GLANZMANN'S DISEASE
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Glanzmann's disease is otherwise known as Glanzmann's Thrombasthenia and was first described in 1918. It is a hereditary condition (autosomal recessive inheritance) and is therefore more common where consanguineous marriages are common. Clinically, it cannot be distinguished from other platelet disorders. It commonly presents in infancy or early childhood with multiple bruises and petechial spots following minimal or unrecognisable trauma. Nose bleeds and bleeding from the mouth is common and may be severe. Large muscle bleeds and bleeding into joints are uncommon but menorrhagia (heavy periods) can be severe in girls. Serious accidental or surgical trauma can be life threatening. The severity of the condition appears to subside with age, probably as a result of greater discretion. The essential diagnostic features are a normal platelet count and morphology and a greatly prolonged bleeding time, associated with a complete failure of platelt aggregation with all agents (ADP, adrenaline, thrombin and collagen) except von Willebrand factor. Having demonstrated the aggregation defect, the diagnosis can be confirmed by measuring the amounts of the platelet glycoproteins Gpllb and llla in the platelet surface membrane which are either deficient or functionally abnormal. A number of different variants of Glanzmann's disease have been described of differing severity. In type 1 there is a severe (<5%) deficiency of the platelet membrane glycoprotein complex whereas in type ll the deficiecy is mild (5 to 20%). Type lll has also been described where the glycoproteins are present in normal or near normal amounts, but are functionally defective. The genes for both glycoproteins llb and llla are contained on chromosome 17. Many different gene abnormalities (in different families) can give rise to the clinical condition. Carriers (heterozygotes) for Glanzmann's disease usually have no significant bleeding symptoms and have normal platelet function tests. Their platelets, however, express about half the normal number of glycoprotein llb/llla complexes. The condition can be diagnosed pre-natally from foetal blood samples, but carries a high risk to an affected person from continuing haemorrhage. If the molecular defect is known (which is not often the case), diagnosis can be performed at 8 to 10 weeks gestation using chronic villus sampling and the use of DNA probes. It is important to remember that detailed counselling of the parents is necessary before antenatal diagnosis, which is contra-indicated if the parents wish the pregnancy to continue even if the foetus is affected. The only curative treatment for Glanzmann's disease is bone marrow transplantation. The risks of this procedure are considerable, however, so as to confine its use to patients in which severe bleeding cannot be adequately by more conservative measures. Meanwhile, the management of Glanzmann's disease consists of the avoidance of trauma and medicines such as aspirin, which may further affect platelet function, and the treatment of major bleeding episodes by platelet transfusion. Minor bleeding from accessible sites (eg teeth and gums) can be controlled by local application of thrombin and adrenaline solutions. Severe nose bleeds may require nasal packing and platelet transfusions. Antifibrinolytic drugs, such as Tranexamic acid (Cyclokapron) may help control bleeding and tooth decay. Heavy periods (menorrhagia) may be a problem and may require hormonal therapy for control. Excessive platelet transfusions should be avoided because of their risk of developing platelet antibodies. These may be antibodies directed against the glycoprotein llb/llla complex or against other more common platelet (HLA) determinants. HLA matched platelets may be necessary. White cell filtration of platelets may reduce the likelihood of developing platelet antibodies. Dr. Richard Stevens |