|Investigation||:||Factor VIII Screen|
|Spec container||:||9ml Citrate (BLUE)|
|Volume required||:||9 ml|
|Special sample requirements||The sample must be received within the laboratory within 4 hours of collection. If the sample cannot reach the laboratory within 4 hours the sample must be centrifuged (3000g for 10 minutes) and separated and frozen|
FVIII is a glycoprotein pro-cofactor. It has been found to be synthesized and released into the bloodstream by the vascular, glomerular, and tubular endothelium, and the sinusoidal cells of the liver, though there is still considerable ambiguity as to what the primary site of release in humans is. In the circulating blood, it is
mainly bound to von Willebrand factor to form a stable complex. Upon activation by thrombin, (Factor IIa), it dissociates from the complex to interact with Factor IXa in the coagulation cascade. It is a cofactor to
Factor IXa in the activation of Factor X, which, in turn, with its cofactor Factor Va, activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using Factor XIII) into a blood clot. No longer protected by vWF, activated FVIII is proteolytically inactivated in the process (most prominently by activated Protein C and Factor IXa) and quickly cleared from the blood stream. Factor VIII is not affected by liver disease. In fact, levels usually are elevated in such instances.
Von Willebrand factor (vWF) is a blood glycoprotein involved in haemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, and possibly hemolytic-uremic syndrome Increased plasma levels in a large numbers of cardiovascular, neoplastic and connective tissue diseases are presumed to arise from adversechanges to the endothelium, and may contribute to an increased risk of thrombosis.
The diagnosis of von Willebrand Disease (VWD), probably the most common congenital bleeding disorder, requires a number of special tests at the laboratory level. The measurement and comparison of von Willebrand Factor Antigen(VWF:Ag), VWF Activity and Factor VIII (FVIII) levels in plasma aid in the differentiation of quantitative defects (type 1 or type 3) or qualitative defect (type2) of VWF and therefore to
diagnose the different types of VWD.
When an extremely low or undetectable level of VWF:Ag is obtained, a type 3VWD could be expected. If a moderate or even normal result is obtained, VWFActivity and FVIII assays must be performed and compared with the VWF:Ag result. If all three values are within the normal range, VWD and Haemophilia A maybe excluded. If at least one parameter is abnormally low, it is necessary to calculate the ratios VWF Activity/VWF:Ag and FVIII/VWF:Ag. If both ratios are close to 1 (some authors suggest 0.7 as cut-off), a VWD type 1 may be diagnosed.
Factor VIIIc is an acute phase reactant, so care needs to be taken in its interpretation as mild deficiency can be masked during an acute episode.
|CPA/UKAS Accredited||ISO 15189; 2012|