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primarily due to intracranial and subarachnoid haemorrhage, ruptured aortic aneurysm, gastrointestinal bleeding from peptic ulcers, and gastric or colonic malignancy. Bleeding due to primary disorders of haemostasis in the elderly is relatively rare. Severe congenital bleeding diatheses are usually diagnosed at a young age, with the majority of them now being treatable and carrying a normal life expectancy, while acquired disorders of haemostasis are an uncommon cause of death except as part of the syndrome of multiorgan failure. Most bleeding in the elderly is localized and the result of a specific underlying pathology, frequently malignancy. Bleeding disorders can be classified as being due to abnormalities of platelet number or function, disorders of the coagulation cascade, and disturbances of the vascular endothelium and connective tissues.

Thrombotic disorders are a far more significant cause of morbidity and mortality in the elderly age group. Arterial thrombosis and atheroma cause cardiovascular disease, cerebrovascular disease, and peripheral vascular disease. Likewise, venous thromboembolism is primarily a disease of older age and is now recognized as being due to a combination of both circumstantial and underlying genetic factors. Ageing itself does not result in either any major or significant changes in the range of the common coagulation tests, such as the activated partial thromboplastin time (APTT), prothrombin time (PT), or thrombin time (TT) or in the level of fibrinogen or other specific coagulation factors and inhibitors. However, fibrinogen levels are often high in the elderly as a result of underlying conditions. Likewise, the platelet count does not alter with age. There is, however, convincing evidence from sensitive markers of coagulation activation that background turnover of the proteins increases with age.¹ Although no major changes in haemostasis occur with increasing age, diseases that may result in bleeding problems or thrombosis are more common, and their consequences are more serious in the elderly (Table 24.1).

Disorders of platelet number

      The normal platelet count is between 150 and 400 × 10⁹/l. There is, however, some reserve, and haemostasis is normal with a platelet count above 80 × 10⁹/l, assuming normal platelet function. If the platelet count falls below this value, the bleeding time progressively prolongs; but spontaneous haemorrhage, in particular intracerebral haemorrhage, does not occur until the platelet count falls below 20 × 10⁹/l. Platelet numbers can be decreased by three mechanisms: decreased production in the bone marrow, increased peripheral destruction due to consumption (DIC), or immune destruction (ITP) and splenic pooling in gross splenomegaly with hypersplenism. In addition, prescription drugs should always be considered as a possible cause in any case of thrombocytopenia.²

      Decreased platelet production

      Decreased platelet production can be due to any condition that causes infiltration and replacement or aplasia of the bone marrow, such as aplastic anaemia, leukaemia, lymphoma, and carcinoma myelodysplasia or deficiency of vitamin B12 and folate in megaloblastic anaemia.

      Increased peripheral destruction

In childhood, immune thrombocytopenic purpura (ITP) is usually an acute self‐limiting condition, frequently precipitated by a viral infection, which spontaneously remits. In adults, ITP often has an insidious onset without an obvious precipitant cause and runs a chronic course over many months and years, occasionally being extremely refractory to treatment. ITP is due to the production of an autoantibody against platelets, usually directed against the platelet membrane‐specific glycoproteins such as glycoprotein 1b and IIb/IIIa. The binding of the antibody to the platelet surface antigen results in the uptake of the platelet–antibody complex by the reticuloendothelial system and premature destruction of the platelet. Destruction occurs primarily in the spleen, but also in the liver and bone marrow, and platelet survival can be decreased from the normal 7–10 days to only a few hours. Diagnosis is based on the finding of true thrombocytopenia, together with normal bone marrow showing normal or increased numbers of megakaryocytes, the progenitor cells of platelets, and an absence of an alternative cause of excessive peripheral platelet destruction, such as normal clotting screen to rule out DIC. A low platelet count from an automated blood cell analyser should always be repeated, and the blood film should be examined to exclude artefactual thrombocytopenia due either to the sample having clotted or to platelet clumping caused by the anticoagulant. The clotting screen should be normal.

Table 24.1 Coagulation tests.

Test	Test of	Causes of abnormality
APTT	Intrinsic and common pathways	Factor VIII, IX, XI, XII, II, V, or X deficiency, or factor inhibitor Lupus anticoagulant Heparin
PT	Extrinsic and common pathways	Factor VIII, II, V, or X deficiency, or factor inhibitor Liver disease Warfarin
TT	Fibrinogen polymerization	A or hypo or dysfibrinogenaemia (some dysfibrinogenaemias cause thrombosis, not bleeding) Heparin
Fibrinogen	Fibrinogen quantity	A or hypo or dysfibrinogenaemia
FDP	Fibrinolysis	Disseminated intravascular coagulation Venous thrombosis
Platelet count	Platelet number	Thrombocytopenia or thrombocytosis
Bleeding time	in vitro platelet function	Thrombocytopenia Functional platelet defect or anti‐platelet drugs
PFA	in vitro platelet function	Aspirin, clopidogrel, or functional platelet disorder

      ITP in adults, unlike in childhood, seldom remits spontaneously. The initial treatment is with prednisolone 1 mg/kg daily or intravenous immunoglobulin 1.0 g/kg daily for two days. In patients with diabetes or renal impairment, an IvIg free from sucrose should be used. The condition is usually steroid‐responsive but frequently steroid‐dependent, and attempts to withdraw the steroids result in recurrence of thrombocytopenia. Often, the platelet count will stabilize at an acceptable level of above 50 × 10⁹/l on no steroids or only a minimal dose, and in the absence of symptoms, this is often well tolerated for many years. If there is no response to steroids or an unacceptably high dose is required to maintain a satisfactory platelet count, alternative therapies include intravenous immunoglobulin, which usually raises the platelet count for around three weeks and sometimes results in a sustained remission, or the new agents that mimic thrombopoietin (TPO), the endogenous hormone that drives platelet production. Romiplostim is given by weekly injection and the dose titrated to produce a safe platelet count, while Eltrombopag is given orally daily with dose titration. Once the correct dosage is achieved, these drugs are given for 12 months; then the dose is reduced to see if remission has been achieved, which occurs in over 50% of cases. Splenectomy – which, although it does not prevent autoantibody production, does prevent premature platelet destruction by the spleen – is reserved for the most refractory cases, as it requires surgical intervention, although a laparoscopic splenectomy is far less invasive than an open splenectomy. A splenectomy successfully achieves complete remission in about 50–75% of cases progressing as far as surgery. However, splenectomy should not be undertaken lightly, as it is not without hazard, particularly in the thrombocytopenic patient. In addition to the operative risks, there is the risk of subsequent overwhelming post‐splenectomy sepsis: preoperative pneumococcal, Haemophilus

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