My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

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My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Should my patient with below-knee venous thrombosis receive anticoagulation?

In contrast to proximal lower extremity deep venous thrombosis for which anticoagulation (AC) is standard therapy, whether below-knee deep venous thrombosis (BKDVT) (eg,  involving peroneal, soleus, tibial, or gastrocnemius veins) should routinely receive AC is a matter of debate because of lack of solid supportive evidence. 1-3

The American College of Chest Physicians (ACCP) recommends AC for patients with BKDVT who are severely symptomatic or have risk factors for extension of the thrombus but this recommendation is based on low-quality scientific evidence (grade 2C or “weak”).3 For other patients, surveillance ultrasound is recommended in 2 weeks to exclude clot propagation more proximally, and therefore the need for AC.  Of course, decision regarding AC should be made in the context of the patient’s risk of serious bleeding.

The following facts about BKDVT may help in therapeutic decision making:1

  • Most cases resolve spontaneously without AC
  • The incidence of propagation varies from 3%-32%
  • Embolization is unlikely in the absence of extension into proximal veins

Also remember that clot propagation usually occurs within 2 weeks of initial diagnosis. That’s why surveillance ultrasound is recommended during this period when watchful waiting is preferred.

References 

  1. Fleck D, Albadawi H, Wallace A, etal. Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns. Cariovasc Diagn Ther 2017;7(Suppl3):S134-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778527/
  2. Olson EJ, Zander AL, Van Gent J-M, et al. Below-knee deep vein thrombosis: An opportunity to prevent pulmonary embolism? J Trauma Acute Care Surg 2014;77:459-63. https://www.ncbi.nlm.nih.gov/pubmed/25159251
  3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST 2012;141 (Suppl):e419S-e494S. https://www.ncbi.nlm.nih.gov/pubmed/22315268

 

Should my patient with below-knee venous thrombosis receive anticoagulation?

Is there any utility to laboratory testing for inherited thrombophilia or antiphospholipid syndrome in my hospitalized patient with unprovoked acute pulmonary embolism?

There is virtually no utility to obtaining heritable thrombophilia testing in acute hospital setting. In fact, there are potential harms due to false-positive and false-negative results which in turn may lead to increasing anxiety in the patient and added cost due to repeat testing.

As many tests obtained as part of this workup are functional assays—eg, the protein S, C, or antithrombin activity, and activated protein C resistance (often used to screen for factor V Leiden)— they are easily impacted by the physiologic effects of acute thrombosis as well as all anticoagulants.1

More importantly, testing for inherited thrombophilia will not impact management in the acute setting, as decisions regarding duration of anticoagulation are often made later in the outpatient setting. The proper time to evaluate the patient for inherited thrombophilias (if indicated) is at least one week following discontinuation of anticoagulation (minimum 3 months from the time of the index event). 2 

Testing for antiphospholipid syndrome (APS) may be considered in this setting though it should be noted that the lupus anticoagulant assay is impacted by nearly every anticoagulant, resulting in frequent false-positive results1, and therefore should be performed before initiation of these agents (or delayed until later if anticoagulation has already begun). A false-positive result has downstream implications as many patients with acute, uncomplicated venous thromboembolism (VTE) are discharged on a direct oral anticoagulant (DOAC), and antiphospholipid syndrome is currently considered a relative contraindication to the use of DOACs in VTE.

References
1. Moll, S. “Thrombophilia: Clinical-practical aspects.” J Thromb Thrombolysis 2015;39:367-78. https://www.ncbi.nlm.nih.gov/pubmed/25724822
2. Connors JM. “Thrombophilia Testing and Venous Thrombosis.” N Engl J Med 2017; 377:1177-1187. http://www.nejm.org/doi/full/10.1056/NEJMra1700365 

Contributed by Hanny Al-Samkari, MD, Mass General Hospital, Boston, MA

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Is there any utility to laboratory testing for inherited thrombophilia or antiphospholipid syndrome in my hospitalized patient with unprovoked acute pulmonary embolism?

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

Simultaneous presence of PE in patients with AE-COPD is not rare, particularly in those with unexplained AE-COPD. A recent systematic review and meta-analysis reported a pooled PE prevalence of 16.1% (95% C.I. 8.3%-25.8%) in unexplained AE-COPD, with 68% of emboli found in the main pulmonary arteries, lobar arteries or inter-lobar arteries (i.e. not subsegmental); the pooled prevalence of deep venous thrombosis (DVT) was 10.5% (95% C.I. 4.3%-19.0%) 1. Pleuritic chest pain and signs of cardiac failure were associated with AE-COPD, while symptoms suggestive of a respiratory tract infection argued against PE.

It remains unclear, however, if the threshold for evaluation of venous thromboembolism (VTE) should necessarily differ between patients with explained vs unexplained AE-COPD. In one small study, the prevalence of VTE in “unexplained” AE-COPD was significantly higher (25%) than “explained” AE-COPD (including cases with  tracheobronchitis, pneumonia, cardiac disorders, exposure to irritant inhalants, and lack of compliance with treatment), but the VTE prevalence for the latter group was still 8.4%2.  Serum D-dimer level and Wells criteria may help exclude VTE in this patient population.

References

  1. Aleva FE, Voets LWLM, Simons SO, et al. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. CHEST (2016), doi: 10.1016/j.chest.2016.07.034.
  2. Gunen H, Gulbas G, In E, Yetkin O, Hacievliyagil SS. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;35:1243-1248.

 

Contributed by Jeff Greenwald, MD, Core Educator Faculty, Department of Medicine, Massachusetts General Hospital

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

My bed-bound, debilitated patient is being transferred to a long-term facility (LTF). Should I continue the venous thromboembolism (VTE) prophylaxis she has been receiving in the hospital?

There are no randomized-controlled studies that examine the effectiveness of VTE prophylaxis in debilitated patients following discharge from the hospital, and currently  the literature does not recommend prophylaxis for chronic immobility as a single risk factor for VTE (1). However, given the expected morbidity, potential mortality and hospital readmission associated with VTE,  prophylaxis should be considered in residents of LTFs with the following comorbidities (2):

  • Acute exacerbation of congestive heart failure
  • Acute exacerbation of chronic obstructive pulmonary disease
  • Acute infection (e. g. pneumonia, urosepsis, skin and soft tissue infections, infectious diarrhea)
  • Acute exacerbation of inflammatory/autoimmune diseases
  • Active malignancy
  • Immobility and prior VTE

 

Unless contraindicated, patients should receive prophylactic doses of unfractionated heparin, enoxaparin, or other approved drugs. Mechanical VTE prophylaxis should be used only when the risk of bleeding is considered unacceptably high or when there are drug intolerances or adverse effects.

The need for VTE prophylaxis should be reassessed regularly taking into account patient’s overall health status, mobility, drug tolerance and goals of care.

 

References

  1. Pai M, Douketis JD. Preventing venous thromboembolism in long-term care residents: Cautious advice based on limited data. Cleveland Clin J Med 2010;77: 123-130.  https://www.ncbi.nlm.nih.gov/pubmed/20124270    
  2. Robinson Am. Venous thromboembolism prophylaxis for chronically immobilized long-term care residents. Ann Long-Term Care 2013;10:30. https://www.managedhealthcareconnect.com/article/venous-thromboembolism-prophylaxis-chronically-immobilized-long-term-care-residents
My bed-bound, debilitated patient is being transferred to a long-term facility (LTF). Should I continue the venous thromboembolism (VTE) prophylaxis she has been receiving in the hospital?

Is anticoagulation (AC) therapy recommended for treatment of vein thrombosis of upper extremities?

The short answer is “yes” when deep veins, such as brachial, axillary or subclavian are involved; cephalic and basilic veins are superficial. Although some have suggested that isolated brachial vein thrombosis may be considered at low risk of complication, this assumption has not been corroborated by objective research (1).

There are no randomized trials of AC therapy in patients with upper extremity deep vein thrombosis (UEDVT).  However,  the American College of Chest Physicians has recommended a 3-month course of AC therapy similar to that of leg DVT for several reasons (1,2):

  •  UEDVT has generally been reported to have complications and consequences comparable to that of leg DVT
  •  Several small cohort studies suggest lower rates of recurrent DVT, PE, and bleeding when UEDVT is treated similar to leg DVT
  •  Known demonstrated benefit of AC therapy in leg DVT

In addition, post-thrombotic syndrome is relatively common (~1 in 5) among patients with UEDVT (3)

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References

1.  Hingorani A, Ascher E, Marks N, et al. Morbidity and mortality associated with brachial vein thrombosis. Ann Vasc Surg 2006; 20:297-299. https://www.ncbi.nlm.nih.gov/pubmed/16779509

2. Kearon C, Akl EA, Comerato AJ, et al. Antithrombotic therapy for VTE disease: American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(suppl):419S-494S. https://www.ncbi.nlm.nih.gov/pubmed/22315268

3. Maynard G. Upper extremity deep vein thrombosis:A call to arms. JAMA Intern Med 2014;696-698. https://www.ncbi.nlm.nih.gov/pubmed/24638129

Is anticoagulation (AC) therapy recommended for treatment of vein thrombosis of upper extremities?

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?

 

Discordance between serum CRP and ESR is not uncommon (1,2). This phenomenon may be due to a variety of factors including the fact that the kinetics of these two tests is quite different, as discussed under “Should I order C-reactive protein (CRP) or erythrocyte sedimentation (ESR) on patients suspected of having a new infection?” in this blog.

In a study of CRP/ESR discordance (defined as results differing by 2 or 3 quartiles) in adults, a high CRP/low ESR profile was more likely to be associated with  urinary, GI, blood stream, and pulmonary infections, myocardial infarction, and venous thromboembolism and less likely to be associated with bone and joint infections (1).

In the same study, a high ESR/low CRP was associated with connective tissue diseases, such as systemic lupus erythematosus and strokes (1).

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References

1. Feldman M, Aziz B, Kang GN, et al. C-reactive protein and erythrocyte sedimentation rate discordance: frequency and causes in adults. Translational Research 2013;161:37-43. https://www.ncbi.nlm.nih.gov/pubmed/22921838

2. Colombet I, Pouchot J, Kronz V. Agreement between erythrocyte sedimentation rate and C-reactive protein in hospital practice. Am J Med 2010;123:864.e7-863.e13.https://www.ncbi.nlm.nih.gov/pubmed/20800157

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?