Disorders of platelet function and vascular purpuras


Disorders of platelet function and vascular purpuras

Platelet dysfunction should be considered wherever there are the clinical symptoms and signs of thrombocytopenia (p. 14) in the presence of a normal or only moderately reduced platelet count. Disorders of platelet function can be divided into inherited disorders which are rare but well characterised in the laboratory, and acquired disorders which are much more common but often of obscure aetiology. Bleeding problems may also arise in a number of inherited and acquired disorders of the vasculature and its supporting connective tissue – the vascular purpuras.

Laboratory testing of platelet function

Ideally, blood samples for testing of platelet function should be taken from fasting and resting subjects who have not smoked, ingested caffeine or drugs known to affect platelet function. A blood count and blood film are routinely performed. The bleeding time, where a small incision is made in the forearm skin and the time to cessation of bleeding recorded, is now less used as it is subjective and has poor reproducibility. A number of dedicated platelet function instruments (e.g. PFA-100) allow screening tests but the results must be interpreted with caution as they are not diagnostic or sensitive for mild platelet disorders.

Platelet aggregation studies assess the ability of platelets to aggregate in response to the addition of a variety of agonists (e.g. ADP, adrenaline (epinephrine), collagen, arachidonic acid, ristocetin). The tracings produced (Fig 35.1) require expert interpretation. The methodology remains the gold standard with the response to agonists giving characteristic patterns in inherited disorders. Other tests of platelet function include flow cytometry for the quantitation of glycoprotein receptor density, and the measurement of total and/or released adenine nucleotides. The latter tests may confirm the findings from platelet aggregation studies (e.g. in Bernard–Soulier syndrome) or reveal abnormalities where aggregation studies are normal or equivocal (e.g. in a storage pool disease or release defect).

Inherited disorders of platelet function

The commonest inherited platelet function and coagulation disorder, von Willebrand disease, is described on page 74.

Bernard–Soulier syndrome

This is a rare autosomal recessive bleeding disorder. There is a combination of platelet dysfunction, thrombocytopenia and abnormal platelet morphology. The mild thrombocytopenia is probably caused by reduced platelet survival. The functional platelet defect arises from mutation in the polypeptides of the glycoprotein (GP) Ib/IX/V complex. This complex is crucial for the initial adhesion of platelets to exposed subendothelium at high shear flow and for binding of platelets to von Willebrand factor. In platelet aggregation studies there is failure to aggregate with ristocetin. Bleeding can be severe and particularly complicates other predisposing events such as peptic ulcers and pregnancy. Patients require platelet transfusion for severe bleeding and prior to surgery. Antifibrinolytic agents and DDAVP (see p. 73) are useful in some cases.

Glanzmann’s thrombasthenia

This rare autosomal recessive disease is also caused by loss or dysfunction of a platelet glycoprotein complex – GP IIb/IIIa. This normally acts as a receptor for adhesive proteins such as fibrinogen and von Willebrand factor. Platelet numbers and morphology are normal but the platelets fail to aggregate with all agonists except ristocetin (see Fig 35.1). Clinical manifestations are variable but there is typically onset in the neonatal period and subsequent cutaneous and gastrointestinal bleeding, and menorrhagia. Platelet transfusions are indicated where local haemostatic measures fail. If there is platelet refractoriness, recombinant factor VIIa can be used.

Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Disorders of platelet function and vascular purpuras

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