dimer is still the recommended initial test of choice. 
    • A ventilation-perfusion scan or a CTPA should follow this test if results are positive while negative test rules out VTE.
  • A positive D-dimer in suspected cases of initial or recurrent lower extremity DVT should be followed up with a proximal lower extremity ultrasound or whole leg ultrasound. 
  • Routine use of anti-factor Xa to guide low molecular weight heparin dosing, even in those with renal failure or with morbid obesity, is not a recommendation. 
    • Dose adjustment or alternate agents are the advised approach in these cases.
  • In cases of life-threatening bleeding from vitamin K antagonist treatment, 4-factor prothrombin complex concentrate (PCC) is the recommended therapy.
  • In cases of life-threatening bleeding from oral direct Xa inhibitor treatment of VTE, 4 factor PCC merits consideration in addition to stopping the anticoagulation agent.
    • Recombinant Xa, inactivated zhzo may also be a consideration.

Enhancing Healthcare Team Outcomes

The burden of VTE is a growing public health concern. Underscoring this concern is the fact that the majority of these cases are hospital-acquired. The treatment of VTE is of extended duration and has associated complications as well. Ensuring proper prophylaxis, diagnosis, and subsequent compliance with adverse effect monitoring is essential in improving patient outcomes. Effective protocols for VTE prophylaxis need to be developed by hospital administrators and implemented efficiently to decrease the incidence of VTE.

An interprofessional approach to the development of effective prophylaxis protocols and their implementation is crucial. Clinical providers, nurses, administrators, and pharmacists should develop these protocols together to ensure the provision of appropriate prophylaxis and treatment. Today almost all hospitals have DVT prophylaxis protocols for surgery patients, and these require close adherence. The role of the clinician rests primarily in identifying those at risk for the development of VTE and in the proper treatment for those diagnosed with it. The role of the pharmacist is critical in maintaining adequate dosing, prevention of drug interactions, and ensuring compliance by the patient for the duration of VTE treatment. Specialty nurses are needed to provide patient education not only to ensure the proper compliance but also for appropriate monitoring of complications of VTE or the adverse effects of the treatment itself. An integrated interprofessional team can significantly reduce the incidence of VTE and improve outcomes in patients diagnosed with the disease. [Level V]


References

[1] Jiménez D,Bikdeli B,Quezada A,Muriel A,Lobo JL,de Miguel-Diez J,Jara-Palomares L,Ruiz-Artacho P,Yusen RD,Monreal M, Hospital volume and outcomes for acute pulmonary embolism: multinational population based cohort study. BMJ (Clinical research ed.). 2019 Jul 29;     [PubMed PMID: 31358508]
[2] Plu-Bureau G,Hugon-Rodin J,Raccah-Tebeka B, [Hormonal contraception and vascular risk]. La Revue du praticien. 2018 Apr;     [PubMed PMID: 30869386]
[3] Gregson J,Kaptoge S,Bolton T,Pennells L,Willeit P,Burgess S,Bell S,Sweeting M,Rimm EB,Kabrhel C,Zöller B,Assmann G,Gudnason V,Folsom AR,Arndt V,Fletcher A,Norman PE,Nordestgaard BG,Kitamura A,Mahmoodi BK,Whincup PH,Knuiman M,Salomaa V,Meisinger C,Koenig W,Kavousi M,Völzke H,Cooper JA,Ninomiya T,Casiglia E,Rodriguez B,Ben-Shlomo Y,Després JP,Simons L,Barrett-Connor E,Björkelund C,Notdurfter M,Kromhout D,Price J,Sutherland SE,Sundström J,Kauhanen J,Gallacher J,Beulens JWJ,Dankner R,Cooper C,Giampaoli S,Deen JF,Gómez de la Cámara A,Kuller LH,Rosengren A,Svensson PJ,Nagel D,Crespo CJ,Brenner H,Albertorio-Diaz JR,Atkins R,Brunner EJ,Shipley M,Njølstad I,Lawlor DA,van der Schouw YT,Selmer RM,Trevisan M,Verschuren WMM,Greenland P,Wassertheil-Smoller S,Lowe GDO,Wood AM,Butterworth AS,Thompson SG,Danesh J,Di Angelantonio E,Meade T, Cardiovascular Risk Factors Associated With Venous Thromboembolism. JAMA cardiology. 2019 Feb 1;     [PubMed PMID: 30649175]
[4] Gyamlani G,Molnar MZ,Lu JL,Sumida K,Kalantar-Zadeh K,Kovesdy CP, Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017 Jan 1;     [PubMed PMID: 28391310]
[5] Piran S,Schulman S, Thromboprophylaxis in Patients with Acute Spinal Cord Injury: A Narrative Review. Seminars in thrombosis and hemostasis. 2019 Mar;     [PubMed PMID: 30743281]
[6] Dean SM,Abraham W, Venous thromboembolic disease in congestive heart failure. Congestive heart failure (Greenwich, Conn.). 2010 Jul-Aug;     [PubMed PMID: 20662869]
[7] McKie K,McLoughlin RJ,Hirsh MP,Cleary MA,Aidlen JT, Risk Factors for Venous Thromboembolism in Children and Young Adults With Inflammatory Bowel Disease. The Journal of surgical research. 2019 Jun 7;     [PubMed PMID: 31181463]
[8] Sejrup JK,Børvik T,Grimnes G,Isaksen T,Hindberg K,Hansen JB,Morelli VM,Brækkan SK, Myocardial Infarction as a Transient Risk Factor for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study. Thrombosis and haemostasis. 2019 Aug;     [PubMed PMID: 31203579]
[9] Zierler BK,Wittkowsky A,Peterson G,Lee JA,Jacobson C,Glenny R,Wolf F,Robins L,Mitchell P,Wolpin S,Payne T,Hendrie P,Han G,Oh H, Venous Thromboembolism Safety Toolkit: A Systems Approach to Patient Safety 2008 Aug;     [PubMed PMID: 21249920]
[10] Wakefield TW,McLafferty RB,Lohr JM,Caprini JA,Gillespie DL,Passman MA, Call to action to prevent venous thromboembolism. Journal of vascular surgery. 2009 Jun;     [PubMed PMID: 19497526]
[11] Grande Ratti MF,Posadas-Martínez ML,Vicens J,González Bernaldo de Quirós F,Vázquez FJ,Giunta DH, Incidence of hospital-acquired venous thromboembolic disease. Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina). 2018 Jun 12;     [PubMed PMID: 30273531]
[12] Mittadodla PS,Kumar S,Smith E,Badireddy M,Turki M,Fioravanti GT, CT pulmonary angiography: an over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism. Journal of community hospital internal medicine perspectives. 2013     [PubMed PMID: 23882398]
[13] Lim W,Le Gal G,Bates SM,Righini M,Haramati LB,Lang E,Kline JA,Chasteen S,Snyder M,Patel P,Bhatt M,Patel P,Braun C,Begum H,Wiercioch W,Schünemann HJ,Mustafa RA, American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood advances. 2018 Nov 27;     [PubMed PMID: 30482764]
[14] Dutton J,Dachsel M,Crane R, Can the use of an age-adjusted D-dimer cut-off value help in our diagnosis of suspected pulmonary embolism? . Clinical medicine (London, England). 2018 Aug;     [PubMed PMID: 30072551]
[15] Lu F,Gao Y,Kong Q,Qiao P,Shao M,Xie M, Application of 640-slice CT wide-detector volume scan in low-dose CT pulmonary angiography. Journal of X-ray science and technology. 2019     [PubMed PMID: 30584179]
[16] Raynal PA,Cachanado M,Truchot J,Damas-Perrichet C,Feral-Pierssens AL,Goulet H,Deltour S,Boussouar S,Donciu V,Simon T,Freund Y,Philippon AL, Prevalence of pulmonary embolism in emergency department patients with isolated syncope: a prospective cohort study. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2019 Oct 11     [PubMed PMID: 31609876]
[17]     [PubMed PMID: 30685960]
[18] Witt DM,Nieuwlaat R,Clark NP,Ansell J,Holbrook A,Skov J,Shehab N,Mock J,Myers T,Dentali F,Crowther MA,Agarwal A,Bhatt M,Khatib R,Riva JJ,Zhang Y,Guyatt G, American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood advances. 2018 Nov 27;     [PubMed PMID: 30482765]
[19] Shargall Y,Litle VR, European perspectives in Thoracic Surgery, the ESTS venous thromboembolism (VTE) working group. Journal of thoracic disease. 2018 Apr;     [PubMed PMID: 29744223]
[20] Key NS,Khorana AA,Kuderer NM,Bohlke K,Lee AYY,Arcelus JI,Wong SL,Balaban EP,Flowers CR,Francis CW,Gates LE,Kakkar AK,Levine MN,Liebman HA,Tempero MA,Lyman GH,Falanga A, Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Aug 5;     [PubMed PMID: 31381464]
[21] Bates SM,Rajasekhar A,Middeldorp S,McLintock C,Rodger MA,James AH,Vazquez SR,Greer IA,Riva JJ,Bhatt M,Schwab N,Barrett D,LaHaye A,Rochwerg B, American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood advances. 2018 Nov 27;     [PubMed PMID: 30482767]
[22]     [PubMed PMID: 31602725]
[23]     [PubMed PMID: 31605702]
[24]     [PubMed PMID: 30025658]
[25]     [PubMed PMID: 31548438]
[26] Gadó K,Kicsi D,Markovics D,Domján G, [Importance of thromboprophylaxis in hospitalized non-surgical patients]. Orvosi hetilap. 2019 Apr;     [PubMed PMID: 31010307]
[27] Ruiz-Iban MA,Díaz-Heredia J,Elías-Martín ME,Martos-Rodríguez LA,Cebreiro-Martínez del Val I,Pascual-Martín-Gamero FJ, [The new guidelines for deep venous thromboembolic disease prophylaxis in elective hip and knee replacement surgery. Are we nearer or further away from a consensus?]. Revista espanola de cirugia ortopedica y traumatologia. 2012 Jul-Aug;     [PubMed PMID: 23594854]