asmi
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what is it,what are the clinical features , lab findings and treatment ?
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| dxtxpx
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Disease type: Platelet disorder
Chromosomes: 17
Pathology: Bernard-Soulier Syndrome (BSS) is an autosomal recessive disoreder for the gene GPIb(alpha). The most common form of BSS is a nonsense mutation where a STOP codon is wrongly inserted into the middle of a gene. This results in a much shortened protein. In the case of BSS, the mutation is a TGG (Tryptophan) codon to a TGA (STOP) codon. The resulting protein is severely shortened, with the entire transmembrane helix, and cytoplasmic domain absent. This results in a total lack of GPIb-complex on platelets, and leads to the aetiology outlined below.
There are a few known variants of BSS. These variants are mutations in the Leucine rich region of GPIb(alpha), which is thought to be important in binding to vWF (a factor important in clotting). Another variant is proposed to be a mutation in one of the other proteins making up the GPI-complex, a possible mutation in either GPIb(beta), GPV, or GPIX.
Etiology: Platelets have a large role in clot formation. When tissues are torn, collagen is exposed to the blood. A clotting factor known as vWF becomes dissolved around the site of injury. GPIb-complex binds with a high affinity to vWF. GPIIb-IIIa, another platelet protein maintains the links between platelets (See Glanzmann Thrombasthenia). GPIIb/IIIa can also bind vWF, but a significant difference between GPIb-complex, and GPIIb-IIIa is that GPIb-complex does not require prior stimulation of the platelet to bind to vWF. Further, GPIb-complex is not involved with binding between platelets (GPIb-complex cannot bing fibronectin).
This leads to the conclusion that GPIb-complex is important in the intitial stages of clot formation, before the platelets are fully stimulated.
There are over 25,000 copies of GPIb-complex on the surface of an average normal platelet. In BSS, there are no copies of GPIb-complex.
This does not make clotting impossible, it means that platelets must be stimulated by, for example, adrenaline, before they will clot normally.
Symptoms: include a combination of the following:
Mucocutaneous bleeding (bleeding of mucosal tissues, e.g. tonsils).
Enlarged, abnormal platelets.
Absent platelet aggregation to vWF, ristoceldin, and bovine vWF.
Gastro-intestinal bleeding (Stomach, intestines, etc..).
Menorhagia (Severe bleeding during menstruation).
Treatment: usually involves infusion of platelet activating factors, and platelet transfusion. For which a common problem is development of allantibodies to the infused platelets.
A new treatment involves using a synthetic vasopressin analogue (DDAVP, 1-deamino-b-D-arginine vasopressin). Vasopressin is a stimulator of platelets. Although DDAVP's mechanism of action is unknown.
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| dxtxpx
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Above info is from this site:
http://www.diseasedir.org.uk/genetic/gene1703.htm
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| asmi
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thanks 
few points to differentiate it (although there r many)from others:
* here in this case pt will have prolonged BT and normal P/C.Pt responds to platelet infusion only.
*in Henoch schonlein purpura pt will have normal BT and normal P/C.
*in idiopathic thromobcyto..purpura BT will be proplonged and P/C will be decreased.common in childrens after viral fevers.
*in thrombotic throbocyto..purpura BT is prolonged and P/C decreased..common in adult females,pt will have fever etc.In this case platelet transfusion is actually contraindicated.
* in VWD BT will be prolonged and P/C will be normal.Here pt responds better to cryoprecipitate infusion.
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