Tests of haemostasis detection of the patient at risk of bleeding
- Jean McPherson, Alison Street
- Aust Prescr 1995;18:38-41
- 1 April 1995
- DOI: 10.18773/austprescr.1995.047
Acquired bleeding disorders are common. They complicate well defined clinical disorders which can be detected by history and examination. Inherited bleeding disorders are uncommon, but can be detected by careful clinical assessment, including family history. Clinical assessment has high sensitivity, although low specificity, for the presence of a bleeding disorder. In contrast, both the sensitivity and specificity of routine laboratory screening are low. Both false negative and false positive results are common with the basic laboratory 'screening tests'. In a patient without a suggestive history, these tests are inappropriate. In a patient with a suggestive history, they may well be inadequate.
Normal haemostasis involves two processes:
These two processes are interactive, although their dominance varies in different sites of the vascular system. Activation of haemostasis is accompanied by activation of the fibrinolytic system which should eventually achieve partial or complete removal of the thrombus.
Clinically important abnormalities of these mechanisms are common and a logical and cost effective approach to the detection of patients at risk of bleeding is required.
Acquired bleeding disorders
These disorders occur in well defined clinical settings and the history and physical examination are a sensitive screen for these problems. The commonest cause of an acquired
bleeding disorder is drug therapy:
Various disorders may also be associated with a bleeding tendency.
Inherited bleeding disorders
These disorders are less common and the vast majority of patients will have a personal and/or family history of excessive bleeding. The history is a sensitive, though not specific, screen for these patients. It is important to enquire into bleeding during and after surgical or dental procedures; a return to the operating theatre, blood transfusion, or a need for packing or suture of dental sockets would increase the likelihood of there being an underlying problem.
Menorrhagia, recurrent epistaxis and easy bruising are sensitive indicators, although associated with a high rate of false positives. The perception of menstrual blood loss is variable and often influenced by family norms; the frequency of pad/tampon change may assist in determining its significance. Menorrhagia commencing after pregnancies and childbirth and uninfluenced by hormone supplements is unlikely to be due to an inherited haemostatic disorder. Peripartum bleeding is rare in patients with von Willebrand's disease (arguably the most common inherited haemostatic disorder) and the absence of such a history should not influence the decision as to whether investigation is required.
'Spontaneous' haemarthroses and major muscle bleeds are characteristic of haemophilia A (factor VIII deficiency) or B (factor IX deficiency).
Gastrointestinal bleeding and/or epistaxis as isolated problems are unlikely to be due to an inherited bleeding disorder. However, mucosal surfaces should always be inspected for the characteristic lesions of hereditary haemorrhagic telangiectasia. This condition is under diagnosed.
If a positive family history is obtained, the pattern of affected individuals may suggest autosomal (e.g. von Willebrand's disease) or Xlinked (e.g. haemophilia) inheritance.
Bleeding time (BT)
The skin bleeding time reflects 'primary haemostasis', the interaction of platelets with arterioles and capillaries to form a platelet plug (Fig. 1). The test is rarely useful and should not be performed if the platelet count is <100 x 109/L and if the patient has taken aspirin in the preceding 7-10 days, or a NSAID in the past 1-4 days (depending on the half life of the specific drug). Although the effect of these drugs on the bleeding time is variable, their use renders a prolonged bleeding time uninterpretable. If the result will be uninterpretable, the test should not be done. As patients may not be aware of the aspirin content of prescribed or over the counter medications, both the requesting doctor and the laboratory should check the drug history before testing.
The bleeding time may be abnormal in acquired and inherited disorders of platelet function, von Willebrand's disease, the rare afibrinogenaemias and inherited disorders of collagen. It may also be prolonged in patients with 'senile purpura', but the test is neither appropriate nor useful in this condition.
The value of the bleeding time as a 'screening test' of haemostasis is severely limited by its lack of specificity and sensitivity and its use cannot be recommended. The lack of specificity is the result of its susceptibility to physiological and technical variables. This so called 'standardised' technique varies between laboratories and between operators within a given laboratory. It is also an insensitive test and may be normal in patients with mild to moderate von Willebrand's disease and in those with disorders of platelet function. Although the BT can be prolonged by aspirin and other NSAIDs, is often abnormal in uraemia and may be abnormal in patients with myeloproliferative disorders, the presence and degree of an abnormality do not correlate with the risk of bleeding. The test cannot be recommended as a predictor of surgical bleeding.1
Activated partial thromboplastin time (APTT)
The APTT reflects the activity of coagulation factors in the intrinsic system and the final common pathway of coagulation (Fig. 1). It is performed by recalcifying citrated plasma in the presence of a 'surface' activator and a 'partial thromboplastin', simulating platelet membrane phospholipid.
A deficiency of a specific coagulation factor (e.g. factor VIII in haemophilia A), a coagulation factor inhibitor, a lupus inhibitor, or inhibition of coagulation by heparin may prolong the APTT. Although it can be prolonged in patients receiving warfarin or those with vitamin K deficiency or severe liver disease, it is less sensitive to these defects than the prothrombin time.
Incorrect specimen collection or handling may result in either a false positive (prolongation) or a false negative (shortening) APTT result.
Causes of an incorrect APTT
Basic tests of haemostatsis.
In practice, the main uses of the APTT are:
Prothrombin time (PT and INR)
The PT reflects the activity of the 'extrinsic system' and 'final common pathway' of coagulation (Fig. 1). It is measured by recalcifying citrated plasma after the addition of a 'complete' thromboplastin (e.g. a suspension of human or animal brain) which simulates tissue factor. Increasingly, thromboplastins produced by recombinant DNA technology are being used for this test. Compared with the APTT, the PT is more sensitive to the coagulation defect induced by oral anticoagulant therapy and less sensitive to the effect of heparin.
In practice, the main uses of the PT are:
A prolonged PT may be seen in patients with a lupus inhibitor, although the APTT is generally more sensitive. The PT has only a limited role in the assessment of patients with a history suggestive of an inherited bleeding disorder, as factor VII deficiency is rare. As with the APTT, use of the PT as a 'routine' preoperative screening test has little or no value.2,3
Thrombin time (TT)
The thrombin time assesses the conversion of fibrinogen to fibrin and is measured by adding thrombin to citrated plasma. The TT only detects abnormalities of fibrinogen and of fibrin formation (Fig. 1).
In practice, the thrombin time is used mainly by the laboratory, rather than as a requested test, to:
Investigations should address a diagnostic question, rather than being applied as a 'routine'. Provision of an accurate history on the request form and consultation with the pathologist as to appropriate testing should assist the laboratory to answer that question.
(See also Dental implications)
The following statements are either true or false.
1. The risk of postoperative bleeding can be calculated from the bleeding time and the activated partial thromboplastin time.
2. Most acquired bleeding disorders are drug induced.
Answers to self-test questions
Senior Lecturer in Medicine, Faculty of Medicine and Health Sciences, University of Newcastle
Visiting Haematologist, Hunter Area Pathology Service and Haemophilia Service, Newcastle Mater Hospital, N.S.W.