Key points
Bleeding can be due to disorders of the coagulation cascade, platelets, or blood vessels.
Bleeding disorders can be congenital or acquired, the latter being more common.
Drugs are a common cause of bleeding disorders.
Thrombotic disorders, both arterial and venous, are common in the elderly.
Recurrent, severe, or unusual episodes of venous thrombosis suggest thrombophilia.
References
1 1. Mari D, Mannucci PM, Coppola R, et al. Hypercoagulability in centenarians: the paradox of successful ageing. Blood. 1995; 85:3144–9.
2 2. Bakchoul T, Marini I. Drug‐associated thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2018 Nov30;2018( 1):576–583.
3 3. Cooper N, Ghanima W. Immune Thrombocytopenia. N Engl J Med. 2019 Sep5; 381(10):945–955.
4 4. Saab S, Brown RS Jr. Management of thrombocytopenia in patients with chronic liver disease. Dig Dis Sci. 2019 Oct; 64(10): 2757–2768.
5 5. Greinacher A. Clinical Practice. Heparin‐induced thrombocytopenia. N Engl J Med. 2015 Jul 16; 373(3): 252–61.
6 6. Lassila R. Platelet function tests in bleeding disorders. Semin Thromb Hemost. 2016 Apr; 42(3):185–90.
7 7. Keeling D, Tait C, Makris M. Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. Haemophilia. 2008 Jul; 14(4):671–84.
8 8. Colvin BT, Barrowcliffe TW. The British Society for Haematology Guidelines on the use and monitoring of heparin 1992: second revision. J Clin Pathol. 1993 Feb; 46(2):97–103.
9 9. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low‐molecular weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy and safety. Chest. 2001 Jan; 119(1 Suppl):64S–94S.
10 10. Tripoldi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011 Jul 14; 365(2):147–56.
11 11. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017 May25; 129(21):2836–2846.
12 12. Hurwitz A, Massone R, Lopez BL. Acquired bleeding disorders. Hematol Clin North Am. 2017 Dec; 31(6):1123–1145.
13 13. De Paepe A, Malfait F. Bleeding and bruising in patients with Ehlers‐Danlos symdrome and other collagen vascular disorders. Br J Haematol. 2004 Dec; 127(5):491–500.
14 14. Kuhnel T, Wirsching K, Wohlgemuth W, Chavan A, Evert K, Vielsmeiser V. Hereditary hemorrhagic telangiectasia. Clin North Am. 2018 Feb; 51(1):237–254.
15 15. Jackson SP. Arterial thrombosis‐ insidious, unpredictable and deadly. Nat Med. 2011 Nov 7; 17(11):1423–36.
16 16. Baglin TP, Keeling DM, Watson HG. Guidelines on oral anticoagulation (warfarin): third edition – 2005 update. Br J Haematol. 2006 Feb; 132(3):277–85.
17 17. Connors JM. Thrombophilia testing and venous thrombosis. N Engl J Med. 2017 Sep 21; 377(12):1177–1187.
18 18. Baglin T, Gray E, Greaves M, et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. 2010 Apr; 149(2):209–20.
19 19. Chaturvedi S, McCrae KR. Diagnosis and management of antiphospholipid syndrome. Blood Rev. 2017 Nov; 31(6):406–417.
20 20. Almarshad F, Alaklabi A, Bakhsh E, Pathan A, Almegren M. Use of direct oral anticoagulants in daily practice. Am J Blood Res. 2018 Dec 10; 8(4):57–72.
CHAPTER 25 When to anticoagulate, and which anticoagulant?
Irene Criado Martin1, Alba Mª Costa Grille2, and Roberto Petidier Torregrossa2
1 Geriatrics Department, Hospital of Sant Joan de Deu, Palma de Mallorca, Spain
2 Geriatrics Department, University Hospital of Getafe, Madrid, Spain
Introduction
The higher risk in older patients of diseases such acute venous thromboembolism (VTE) and atrial fibrillation (AF), and their higher VTE/AF‐related morbidity, mortality, and cost of care, promote a higher use of anticoagulants for prophylaxis and treatment.
As life expectancy increases and the proportion of adults age 65 and older rises, it is likely that the burden of thrombotic disease in elderly adults will become even greater. But actual guidelines and recommendations commonly extrapolate study results from younger patients to the sicker elderly because elderly multimorbid patients are underrepresented in many randomized and nonrandomized clinical studies of VTE1 and AF.2
Many landmark clinical trials of VTE prophylaxis and treatment excluded patients with an increased bleeding risk, renal failure, or recent stroke. In the last century, several prospective cohort studies and registries, such as the RIETE registry,3 the Elderly Patients followed by Italian Centres for Anticoagulation (EPICA) study,4 and the SWIss venous Thromboembolism Cohort (SWITCO65+)5 have been carried out to study short‐ and long‐term clinical outcomes in older patients with VTE.
AF is a major risk for thrombotic disease, and many patients with AF are managed with anticoagulation for primary or secondary prevention of these events. Nonetheless, studies specifically designed in the elderly population are not yet available, and the current evidence excludes multimorbidity patients, polypharmacy, geriatric syndromes and evaluates benefits using health indicators with low clinical impact in this population.6–8 In addition, the mean age of the patients included in clinical trials is 5 to 10 years younger than the mean age of real‐life patients with non‐valvular atrial fibrillation (NVAF). Because of that, the current guidelines cannot make strong recommendations for individuals 85 years of age or older.9,10 In an effort to solve this lack of evidence, data from subgroup phase III pivotal trials have been used, including over 30,000 patients older than 75, to demonstrate the efficacy of direct oral anticoagulants (DOACs) in comparison to vitamin K antagonists (VKAs), showing an equal safety profile in older and younger people11–13. The ARISTOPHANES (Anticoagulants for Reduction in Stroke: Observational Pooled analysis on Health Outcomes and Experience of Patients [NCT03087487]) study aimed to provide complementary information for older patients (age ≥80) by evaluating and comparing the rates of stroke/systemic embolism and major bleeding among NVAF patients newly prescribed apixaban, dabigatran, rivaroxaban, or warfarin.14 Additionally, extracted data from two large real‐world prospective European registries (PREFER in AF and Prefer in AF PROLONGATION15) evaluated the net clinical benefit at one year with DOACs versus VKAs; the results showed that major bleeding with DOACs was also lower in higher‐risk patients with low body mass index or age ≥85.16
This family of oral anticoagulants has been available in Europe since 2011 with different therapeutic indications: (i) prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery; (ii) prevention of stroke and systemic embolism in adult patients with non‐valvular atrial fibrillation (NVAF), and one or more risk factors (such as prior stroke or transient ischaemic attack [TIA]), age ≥75, hypertension, diabetes mellitus, or symptomatic heart failure (NYHA Class ≥II); and (iii) treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of recurrent DVT and PE in adults. The emergence of this novel oral anticoagulant offers patients and providers options to consider beyond warfarin.17 Decision‐making should address safety, tolerability, efficacy, price, simplicity of use, and patient preference, so decisions should be individualized for each patient.
The elderly are more prone to thromboembolism
The