Thromboembolism;

Is intermittent pneumatic compression effective in reducing the risk of deep vein thrombosis in non-surgical hospitalized patients at high risk of major bleed?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

The weight of the evidence to date suggests that intermittent pneumatic compression (IPC) is effective in reducing the risk of deep venous thrombosis (DVT) in hospitalized patients with stroke. 1,2 Whether IPC is also effective in non-surgical hospitalized patients without stroke at high risk of DVT and major bleed needs further studies.

A 2013 multicenter randomized trial (CLOTS 3) involving over 2,000 immobile hospitalized patients post-stroke found a significantly lower risk of DVT in proximal veins or any symptomatic DVT in the proximal veins within 30 days of randomization (8.5% vs 12.1%; absolute reduction risk 3.6%, 95% C.I. 1.4-5.8). Of note, the rate of concurrent heparin or low molecular weight heparin (LMWH) prophylaxis was similar between the 2 groups (17%). 1

A meta-analysis including the CLOTS 3 study and 2 other smaller trials 2 in patients with stroke found a risk reduction for proximal DVT (O.R. 0.66, 95% C.I 0.52-0.84) with nearly significant reduction in deaths by the end of the treatment period (O.R. 0.81, 95% 0.65-1.01).1

Although IPC may also be effective in non-surgical hospitalized patients without stroke but at high risk of DVT and bleed, proper trials in this patient population is lacking. In fact, the 2012 American College of Chest Physicians guidelines on antithrombotic therapy and prevention of thrombosis classifies use of IPC in preventing DVT’s in non-surgical acutely ill hospitalized patients as category 2C recommendation (weak, low quality evidence). 3

The patient population and methodology of above studies should be distinguished from those of a 2019 published trial involving only critically ill patients—all receiving pharmacologic thromboprophylaxis—which reported no reduction in the incidence of proximal lower-limb DVT with the addition of IPC. 4

 

Bonus Pearl: Did you know that venous thromboembolism has been reported in up to 42% of hospitalized patients who have had a stroke? 1

 

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References

  1. Dennis M, Sandercock P, Reid J, et al. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicenter randomized controlled trial. Lancet 2013;382:516-24. https://www.thelancet.com/cms/10.1016/S0140-6736(13)61050-8/attachment/1a0438d2-86eb-4da1-8bdb-92c0aec18b8d/mmc1.pdf
  2. Naccarato M, Chiodo Grandi F, Dennis M, et al. Physical methods for preventing deep vein thrombosis in stroke. Cochrance Database Syst Rev 2010;8:CD001922. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001922.pub3/full
  3. Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;141 (suppl):7S-47S. http://www.sphcs.org/workfiles/CardiacVascular/7S-full.pdf
  4. Arabi YM, Al-Hameed F, Burns KEA, et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Engl J Med 2019;380:1305-15. https://pubmed.ncbi.nlm.nih.gov/30779530/

 

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is intermittent pneumatic compression effective in reducing the risk of deep vein thrombosis in non-surgical hospitalized patients at high risk of major bleed?

How does older people’s immune system place them at high risk of sepsis and death?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Increased risk of sepsis and death from infectious causes among the elderly is a well-known phenomenon—particularly as witnessed in the Covid-19 era— and is in part due to 2 major age-related alterations of their immune system: 1. Defective T and B cell functions in response to acute infections; and 2. Once infection sets in, inadequate control of sepsis-induced pro-inflammatory response and its attendant procoagulant state. Interestingly, the essential elements of the innate immunity (eg, neutrophils, dendritic cells, complements) are generally spared from the effects of aging.1,2

Increased susceptibility of the elderly to acute infections is in part caused by poorer T helper cell function and suboptimal B cell humoral response to neoantigens. Despite this, serum levels of pro-inflammatory cytokines such as IL-1, IL-6,TNF-alpha, and IFN-gamma are intact.  In fact, production of IL-6 and its duration of response is actually increased in the elderly.1,2

Poor control of the inflammatory state due to sepsis in older patients may be related to the difficulty in clearing a pathogen or dysfunction in the signaling by counter-regulatory cytokines, such as IL-10.2 Either way, unchecked inflammatory response is deleterious to the patient and is associated with increased risk of thrombosis and thromboembolism, multiorgan system failure, septic shock and death. 

Bonus Pearl: Did you know that even in the absence of infection, older people are more prone to thrombosis and thromboembolism , in part related to elevated plasma levels of fibrinogen, as well as factor VII, VIII, and IX, among others?2,3  

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 References

  1. Ticinesi A, Lauretani F, Nouvenne A, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med 2017;37:7-12. https://pubmed.ncbi.nlm.nih.gov/27594414/
  2. Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41: (Suppl 7) S504-12. https://pubmed.ncbi.nlm.nih.gov/16237654/
  3. Mari D, Coppola R, Provenzano R. Hemostasis factors and aging. Experimental Gerontology 2008;43:66-73. https://www.sciencedirect.com/science/article/abs/pii/S0531556507001404?via%3Dihub

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

How does older people’s immune system place them at high risk of sepsis and death?

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

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

The weight of the evidence to date seem to suggest 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 von Willebrand factor (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 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 NVAF is affected by blood group, one explanation is 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?