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

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?

Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

Thrombocytosis or elevated platelet count is not uncommon among hospitalized patients and may be related to several factors, including “tissue damage” from a surgical procedure, infection, acute blood loss, iron deficiency, and less well known, enoxaparin.1-4 

Postoperative thrombocytosis is thought to be related to increased platelet production as well as redistribution of platelets from the splenic platelet pool to the general circulation.1  Increased levels of megakaryocytic growth factors such as thrombopoietin, and pro-or anti-inflammatory cytokines such as interleukin (IL)-1, 3, 6, or 11 may also stimulate megakaryopoeisis in the setting of inflammation.2 The mechanism of iron deficiency causing thrombocytosis is unknown.4

Enoxaparin-related thrombocytosis usually develops within the first 2 weeks of therapy and resolves 2 weeks following its discontinuation.3

In our patient, although malignancy is also associated with secondary thrombocytosis, given its acute nature in our patient, it is less likely to be playing a role.

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References

  1. Griesshammer M, Bangerter M, Sauer T, et al. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999;245:295-300. https://www.ncbi.nlm.nih.gov/pubmed/10205592
  2. Kulnigg-Dabsch S, Schmid W, Howaldt S, et al. Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial. Inflamm Bowel Dis 2013;published online, DOI10.1097/MIB.0b013e318281f4db. https://www.ncbi.nlm.nih.gov/pubmed/23644823
  3. Hummel MC, Morse BC, Hayes LE. Reactive thrombocytosis associated with enoxaparin. Pharmacotherapy 2006;26:1667-1670. https://www.ncbi.nlm.nih.gov/pubmed/17064215
  4. Dan K. Thrombocytosis in iron deficiency anemia. Intern Med 2005;44: 1025-6. https://www.jstage.jst.go.jp/article/internalmedicine/44/10/44_10_1025/_pdf

 

Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

Heparin is one of the most overlooked causes of hyperkalemia in hospitalized patients, occurring in 5-8% of treated patients, including those on thromboprophylaxis1.

The mechanism of heparin-induced hyperkalemia appears to be through suppression of aldosterone synthesis by inhibiting the function of the glomerulosa zone of the adrenal medulla2,3.  Such inhibitory action is usually of no consequence when renal function is normal and potassium excretion is not otherwise impaired.

The risk of heparin-induced hyperkalemia is increased in the elderly, those with preexisting diabetes mellitus or renal insufficiency, as well patients on concomitant use of certain drugs such as spironolactone, ACE inhibitors, NSAIDs, and trimethoprim2

Hyperkalemia is usually detected after at least 3-4 days of treatment with subcutaneous heparin, and usually resolves within a few days of  discontinuation of therapy1,2.  Fractionated heparin products such as enoxaparin may also be associated with hyperkalemia2 but the risk appears to be lower1.

Fludrocortisone has been used to normalize serum potassium in patients who  remain on heparin.4

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References

  1. Potti A, Danielson B, Badreddine R, et al. Potassium homeostasis in patients receiving prophylactic enoxaparin therapy. J Thromb Haemost 2004;2:1208-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00791.x/pdf
  2. Thomas CM, Thomas J, Smeeton F, et al. Heparin-induced hyperkalemia. Diabetes Res Clin Pract 2008;80:e7-e8. https://www.ncbi.nlm.nih.gov/pubmed/18343525
  3.  Liu AA, Bui T, Nguyen HV, et al. Subcutaneous unfractionated heparin-induced hyperkalemia in an elderly patient. Australas J Ageing 2009;28:97. https://www.ncbi.nlm.nih.gov/pubmed/19566805
  4. Brown G. Fludrocortisone for heparin-induced hyperkalemia. CJHP 2011;64:463-4. https://www.cjhp-online.ca/index.php/cjhp/article/view/1091/1394

 

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

Can novel oral anticoagulants (NOAC) be reversed?

Since their relatively recent introduction, a major concern over NOAC use has been the lack of available reversal agents akin to vitamin K or fresh frozen plasma used to reverse anticoagulation effect of warfarin.

Fortunately, there are currently 2 FDA-approved NOAC reversal agents (idarucizumab and andexanet alfpha) and 1 NOAC on breakthrough or fast-track status at the FDA (1,2):

  • Idarucizumab, a humanized mouse antibody fragment, or Fab, targeted specifically for reversal of dabigatran. FDA approved
  • Andexanet alfa, a class-specific antidote for reversal of direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban), as well as an indirect factor Xa inhibitor, enoxaparin. FDA approved
  • Ciraparantag (PER977), a synthetic water-soluble compound that reverses direct thrombin (dabigatran), direct factor Xa (apixaban, rivaroxaban, edoxaban), and indirect factor Xa inhibitors (enoxaparin). Currently under investigation.

 

1. Ansell JE. Universal, class-specific, and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis 2016;41:248-52.  https://www.ncbi.nlm.nih.gov/pubmed/26449414

2. Connolly SJ, Milling TJ, Eikelboom JW, etal.  Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Eng J Med 2016;375:1131-41. https://www.nejm.org/doi/full/10.1056/NEJMoa1607887

Contributed in part by William L. Hwang, MD, Mass General Hospital, Boston, MA.

Can novel oral anticoagulants (NOAC) be reversed?