Doctors' Newsletter - Autumn 2008 - Douglass Hanly Moir Pathology

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Acquired Bleeding Disorders Dr Vera Stoermer Haematologist Acute and chronic acquired bleeding disorders in outpatients are common and often difficult to evaluate. They are initially dependent on subjective evaluation of an increased tendency to bleed, firstly by the patient and secondly by the clinician. What is considered significant bleeding by one patient may be disregarded by another. If a significant bleeding tendency is being considered, subsequent laboratory testing is guided by the clinical history and physical examination of the patient. A correct diagnosis is essential if appropriate therapy is to be instigated, particularly for those patients undergoing a diagnostic or invasive procedure. Picture 1: Ginko biloba leaf Initial assessment In the initial consultation, questions need to be asked to ascertain whether the patient has excessive, prolonged, recurrent, or delayed bleeding, or abnormal bruising. A family history of significant bleeding should be excluded, even if the onset of abnormal bleeding is recent. Any history of excessive bleeding after physical trauma, skin lacerations, dental extractions, or surgery, is likely to be significant. The presence of epistaxis, gum bleeding and menorrhagia should also be ascertained. Ecchymoses after trauma are normal; however, the sudden development of new or multiple ecchymoses may be due to an underlying medical condition. Questions should concern general health and possible underlying disease which may be associated with a bleeding tendency. Examples include chronic liver and renal disease, and myelodysplastic or myeloproliferative disorders. In addition, medication or nutritional supplements which affect platelet function will enhance bruising or bleeding due to an underlying bleeding tendency. A detailed history of all drugs and medications is essential, especially with regard to any 'over-the-counter' medication or herbal remedies which the patient may not consider relevant. The commonest cause of an acquired bleeding disorder is drugrelated, due to the increasing use of anticoagulant therapy, which includes antiplatelet therapy and warfarin. Antiplatelet agents, such as aspirin, clopidogrel and non-steroidal antiinflammatory drugs are in widespread use throughout the community. Individual response to these drugs is extremely variable and will produce a significant bleeding tendency in some patients. Herbal remedies and other over-the-counter medications may have antiplatelet or other haemostatic effects, and produce a bleeding tendency. This may especially be seen when these medications are taken in combination with other anticoagulants; for example, Gingko biloba in addition to warfarin. Another common cause of an acquired bleeding or bruising tendency is thrombocytopenia which may result from a wide variety of causes. Primary or secondary immune-mediated destruction, including drug-induced, viral infections, or autoimmune diseases, should be considered. Decreased production, sequestration, or increased consumption of platelets are all possible causes. A less common cause of a bleeding tendency includes inhibitors or antibodies directed against specific factors e.g. factor VIII or IX, which may arise spontaneously in elderly patients, in pregnancy or in patients with autoimmune disorders. These inhibitors, although rare, may result in catastrophic bleeding, especially in patients undergoing surgery. Paraproteins also act as inhibitors by interfering with platelet or coagulation factor function. Common medical conditions have a range of effects on the haemostatic system. 4
Acquired Bleeding Disorders Chronic liver disease produces thrombocytopenia and reduced synthesis of almost all coagulation factors as well as abnormal fibrinogen synthesis. In severe liver disease, chronic disseminated intravascular coagulation (DIC) is often present. Vitamin K deficiency occurs especially with cholestatic jaundice and results in impaired synthesis of vitamin K-dependent coagulation factors. Other systemic disorders with increased bleeding include severe renal impairment resulting in platelet dysfunction and hypothyroidism with an acquired von Willebrand disorder. Conditions such as myeloproliferative disease and myelodysplasia are often associated with a bleeding tendency. Patients with myeloproliferative disorders may develop a range of defects, including acquired von Willebrand disorder. The bleeding tendency in these disorders is compounded by the use of aspirin to reduce the risk of thrombosis which also occurs in these conditions. In myelodysplasia, not only thrombocytopenia but also dysfunctional platelets are a common occurrence, and may cause significant bleeding if the patient undergoes surgery. A less common cause of a bleeding tendency is disseminated intravascular coagulation (DIC), which may arise with some malignancies, such as adenocarcinoma, or suddenly in acute promyelocytic leukaemia (APML), and may have catastrophic effects. Disseminated intravascular coagulation in association with cancer does not generally result in bleeding, unless the patient undergoes surgery. and blood film, platelet function analysis (PFA-100) if available, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level are indicated. These tests, if abnormal, warrant further investigation, such as factor assays, von Willebrand and platelet aggregation studies, depending on the abnormality. If the haemostatic screening tests are normal, as may be the case for mild defects in haemostasis, further investigation may still be required if the clinical history is highly suspicious or the patient is to undergo a higher risk procedure, such as cardiovascular surgery. A recent onset of a bleeding tendency may be due to a previously undiagnosed mild inherited bleeding disorder. This may not become evident until the patient has undergone a haemostatic challenge, such as surgery, or complains of menorrhagia. In these cases, the haemostatic screening tests, which are insensitive to mild reductions in factor levels, may be within reference limits, so that further investigation is warranted. In the investigation of all bleeding disorders, the importance of a careful history cannot be overemphasised, as it is the key to directing both the initial tests and judging the extent to which further investigation will be required. If you have any questions regarding the investigation of a bleeding diathesis, Dr Vera Stoermer, Director of Coagulation at Douglass Hanly Moir Pathology, or any of our Haematologists, will be pleased to advise. Suggested Initial Haematological Tests for an Acquired Bleeding Disorder FBC/platelet count and blood film examination PT, APTT, TT and fibrinogen PFA-100 (if available) Picture 2: Petechial rash due to DIC in patient with APML Investigations For those patients with a clinical history or physical examination suspicious of a bleeding tendency, haemostatic screening tests which include a FBC/platelet count If you have any enquiries, please contact Dr Vera Stoermer on (02) 98 555 312 5
Page 1 and 2: Doctors’ Newsletter Autumn 2008 P
Page 3: New Pathologists Dr Nick Taylor B.M
Page 7 and 8: Neutrophils: The Good, The Bad and
Page 9 and 10: Allergy to Stinging Insects Dr Karl
Page 11 and 12: Medicare Update Tryptase Measuremen

Doctors' Newsletter - Autumn 2008 - Douglass Hanly Moir Pathology

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