Investigation of bleeding disorders

Although the  precise diagnosis of a bleeding disorder may depend on laboratory tests, much information may be obtained from  the history and physical examination, which should   aim to determine the following:
1 Is there ageneralized haemostatic defect? Supportive evidence for this includes bleeding from multiple sites, spontaneous bleeding and bleeding into the skin. 2 Is the feet inherited or acquired? A family history of a a bleeding disorder should be sought. Severe inherited defects usually become apparent in infancy, while mild inherited defects may only come to attention later in life, for example with excessive bleeding after surgery, childbirth, dental extractions or trauma.

3 Is the bleeding suggestive of a vascular/platelet defect or a coagulation defect?
VASCULAR/PLATELET BLEEDING is characterized by easy bruising and spontaneous bleeding from small vessels. The bleeding is mainly into the skin (the term purpura includes both petechiae, which are small skin haemorrhages varying from pinpoint size to a few millirnetres in diameter and which do not blanch on pressure, and ecchymoses, which are small bruises) and from mucous membranes, often from the nose and mouth.
COAGULATION DISORDERS are typically associated with haem arthroses and muscle haematomas.


BLOOD COUNT AND FILM show the number and morphology of platelets and any blood disorder such as leukaemia.
BLEEDING TIME measures platelet plug formation in vivo. It is determined by applying a sphygmoman ometer cuff to the arm and inflating it to 40 mmHg.
Two 1 mm deep, 1 cm long incisions are made in the forearm with a template. Each wound is blotted every 30 s and the time taken for bleeding to stop is recorded, normally between 3 and 10 min. Prolonged bleeding times are found in patients with platelet function defects and there is a progressive prolongation with platelet counts less than 80 X 109/litre. The Hess or capillary resistance test parallels the bleeding time but is unreliable and not routinely used.


COAGULATION TESTS are performed using blood collected into citrate, which neutralizes calcium ions and prevents clotting. The prothrombin time (PT) is measured by adding tissue thromboplastin in the form of animal brain extract and calcium to patient’s plasma. The normal PT is 16-18 s and it is prolonged with abnormalities of either the extrinsic or common pathways. The partial thromboplastin time with kaolin (PTTK) is also known as the APTT (activated PTT). It is performed by adding a surface activator, kaolin, phospholipid (as platelet substitute) and calcium to patients’ plasma. The normal PTTK is 30-50 s depending on the exact methodology, and it is prolonged with abnormalities of either the intrinsic or common pathways. The thrombin time (TT) is performed by adding thrombin to patients’ plasma. The normal TT is about 12 s, and it is prolonged with fibrinogen deficiency, dysfibrinogenaemia (normal level of fibrinogen but abnormal function) or inhibitors such as heparin or FDPs. Correction tests are used to differentiate prolonged times in the PT, PTTK and TT due to coagulation factor deficiencies and inhibitors of coagulation. Prolonged PT, PTTK or TT due to coagulation factor deficiencies are corrected by addition of normal plasma to the patient’s plasma; no correction of an abnormal result after the addition of normal plasma is suggestive of the presence of an inhibitor of coagulation. Special tests of coagulation will often be required to confirm the precise haemostatic defect. Such tests include estimation of fibrinogen and FDPs, assays of coagulation factors, platelet function tests such as platelet aggregation and tests of the fibrinolytic pathway which include the euglobulin clot lysis time (ELT) and assays of plasminogen, t-PA and PAl-I. The ELT involves precipitation by acidification of the euglobulin fraction of plasma which contains fibrinogen, plasminogen and plasminogen activators. The euglobulin is clotted with thrombin and the time taken for lysis of the fibrin clot is a measure of fibrinolytic activity; the normal range is 60-270 min.

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