of platelets to the endothelial cells, causing microvascular thrombosis and hence the symptoms of TTP. High‐volume plasma exchange removes the antibody and the ultra‐high‐molecular‐weight multimers, while replacement with plasma results in the patient receiving active enzyme and normal von Willebrand factor multimers. The autoimmune component can be treated either with prednisolone or, more recently, infusions of rituximab. However, the coagulation tests usually remain normal or only very mildly deranged, in contradistinction to the case in disseminated intravascular coagulation, where thrombocytopenia is accompanied by profound disturbances of coagulation. The treatment is with aggressive, large‐volume plasma exchange and plasma transfusion and will involve liaison with haematologists and renal physicians.11
Acquired factor VIII inhibitors are rare, but their incidence is increasing as the population ages. They can occur spontaneously or in association with an underlying autoimmune or lymphoproliferative disorder. Their management involves both treating the active bleeding episode and subsequent efforts to remove or neutralize the antibody. The latter usually involves immunosuppression, although occasionally acquired inhibitors will resolve spontaneously. Treatment of bleeding episodes may require high doses of factor VIII and the use of activated prothrombin complex concentrates or recombinant factor VIIa. Data from the United Kingdom Haemophilia Centre Doctors Organisation has recently shown that the mortality from acquired haemophilia is surprisingly low and that in the elderly patient group, sepsis – an effect of immunosuppression – actually causes more death than bleeding.
Paraproteinaemias can affect coagulation either by non‐specific inhibition of fibrin polymerization by the paraprotein – which can occur in myeloma, Waldenstrom’s macroglobulinaemia, and other lymphoproliferative disorders – or by the paraprotein having specific activity against one or more of the proteins of the coagulation cascade. This is a relatively rare phenomenon, but activity against factor VIII, giving acquired haemophilia, and von Willebrand factor, giving acquired von Willebrand’s disease, is recognized.12
Vascular disorders
In these disorders (Table 24.4), coagulation tests and platelet number and function are normal. The defect lies in the vascular endothelium and supporting tissues.13 Senile purpura is relatively common and occurs on the extensor surfaces of the forearms and hands in particular. It is due to decreased amounts of collagen supporting the small blood vessels, which rupture with minor trauma or apparently spontaneously. The process is considerably accelerated by long‐term treatment with corticosteroids. There is no specific treatment and, other than being cosmetically disturbing, it does not constitute a significant haemorrhagic diathesis. Hereditary haemorrhagic telangiectasia is an autosomally dominantly inherited disease with multiple telangiectasia of the lips, conjunctiva, and oral cavity associated with telangiectasia throughout the gastrointestinal tract and also with pulmonary arteriovenous malformations. The condition tends to become progressively more severe with age and frequently presents in later life, usually as chronic iron deficiency anaemia. Troublesome gastrointestinal bleeding can usually be managed by iron supplementation but may require a chronic transfusion regimen. The fibrinolytic inhibitor tranexamic acid and oestrogens have been used with some success. Owing to the widespread nature of the lesions, surgery is not usually a feasible treatment option.14
Table 24.4 Haemorrhagic vascular defects.
| Senile purpura |
| Steroid purpura |
| Hereditary haemorrhagic telangiectasia |
| Gastrointestinal angiodysplasia |
| Ehlers–Danlos syndrome |
| Henoch–Schönlein purpura |
Scurvy (vitamin C deficiency) is associated with purpura and widespread bleeding, particularly from mucosal surfaces and subperiostally. It is due to both abnormal collagen synthesis and a defect in platelet function but is rare in the Western world, except in association with malnutrition and alcoholism. Amyloidosis may be primary or complicate paraproteinaemias, collagen vascular disorders, and chronic infection. The deposition of amyloid protein in the blood vessels leads to fragility, and consequently purpura is common. Cases of a specific coagulation defect due to absorption of the coagulation factor X by the amyloid protein have occasionally been reported. Ehlers–Danlos syndrome, especially type IV with a deficiency of type III collagen, results in structural weakness of major blood vessels with a tendency to rupture and consequent severe haemorrhage. Henoch–Schönlein purpura is rare in the elderly, being primarily a condition of childhood. It is an anaphylactoid purpura with cutaneous petechia and urticaria, associated with joint swelling, abdominal colic, and melena. Despite the purpura, which is usually a manifestation of severe thrombocytopenia, the platelet count remains normal in this condition. Precipitating drugs should be withdrawn; steroids give relief from the joint and abdominal symptoms.
Thrombotic disorders
Although arterial thrombosis is a major cause of morbidity and mortality, its prevention is not possible at present; likewise, its pathophysiology is not well characterized. Smoking, hyperlipidaemia, and a raised fibrinogen concentration are associated with accelerated atheroma, which accounts for the majority of arterial disease (see Chapter 36). In addition, atrial fibrillation (see Chapter 29) and valvular cardiac defects are associated with arterial embolization, but a full understanding of arterial thrombosis does not exist at present.15
The situation with venous thrombosis is somewhat different, and there have been rapid advances in the understanding, diagnosis and management of venous thrombosis (see Chapter 37) over the last few years. Venous thrombosis is primarily a disease of old age; until recently, it was thought that in the majority of cases the cause was circumstantial, with predisposing factors being immobilization and surgery, particularly to the hip, knee and pelvis, together with accessory factors such as obesity and malignancy. However, it has become clear that in up to 50% of cases of venous thrombosis, an additional underlying genetic predisposition to thrombosis becomes manifest under the above circumstances. The importance of thromboembolic prophylaxis of both surgical and medical patients at medium and high risk of developing thrombosis is increasingly recognized and practised. Likewise, the need for objective diagnosis of venous thrombosis by ultrasound examination or venography in the lower limb, and ventilation–perfusion lung scanning and pulmonary angiography in cases of suspected pulmonary embolus, has become established. Objective validation of the diagnosis of venous thromboembolic disease should always precede the initiation of treatment. Treatment should be initially with either unfractionated or low‐molecular‐weight heparin and subsequently with oral warfarin. Warfarin in the elderly is not without hazards, there being an increased chance of drug interactions; and in general, the dose required in elderly patients is somewhat lower than in younger patients. Furthermore, the risk of bleeding is increased at both high and normal INRs because of the increased incidence of underlying pathology, such as peptic ulcer, gastrointestinal malignancy, and angiodysplasia. Consequently, it is important that recommended target ranges and duration of anticoagulation are adhered to and that patients are not anticoagulated without good cause (Table 24.5).16
Thrombophilia
The proteins of the natural anticoagulant pathway act to limit and regulate thrombin generation (Figure 24.2). Deficiency of these proteins results in increased thrombin generation and consequently increased fibrin