these antiphospholipid antibodies decrease the efficiency of the coagulation cascade and prolong the clotting time. The diagnosis can be confirmed using the dilute Russell viper venom test (DRVVT), in which the test is optimized so that phospholipid availability is rate‐limiting; this accentuates the effect of antiphospholipid antibody. Confirmation is achieved by showing that the clotting time returns to normal when excess phospholipid (in the form of freeze‐fractured platelets) is added to quench the antibodies and that the test is not corrected by the addition of normal plasma that contains only additional coagulation factors.
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).19 Likewise, 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.
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.
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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
