Tag: Venous Thrombo Embolism

SUMMARY: Secondary hypogammaglobulinemia is a common immune defect in malignancies such as Chronic Lymphocytic Leukemia, Multiple Myeloma and Non-Hodgkin B cell lymphomas. Approximately 20-70% of these patients may experience hypogammaglobulinemia during the course of their illness. Secondary hypogammaglobulinemia generally correlates with duration and stage of the disease and there is a direct relationship between the frequency/severity of infections and low IgG levels. The infection risk may be further exacerbated by treatment induced hypogammaglobulinemia.

IntraVenous Immune globulin (IVIg) is a purified plasma fraction and contains more than 95% unmodified Immunoglobulin G (IgG). It is derived from large donor pools and is often recommended for patients with hypogammaglobulinemia, to reduce the risk of serious infection. With the recognition of serious IVIg-associated ThromboEmbolic Events (TEEs) dating back to the 1980’s, the FDA in 2013 mandated boxed warning for IVIg products. The TEE risk has been attributed to increased blood viscosity secondary to erythrocyte aggregation following administration of IVIg, resulting in stasis and thrombosis, platelet activation by exogenous IgG, arterial vasospasm and other plasma components such as coagulation factor XIa, that is not completely removed in some IVIg manufacturing processes. However, it is not clear if the TEEs are directly attributable to the IVIg itself or whether other risk factors such as patient’s age, disease state or other factors play a role.

The authors in this study conducted a retrospective review of data from the Surveillance, Epidemiology and End Results (SEER) cancer registries for Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM) patients, linked to Medicare claims and enrollment data. This study included CLL and Myeloma patients (N=2724), 66 years or older, who were new users of IVIg and this group was propensity matched to non recipients of IVIg (N=8035). Propensity matching allowed comparison of groups across measured demographic and clinical characteristics and other variables. The primary endpoint was the occurrence of serious arterial ThromboEmbolic Event (TEE), defined as hospitalization for Acute Myocardial Infarction or Ischemic Stroke. Secondary endpoints included venous TEE (hospitalization for Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE). Based on previously published studies, the authors hypothesized that the prothrombotic effects of IVIg would most likely be acute but could last for as long as 1 month after an IVIg infusion.

It was noted that patients receiving IVIg were significantly more likely to develop a TEE such as Acute Myocardial Infarction or Stroke within the first 24 hours compared to IVIg nonrecipients (HR=3.40). This arterial thrombotic risk declined during the following 30 days. There was however, no significant increase in venous thrombotic events during the first 30 days after IVIg infusion. The risk for any ThromboEmbolic Events (TEEs) increased with age during the first 30 days following IVIg therapy (P=0.03), but was not associated with the type or duration of malignancy, history cardiovascular disease, history of venous thromboembolism or IVIg brand.

It was concluded that based on this study, arterial thrombotic events (Myocardial Infarction and Stroke) are likely to occur within the first 24 hours following IVIg administration, in patients with immunodeficiency, secondary to Chronic Lymphocytic Leukemia or Multiple Myeloma and this thrombotic risk is more common with increasing patient age. Clinicians should therefore weigh the risk/benefits with IVIg use and elderly patients should be well hydrated and closely monitored for the first 24 hours following IVIg infusion. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy. Eric M. Ammann EM, Jones MP, Link BK, et al. Blood 2016; 127:200-207

SUMMARY: There are presently four Direct Oral AntiCoagulants (DOACs) approved in the United States for the treatment of Venous ThromboEmbolism. They include PRADAXA® (Dabigatran), which is a direct thrombin inhibitor and XARELTO® (Rivaroxaban), ELIQUIS® (Apixaban), SAVAYSA® (Endoxaban), which are Factor Xa inhibitors. Compared to Vitamin K Antagonist COUMADIN® (Warfarin), the Direct Oral AntiCoagulants have a rapid onset of action, wider therapeutic window, shorter half-lives (7-14 hours in healthy individuals), no laboratory monitoring and fixed dosing schedule. The half life of these agents can however be prolonged in those with renal insufficiency. The FDA in October, 2015, granted accelerated approval to PRAXBIND® (Idarucizumab), for those patients treated with PRADAXA® (Dabigatran), when reversal of the anticoagulant effects of PRADAXA® is needed for emergency surgery/urgent procedures, or in life-threatening or uncontrolled bleeding. Unlike bleeding caused by COUMADIN® which can be reversed using Vitamin K or Fresh Frozen Plasma, there are no specific agents presently available, for reversing bleeding caused by the other Direct Oral AntiCoagulants or for stopping the anticoagulant effects of these drugs, in patients who need urgent surgical intervention.

A recently published study has shown that the availability of Direct Oral AntiCoagulants has increased the number of doctor office visits, driven by new visits related to Direct Oral AntiCoagulant (DOAC) use in Atrial Fibrillation patients. It was noted that the utilization of DOAC’s was comparable to the use of COUMADIN® (Warfarin) for Atrial Fibrillation patients (Am J Med. 2015;128:1300-1305).

The discussion by the authors in this article, revolve around a 86-year old female weighing 55 kg, who presented to the ED with persistent Epistaxis. She had a history of Atrial Fibrillation and has been taking XARELTO® (Rivaroxaban) 20 mg, once daily, for stroke prevention for 1 year. She also had a history of peripheral arterial disease and was on Aspirin 80 mg, daily for primary prevention for 9 months. It was noted that the chromogenic anti–Factor Xa assay showed that her plasma concentration of XARELTO® was supratherapeutic. So, treatment with XARELTO® was discontinued. Nonetheless, two days later, the plasma XARELTO® concentration was still within the therapeutic range rather than subtherapeutic, suggesting slow drug elimination. The medical team discontinued her Aspirin and switched her from XARELTO® to COUMADIN® (Warfarin) and discharged her.

Several valuable recommendations made from this case are worth mentioning-

1) Older age and renal insufficiency are important factors contributing to bleeding while on DOACs. Because DOACs are partially excreted by the kidneys, dose reductions are recommended in the event of renal impairment. In a study evaluating the bleeding risk with PRADAXA® (Dabigatran) in the frail elderly, two thirds of patients were older than 80 years, and close to 60% of these patients had moderate or severe renal impairment.

2) Because patients with severe renal impairment have been excluded from phase III studies, DOACs should be avoided in this population along with those patients with extreme body weights.

3) Addition of Aspirin to oral anticoagulants is appropriate for up to 12 months after acute coronary syndromes, percutaneous coronary interventions, or stenting procedures. However, this combination therapy increases the risk of major bleeding by 50% compared with oral anticoagulant use alone.

4) For patients with mechanical heart valves, a combination of Aspirin plus oral anticoagulant may be appropriate. However, only a Vitamin K Antagonist (VKA) such as COUMADIN® should be used and DOACs are not recommended.

5) Although routine laboratory testing of patients taking a DOAC is not required, elderly patients should be closely monitored, with particular attention to renal function. A normal Prothrombin Time excludes supratherapeutic XARELTO® plasma levels, and XARELTO® levels can be measured using anti–Factor Xa chromogenic assays.

In conclusion, even though DOACs have several advantages compared with VKAs, DOACs should be avoided in frail elderly patients.

Optimizing the Safe Use of Direct Oral Anticoagulants in Older Patients – A Teachable Moment. Sennesael A, Dogné J and Spinewine A. JAMA Intern Med. 2015;175:1608-1609

SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000 – 100,000 deaths. VTE is the third leading cause of cardiovascular mortality with a mortality rate of up to 25% in those with untreated acute Pulmonary Embolism. The American College of Physicians in 2015 released pulmonary embolism guidelines after noting that there has been a dramatic increase in the testing for suspected acute Pulmonary Embolism (PE). There has also been an overuse of CT imaging and plasma d-Dimer measurement, without improvement in care, but rather harming the patient and increasing expenditure. The validated clinical decision tools, in addition to physician’s clinical judgment include the Wells and Geneva Scoring System. The PERC (see table) criteria includes 8 elements, which if absent in low risk patients rules out PE. These practice guidelines were developed to provide practical advice, based on the best available evidence.

Best Practice Advice 1: Clinicians should use validated clinical prediction tools to estimate pretest probability, in patients in whom acute PE is being considered. These clinical decision tools include physician’s clinical judgment as well as Wells and Geneva Scoring System.

Best Practice Advice 2: The PERC (see table) criteria includes 8 elements. Clinicians should not obtain d-Dimer measurements or imaging studies in patients with a low pretest probability of PE and who meet all Pulmonary Embolism Rule-Out (PERC) Criteria.

Best Practice Advice 3: For patients who have an intermediate pretest probability of PE or in patients with low pretest probability of PE who do not meet all PERC Criteria, clinicians should obtain a high-sensitivity d-Dimer measurement as the initial diagnostic test in patients. Clinicians should not use imaging studies as the initial test in patients who have a low or intermediate pretest probability of PE.

Best Practice Advice 4: Clinicians should use age-adjusted d-Dimer thresholds (age × 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years because, normal d-Dimer levels increase with age.

Best Practice Advice 5: Clinicians should not obtain any imaging studies in patients with a d-Dimer level below the age-adjusted cutoff.

Best Practice Advice 6: Clinicians should obtain imaging with CT pulmonary angiography (CTPA) in patients with high pretest probability of PE. Clinicians should reserve ventilation–perfusion scans for patients who have a contraindication to CTPA or if CTPA is not available. Clinicians should not obtain a d-Dimer measurement in patients with a high pretest probability of PE because, a negative d-Dimer test will not preclude the need for imaging.

Evaluation of Patients with Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Raja AS, Greenberg JO, Qaseem A, et al. Ann Intern Med. 2015;163:701-711

SUMMARY: The FDA on October 16, 2015, granted accelerated approval to Idarucizumab (PRAXBIND®) for the treatment of patients treated with Dabigatran (PRADAXA®), when reversal of the anticoagulant effects of PRADAXA® is needed for emergency surgery/urgent procedures, or in life-threatening or uncontrolled bleeding. There are presently four New Oral Anticoagulants approved in the United States for the treatment of Venous ThromboEmbolism. They include PRADAXA® (Dabigatran), which is a direct thrombin inhibitor and XARELTO® (Rivaroxaban), ELIQUIS® (Apixaban), SAVAYSA® (Endoxaban), which are Factor Xa inhibitors. Compared to COUMADIN® (Warfarin), the New Oral Anticoagulants have a rapid onset of action, wider therapeutic window, shorter half-lives (7-14 hours in healthy individuals), no laboratory monitoring and fixed dosing schedule. The half life of these agents can however be prolonged in those with renal insufficiency. In several clinical studies, these New Oral Anticoagulants have been shown to reduce the rate of major bleeding by 28% and the rates of intracranial and fatal hemorrhage by 50%, when compared to COUMADIN®. Unlike bleeding caused by COUMADIN®, which can be reversed using Vitamin K or Fresh Frozen Plasma, there are no specific agents presently available, for reversing bleeding caused by the New Oral Anticoagulants or for stopping the anticoagulant effects of these drugs, in patients who need urgent surgical intervention.

To address this concern, the RE-VERSE AD study was conducted to evaluate the efficacy and safety of Idarucizumab, to reverse the anticoagulant effects of PRADAXA®, in patients who had serious bleeding (Group A) or required an urgent surgical procedure (Group B). PRAXBIND® (Idarucizumab) is a humanized monoclonal antibody fragment with high affinity for both free and thrombin-bound PRADAXA® and neutralizes the anticoagulant activity of PRADAXA®. In this prospective cohort study, results from the first 90 patients enrolled in the study were presented (Interim analysis). Group A included 51 patients and Group B included 39 patients and PRAXBIND® 5 grams IV was administered, to reverse the anticoagulant effects of PRADAXA®. The median age was 76 years and the median creatinine clearance was 58 ml/minute. The primary end point was the maximum percentage reversal of the anticoagulant effect of PRADAXA® within 4 hours after the administration of PRADAXA®, based on the dilute thrombin time or ecarin clotting time. An important secondary end point was the restoration of hemostasis. Among the patients with an elevated dilute thrombin time and ecarin clotting time at baseline, the median maximum percentage reversal was 100% and this benefit was seen within minutes after the first infusion with PRAXBIND®. The median time to restoration of hemostasis in Group A was 11.4 hours. In Group B, normal intraoperative hemostasis was reported in more than 90% of the patients who underwent procedures after the administration of PRAXBIND®.

The authors concluded that PRAXBIND® was, within minutes, able to completely reverse the anticoagulant effect of PRADAXA®. This reversal agent will fulfill an unmet need and with the availability soon of Factor Xa inhibitor antidotes, it is anticipated that Health Care Providers will be more willing to replace COUMADIN® with the Newer Oral Anticoagulants. Idarucizumab for Dabigatran Reversal. Pollack CV, Reilly PA, Eikelboom J, et al. N Engl J Med 2015; 373:511-520

SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000-100,000 deaths. Venous ThromboEmbolism (VTE) is the third leading cause of cardiovascular mortality. Clinicians are often confronted with the dilemma of using bridge therapy for patients with a history of VTE on Warfarin therapy, requiring invasive diagnostic or surgical procedures. Bridge therapy involves the use of rapid onset, short acting anticoagulant preparation such as Low Molecular Weight Heparin during the peri-procedural period (usually 5-10 days), to minimize the risk of subtherapeutic anticoagulation, during peri-procedure Warfarin withdrawal and reinitiation. Even though published studies have largely reviewed the risk of thrombotic events in patients with atrial fibrillation or mechanical heart valves, the risk for bleeding and VTE, associated with bridge therapy in patients receiving Warfarin for the secondary prevention of VTE, has remained unclear. Presently available guidelines that classify peri-procedural risk of recurrent VTE, off anticoagulant therapy, into high risk , medium risk and low risk, is based on indirect, low quality evidence and is not completely reliable. It is well established however, that anticoagulants stopped during the first four weeks of treatment, following diagnosis of VTE, predisposes an individual to increased risk of recurrent VTE.

To clarify the risk/benefits of bridge therapy, the authors conducted a retrospective cohort study, to assess the rates of clinically relevant bleeding and recurrent VTE, among patients in whom Warfarin therapy was interrupted for invasive procedures. They then compared the incidence of peri-procedure bleeding and recurrent VTE when a bridging strategy was used or not used. This study included 1178 patients and the most common indication for Warfarin therapy was DVT (56.3%). Majority of the patients (79%) were considered as low risk (acute VTE more than 12 months previously, with no other risk factors). The primary outcome of the study was clinically relevant bleeding resulting in hospitalization, ER visit or complicating the procedure in the first 30 days following the index procedure. Secondary outcomes included recurrent VTE, and all-cause mortality occurring in up to 30 days, following the index procedure.

It was noted that the 30-day rate of clinically relevant bleeding was significantly higher in the bridging group compared with the control group (2.7% versus 0.2%, HR=17.2; P=0.01). Further, there was no significant difference in the rate of recurrent VTE between the bridge and non-bridge therapy groups. No deaths occurred in either treatment groups. The authors concluded that bridge therapy for invasive procedures in patients receiving Warfarin for secondary VTE prevention, is associated with a significant increase in the incidence of bleeding complications, without any decrease in the rate of recurrent VTE. Warfarin can be safely interrupted in this patient group without bridge therapy. Further research is needed to address the value of bridge therapy in the medium and high risk groups. Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures. Clark NP, Witt DM, Davies LE, et al. JAMA Intern Med 2015;175:1163-1168.

SUMMARY: There are presently four New Oral Anticoagulants approved in the United States for the treatment of Venous ThromboEmbolism. They include PRADAXA® (Dabigatran), which is a direct thrombin inhibitor and XARELTO® (Rivaroxaban), ELIQUIS® (Apixaban), SAVAYSA® (Endoxaban), which are Factor Xa inhibitors. Compared to COUMADIN® (Warfarin), the New Oral Anticoagulants have a rapid onset of action, wider therapeutic window, shorter half-lives (7-14 hours in healthy individuals), no laboratory monitoring and fixed dosing schedule. The half life of these agents can however be prolonged in those with renal insufficiency. In several clinical studies, these New Oral Anticoagulants have been shown to reduce the rate of major bleeding by 28% and the rates of intracranial and fatal hemorrhage by 50%, when compared to COUMADIN®. Unlike bleeding caused by COUMADIN®, which can be reversed using Vitamin K or Fresh Frozen Plasma, there are no specific agents presently available, for reversing bleeding caused by the New Oral Anticoagulants or for stopping the anticoagulant effects of these drugs, in patients who need urgent s

SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000 – 100,000 deaths. VTE is the third leading cause of cardiovascular mortality. Patients with unprovoked DVT and PE are two to four times more likely to be diagnosed with cancer within the following 12 months compared to the general population. It is however unknown if Splanchnic Venous Thrombosis (splanchnic veins carry blood through the liver and other abdominal organs) is a marker of occult cancer and a prognostic factor for cancer survival.

To address this question the authors from Denmark conducted a nationwide cohort study using Danish medical registries and included 1,191 patients with first time Splanchnic Venous Thrombosis (SVT) between 1994 and 2011, and followed them for subsequent cancer diagnosis, for a median of 1.6 years. They compared these results with the expected cancer risk in the general population. Additionally, to evaluate the impact of SVT on survival in those patients with cancer, the researchers compared survival in these cancer patients with a matched cohort of cancer patients without SVT. In the cohort of 1,191 patients with first time Splanchnic Venous Thrombosis (SVT), 183 patients were later diagnosed with cancer, of whom, 95 patients were diagnosed within 3 months of their SVT diagnosis. When compared to the general population, individuals diagnosed with SVT were 33 times more likely to be diagnosed with cancer within 3 months and their 3 month risk of developing cancer was 8%. The increased risk was for liver cancer, pancreatic cancer and myeloproliferative neoplasms and there was a continued twofold increase after one or more years of follow up. It was noted that Splanchnic Venous Thrombosis was also a poor prognostic factor for survival, in patients with liver and pancreatic cancer. The authors concluded that Splanchnic Venous Thrombosis (SVT) is a marker of occult malignancy, particularly liver cancer, pancreatic cancer and myeloproliferative neoplasms and SVT diagnosed in patients with liver or pancreatic cancer remains a poor prognostic factor. Therefore, patients presenting with Splanchnic Venous Thrombosis may require a more thorough diagnostic evaluation. Splanchnic venous thrombosis is a marker of cancer and a prognostic factor for cancer survival. Søgaard KK, Farkas DK, Pedersen L, et al. Blood, June 2015 DOI: 10.1182/blood-2015-03-631119

SUMMARY: The American Society of Clinical Oncology (ASCO) recently provided an update on recommendations, for the prophylaxis and treatment of Venous ThromboEmbolism (VTE) in patients with cancer, following a systematic review of 53 publications. They are as follows-

VTE prophylaxis in hospitalized patients

Majority of the hospitalized patients with active malignancy should receive VTE prophylaxis in the absence of contraindications. However there are no definitive data for VTE prophylaxis in patients admitted for short chemotherapy infusions, minor procedures or those undergoing stem-cell or bone marrow transplantation.

VTE prophylaxis in ambulatory patients

Routine VTE prophylaxis is not recommended although prophylaxis with low molecular-weight heparin can be considered in select group of outpatients with solid tumors who are receiving chemotherapy, after discussing the risk/benefits of such intervention. Patients with Myeloma receiving THALOMID® (Thalidomide) or REVLIMID® (Lenalidomide) should receive VTE prophylaxis with either aspirin or low molecular-weight heparin.

VTE prophylaxis in patients undergoing surgery

All cancer patients undergoing major surgical procedures should be considered for VTE prophylaxis with heparin unless there is a bleeding risk. This should be commenced preoperatively and can be complemented with mechanical methods to improve efficacy. This should be continued for at least 7-10 days and for up to 4 weeks postoperatively, in those undergoing major abdominal or pelvic surgery with restricted mobility, obesity, history of VTE or additional risk factors. Decision to consider prophylaxis, for patients undergoing low risk surgery, should be made on an individual basis.

Choice of Anticoagulation for cancer patients with VTE

For cancer patients who have a creatinine clearance of more than 30 ml/min and have newly diagnosed VTE , low molecular-weight heparin is preferred over unfractionated heparin for the initial 5 to 10 days. Low molecular-weight heparin, due to its superiority, is preferred over vitamin K antagonists for long term anticoagulation (6 months). Select cancer patients with metastatic disease or those receiving chemotherapy may be considered for anticoagulation with low molecular-weight heparin or vitamin K antagonists beyond the initial 6 months. A vena cava filter is indicated only for patients with contraindications to anticoagulant therapy and may be considered for those who progress despite optimal anticoagulation with low molecular-weight heparin. Patients with CNS malignancies and VTE should be anticoagulated like any other patient with VTE, monitoring closely for bleeding. Incidental VTE’s should be treated like symptomatic VTE. Decision to treat splanchnic or visceral vein thrombi diagnosed incidentally should be considered on an individual basis. The new novel oral anticoagulants are presently not recommended for prophylaxis or treatment of VTE in patients with cancer because of limited data.

Anticoagulation and survival benefit in patients without VTE

Cancer patients without VTE should not receive anticoagulants to improve survival, as there are no data to support this recommendation.

Monitoring and patient counseling

Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Predicting VTE in cancer patients using Risk Score

The risk score model for VTE in cancer patients was developed and validated in multiple studies. The risk of VTE can be significantly reduced amongst these high risk patients by thromboprophylaxis.

Lyman GH, Bohlke K, Khorana AA, et al. J Clin Oncol 2015; 33:654-656

SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000 – 100,000 deaths. VTE is the third leading cause of cardiovascular mortality with a mortality rate of up to 25% in those with untreated acute pulmonary embolism. Even though the risk of recurrent VTE is high after anticoagulant treatment is discontinued in patients with a first unprovoked venous thromboembolism (10-30% risk of a recurrence within 5 years following cessation of anticoagulation), a significant number of these patients receive therapy for 6-12 months and are not routinely treated with long term anticoagulant therapy. This may be due to bleeding risks, cost of therapy and need for diligent monitoring while on long term anticoagulation. Aspirin is a non-selective, irreversible inhibitor of both COX-1 and COX-2 (Cyclooxygenases 1 and 2). It inhibits the production of Prostaglandins and Thromboxane A2 and there by decreases platelet aggregation. Both ASPIRE and WARFASA trials support the role of aspirin for the prevention of recurrent VTE in patients with an unprovoked VTE, after 6-18 months of anticoagulation therapy. These trials however were not individually powered to detect benefits of treatment for particular outcomes or subgroups of patients. The INSPIRE Collaboration involved further analysis of these trials to detect outcomes in pre-specified subgroups of patients. The intent-to-treat analysis included 1,224 patients and at a median follow up of 30.4 months, daily Aspirin given at a dose of 100mg reduced recurrent VTE events by 32% (HR=0.68; P=0.008) and this included reduction in recurrent Deep Vein Thrombosis by 34% (HR=0.66; P=0.01) and Pulmonary Embolism by 34% (HR=0.66; P=0.08), compared to Placebo. After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR=0.58; P=0.005). Subgroup analyses indicated similar relative, but larger absolute, risk reductions in men and older patients. Aspirin also reduced major vascular events by 44% (HR=0.66; P=0.002). The major bleeding rate was low at 0.5%/year for Aspirin and 0.4%/year for Placebo. The authors concluded that aspirin reduces the risk of recurrent VTE. Even though the efficacy of aspirin is inferior to that of Warfarin or the new oral anticoagulants, this data suggests that Aspirin should be strongly considered in patients with unprovoked VTE for whom long-term anticoagulation therapy with Warfarin or one of the new oral anticoagulants has to be discontinued or is not an appropriate option. Aspirin however, should not be considered a replacement option for conventional anticoagulation. Simes J, Becattini C, Agnelli G, et al. Circulation. 2014; 130:1062-1071