Fibrinogen in cryoprecipitate and its relationship to factor VIII (AHF) levels

Very little has been published to indicate the quantity of fibrinogen in cryoprecipitates. We assayed 88 preparations from five blood banks for factor VIII(AHF) and fibrinogen to assess whether the AHF assay can predict the fibrinogen content. Cryoprecipitate was considered to be consistent with FDA standards with 80 units of factor VIII/bag (40% yield from 200 ml plasma). Fibrinogen was considered adequate if 200 mg were recovered (40% yield, 200 ml plasma, normal range 150–350 mg/dl). The mean AHF was 145 units/bag and fibrinogen. In 64/88 bags, the fibrinogen and AHF were concordant, but in 24/88 bags the results were discordant. Although it appears safe to conclude that a bag of cryoprecipitate will average 250 mg fibrinogen, adequate control may require separate assays for fibrinogen.     

Modulation of fibrinogen content in cryoprecipitate by temperature manipulation during plasma processing

In routine blood bank production of single-donation cryoprecipitate, the introduction of a 16-hour hold at 4 degrees C, with the frozen plasma units packed into polystyrene containers, resulted in plasma prethaw temperatures of -4 degrees C to -8 degrees C. This in turn resulted in cryoprecipitate fibrinogen levels that were 214 percent of those obtained when units were thawed immediately after removal from -30 degrees C storage. In scale-model production of factor VIII concentrate, plasma warmed from -30 to -10 to -15 degrees C over 18 hours before pooling and thawing yielded cryoprecipitate fibrinogen levels that were 66 percent of those found in plasma warmed to -2 to -5 degrees C over the same period. Processing -30 degrees C plasma without a warming period led to cryoprecipitate fibrinogen levels that were 40 percent of those obtained from plasma warmed to -2 to -5 degrees C. These differences were accentuated after purification of the cryoprecipitates to an intermediate-purity factor VIII concentrate. These results suggest that simple modifications in production methods allow the fibrinogen content of cryoprecipitate to be tailored to specific uses.     

Comparison of coagulation factor XIII content and concentration in cryoprecipitate and fresh-frozen plasma

BACKGROUND: For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh‐frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study. STUDY DESIGN AND METHODS: FFP and cryoprecipitate (10 bags each from blood group O donors) were analyzed to quantify pFXIII activity and antigen. Coagulation FVIII, fibrinogen, and von Willebrand factor (VWF) were also quantitated. RESULTS: Mean (±SD) pFXIII activity in cryoprecipitate and FFP bags was 60 ± 30 and 288 ± 77 U per bag, respectively, and pFXIII antigen and activity levels were concordant. Other comparisons (mean ± SD) between cryoprecipitate and FFP, respectively, were as follows: coagulation FVIII activity, 133 ± 37 and 265 ± 83 U per bag; fibrinogen content (Clauss kinetic assay), 183 ± 44 and 725 ± 199 mg per bag; VWF antigen content, 181 ± 53 and 218 ± 70 U per bag; VWF ristocetin cofactor activity, 168 ± 34 and 221 ± 65 U per bag; VWF collagen‐binding activity, 164 ± 40 and 208 ± 71 U per bag; and fluid (plasma) volumes per bag, 21.3 ± 2.7 and 245 ± 29 mL. CONCLUSION: In contrast to other cryoprecipitable coagulation proteins, pFXIII is only mildly enriched in cryoprecipitate when compared with FFP (approx. two‐ to threefold). Although both products can provide effective pFXIII replacement, FFP may be preferred when infusion volume is not a major consideration and pFXIII concentrates are not available. VWF is substantially enriched in cryoprecipitate (approx. ninefold compared with its concentration in FFP), with VWF activity content exceeding that of FVIII by approximately 26 percent on average.     

Variations in cryoprecipitate production

Several variables influencing the recovery of Factor VIII in the cold- precipitated protein fraction were examined. The actual rate at which the physical-chemical conversion of plasma from a solid to a liquid state occurs does not seem to affect the yield. Rather, it is the amount of time immediately postthaw and prior to centrifugation that determines the Factor VIII activity in the cryoprecipitate. With prolonged periods at 4 C the Factor VIII activity leaves the cold precipitate and lifts into the supernatant. Even distribution of the plasma layer and close attention to the thawing procedure facilitate Factor VIII recovery.     

冷沉淀的临床应用分析

目的了解冷沉淀在临床的应用情况。方法收集我院2009年1月-2011年1月冷沉淀输注情况,将冷沉淀的使用情况按专业科室分别归类。结果冷沉淀的使用主要集中在胸外ICU、血液内科,消化内科及普外科。其中血液内科、胸外ICU的用量最多。结论冷沉淀的止血功效逐渐被临床认识并在各类痰病中得到大量应用。     

In vivo stability of cryoprecipitate fibrinogen

Because of its lower hepatitis risk, cryoprecipitate has been advocated as a substitute for commercial fibrinogen. Previous literature on cryofibrinogen has demonstrated a short blood t1/2, rendering it unsuitable for therapeutic use. The in vivo clearance of 131I- cryoprecipitate was compared with that of 125I-standard fibrinogen. A small amount of cryoprecipitate was rapidly cleared and apparently was cryofibrinogen. However, the bulk of the cryoprecipitate was cleared with a normal half life, as was cryoprecipitated that was in 10-bag pools. The data indicated cryoprecipitate was an effective in vivo form of fibrinogen and thus the preferred fibrinogen source because of its combining normal t1/2 with single donor procurement.     

A protocol for cryoprecipitate production

A three-year contract research program to study the production of cryoprecipitate has been completed. The investigators have collaborated to propose changes in the methods of production of cryoprecipitate. The investigators believe that the problem of low and variable yield of cryoprecipitate can be overcome and cryoprecipitate can be produced which contains, on an average, at least 100 Factor VIII units in nearly every bag. It is emphasized that breaches of technique and time delays in cryoprecipitate processing must be scrupulously avoided to achieve optimum, standardized yields.     

Prepooled cryoprecipitate for treatment of hemophilia A

Lyophilized factor VIII concentrates, because of their convenience, are the most commonly used products for providing antihemophilic factor to patients with hemophilia A. Heightened concerns about associated complications indicate that cryoprecipitate usage will increase in the immediate future. We present a protocol for making cryoprecipitate more usable by "prepooling" individual units of cryoprecipitate in an "open" system. Our experience indicates this approach is safe, effective and acceptable to patients, including those on home therapy programs.     

Determinants of factor VIII recovery in cryoprecipitate

Many aspects of the production of cryoprecipitate were studied to determine which methods resulted in the greatest recovery of Factor VIII. The following recommendations resulted: 1) blood should be mixed with anticoagulant throughout phlebotomy; 2) blood should be centrifuged within a few hours of collection; 3) larger satellite bags should be used to contain the usual volume of plasma, for example, 200 ml of plasma should be frozen in a 600-ml capacity bag; 4) plasma should be centrifuged as soon as thawing is complete; 5) cryoprecipitate should be refrozen on dry ice; 6) cryoprecipitate should be stored at or below -30 C.; and 7) prolonged storage of frozen plasma or cryoprecipitate should be avoided. Variations in Factor VIII content from one bag of cryoprecipitate to another, under uniform production conditions, depends largely on two donor-specific attributes which tend to remain constant from time to time, namely, the donor's plasma Factor VIII level and the cryoprecipitability of his Factor VIII.     

The effects of temperature variations on cryoprecipitate

The effect of temperature on Factor VIII levels in blood and cryoprecipitate was assessed. Freshw collected units of blood required several hours to reach 4 C, but this delay seemed of little importance since equal amounts of cryoprecipitated Factor VIII were recovered from blood stored either at 22 C or at 4 C. Freezing at -80, -60, or −40 C produced identical yields of Factor VIII, whereas freezing at −20 C resulted in significantly lower recoveries. This might be expected if one considers the physiochemical changes that occur during the freezing process.     

Preparation of factor VIII concentrates by cryoprecipitate sedimentation

A new method for factor VIII concentrate preparation is proposed. The method is the collection of cryoprecipitate after sedimentation at 4 C in a jacketed glass vessel. The final product is standardized (4.0 +/- 0.3 factor VIII units per ml) and can be infused in hemophilic patients regardless of their ABO blood type. Factor VIII recovery (52.2 +/- 6.4%) is comparable to other processes.     

血浆纤维蛋白原水平的影响因素及其临床意义

目的探讨遗传与环境因素对血浆纤维蛋白原水平的影响;研究血浆纤维蛋白原在冠心病发病中的作用.方法从正常查体人员中随机选择105例血浆纤维蛋白原水平大于4 g/L者作为实验组,在同一人群中按年龄、性别11配比的原则,选择血浆纤维蛋白原水平小于4 g/L者作为对照组;深入现场,检测可能与血浆纤维蛋白原水平有关的因素,采用条件Logistic回归分析研究各因素对血浆纤维蛋白原水平的影响;并随访比较了不同血浆纤维蛋白原水平者一级亲属的血浆纤维蛋白原水平和心血管疾病的发生情况.结果体重指数,高脂肪饮食,吸烟,体力活动少,高血压,甘油三酯,高密度脂蛋白,低密度脂蛋白,一级亲属的血浆纤维蛋白原水平等9个因素进入回归方程;高纤维蛋白原者的一级亲属(6.1±0.8 g/L)明显高于低纤维蛋白原者的一级亲属的(4.4±0.5 g/L);血浆纤维蛋白原浓度高者CHD的发病率(24%)高于血浆纤维蛋白原低者(10%).结论遗传和环境因素均对血浆纤维蛋白原水平有一定的影响;血浆纤维蛋白原浓度升高是CHD发病的独立危险因素.     

Long-term frequent plasma exchange donation of cryoprecipitate

Plasma exchange donation accomplishes the selective donation of cryoprecipitate. It facilitates the repeated donation of large quantities of factor VIII by individual donors and reduces donor exposure for recipients. A highly motivated donor is described who has undergone 103 donations between May 1983 and March 1987, producing 359,460 IU of factor VIII and supplying all the factor VIII needed since August 1983 by his severely affected hemophiliac son, now age 14. The donor has remained in good health, and no significant abnormalities have been noted in hematologic, biochemical, immunologic, coagulation, and serum protein testing. Extensive experience with this donor suggests that repeated plasma-exchange donation is safe and can sometimes allow single-donor support of severe hemophiliacs.     

Chromatography of Human Fibrinogen

Considerable volumes of iso-osmotic glucose solution were infused intravenously into healthy volunteers and patients with arterial hypertension. The aldosterone escretion decreased during and subsequently to the infusion in the normotensives whereas it did not change in the majority of the hypertensives. In some cases the excretion even rose.

A thiazide diuretic was given to normal subjects and to hypertensive patients on an ordinary diet and on a sodium restricted diet. In the normotensives the ensuing sodium and water loss was rapidly followed by a considerable, compensatory increase of the aldosterone excretion in the urine. The hypertensive patients, when given the thiazide derivative, lost similar amounts of sodium chloride and water, but, with only three exceptions, their aldosterone excretion did not increase. When potassium chloride was given during the thiazide treatment, wither to healthy subjects or to patients with hypertensive disease, the aldosterone excretion always became considerably augmented.

It is suggested that the aldosterone production in patients with hypertensive disease the body water volume and/or to changes in the potassium supply.