Is there a connection between my patient’s blood type and risk of thromboembolic events?

There seems to be, given the weight of the evidence to date suggesting that non-blood group O may be associated with non-valvular atrial fibrillation (NVAF)-related peripheral cardioembolic complications, myocardial infarction (MI) and ischemic stroke. 1-4

A 2015 retrospective Mayo Clinic study involving patients with NVAF adjusted for CHADS2 score found significantly lower rate of peripheral embolization in those with blood group O compared to those with other blood groups combined (3% vs 2%, O.R. 0.66, 95% CI, 0.5-0.8); rates of cerebral thromboembolic events were not significantly different between the 2 groups, however. 1

A 2008 systematic review and meta-analysis of studies spanning over 45 years reported a significant association between non-O blood group and MI, peripheral vascular disease, cerebral ischemia of arterial origin, and venous thromboembolism.2 Interestingly, the association was not significant for angina pectoris or for MI when only prospective studies were included.  Some studies have reported that the association between VWF and the risk of cardiovascular mortality may be independent of blood group. 5,6

Although the apparent lower risk of thromboembolic conditions in O blood group patients may be due to lower levels of von Willebrand factor (VWF) and factor VIII in this population 1,4, other pathways likely  play a role.7  

As for why the rate of peripheral (but not cerebral) thromboembolic events in NVAP is affected by blood group, it is suggested that, because of their size, larger clots (facilitated by lower VWF levels) may bypass the carotid and vertebral orifices in favor of their continuation downstream to the “peripheral bed”.1

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References

  1. Blustin JM, McBane RD, Mazur M, et al. The association between thromboembolic complications and blood group in patients with atrial fibrillation. Mayo Clin Proc 2015;90;216-23. https://www.sciencedirect.com/science/article/abs/pii/S002561961401043X
  2. Wu O, Bayoumi N, Vickers MA, et al. ABO (H) groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemostasis 2008;6:62-9. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02818.x
  3. Medalie JH, Levene C, Papier C, et al. Blood groups, myocardial infarction, and angina pectoris among 10,000 adult males. N Engl J Med 1971;285:1348-53. https://www.nejm.org/doi/pdf/10.1056/NEJM197112092852404
  4. Franchini M, Capra F, Targher G, et al. Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications. Thrombosis Journal 2007, 5:14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042969/
  5. Meade TW, Cooper JA, Stirling Y, et al. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88:601-7. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1994.tb05079.x
  6. Jager A, van Hinsbergh VW, Kostense PJ, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscl Thromb Vasc Biol 1999;19:3071-78. https://www.researchgate.net/publication/12709043_von_Willebrand_Factor_C-Reactive_Protein_and_5-Year_Mortality_in_Diabetic_and_Nondiabetic_Subjects_The_Hoorn_Study
  7. Sode BF, Allin KH, Dahl M, et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013.DOI:10.1503/cmaj.121636. https://www.ncbi.nlm.nih.gov/pubmed/23382263
Is there a connection between my patient’s blood type and risk of thromboembolic events?

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 hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?

Yes! Ample epidemiological studies implicate infection as an important risk factor for MI.1 The increased risk of MI has been observed during the days, weeks, months or even years following an infection.

A 2018 paper reported a several-fold risk of MI during the week after laboratory-confirmed infection caused by a variety of respiratory pathogens such as influenza virus (6-fold), respiratory syncytial virus (4-fold), and other respiratory viruses (3-fold). 2 Among patients hospitalized for pneumococcal pneumonia, 7-8% may suffer an MI.3,4 One study found a 48-fold increase in the risk of MI during the first 15 days after hospitalization for acute bacterial pneumonia.5 Similarly, an increase in the short-term risk of MI has been observed in patients with urinary tract infection and bacteremia.6

The risk of MI appears to be the highest at the onset of infection and correlates with the severity of illness, with the risk being the highest in patients with pneumonia complicated by sepsis, followed by pneumonia and upper respiratory tract infection. Among patients with pneumonia, the risk exceeds the baseline risk for up to 10 years after the event, particularly with more severe infections.1

Potential mechanisms of MI following infections include release of inflammatory cytokines (eg, interleukins 1, 6, tumor necrosis factor alpha) causing activation of inflammatory cells in atherosclerotic plaques, in turn resulting in destabilization of the plaques. In addition, the thrombogenic state of acute infections, platelet and endothelial dysfunction may increase the risk of coronary thrombosis at sites of plaque disruption beyond clinical resolution of the acute infection. 1

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References

  1. Musher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med 2019;380:171-6. https://www.ncbi.nlm.nih.gov/pubmed/30625066
  2. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med 2018;378:345-53. https://www.nejm.org/doi/full/10.1056/NEJMoa1702090
  3. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremic and nonbacteremic pneumococcal pneumonia: a prospective study. Medicine (Baltimore) 2000;79:210-21. https://www.ncbi.nlm.nih.gov/pubmed/10941350
  4. Musher DM, Rueda Am, Kaka As, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis 2007;45:158-65. https://www.ncbi.nlm.nih.gov/pubmed/17578773
  5. Corrales-Medina VF, Serpa J, Rueda AM, et al. Acute bacterial pneumonia is associated with the occurrence of acute coronary syndromes. Medicine (Baltimore) 2009;88:154-9. https://www.ncbi.nlm.nih.gov/pubmed/19440118
  6. Dalager-Pedersen M, Sogaard M, Schonheyder HC, et al. Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study. Circulation 2014;129:1387-96. https://www.ncbi.nlm.nih.gov/pubmed/24523433

 

My hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?