Int J Clin Exp Med 2019;12(12):13487-13493 www.ijcem.com /ISSN:1940-5901/IJCEM0100757. Original Article Effect of platelet and cryoprecipitation transfusion on coagulation function and therapeutic effect in obstetric patients with acute disseminated intravascular coagulation. Shun Jiao, Shouyu Wang, Hui Li. Department of Obstetrics and Gynecology, Jingzhou Central Hospital Affiliated The Second Clinical Medical Col- lege, Yangtze University, Jingzhou, Hubei, China. Received August 9, 2019; Accepted October 8, 2019; Epub December 15, 2019; Published December 30, 2019. Abstract: Objective: To analyze the effect of platelet transfusion and cryoprecipitation on coagulation function and therapeutic effect in obstetric patients with acute disseminated intravascular coagulation (DIC). Methods: 62 DIC patients in our hospital were collected as subjects. Random number table was used to divide patients into platelet group (n = 31) and cryoprecipitation group (n = 31). Patients in platelet group were given platelet transfusion, and patients in cryoprecipitation group were given cryoprecipitation transfusion therapy. 4 mL of venous blood was drawn separately before transfusion (T0), 2 hours after transfusion (T1), 24 hours after transfusion (T2) and 48 hours after transfusion (T3). The activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrin- ogen content (Fbg) and thrombin time (TT) were detected. The therapeutic effect and recovery time of coagulation function were recorded. Results: The platelet group APTT, PT, TT, cure rate, and coagulation function recovery time were significantly increased (P<0.001), and Fbg was significantly decreased (P<0.001). Conclusion: The effect of cryoprecipitation transfusion on obstetric DIC patients is better than platelet transfusion, and the effect on coagula- tion function is more remarkable. Cryoprecipitation is worth popularizing in clinic.. Keywords: Platelet, cryoprecipitation, disseminated intravascular coagulation, coagulation function. Introduction. Disseminated intravascular coagulation (DIC) refers to the common final pathway of coagula- tion disorders caused by various diseases, and it belongs to clinicopathologic syndrome . DIC causes widespread formation of micro- thrombus, and it results in massive loss of platelets and coagulation factors, leading to systemic hemorrhage and microcirculatory fail- ure . DIC has the characteristics of rapid onset, rapid progress and no obvious hyperco- agulation period, and the threat to human body is great . Once the patient does not receive timely and effective treatment, DIC will directly cause systemic hemorrhage and death . Therefore, the treatment of DIC has been a hot topic for a long time in clinic. With the develop- ment of medical technology and in-depth research, it has been proved that DIC is hemor- rhage due to the consumption of a large num-. ber of coagulation factors during the course of disease, and secondary fibrinolytic antibody is caused. Therefore, for the treatment of DIC, timely supplementation of coagulation factors is very important to promote the recovery of blood coagulation function [5-7]. In recent years, with the continuous improvement of blood supply and transfusion technology, the treatment on DIC has achieved stable thera- peutic effects .. Cryoprecipitation is one kind of component transfusion, and concentrated preparation is prepared by collecting fresh blood from healthy people, separating hemorrhagic plasma and gradually freezing plasma [10, 11]. Cryopreci- pitation contains a large number of coagulation factors, and they can provide power for the nor- mal operation of blood coagulation function for patients with reduced volume . Currently, studies have confirmed that cryoprecipitation. http://www.ijcem.com. Effect of platelet transfusion and cryoprecipitation. 13488 Int J Clin Exp Med 2019;12(12):13487-13493. has a significant effect in the treatment of DIC [13, 14]. However, compared with tradition- al platelet transfusion, it is still controversial on which method is more suitable for DIC. Therefore, we compared the efficacy and the difference of coagulation function between platelet transfusion and cryoprecipitation, to explore which method is more suitable for the treatment of DIC, and to provide reference and guidance for future clinical practice.. Materials and methods. General data. 62 DIC patients in our hospital were collect- ed as subjects, and all patients were female. The ages of patients were between 22 to 34 years old, with an average age of 26.15 ± 4.22 years. Random number table was used to divide patients into platelet group (n = 31) and cryoprecipitation group (n = 31). Patients in platelet group were given platelet transfusion, and patients in cryoprecipitation group were given cryoprecipitation transfusion therapy. This experiment has been approved by the eth- ics committee of Jingzhou Central Hospital affiliated The Second Clinical Medical College, Yangtze University, and all the subjects signed informed consent.. Inclusion and exclusion criteria. Inclusion criteria: patients were in gestational period; patients conformed to DIC diagnostic standard ; patients were diagnosed as DIC by Department of Hematology and Department of Critical Care Medicine in our hospital; after diagnosis, patients continued treatment in our hospital; data of cases were complete; patients cooperated with the medi- cal staff in our hospital; the ages of patients were 18~50 years old. Exclusion criteria: can- cer patients; severe organ failure patients; patients with cardiovascular and cerebrovascu- lar diseases; patients with pregnancy; patients with liver and kidney dysfunction; drug allergy patients; mental patients; patients with physi- cal disabilities; patients who cannot take care of themselves; transferred patients.. Methods. Two groups of patients were given routine emer- gency treatment, including heparin and anti- fibrinolytic drugs. In cryoprecipitation group, 10 U of frozen platelet and 10 U of cryoprecipita-. tion were infused rapidly, and red blood cell fluid was added according to blood loss. Observe whether there were clots during trans- fusion. If there was no clot, appropriate fibrino- gen (2.0-2.5 g/L) could be supplemented according to body weight. The platelet group was given 10 U frozen platelet, and the transfu- sion dose was based on patient’s inspection results. All blood products used in this experi- ment were provided by local blood donor center.. Outcome measures. Coagulation function: 4 mL of venous blood was drawn separately before transfusion (T0), 2 hours after transfusion (T1), 24 hours after transfusion (T2) and 48 hours after transfusion (T3). Automatic coagulation analyzer and origi- nal kits were used to detect coagulation func- tion, including activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrinogen content (Fbg) and thrombin time (TT). Therapeutic effect: DIC rehabilitation guidelines were used to evaluate the effect after 48 hours . If DIC symptoms disap- peared completely, and coagulation function test results were completely normal, then it was evaluated to be cured. If DIC symptoms were significantly alleviated, and the improve- ment of coagulation function was more than 50%, then it was evaluated to be effective. If the results of DIC symptoms and blood coagu- lation function tests showed no significant improvement, or even deterioration happened, then it was evaluated to be ineffective. The cure rate = (the number of cure cases + the number of effective cases)/total number of cases ×100%. Recovery time of coagulation function: the total time from starting treatment to normal blood coagulation function was re- corded.. Statistical methods. SPSS24.0 statistical software (from Beijing Sichuang Weida Information Technology Co., Ltd.) was used to calculate all the experimental results. Graphpad 8 (from Shenzhen Tianruiqi Software Co., Ltd.) software was used to draw all the graphics, and the results were checked twice. Counting data were expressed in the form of (rate), such as cure rate. Groups com- parison was using Chi-square test. The data were showing in the form of mean ± standard deviation. Results at multiple time points were. Effect of platelet transfusion and cryoprecipitation. 13489 Int J Clin Exp Med 2019;12(12):13487-13493. compared by repeated measures analysis of variance, and LSD t test was used for pairwise comparison. Independent t test was used for between-group comparison. P<0.05 means statistically significant difference.. Results. Comparison of general data. There was no significant difference in age, BMI, platelet, red blood cell, white blood cell, gesta- tional age, smoking history, residence, educa- tional background, times of pregnancy and exercise habits between two groups (P>0.05). It indicated that the general data of two groups were comparable (Table 1).. higher than those in cryoprecipitation group (P<0.05), and Fbg in platelet group was lower than that of cryoprecipitation group (P<0.05). In platelet group and cryoprecipitation group, APTT, PT and TT at T1 were all lower than values at T0 (P<0.05); APTT, PT and TT at T2 were lower than values at T1 (P<0.05), and APTT, PT and TT were the lowest at T3 (P<0.05). In both groups, Fbg at T1 was higher than Fbg at T0 (P<0.05), and Fbg at T2 was higher than Fbg at T1 (P<0.05), and it was the highest at T3 (P<0.05) (Tables 2-5 and Figures 1-4).. Comparison of therapeutic effects. In cryoprecipitation group, 58.06% cases (18 cases) were evaluated to be cured, 35.48%. Table 1. Comparison of clinical data [n (%)] Platelet group (n = 31) Cryoprecipitate group (n = 31) t/X2 P. Age 24.62 ± 4.82 25.12 ± 5.05 0.399 0.692 BMI 26.12 ± 4.92 27.05 ± 5.16 0.726 0.471 Treatment time after diagnosis (d) 6.21 ± 1.25 6.18 ± 1.17 0.098 0.923 Platelet (×109/L) 89.62 ± 31.55 92.85 ± 33.92 0.388 0.699 Red blood cell (×12/L) 2.13 ± 0.86 2.05 ± 0.97 0.344 0.732 White blood cell 1.86 ± 0.56 1.75 ± 0.60 0.746 0.458 Gestational age 21.86 ± 5.32 22.15 ± 5.84 0.204 0.839 Smoking history 0.066 0.798 Yes 14 (45.16) 13 (41.94) No 17 (54.84) 18 (58.06) Residence 0.295 0.587 Town 20 (64.52) 22 (70.97) Rural 11 (35.48) 9 (29.03) Educational background 0.313 0.576 < high school 10 (32.26) 8 (25.81) ≥ high school 21 (67.74) 23 (74.19) Times of pregnancy 0.574 0.449 1 time 28 (90.32) 26 (83.87) More than 1 time 3 (9.68) 5 (16.13) Exercise habits 0.097 0.755 Yes 7 (22.58) 6 (19.35) No 24 (77.42) 25 (80.65). Table 2. Comparison of APTT between the two groups (Reference value: 24~36 s). Platelet group (n = 31) Cryoprecipitate group (n = 31) t P T0 67.82 ± 21.82 68.15 ± 20.59 0.061 0.951 T1 62.68 ± 16.82 60.82 ± 17.52 0.426 0.671 T2 55.87 ± 12.16 42.39 ± 15.47 3.814 0.003 T3 48.62 ± 8.97 32.63 ± 10.58 6.418 <0.001. Comparison of ccoagulation function. There was no significant dif- ference in APTT, PT, Fbg and TT at T0 and T1 between two groups (P>0.05). APTT, PT and TT at T2 and T3 in plate- let group were significantly. Effect of platelet transfusion and cryoprecipitation. 13490 Int J Clin Exp Med 2019;12(12):13487-13493. cases (11 cases) were evaluated to be effec- tive, and 6.45% cases (2 cases) were evaluated to be ineffective. In platelet group, 32.26% cases (10 cases) were evaluated to be cured, 41.94% cases (13 cases) were evaluated to be effective, and 25.81% cases (8 cases) were evaluated to be ineffective. The cure rate of. cryoprecipitation group was 93.55%, and it was signifi- cantly higher than 74.19% of platelet group (P = 0.038) (Table 6).. Comparison of recovery time of coagulation function. The recovery time of coagula- tion function in platelet group was 5.14 ± 1.12 days, and it was significantly longer than 3.18 ± 0.92 days of cryopre- cipitation group, P<0.001 (Figure 5).. Discussion. The main pathogenic mech- anism of DIC is that wide- spread formation of micro- thrombosis in microcirculation leads to large consumption of platelets and coagulation factors, causing secondary hyperfibrinolysis . DIC can cause multiple organ hemor- rhage, shock and damage to vital organs, with a mortality rate of 30.0%-80.0% .. Table 3. Comparison of PT between the two groups (Reference value: 11~14 s). Platelet group (n = 31) Cryoprecipitate group (n = 31) P T0 48.62 ± 25.93 49.13 ± 23.18 0.935 T1 43.17 ± 13.84 41.59 ± 14.86 0.666 T2 36.15 ± 9.86* 35.32 ± 11.30* <0.001 T3 30.58 ± 9.14* 29.24 ± 6.24* <0.001 Note: *represents a comparison with the normal value of PT of T0. The PT of T2 and T3 in both groups is significantly higher than the normal value, *P<0.001.. Table 4. Comparison of Fbg between the two groups (Reference value: 2~4 g/L). Platelet group (n = 31) Cryoprecipitate group (n = 31) P T0 1.26 ± 0.42 1.22 ± 0.46 0.722 T1 1.38 ± 0.62 1.40 ± 0.58 0.896 T2 1.59 ± 0.45 1.98 ± 0.62 0.006 T3 1.74 ± 0.35 2.63 ± 0.39 <0.001. Table 5. Comparison of TT between the two groups (Reference value: 11~17 s). Platelet group (n = 31) Cryoprecipitate group (n = 31) t P T0 36.82 ± 8.14 37.05 ± 8.26 0.110 0.912 T1 32.73 ± 10.52 31.66 ± 9.72 0.416 0.679 T2 28.36 ± 5.94 24.68 ± 6.91 2.249 0.028 T3 26.93 ± 6.82 20.55 ± 5.60 4.025 <0.001. Activated platelets and their splitting products play an important role in maintaining normal blood coagulation. The fibrin and various coag- ulation factors in cryoprecipitation are benefi- cial to the release and adhesion of platelet fac- tors, and the formation of thrombin can be accelerated . Therefore, platelet and cryo- precipitate can both repair and maintain the normal coagulation function of patients with DIC . The curative effect of platelet and cryoprecipitation on DIC has been confirmed, but domestic and foreign researches were mostly limited to the guidance of the two meth- ods. For example, Pigozzi L et al.  proposed that the cure rate of platelet transfusion on DIC was about 80%. Philip  proved that the effect of cryoprecipitation can maintain normal coagulation function for 24 hours. In this paper, through rigorous inclusion and exclusion crite- ria, advanced statistical software, different sta- tistical software for secondary checking and strict spirit of scientific research, curative effect and coagulation function under platelet trans- fusion and cryoprecipitate transfusion were compared.. Figure 1. APTT comparison at different time points between two groups. a means APTT compared with same group at T0, P<0.05; b means APTT compared with same group at T1, P<0.05; c means APTT com- pared with same group at T2, P<0.05.. Effect of platelet transfusion and cryoprecipitation. 13491 Int J Clin Exp Med 2019;12(12):13487-13493. The experimental results showed that there was no significant difference in coagulation function between two groups. The coagulation function of cryoprecipitation group was signifi- cantly better than that in the platelet group. It indicated that platelet transfusion and cryopre- cipitation had good effect on coagulation func- tion in DIC patients, but cryoprecipitation trans- fusion was more conducive to the recovery of coagulation function. The main reason for the difference in coagulation function is speculated that the mechanism of platelet transfusion therapy is to improve and maintain coagulation dysfunction by supplementing platelet. Some studies pointed out that the content of coagula- tion factor in whole blood is low, and the plate- let dilution is small. If the coagulation factor is added by injecting whole blood, it will cause coagulation disorder . Cryoprecipitation is a. coagulation factor prepared by fresh frozen plasma. The main components are FXIII, von Willebrand factor and fibronectin. Among them, FXIII mainly promotes platelet aggregation and synthesis of endogenous thrombin by acceler- ating the activation of FX , and it can replace the effect of platelet transfusion in DIC treat- ment. Besides, Von Willebrand factor is a glyco- protein with adhesion function. It maintains the activity of FVIII in blood, and it also binds to the protein structure of platelet receptor. Von Willebrand factor mediates the adhesion and aggregation ability of platelets, and it acceler- ates the coagulation of blood . Therefore, von Willebrand factor can be used as auxiliary in the process of cryoprecipitation transfusion. The most important activation factors in cryo- precipitation are maintained, and coagulation function is improved. Besides, the operation of platelets is accelerated, so that coagulation function is treated quickly. Fibronectin is a pro- tein complex with regulatory activity. It has phagocytic capacity for senescent cells and bacterial foreign bodies . This also enables DIC patients to disinfect wound through devour- ing reticular cell during cryoprecipitation. Compared with platelet transfusion, cryopre- cipitation has higher safety. However, because the safety of two methods has not been investi- gated in this paper, we need further experi- ments to verify our conjecture.. The cure rate of cryoprecipitation group was 93.55%, and it was significantly higher than 74.19% of platelet group. The recovery time of coagulation function in cryoprecipitation group was significantly shorter than that of platelet. Figure 2. PT comparison at different time points be- tween two groups. a means PT compared with same group at T0, P<0.05; b means PT compared with same group at T1, P<0.05; c means PT compared with same group at T2, P<0.05.. Figure 3. Fbg comparison at different time points be- tween two groups. a means Fbg compared with same group at T0, P<0.05; b means Fbg compared with same group at T1, P<0.05; c means Fbg compared with same group at T2, P<0.05.. Figure 4. TT comparison at different time points be- tween two groups. a means TT compared with same group at T0, P<0.05; b means TT compared with same group at T1, P<0.05; c means TT compared with same group at T2, P<0.05.. Effect of platelet transfusion and cryoprecipitation. 13492 Int J Clin Exp Med 2019;12(12):13487-13493. group. It is suggested that the effect of cryopre- cipitation is better for DIC patients. However, cryoprecipitation usually requires a large dose in clinic, and the incidence of homologous immunity between blood-borne diseases and leukocyte system increases greatly . Therefore, during cryoprecipitation transfusion, we need to pay more attention to blood quality and the operation of virus inactivation. Besides, the dosage should be strictly used according to actual clinical situation of patients.. The therapeutic effect and coagulation func- tion of platelet transfusion and cryoprecipita- tion transfusion on DIC were compared in this experiment, but there are still some shortcom- ings due to limited experimental conditions. For example, the base of research subject was small, and subjects were relatively single, so statistical analysis of large data could not be carried out. Besides, the experimental time span was small, and long-term prognosis . experimental design. We will continue to explore the treatment of DIC in depth, to obtain the best experimental results.. In conclusion, the effect of cryoprecipitation on DIC patients is better than platelet transfusion, and the effect of cryoprecipitation on repairing coagulation function is more remarkable. So cryoprecipitation is worth popularizing in clinic.. Disclosure of conflict of interest. None.. Address correspondence to: Hui Li, Department of Obstetrics and Gynecology, Jingzhou Central Hos- pital Affiliated The Second Clinical Medical College, Yangtze University, Jingzhou 434000, Hubei, China. Tel: +86-0716-8498193; E-mail: huili0808@163. com. References.  Gando S, Levi M and Toh CH. Disseminated in- travascular coagulation. Nat Rev Dis Primers 2016; 2: 16037..  Okamoto K, Tamura T and Sawatsubashi Y. Sepsis and disseminated intravascular coagu- lation. J Intensive Care 2016; 4: 23..  Iba T, Ito T, Maruyama I, Jilma B, Brenner T, Muller MC, Juffermans NP and Thachil J. Po- tential diagnostic markers for disseminated intravascular coagulation of sepsis. Blood Rev 2016; 30: 149-155..  Boral BM, Williams DJ and Boral LI. Dissemi- nated intravascular coagulation. Am J Clin Pathol 2016; 146: 670-680..  Iba T and Thachil J. Present and future of anti- coagulant therapy using antithrombin and thrombomodulin for sepsis-associated dis- seminated intravascular coagulation: a per- spective from Japan. Int J Hematol 2016; 103: 253-261..  Levi M and Scully M. How I treat disseminated intravascular coagulation. Blood 2017; 845- 854..  Murata A, Okamoto K, Mayumi T, Muramatsu K and Matsuda S. Recent change in treatment of disseminated intravascular coagulation in. Table 6. Comparison of therapeutic effects [n (%)] Platelet group (n = 31) Cryoprecipitate group (n = 31) X2 P. Cure 10 (32.26) 18 (58.06) 5.321 0.032 Effective 13 (41.94) 11 (35.48) 2.358 0.057 Invalid 8 (25.81) 2 (6.45) 6.371 0.021 Cure rate (%) 74.19 93.55 4.292 0.038. Figure 5. The comparison of recovery time of coag- ulation function. a means recovery time compared with platelet group, P<0.001.. and the changes of coagulation function in two groups could not be evaluated. We will conduct follow- up surveys on sub- jects, expand sample size, and improve the. mailto:email@example.com mailto:firstname.lastname@example.org. Effect of platelet transfusion and cryoprecipitation. 13493 Int J Clin Exp Med 2019;12(12):13487-13493. Japan: an epidemiological study based on a national administrative database. Clin Appl Thromb Hemost 2016; 22: 21-27..  Iba T and Thachil J. Is antithrombin III for sep- sis-associated disseminated intravascular co- agulation really ineffective? Intensive Care Med 2016; 42: 1193-1194..  Davis RP, Miller-Dorey S and Jenne CN. Plate- lets and coagulation in infection. Clin Transl Immunology 2016; 5: e89..  Okerberg CK, Williams LA 3rd, Kilgore ML, Kim CH, Marques MB, Schwartz J and Pham HP. Cryoprecipitate AHF vs. fibrinogen concen- trates for fibrinogen replacement in acquired bleeding patients - an economic evaluation. Vox Sang 2016; 111: 292-298..  Jensen NH, Stensballe J and Afshari A. Com- paring efficacy and safety of fibrinogen con- centrate to cryoprecipitate in bleeding pa- tients: a systematic review. Acta Anaesthesiol Scand 2016; 60: 1033-1042..  Sheffield WP, Bhakta V and Jenkins C. Stability of coagulation protein activities in single units or pools of cryoprecipitate during storage at 20-24°C for up to 24 h. Vox Sang 2016; 110: 12-19..  Asakura H, Ontachi Y, Mizutani T, Kato M, Ito T, Saito M, Morishita E, Yamazaki M, Aoshima K, Takami A, Yoshida T, Suga Y, Miyamoto K and Nakao S. Decreased plasma activity of anti- thrombin or protein C is not due to consump- tion coagulopathy in septic patients with dis- seminated intravascular coagulation. Eur J Haematol 2001; 67: 170-175..  Harhangi BS, Kompanje EJ, Leebeek FW and Maas AI. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien) 2008; 150: 165-75..  Toh CH, Alhamdi Y and Abrams ST. Current pathological and laboratory considerations in the diagnosis of disseminated intravascular coagulation. Ann Lab Med 2016; 36: 505-512..  Levi M and van der Poll T. Disseminated intra- vascular coagulation: a review for the internist. Intern Emerg Med 2013; 8: 23-32..  Kander T, Larsson A, Taune V, Schött U and Tynngård N. Assessment of haemostasis in disseminated intravascular coagulation by use of point-of-care assays and routine coagulation tests, in critically Ill patients; a prospective observational study. PLoS One 2016; 11: e0151202..  Hayakawa M, Kudo D, Saito S, Uchino S, Ya- makawa K, Iizuka Y, Sanui M, Takimoto K, Ma- yumi T, Ono K, Azuhata T, Ito F, Yoshihiro S, Hayakawa K, Nakashima T, Ogura T, Noda E, Nakamura Y, Sekine R, Yoshikawa Y, Sekino M, Ueno K, Okuda Y, Watanabe M, Tampo A, Saito. N, Kitai Y, Takahashi H, Kobayashi I, Kondo Y, Matsunaga W, Nachi S, Miike T, Takahashi H, Takauji S, Umakoshi K, Todaka T, Kodaira H, Andoh K, Kasai T, Iwashita Y, Arai H, Murata M, Yamane M, Shiga K and Hori N. Antithrombin supplementation and mortality in sepsis-in- duced disseminated intravascular coagula- tion: a multicenter retrospective observational study. Shock 2016; 46: 623-631..  Kossmann S, Lagrange J, Jäckel S, Jurk K, Ehlken M, Schönfelder T, Weihert Y, Knorr M, Brandt M, Xia N, Li H, Daiber A, Oelze M, Rein- hardt C, Lackner K, Gruber A, Monia B, Kar- bach SH, Walter U, Ruggeri ZM, Renné T, Ruf W, Munzel T and Wenzel P. Platelet-localized FXI promotes a vascular coagulation-inflam- matory circuit in arterial hypertension. Sci Transl Med 2017; 9..  Tomaiuolo M, Brass LF and Stalker TJ. Regula- tion of platelet activation and coagulation and its role in vascular injury and arterial thrombo- sis. Interv Cardiol Clin 2017; 6: 1-12..  Pigozzi L, Aron JP, Ball J and Cecconi M. Under- standing platelet dysfunction in sepsis. Inten- sive Care Med 2016; 42: 583-586..  Philip J, Kumarage S, Chatterjee T, Kumar S and Mallhi R. The possible advantages of cryo- precipitate prepared from fresh frozen plasma from blood stored for 24 hours. Lab Med 2014; 45: 111-115..  Gupte SC and Jhaveri AG. Blood component utilization for disseminated intravascular co- agulation (DIC) cases with respect to underly- ing condition. Indian J Hematol Blood Transfus 2016; 32: 202-207..  McQuilten ZK, Bailey M, Cameron PA, Stan- worth SJ, Venardos K, Wood EM and Cooper DJ. Fibrinogen concentration and use of fibrin- ogen supplementation with cryoprecipitate in patients with critical bleeding receiving mas- sive transfusion: a bi-national cohort study. Br J Haematol 2017; 179: 131-141..  Tien H, Nascimento B Jr, Callum J and Rizoli S. An approach to transfusion and hemorrhage in trauma: current perspectives on restrictive transfusion strategies. Can J Surg 2007; 50: 202-209..  Cushing MM, Fitzgerald MM, Harris RM, Asmis LM and Haas T. Influence of cryoprecipitate, Factor XIII, and fibrinogen concentrate on hy- perfibrinolysis. Transfusion 2017; 57: 2502- 2510..  Burnouf T, Goubran HA, Radosevich M and El- Ekiaby M. Preparation and viral inactivation of cryoprecipitate in blood banks in resource-lim- ited countries. ISBT Scien Series 2010; 2: 121- 128.