Variables Involved in Cryoprecipitate Production and their Effect on Factor VIII Activity

Abstract

Summary. The Regional Transfusion Centres in England and Wales have studied the following variables in the preparation of cryoprecipitate: blood group of the donor, choice of anticoagulant (ACD or CPD), conditions of freezing, thawing and centrifugation of the plasma and age of the starting plasma. Mean factor VIII activity in cryoprecipitates derived from group A plasma was significantly higher than from group O plasma. CPD may lead to increased potency of factor VIII when freshly collected plasma is used to prepare cryoprecipitates; rapidity of thawing may also be advantageous. None of the other variables studied produced significant effects on the factor VIII activity of the cryoprecipitates and particular attention has been drawn to the results of experiments concerned with the age of starting plasma.

Preparation of Improved Cryoprecipitated Factor VIII Concentrate

“…Although the main experiment failed to demonstrate a convincing difference between cryos derived from 4 h and 18 h plasma, a result similar to that of the Cryoprecipitate Working Party [7], a supplementary ex periment, using the most advantageous anti coagulant / thaw time combination (CPD / 2h thaw) demonstrated a significant im provement in VIII:C yield when very fresh plasma was used.…”

“…A major disadvantage of this method is that the end-point of thawing, i.e. plasma con taining a small amount of diffuse 'soft' ice, found by Slichter et al [9] to be associated with higher VIII:C cryo yields, can be reach ed and passed all too easily [5,7]. Another disadvantage is that an aqueous thawing medium could readily convey micro-organ isms through unrecognized 'pin-hole' leaks in the plastic bags.…”

“…Selection of the correct end-point of thawing may be a difficulty when the water bath thaw method is employed [5,7] but this should be outweighed by the real advan tage of reduction of the time-dependent de cay of VIILC. The rapidity of the process, together with the control of the thawing end-point implicit in the method, probably accounts for the good yields of VIII :C re ported by Mason [8] whose method gives a thaw time of 1 h, despite fairly high losses into the supernatant plasma.…”

“…gation by a working party into the quality of cryo in England and Wales [7] showed the important influence of the ABO blood group of the plasma donors, group A cryos con taining on average28% more VIII:C activity than group O cryo. That report also pro duced suggestive, but no means conclusive, evidence that two other variables influenced the quality of cryo.…”

Control of Large-Scale Plasma Thawing for Recovery of Cryoprecipitate Factor VIII

“…These two essential requirements are in conflict with one an other and the extent of this is related to the scale of manufacture. Hence, though good recovery may be possible at an analytical scale [6], loss is already significant in the routine preparation of single-donation cryo precipitate [7] and increases further at the industrial scale [8], where plasma pools of up to 1,000 litres may be processed as a single batch [9].The essential process design problem is to maximise the rate of thaw within the tem perature constraint provided by the solubil ity of factor VIII. To achieve this, the surface area available for heat transfer must be max introduction…”