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“This chapter contains sections titled: Rationale for gene transfer in hemophilia Basic components of a gene transfer protocol The transgene vehicle (Table 35.2) Adenoviral vectors Retroviral vectors Adeno-associated viral vectors Future challenges for gene therapy References “
“Summary.  For patients affected by severe inherited platelet dysfunctions, e.g. Glanzmann Sirolimus research buy thrombasthenia (GT) or Bernard-Soulier syndrome (BSS), platelet transfusion is frequently needed for controlling spontaneous bleeding, and is always needed when trauma

occurs or surgery is performed. For the mild-to-moderate bleeding entities, e.g. storage pool disease, thrombaxane A2 receptor defect, platelet transfusion is usually unnecessary. Transfusion of platelets should be used selectively and sparingly because of the substantial risk of alloimmunization against HLA antigens and/or platelet glycoproteins (GP) αIIb, β3, or αIIbβ3 in GT, and GPI-IX-V in BSS, which may lead to refractoriness to therapy. To reduce the risk, HLA-matched single donors of platelets should be used. If such donors are unavailable, leucocyte-depleted blood components should be used. Therapy other than platelet transfusion includes: (i) Prevention (vaccination against hepatitis B, avoidance of non-steroidal anti-inflammatory drugs,

preservation of dental hygiene, correction of iron Sirolimus nmr deficiency and prenatal diagnosis). (ii) Topical measures (compression with gauze soaked with tranexamic acid, fibrin sealants, splints for dental extractions and packing for nose bleeds). (iii) Antifibrinolytic Cisplatin research buy agents that are useful for minor surgery and as adjuncts for other treatment modalities. (iv) Desmopressin that increases plasma levels of von Willebrand factor and factor VIII giving rise to increased platelet adhesiveness and aggregation associated with shortened bleeding

time. (v) Recombinant factor VIIa (rFVIIa). GT patients have been treated for bleeding episodes by rFVIIa with partial success. The mechanism by which rFVIIa arrests bleeding is probably related to increased thrombin generation by a tissue factor-independent process, enhanced platelet adhesion and restoration of platelet aggregation. (vi) Female hormones. Excessive bleeding during menarche in patients with GT or BSS can be controlled by high doses of oestrogen followed by high doses of oral oestrogen–progestin. Menorrhagia later in life can be managed by continuous oral contraceptives. Depo-medroxyprogesterone acetate administered every 3 months is an alternative when combined oral contraceptives are contraindicated. Inherited platelet dysfunctions are rare disorders manifested in affected patients by mild-to-severe mucocutaneous bleeding tendencies. For patients affected by severe platelet dysfunctions, e.g.