Acute Care

Life-threatening, uncontrolled bleeding

Around 1% of the Swiss population take anticoagulants every day.1 The main reasons for this treatment are an artificial heart valve, repeated thromboses and pulmonary embolisms, as well as cardiac arrhythmia (atrial fibrillation).1 With increasing age, the number of patients for whom there is an indication to initiate oral anticoagulation increases:2 in over 85-year-olds, this is 20% due to atrial fibrillation alone.3

Various classes of active substances are available for anticoagulation: direct oral anticoagulants (DOACs) have quickly become an attractive alternative to the long-term standard for anticoagulation, vitamin K antagonists.4 Compared to vitamin K antagonists, DOACs are a convincing alternative as they offer a better benefit/risk ratio, a predictable effect without the need for routine laboratory tests and fewer interactions with food and drugs.5

Despite the positive benefit/risk ratio for DOACs, major bleeds occur in around 2 to 3.5% of patients every year.6 The mortality rate after major DOAC-related bleeds is 17.7% and without the achievement of effective haemostasis, the mortality risk increases by a factor of 3.6.7

Switzerland

Around 1% of Swiss people take anticoagulants every day1

Mortality

The mortality rate after major bleeds is 17.7%7

Haemostasis

Without effective haemostasis, mortality increases by a factor of 3.67

The bleeding site of patients with atrial fibrillation who were hospitalized due to severe DOAC-related bleeding is gastrointestinal in 57.6% of all patients, 25.4% at critical sites, 9.1% intracranial and 1.9% due to severe trauma or surgical complications.

patient-image

Risk factors for bleeds include age (over 65 years), untreated high blood pressure, severe liver or kidney dysfunction, a history of bleeding or stroke, fluctuating INR values and the use of other medication.8

anzahal-graph

Figure 1: Adapted from Held C et al. Eur Heart J. 2015;36(20):1264-1272; Hankey GJ et al. Stroke. 2014;45(5):1304-1312.

DOAC-related major gastrointestinal bleeding is associated with a significant risk of 30-day mortality.9

anzahal-graph

Figure 2: Adapted from Milling TJ Jr, et al. Am Emerg Med 2018;36:396-402; 2. Coleman CI, et al. Future Cardiol 2021;17:127-135; 3. Pannach S, et al. J Gastroenterol 2017;52:1211-1220; 4. Singer AJ, et al. J Emerg Med 2017;52:1-7; 5. Fermann GJ et al. J Med Econ 2020;23(12):1409-1417; 6. Hearnshaw SA et al. Gut 2011;60(10):1327-1335.

Symptoms

Symptoms of a gastrointestinal bleed may include:10

  • black or tarry stools
  • bright red blood in vomit
  • lower abdominal cramps
  • blood in the stool
  • dizziness or fainting
  • fatigue
  • pallor
  • shortness of breath
  • weakness

Possible signs of an intracranial bleed include:11

  • headache
  • nausea, vomiting
  • impairment of consciousness
  • lethargy
  • motor deficits
  • speech disorders
  • seizures

In the event of an acute bleed, patients may go into shock, which can lead to a drop in blood pressure, a rapid pulse and loss of consciousness.10

Diagnosis

A structured assessment based on a risk score (e.g. the HAS-BLED score) is recommended to evaluate the risk of bleeding during treatment with DOACs to identify patients at higher risk of bleeding (HAS-BLED score ≥ 3) and to schedule them for more frequent clinical reviews and follow-up.12

There is no characteristic clinical sign of internal bleeding, so the patient's clinical judgement is crucial. Major bleeds lead to low haemoglobin and haematocrit levels in the blood, although it may take many hours for the laboratory tests to show these effects.13

Imaging procedures are crucial in the diagnosis of bleeds. An intracranial 

bleed can be confirmed by either a non-contrast CT or an MRI. Gastrointestinal endoscopy helps to diagnose gastrointestinal bleeds.13

Treatment

Thanks to the short half-life of DOACs, the anticoagulant effect decreases rapidly and only a minor influence on haemostasis is to be expected 16-24 h after the last DOAC intake.11

However, it should be noted that in emergency patients treated with a DOAC, the concentration of anticoagulants at the start of treatment may vary widely.14

In the event of minor bleeds during treatment with DOACs, delayed administration of the next dose or discontinuation of treatment and a review of the concomitant medication are recommended.5,12

The management of moderate to severe bleeding includes both basic measures and specific measures to optimise haemostasis. Basic measures for haemostasis can be adapted to the severity and location of the bleed and include the following:12

  • Mechanical compression, surgical/interventional procedure
  • Fluid replacement and haemodynamic support
  • Blood products or transfusion of blood components

Other measures include giving specific antidotes or procoagulants for life-threatening or uncontrollable bleeding.12

ttr

CT: computed tomography; DOAC: direct oral anticoagulant; HAS-BLED: scoring system for estimating the 1-year risk of severe bleeding; INR: international normalised ratio; MRI: magnetic resonance imaging; NVAF: non-valvular atrial fibrillation.

References:

  1. Coagulation care, Swiss foundation for patients receiving anticoagulants. Available online at: https://www.coagulationcare.ch/blutverduennung.html, Last accessed on: 23/05/2024.
  2. Jürgen Bauer, Cornel C. Sieber. Antikoagulation bei älteren Menschen. Schweiz Med Forum 2004;4:824-831. Available online at https://smf.swisshealthweb.ch/fiIeadmin/assets/SMF/2004/fms.2004.05279/fms-2004-05279.pdf. Last accessed on: 23/05/2024.
  3. Roland Fath, Notfallmanagement: Direkte Antikoagulation aufheben. Dtsch Arztebl 2020; 117(5): A-213. Available online at: https://www.aerzteblatt.de/archiv/212290/Notfallmanagement-Direkte-Antikoagulation-aufheben. Last accessed on: 23/05/2024.
  4. Chen A, et al. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020 Jul 7;9(13):e017559.
  5. Heidbuchel H, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015 Oct;17(10):1467-507.
  6. Deitelzweig S, et al. Incremental economic burden associated with major bleeding among atrial fibrillation patients treated with factor Xa inhibitors. J Med Econ. 2017 Dec; 20(12):1217-1223.
  7. Gómez-Outes A, et al. Meta-Analysis of Reversal Agents for Severe Bleeding Associated with Direct Oral Anticoagulants. J Am Coll Cardiol. 2021 Jun 22;77(24):2987-3001.
  8. Habert JS. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention. Int J Gen Med. 2016 Oct 11;9:337-347.
  9. Nicholas L.J. Chornenki, Roupen Odabashiain, Jenneke Lenteejens, Fabian Stucki, Tobias Tritschler, Deborah Siegal; All-Cause Mortality after Major Gastrointestinal Bleeding Among Patients Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis. Blood 2023; 142 (Supplement 1): 4014. doi: https://doi.org/10.1182/blood-2023-174340).
  10. NIH, National Institute of Diabetes and Digestive and Kidney Diseases. Symptoms and causes of GI Bleeding. Available online at: https://www.niddk.nih.gov/health-information/digestive-diseases/gastrointestinal-bleeding/symptoms-causes. Last accessed on: 23.05.2024.
  11. Tenny S, Thorell W. Intracranial Hemorrhage. Stand: 17.02.2024. Available online at: https://www.ncbi.nlm.nih.gov/books/NBK470242/. Last accessed on: 23.05.2024.
  12. Rosemann A, et al. Neue/Direkte orale Antikoagulantien (DOAK). IHAMZ-Guideline, Institut für Hausarztmedizin, Universitätsspital Zürich. Erstellt: 11/2023. Available online at: https://guidelines.fmh.ch/downloads/19190258/download-de.pdf. Last accessed on: 23.05.2024.
  13. Gunasekaran K, et al. A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J Clin Med. 2020 Sep 15;9(9):2984.
  14. Lindhoff-Last E, Birschmann I, Kuhn J, Lindau S, Konstantinides S, Grottke O, Nowak-Göttl U, Lucks J, Zydek B, von Heymann C, Sümnig A, Beyer-Westendorf J, Schellong S, Meybohm P, Greinacher A, Herrmann E; RADOA-Registry Investigators (Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists Registry). Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry. Thromb Haemost. 2022 Apr;122(4):552-559. doi: 10.1055/a-1549-6556.

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