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?

My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

There is no firm evidence either for or against the use of systemic anticoagulants (ACs) in patients with asymptomatic pulmonary embolism (PE) following hemodialysis vascular access declotting (HVAD).  

However, despite the common occurrence of asymptomatic PE following HVAD procedures (~40%), symptomatic PE—at times fatal—has also been reported in these patients1,2.

In the absence of hard data and any contraindications, anticoagulation can be justified in our patient for the following reasons:

  • Asymptomatic segmental PE is commonly treated as symptomatic PE irrespective of setting2,3
  • Hemodialysis patients are often considered hypercoagulable due to a variety of factors eg, platelet activation due to extracorporeal circulation, anti-cardiolipin antibody, lupus anticoagulant, decreased protein C or S activity, and/or reduced anti-thrombin III activity4-7
  • Overall, chronic dialysis patients have higher incidence of PE compared to the general population8
  • There is no evidence that asymptomatic PE following HVAD has a more benign course compared to that in other settings
  • Untreated PE may be associated with repeated latent thrombosis or progression of thrombosis in the pulmonary artery5

 

References

  1. Calderon K, Jhaveri KD, Mossey R. Pulmonary embolism following thrombolysis of dialysis access: Is anticoagulation really necessary? Semin Dial 2010:23:522-25. https://www.ncbi.nlm.nih.gov/pubmed/21039878
  2. Sadjadi SA, Sharif-Hassanabadi M. Fatal pulmonary embolism after hemodialysis vascular access declotting. Am J Case Rep 2014;15:172-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004792/pdf/amjcaserep-15-172.pdf
  3. Chiu V, O’Connell C. Management of the incidental pulmonary embolism. AJR 2017;208:485-88. http://www.ajronline.org/doi/pdf/10.2214/AJR.16.17201
  4. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: Chest guideline and expert panel report. CHEST 2016;149:315-52. http://journal.chestnet.org/article/S0012-3692(15)00335-9/fulltext
  5. Yamasaki K, Haruyama N, Taniguchi M, et al. Subacute pulmonary embolism in a hemodialysis patient, successfully treated with surgical thrombectomy. CEN Case Rep 2016;5:74-77 https://link.springer.com/article/10.1007/s13730-015-0195-9
  6. Nampoory MR, Das KC, Johny KV, et al. Hypercoagulability, a serious problem in patients with ESRD on maintenance hemodialysis, and its correction after kidney transplantation. Am J Kidney Dis 2003;42:797-805. https://www.ncbi.nlm.nih.gov/pubmed/14520631
  7. O’Shea SI, Lawson JH, Reddan D, et al. Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis. J Vasc Surg 2003;38: 541-48. http://www.jvascsurg.org/article/S0741-5214(03)00321-5/pdf
  8. Tveit DP, Hypolite IO, Hshieh P, et al. Chronic dialysis patients have high risk for pulmonary embolism. Am J Kidney Dis 2002;39:1011-17. https://www.ncbi.nlm.nih.gov/pubmed/11979344
My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

What is the significance of a prolonged activated partial thromboplastin time (aPTT) in my patient with suspected antiphospholipid syndrome (APS)?

APS is an acquired hypercoagulable state which presents classically as recurrent arterial and/or venous thrombosis and is a major cause of late first- and second-trimester spontaneous fetal loss. In addition to thrombotic complications, diagnosis of APS requires the presence of ≥ 1 of the following antiphospholipid antibodies on 2 occasions ≥12 weeks apart: 1) anti-ß2-glycoprotein 1 antibodies; 2) anticardiolipin antibodies; and 3) lupus anticoagulant (LA)1.  

An unexpected prolongation of aPTT may be a clue to the presence of APS and may be explained by the in vitro prevention of the assembly of the prothrombinase complex—which catalyzes the conversion of prothrombin to thrombin— by LA2,3.  

Because the phospholipid component of the reagent used in aPTT tests determines its sensitivity to LA, aPTT results may vary, influenced by the type and concentration of phospholipids used in the assay. Other factors such as acute phase reaction associated with increased fibrinogen and factor VIII levels may also impact the results by shortening the aPTT and potentially masking a weak LA2.

 

 

References 

  1. Giannakopoulos B, Passam F, Ioannou Y, Krilis SA. How we diagnose the antiphospholipid syndrome.Blood. 2009;113:985-94.
  2. 2. Abo SM, DeBari VA. Laboratory evaluation of the antiphospholipid syndrome. Ann Clin Lab Sci 2007;37:3-14.
  3. Smock KJ, Rodgers GM. Laboratory identification of lupus anticoagulants. Am J Hematol. 2009;84(7):440-2.

 

 

Contributed by Ricardo Ortiz, medical student, Harvard Medical School

What is the significance of a prolonged activated partial thromboplastin time (aPTT) in my patient with suspected antiphospholipid syndrome (APS)?