BACKGROUND: Coagulation factor XIII deficiency, in either its acquired or inherited form, is a rare cause of abnormal bleeding. In patients with Factor XIII (F XIII) deficiency, recommended means of factor replacement include infusion of fresh frozen plasma (FFP), cryoprecipitated plasma (Cryo), or F XIII concentrates1. Comparisons of F XIII concentration in FFP and Cryo are not well defined. To aid management of F XIII deficiency, we measured F XIII activity and antigen in FFP and Cryo. In addition, we determined concentrations of fibrinogen, factor VIII (F VIII) and von Willebrand factor (VWF), including antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and collagen binding activity (VWF:CB).

STUDY DESIGNS AND METHODS: 10 bags each of FFP and of Cryo from blood group O donors obtained from the Mayo Clinic Division of Transfusion Medicine blood bank, were analyzed. F XIII activity was assayed by ELISA detecting activated F XIII-mediated amine incorporation into solid phase fibrinogen (Pefakit, Pentapharm). F XIII antigen was measured using radial immunodiffusion (The Binding Site). Fibrinogen was measured by Clauss kinetic clotting assay (Fibriquik, Biomerieux) and also by endpoint delta OD derived from the prothrombin time (ACL, Instrumentation Lab). F VIII was measured by 1-stage APTT-based assay; VWF:Ag by automated LIA (Diagnostica Stago); VWF:RCo by aggregometry of washed platelets; and VWF:CB by ELISA (Corgenix).

RESULTS: Mean concentrations of F XIII activity were 60 U/bag (+/−30) in Cryo and 288 U/bag (+/− 77) in FFP. F XIII antigen concentrations paralleled the activity results and are depicted in Table 1, which also includes results for the other analytes. The mean fluid volumes of Cryo and FFP were 21.3 ml/bag (+/− 2.7) and 245 mL/bag (+/− 29), respectively.

Table 1.

Comparison of Hemostatic Components in Cryoprecipitated Plasma (Cryo) versus Fresh Frozen Plasma (FFP)

CryoprecipitateFresh Frozen Plasma
ComponentMean (SD)Mean (SD)
Factor XIII activity 60 U/bag (+/− 30) 288 U/bag (+/− 77) 
Factor XIII antigen 0.65 mg/bag (+/− 0.23) 2.36 mg/bag (+/− 0.76) 
Factor VIII 133 U/bag (+/− 36.5) 265 U/bag (+/− 83) 
Fibrinogen Clauss 184 mg/dl (+/− 44) 725 mg/dl (+/− 199) 
Fibrinogen ACL 319 mg/dl (+/− 76) 864 mg/dl (+/− 327) 
VWF:Ag 181 U/bag (+/− 53) 218 U/bag (+/− 70) 
VWF:RCo 168 U/bag (+/− 34) 221 U/bag (+/− 65) 
VWF:CB 165 U/bag (+/− 40) 208 U/bag (+/− 71) 
Bag volume 21.3 ml/bag (+/− 2.7) 245 ml/bag (+/− 29) 
CryoprecipitateFresh Frozen Plasma
ComponentMean (SD)Mean (SD)
Factor XIII activity 60 U/bag (+/− 30) 288 U/bag (+/− 77) 
Factor XIII antigen 0.65 mg/bag (+/− 0.23) 2.36 mg/bag (+/− 0.76) 
Factor VIII 133 U/bag (+/− 36.5) 265 U/bag (+/− 83) 
Fibrinogen Clauss 184 mg/dl (+/− 44) 725 mg/dl (+/− 199) 
Fibrinogen ACL 319 mg/dl (+/− 76) 864 mg/dl (+/− 327) 
VWF:Ag 181 U/bag (+/− 53) 218 U/bag (+/− 70) 
VWF:RCo 168 U/bag (+/− 34) 221 U/bag (+/− 65) 
VWF:CB 165 U/bag (+/− 40) 208 U/bag (+/− 71) 
Bag volume 21.3 ml/bag (+/− 2.7) 245 ml/bag (+/− 29) 

CONCLUSION: In contrast to some of the other cryoprecipitable coagulation proteins, F XIII is only mildly enriched in Cryo when compared with FFP (about 2- to 3-fold). Although both products are practical means of F XIII replacement, and F XIII is somewhat enriched in Cryo, FFP may be a preferred product for F XIII replacement when infusion volume is not a major consideration (eg, in adults versus small children) and risks of exposure to multiple donors are considered. While Cryo is no longer recommended as the product of choice for VWF (or F VIII) replacement, our studies also demonstrate that Cryo is significantly enriched in VWF (which is not routinely assayed as a quality control measure for Cryo, in contrast to requirements for F VIII and fibrinogen content).

1
OShaughnessy, D. F., C. Atterbury, et al. (2004). Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant.
Br J Haematol
126
(1):
11
–28.

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