Fresh Frozen Plasma Transfusion Research Articles

Research advances in pathophysiology, diagnosis and therapy of trauma-induced coagulopathy

Objective Trauma-induced coagulopathy(TIC)is an acute coagulopathy in which coagulation, fibrinolysis, and anticoagulant pathways are activated after trauma due to massive hemorrhage and tissue damage. TIC is caused by hypothermia, acidosis, blood dilution, hyperfusion, tissue injury, etc. To diagnose TIC, we mainly rely on traditional coagulation function analysis and thrombelastogram (TEG). At present, the key to treat TIC is quick hemostasis. The basic treatment procedure includes transfusion of packed red blood cells and fresh frozen plasma by appropriate proportion, and timely infusion of platelets and coagulant material so as to stabilize blood pressure and reconstruct the blood coagulation mechanism. In this paper, we reviewed recent advances in the pathophysiological and treatment of TIC in order to provide references for further research in related fields. Key words: Blood coagulation disorders; Wounds and injuries; Pathology; Physiology; Diagnosis and treatment

Effect of FFP Transfusion on International Normalized Ratio in Liver Disease Patients.

Fresh frozen plasma (FFP) is widely used in liver diseases to rectify coagulation derangements. In this study we have analysed the pattern of FFP usage in liver diseases and its effect on International normalized ratio (INR). A retrospective study of liver disease patients who received FFP transfusions from January 2016 to June 2016 was done. FFP used for liver transplant surgeries and plasma exchange procedures were excluded from the study. A total of 1935units of FFP were transfused to 576 patients. We found a high linear correlation between pre transfusion INR and change in INR per unit of FFP. Patients receiving 6units or more FFP have shown significant INR improvement. Improvement was more in acute liver failure and acute on chronic liver failure cases compared to chronic liver disease. FFP is not effective in correcting mild to moderate coagulation defects in liver diseases. Large volumes are required to cause significant INR improvement. Considering the risks associated with FFP transfusion, decision of transfusion should be carefully weighed. Future prospective randomized control trails are required for understanding the risk benefit ratio better and formulating plasma transfusion guidelines in liver diseases.

Impact of fresh frozen plasma transfusion on postoperative inflammation and prognosis of colorectal liver metastases

BackgroundBlood transfusion has been reported to be associated with immunomodulation and poor oncologic outcomes in several malignancies. The aim of the study is to investigate the influence of the use of fresh frozen plasma (FFP) on long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. Materials and methodsThe study comprised 127 patients who had undergone first hepatic resection for CRLM between April 2000 and December 2013. We retrospectively investigated the influence of the use of FFP on disease-free survival as well as overall survival and assessed the impact of such a practice on postoperative inflammation markers. ResultsIn multivariate analysis, more than four lymph node metastases of the primary cancer (P = 0.001), bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005) were independent risk factors for cancer recurrence, while more than four lymph node metastases of the primary cancer (P < 0.001), presence of neoadjuvant chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were independent risk factors for poor overall survival. In patients who underwent FFP transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of operation (P = 0.039), and intraoperative blood loss (P < 0.001) were significantly greater. Moreover, FFP transfusion was associated with a higher white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010) and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and day 3 (P = 0.017). ConclusionsPerioperative FFP transfusion is independently associated with poor long-term outcomes in patients with CRLM after hepatic resection. FFP may have an influence on postoperative inflammation because of its immunosuppressive effects.

Mini-extracorporeal circulation technology, conventional bypass and prime displacement in isolated coronary and aortic valve surgery: a propensity-matched in-hospital and survival analysis.

Conventional cardiopulmonary bypass is the most commonly used means of artificial circulation in cardiac surgery. However, it suffers from the effects of haemodilution and activation of inflammatory/coagulation cascades. Prime displacement (PD) can offset haemodilution and mini-extracorporeal technology (MIECT) can offset both. So far, no study has compared all of these modalities together; hence, we compared the outcomes of these 3 modalities at our institution. This was a retrospective analysis of our cardiac surgical database. A total of 9626 patients underwent conventional bypass (CB), 3125 patients underwent a modification of CB, called PD, and 904 underwent MIECT. A 1:1 propensity-matching algorithm was employed using IBM SPSS 24 to match (i) 813 MIECT patients with 813 CB patients and (ii) 717 MIECT patients with 717 PD patients. The patients included coronary artery bypass grafting and valve surgery. MIECT had significantly (P < 0.05) longer bypass and cross-clamp times compared to CB and PD. MIECT had significantly higher rates of postoperative atrial fibrillation associated with it compared to CB. The mean red cell blood transfusion was significantly lower in the MIECT group compared to the CB group as was the mean platelet transfusion and fresh frozen plasma transfusion. The overall 5-year survival was higher in the MIECT group compared to the CB group (log-rank, P = 0.018). Between the MIECT and the PD groups, we found the incidence of renal failure and gastrointestinal complications to be significantly higher in the PD group compared to the MIECT group. MIECT has short-term advantages over CB and PD. However, due to the retrospective limitations of the study, including calendar time bias, a multicentre randomized controlled trial comparing all 3 modalities will be beneficial for the larger cardiac community.

Redox Status, Procoagulant Activity, and Metabolome of Fresh Frozen Plasma in Glucose 6-Phosphate Dehydrogenase Deficiency.

Transfusion of fresh frozen plasma (FFP) helps in maintaining the coagulation parameters in patients with acquired multiple coagulation factor deficiencies and severe bleeding. However, along with coagulation factors and procoagulant extracellular vesicles (EVs), numerous bioactive and probably donor-related factors (metabolites, oxidized components, etc.) are also carried to the recipient. The X-linked glucose 6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme genetic defect, mainly affects males. By undermining the redox metabolism, the G6PD- cells are susceptible to the deleterious effects of oxidants. Considering the preferential transfusion of FFP from male donors, this study aimed at the assessment of FFP units derived from G6PD- males compared with control, to show whether they are comparable at physiological, metabolic and redox homeostasis levels. The quality of n = 12 G6PD- and control FFP units was tested after 12 months of storage, by using hemolysis, redox, and procoagulant activity-targeted biochemical assays, flow cytometry for EV enumeration and phenotyping, untargeted metabolomics, in addition to statistical and bioinformatics tools. Higher procoagulant activity, phosphatidylserine positive EVs, RBC-vesiculation, and antioxidant capacity but lower oxidative modifications in lipids and proteins were detected in G6PD- FFP compared with controls. The FFP EVs varied in number, cell origin, and lipid/protein composition. Pathway analysis highlighted the riboflavin, purine, and glycerolipid/glycerophospholipid metabolisms as the most altered pathways with high impact in G6PD-. Multivariate and univariate analysis of FFP metabolomes showed excess of diacylglycerols, glycerophosphoinositol, aconitate, and ornithine but a deficiency in riboflavin, flavin mononucleotide, adenine, and arginine, among others, levels in G6PD- FFPs compared with control. Our results point toward a different redox, lipid metabolism, and EV profile in the G6PD- FFP units. Certain FFP-needed patients may be at greatest benefit of receiving FFP intrinsically endowed by both procoagulant and antioxidant activities. However, the clinical outcome of G6PD- FFP transfusion would likely be affected by various other factors, including the signaling potential of the differentially expressed metabolites and EVs, the degree of G6PD-, the redox status in the recipient, the amount of FFP units transfused, and probably, the storage interval of the FFP, which deserve further investigation by future studies.

Safety and Outcomes of Transradial Access in Patients with International Normalized Ratio 1.5 or above

PurposeTo examine the safety and outcomes for patients undergoing transradial noncoronary interventions with international normalized ratio (INR) ≥1.5. Materials and MethodsA retrospective review of 2,271 transradial access (TRA) cases performed from July 2012 to July 2016 was conducted. Criteria for inclusion were moderate bleeding risk cases with preprocedure INR ≥1.5. Within the study period, there were 176 moderate bleeding risk procedures (transarterial chemoembolization: 70/176 [39.8%]; Barbeau B: 121/176 [68.8%]; 5-F sheath: 157/176 [89.2%]) performed on 122 patients (age 61.6 ± 12.1 years, 68.9% male, body mass index 28.0 kg/m2) with INR ≥1.5. ResultsTechnical success was achieved in 98.9% of cases. Grade 1/2 hematomas developed in 10 cases (5.7%). Age ≥65 years (P = .042) and female sex (P = .046) were predictive of access site bleeding complications. Fresh frozen plasma (FFP) transfusion was administered in 11.4% of cases (n = 20). Baseline INR and creatinine were significantly different between transfused and nontransfused cases (P values .006 and .028, respectively). Minor access site bleeding occurred in 3/20 cases (15%) receiving prior FFP transfusion and 7/156 nontransfused cases (4.5%), with no significant difference between these 2 groups (P = .072). ConclusionsTRA in patients with elevated INR appears to be safe in our experience. Age ≥65 years and female sex were associated with increased incidence of access site bleeding. Although INR correction was not standardized in this cohort, preprocedure FFP transfusion did not decrease bleeding complications.

11q23 deletion syndrome (Jacobsen syndrome) with severe bleeding: a case report

Background11q23 deletion syndrome, also known as Jacobsen syndrome, is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, and thrombocytopenia. In 11q23 deletion syndrome, it is often difficult to anticipate the severity of bleeding. We report a neonatal case of 11q23 deletion syndrome with bleeding that was more severe than predicted by the platelet count.Case presentationWe report a case of 11q23 deletion syndrome in an Asian male newborn with severe bleeding just after birth. The diagnosis of 11q23 deletion syndrome was made prenatally by amniocentesis. An array comparative genomic hybridization analysis revealed a deletion of the 13.0 Mb regions ranging from 11q24.1 to the q terminus encoding FLI1. Our patient was delivered by cesarean section and exhibited skull deformities, facial asymmetry, low-set ears, inguinal hernia, flat feet, and crowded toes. He had a low platelet count (45,000/μL) and a coagulation abnormality with a prothrombin time–international normalized ratio of 1.92 and an activated partial thromboplastin time of 158.6 seconds. Bleeding at the site of a peripheral vessel puncture was more severe than expected with thrombocytopenia. The peripheral blood featured two different sizes of platelets containing large α-granules. As a result, he required eight platelet transfusions and two fresh frozen plasma transfusions within 13 days of birth. Massive bleeding was avoided, and cerebral magnetic resonance imaging indicated the occurrence of only petechial hemorrhage.ConclusionsOur patient with 11q deletion including FLI1 avoided massive bleeding and serious sequelae because of careful management after prenatal diagnosis. We suggest that prenatal diagnosis and vigilant perinatal care including a cesarean section are warranted for patients with 11q23 deletion syndrome.

Effect of plasma component transfusion on conventional coagulation screening tests.

BACKGROUND:Conventional coagulation screening tests such as Prothrombin time, International normalized ratio (INR) and activated partial thromboplastin time are often used to predict bleeding in various clinical situations. We aimed to observe the effect of Fresh-frozen plasma (FFP) on these parameters.Methods:Patients' demographics, pre- and post-transfusion coagulation parameters were noted to assess the level of correction. The magnitude of improvement in INR was determined using the formula given by Holland and Brooks. Data was analyzed using IBM SPSS Statistics 20.RESULTS:Among 2082 episodes, 4991 units of FFP were transfused at an average of 5 units per patient. Median dose of FFP administered per episode was 10 mL/kg (5.8–13.4). The mean change in INR following transfusion was 8.9% of the pre-transfusion INR and thus considered to be statistically significant.CONCLUSION:FFP transfusions as a prophylactic measure especially in patients with mildly deranged conventional coagulation screening tests without any empirical evidence of clinical bleeding needs further scrutiny. Reduction in INR following FFP transfusions was better in cohort having higher pre-transfusion INR value (> 3.0).

Analysis of Acute Transfusion Reactions and Their Occurrence Times

Acute transfusion reactions (ATRs) are significantly relevant to the morbidity and mortality of patients. ATRs are mostly not severe and rarely cause severe conditions, including anaphylactic shock. The aim of this study was to clarify the frequency of ATRs and the time of event occurrence. A total of 18,745 transfusions were administered to 11,718 patients during a 3-year period. Adverse reactions including at least one sign or symptom were collected through a report system in 143 of 2,478 (5.7%) platelet concentrate transfusions, 105 of 6,629 (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse events. Severe signs and symptoms were observed in 7.1% of patients. These events appeared significantly earlier than those of non-severe signs and symptoms (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive transfusion-associated adverse events, preventive treatments for adverse events should be proactively promoted.

Liver transplantation for acute liver failure due to hepatitis E in a pregnant patient.

Liver transplantation for acute liver failure due to hepatitis E in a pregnant patient.

Association Between Platelet Count and Postoperative Blood Loss in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass and Fresh Frozen Plasma Administration Guided by Thromboelastometry.

Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple factors, including reduced coagulation factors and a low platelet count.Methods and Results:In this study, we undertook a post hoc analysis to identify factors associated with increased postoperative blood loss in 97 patients undergoing cardiac surgery with CPB, with fresh frozen plasma administered according to a ROTEM-guided algorithm. We identified 24 patients for the top quartile of postoperative blood loss, >528 mL and defined as having excessive blood loss. Using Spearman's rank correlation test and multivariable linear regression, we reanalyzed the participants' demographic, surgical and anesthetic variables, laboratory test results, blood loss, and transfusion data. Univariate analysis indicated that patients who experienced higher postoperative blood loss received a significantly higher heparin dose, had a higher requirement for fresh frozen plasma transfusion during surgery, and had a significantly lower hematocrit and platelet count at the end of surgery compared with patients without excessive blood loss. Multivariate analysis showed that platelet count at the end of surgery (odds ratio 0.780, 95% confidence interval 0.629-0.967; P=0.024) was an independent factor for excessive blood loss. Low platelet count at the end of surgery was associated with excessive postoperative bleeding during cardiac surgery with CPB.

Evaluation of utilization pattern of fresh frozen plasma in a tertiary care oncology center

Introduction: Blood component therapy is widely used in an oncology center. Fresh frozen plasma (FFP) transfusions are mainly used for the treatment of certain clinical conditions such as coagulation derangements. Transfusion audits are important to understand clinical transfusion practices. This study evaluates the utilization pattern of FFP in a tertiary care oncology center. Materials and Methods: Retrospective analysis of 1338 FFP transfusions in 216 patients was done for 3 months. Analysis according to age, sex, clinical indications, requesting clinical unit, time of requisition and pre- and post-transfusion prothrombin time (PT), activated plasma thromboplastin time (aPTT), and international normalized ratio (INR) was carried out. Results: Of 1338 FFP transfusions, 63% transfusions were in males and 37% in females. Adult patients received 75% while pediatrics received 25% of all transfusions. Surgical oncology patients received maximum transfusions (56%), followed by medical oncology (41%) and least by radiation oncology (3%). Based on clinical indications, patients with deranged coagulation profile required maximum transfusions (55%) followed by bleeding patients (43%) and least for patients with disseminated intravascular coagulation (2%). Mean pre- and post-transfusion PT, aPTT, and INR values were 25.6 s, 36.8 s, 2.1 and 20.56 s, 31.9 s, and 1.6 respectively; it was statistically significant (P

Tromboelastometría como guía de administración de hemoderivados en cirugía cardiaca

ObjectiveThromboelastometry is a viscoelastometric method for haemostasis testing in a whole blood sample. The aim of this study was to assess the results of using thromboelastometry as guidance for blood management in cardiac surgery, postoperative adverse events and ICU stay. Material and methodAnalytical and comparative non-randomised quasi-experimental prospective study with a retrospective control group. The inclusion criteria for the 80 patients were: patients undergoing cardiac surgery who had had prior cardiac surgery, endocarditis surgery or aortic arch surgery. Thirty-one patients were treated following routine transfusion practice during surgery (group A). The other 49 patients were treated with thromboelastometrically guided transfusion algorithms (group B).The main objective was blood products transfused, and postoperative adverse events and ICU stay were the secondary objectives. ResultsStatistical analysis showed lower transfusion rates of fresh-frozen plasma in group B compared to group A (P<.001), as well as red blood cell transfusion during surgery with an average transfusion rate of 3.9 units in group A in comparison to 2.67 units in group B (P=.125). Moreover, fibrinogen infusion was increased in group B compared to group A (P=.019). In addition, a lower rate of respiratory adverse events was found in group B (P=.019). There was a significant decrease in ICU stays over 7 days in group B compared to group A (P=.031). ConclusionsUsing thromboelastometry guidance for blood management led to a meaningful reduction of fresh frozen plasma transfusion during surgery. This probably resulted in a reduction in respiratory adverse events after surgery and length of ICU stay in our patients.

The administration of blood components: a British Society for Haematology Guideline.

The administration of blood components: a British Society for Haematology Guideline.

Management of peripartum hysterectomies performed on patients with placenta percreta in a tertiary central hospital

Objective: The main objective of this study is to analyse the circumstances and management of peripartum hysterectomies performed on patients with placenta percreta.Methods: This study included 37 patients who were diagnosed with placenta percreta, a condition in which the placenta invades the uterine wall, and who therefore underwent a peripartum hysterectomy. Their demographic characteristics, history of past caesareans, uterine surgery and curettage, duration of hospitalization, admission to an intensive care unit, neonatal outcomes, skin and uterus incision type, hypogastric artery ligation (HAL), complications, quantities of transfused ES (erythrocyte suspensions), and FFP (fresh frozen plasma), maternal morbidity and mortality and postoperative pathology results were retrospectively reviewed.Results: All pregnant patients who underwent a caesarean hysterectomy due to placenta percreta had a history of caesarean section and also of placenta praevia totalis. Bilateral HAL was performed in two patients (5.4%), owing to uncontrollable bleeding during the bladder dissection. The complications most frequently observed were bladder injury (13.5%), followed by infection (8.1%) and relaparotomy (5.4%). There was no mortality. Twenty-three (62.2%) of the patients had ES and 11 patients (29.7%) had FFP transfusions. According to the histopathology findings, 33 of the 37 patients (89.1%) reportedly had placenta percreta, three patients had placenta increta, and one patient had placenta accreta. Analysis of the neonatal status at birth showed that the gestational age was, on average, the 35th week. The birth weight was normal in relation to the gestational week, but the first and fifth minute Apgar score, which measures the physical condition of an infant, was found to be lower than the normal range.Conclusions: If a pregnant patient undergoes uterine surgery or has a history of a caesarean with placenta praevia, she is likely to have placenta percreta. In placenta percreta cases with bladder invasion; careful suturing of the high-volume vessels on the posterior wall of the bladder, through the bladder serosa is important in reducing the amount of bleeding and preventing future fistula formation.

Rotational Thromboelastometry or Conventional Coagulation Tests in Liver Transplantation: Comparing Blood Loss, Transfusions, and Cost

IntroductionOrthotopic liver transplantation (OLT) can be associated with significant bleeding requiring multiple blood product transfusions. Rotational thromboelastometry (ROTEM) is a point-of-care device that has been used to monitor coagulation during OLT. Whether it reduces blood loss/transfusions during OLT remains controversial. Materials and MethodsWe aim to compare ROTEM with conventional coagulation tests (aPTT, PT, INR, platelet count, fibrinogen) to guide transfusion of platelets, cryoprecip-itate, and fresh frozen plasma (FFP) during OLT over 3 years. Thirty-four patients who had transfusions guided by ROTEM were compared to 34 controls who received transfusions guided by conventional coagulation tests (CCT). Intraoperative blood loss, type/ amount of blood products transfused, and direct costs were compared between the two groups. ResultsThe ROTEM group had significantly less intra-operative blood loss (2.0 vs. 3.0 L, p = 0.04) and fresh frozen plasma (FFP) transfusion (4 units vs. 6.5 units, p = 0.015) compared to the CCT group (2.0L vs. 3.0L, p = 0.04). However, total number of patients transfused cryoprecipitate was increased in ROTEM (n = 25;73%) as compared to CCT (n = 19; 56%), p = 0.033. The direct cost of blood products plus testing was reduced in the ROTEM group ($113,142.89 vs. $127,814.77). Conclusion. In conclusion implementation of a ROTEM-guided transfusion algorithm resulted in a reduction in intra-operative blood loss, FFP transfusion and a decrease in direct cost during OLT. ROTEM is a useful and safe point of care device in OLT setting.

Effectiveness and safety of anti-fibrinolytic therapy in on-pump CABG

Objective: To evaluate the effectiveness and safety of anti-fibrinolytic therapy in on-pump coronary artery bypass grafting (CABG). Methods: Two hundred and eleven patients receiving on-pump CABG in Fuwai Hospital were recruited and randomized into treatment group (group T) and control group (group C) between October 2014 and February 2017. Tranexamic acid was given with a 10 mg/kg loading dose and 10 mg·kg(-1)·h(-1) infusion dose to group T and equal volume of saline was given to group C throughout the surgery. Postoperative drainage, allogeneic transfusion, complications, adverse events and mortality were recorded. Results: Patients of group T had less postoperative drainage [860 (670, 1 190)ml vs 985 (783, 1 365)ml], decreased red blood cell [2 (0, 8)U vs 6 (2, 10)U] and fresh frozen plasma [1 (0, 3) U vs 2 (0, 3)U] transfusion volume, lower fresh frozen plasma transfusion rate (53.33% vs 70.75%) than patients of group C (all P<0.05). No statistically significant differences existed in the rate of postoperative complications, adverse events and death between the two groups (all P>0.05). Conclusion: Tranexamic acid has definite anti-fibrinolytic effect, which can significantly reduce postoperative bleeding and allogeneic transfusion while no severe side effects were observed.

Thermal ablation of hepatocellular carcinoma in patients with abnormal coagulation function

Objective: To evaluate the safety of thermal ablation for hepatocellular carcinoma (HCC) in patients with abnormal coagulation function.Methods: Fifty-seven HCC tumours in 50 patients were treated with thermal ablation. All patients had a meted platelet count <50 × 109/L or international normalised ratio (INR) ≥ 1.7. Gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and contrast enhanced ultrasoundgraphy (CEUS)-guided ablation to cease needle tract bleeding were performed to reduce haemorrhage. The incidences of haemorrhage and other major complications were recorded and patients were followed up to observe the local tumour progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS) and recurrence-free survival (RFS) rates.Results: Two incidences of needle tract bleeding and one needle tract bleeding together with bleeding at the suture of the spleen fossa were found. Three needle tract bleeding events were detected by CEUS and ceased after CEUS-guided complementary ablation. CEUS failed to detect bleeding at the suture of the spleen fossa. Therefore, a laparotomy was conducted for haemostasis. No other major complications were found after ablation. The median follow-up periods were 18.7 ± 12.0 months (range 1 ∼ 42 months) and 1 LTP and 15 IDRs occurred. The 1-, 2- and 3-year OS rates were 84.8%, 82.7% and 82.7%, and RFS rates were 67.9%, 64.0% and 64.0%, respectively.Conclusion: With gastroscopy before ablation, platelet concentrate or fresh frozen plasma transfusion during ablation and CEUS-guided ablation to cease needle tract bleeding, thermal ablation is a safe treatment for HCC in patients with abnormal coagulation function.

Obituary: Prof Johannes Joseph van Rood (1926‐2017)

Obituary: Prof Johannes Joseph van Rood (1926‐2017)

Patient blood management and transfusion therapy for hemostasis.

Restrictive transfusion is the most common and appropriate treatment for patients with bleeding disorders because it is associated with better prognosis. However, hematologists are not familiar with the indication for and effect of using fresh frozen plasma (FFP) for transfusions, which has been inappropriately used to date. FFP should not be transfused for preventing bleeding or improving coagulation test results (i.e., PT and APTT). Instead, FFP transfusion should be performed to manage hemostasis, based on the fibrinogen levels of <150 mg/dl in patients' plasmas. Severe hypofibrinogenemia can cause critical coagulopathy, which results in massive bleeding. Early and sufficient FFP transfusion can overcome this condition. In addition, in patients with severe hypofibrinogenemia and active bleeding due to hyperfibrinolytic DIC associated with acute leukemia, the administration of concentrated fibrinogen products (e.g., cryoprecipitate or fibrinogen concentrates) is effective for maintaining hemostasis.