Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 577

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 influenza B, and meningococcal vaccination should be given, and postoperative penicillin prophylaxis should be considered, although compliance can be poor and the prevalence of resistant organisms is increasing. For those in whom a splenectomy is contraindicated or fails, the last resort is immunosuppressive therapy with azathioprine or cyclophosphamide, which is sometimes effective. Danazol, vitamin C, interferon, and ciclosporin have all been tried with varying efficacy, as has extracorporeal absorption of the antibody with a protein A column. In difficult and refractory cases, none of these therapies is frequently or consistently successful.³