Pathy's Principles and Practice of Geriatric Medicine

The name lupus anticoagulant is somewhat unfortunate. The lupus refers to systemic lupus erythematosus (SLE), and it was in patients with this condition that the phenomenon was first observed. However, it has subsequently become clear that the majority of patients do not have SLE. Likewise, although it appears to be anticoagulant in vitro by prolonging the activated partial thromboplastin time (APTT), in vivo some lupus anticoagulants are associated with an acquired predisposition to thrombosis, and bleeding does not occur. Consequently, the finding of a lupus anticoagulant may be an indication for thromboprophylaxis or even anticoagulation.

The significance of the finding of a lupus anticoagulant can be very variable. Transiently positive tests frequently occur after infections, and many drugs can precipitate these antibodies, as can chronic infection such as syphilis. In these circumstances, the antibody does not appear to be associated with an increased incidence of either arterial or venous thrombosis. In patients with an underlying collagen vascular disease or in whom a primary antiphospholipid syndrome (APS) is diagnosed, there is an association between the finding of a positive test and recurrent arterial or venous thrombosis. The primary antiphospholipid syndrome consists of a positive lupus anticoagulant test and an association with livedo reticularis, thrombocytopenia, and recurrent miscarriages in females. The lupus anticoagulant can precipitate both arterial and venous thrombosis, and within an individual, the site of second and subsequent thrombosis tends to occur in the same system; these patients may require long‐term anticoagulation. There is no evidence that the antibodies causing the prolongation of the APTT in vitro are those that cause thrombosis; indeed, they may be an epiphenomenon, as a wide range of autoantibodies are found in these conditions, including antibodies against cardiolipin, which can be IgG or IgM, and are detected by a solid‐phase enzyme‐linked immunosorbent assay (ELISA). 19Likewise, antibodies against the protein beta‐2 glycoprotein‐1 are also associated with APS. Thrombotic events are particularly prevalent in patients with so‐called triple positivity: LA, ACA, and anti‐beta‐2 glycoprotin‐1 antibodies. These patients have recurrent thrombosis and should not be treated with DOAC anticoagulation; they require warfarin treatment, often with a target INR above 3.

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.

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Irene Criado Martin1, Alba Mª Costa Grille2, and Roberto Petidier Torregrossa2

1Geriatrics Department, Hospital of Sant Joan de Deu, Palma de Mallorca, Spain

2Geriatrics Department, University Hospital of Getafe, Madrid, Spain

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 VTE 1and 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, 3the Elderly Patients followed by Italian Centres for Anticoagulation (EPICA) study, 4and the SWIss venous Thromboembolism Cohort (SWITCO65+) 5have 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. 6–8In 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. 9,10In 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 people 11–13. 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. 14Additionally, extracted data from two large real‐world prospective European registries (PREFER in AF and Prefer in AF PROLONGATION 15) 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