Initial Fibrinogen Level Research Articles

Association between Initial Fibrinogen Levels and the Need for Massive Transfusion in Emergency Department Patients with Primary Postpartum Hemorrhage: A Retrospective Study from a Single Center in Korea.

This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.

Effect of fibrinogen concentrate on the initial fibrinogen level in trauma and postpartum hemorrhage.

Massive hemorrhage is a serious event that threatens the lives of patients. Fibrinogen concentrate (FC) can control bleeding without causing viral complications and without volume loading, which can happen in transfusion-associated circulatory overload and transfusion-associated acute lung injury. FC application is easy and does not require dissolution or extra devices. It is a cost-effective agent when considering the blood and products used in large quantities. A total of 67 postpartum hemorrhage (PPH) and trauma patients' medical records, who had ASA I-III classification (The American Society of Anesthesiologists classification of physical status), were obtained. Patients were divided into two groups (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The following information was obtained from patient files: demographic parameters, history of operations, and laboratory findings (i.e., complete blood counts, coagulation tests, and fibrinogen levels). Also, the duration of intensive care unit stays and mechanical ventilation application days, the administration of fresh frozen plasma (FFP), erythrocytes, platelets, and FC numbers, and tranexamic acid infusion were recorded. There was no mortality in PPH patients in either group (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The mortality rate in trauma patients was significantly higher in the group with fibrinogen levels ≤ 100. A total of 170 g of FC were given to PPH patients and 92 g to trauma patients. There were statistically significant differences between the preoperative PT (prothrombin time), postoperative APTT (activated partial thromboplastin time), postoperative PT, and postoperative INR (international normalized ratio) levels of the patients in the group with fibrinogen levels ≤ 100. Mortality rates were also significantly higher, and hospital stays significantly longer in trauma patients in the group with fibrinogen levels ≤ 100. Therapy may be considered during massive bleeding and transfusion, as it can help to increase fibrinogen levels quickly and efficiently. Compared with FFP, fibrinogen concentrate may have some advantages in reducing the risk of fluid overload. FFP contains a range of clotting factors, including fibrinogen. It also contains other proteins and fluids that can lead to fluid overload, especially when given in large volumes during massive transfusions.

Abstract P100: Hemorrhagic Stroke in the Setting of COVID-19 is Associated With Anticoagulation Use

Introduction: While the thrombotic complications of COVID-19 have been described, there are limited data on its implications in hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this group of patients are especially salient as empiric therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between 3/1/20-5/15/20 at a NYC hospital system, during the coronavirus pandemic. We compared the demographic and clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital between 3/1/20-5/15/20 (contemporary controls) and 3/1/19-5/15/19 (historical controls), using Fischer’s exact test and non-parametric testing. We adjusted for multiple comparisons using the Bonferroni method. Results: During the study period, 19 out of 4071 (0.5%) patients who were hospitalized with COVID-19 had hemorrhagic stroke on imaging. Of all COVID-19 with hemorrhagic stroke, only 3 had non-aneurysmal SAH without intraparenchymal hemorrhage. Among hemorrhagic stroke and COVID-19 patients, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% vs 4.2% of contemporary and 10.0% of historical controls (both with p =&lt;0.001). Compared to contemporary and historical controls, COVID-19 patients had higher initial NIHSS scores, INR, PTT and fibrinogen levels. These patients also had higher rates of in-hospital mortality [84.6% vs. 4.6%, p =&lt;0.001]. Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in COVID-19 patients occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in COVID-19 patients.

157. The efficacy of recombinant human soluble thrombomodulin in preeclampsia

Introduction Recombinant human soluble thrombomodulin (rhTM) is a novel anti-coagulant agent that regulates the imbalanced coagulation system by reducing the excessive activation of thrombin. rhTM potentially reduces the morbidity and mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC). However, the efficacy of rhTM in obstetric DIC, especially in patients with preeclampsia, has not yet been established. Objectives We performed this study to examine whether the administration of rhTM was a potentially effective treatment for DIC and organ damage in preeclamptic patients. Methods This is a single-center, retrospective cohort study conducted between January 2007 and December 2017 using the records of our hospital. The eligibility criteria were known or suspected obstetric DIC documented on the basis of clinical and laboratory data. Baseline imbalance between patients with and without treatment of rhTM was adjusted using an inverse probability of treatment weighting using propensity scores composed of the following independent variables: initial platelet counts, D-dimer levels, fibrinogen levels, and prothrombin time–international normalized ratio. We evaluated laboratory changes and clinical outcomes in the early phase of obstetric DIC in preeclampsia patients. Results In total, 21 patients admitted to our department during the study period fulfilled the required criteria; of these, 10 and 11 patients were included in the rhTM and control group, respectively. After adjustment, treatment with rhTM was associated with significant improvements in platelet counts (p = 0.036), D-dimer levels (p = 0.009), compared with the control group. Serum creatinine level was significantly improved in rhTM group (p = 0.036), but other laboratory data of organ damage and failure showed no significant difference between the two groups. Discussion rhTM administration was associated with clinical and laboratory improvement in patients with DIC caused by underlying obstetric conditions in patient with preeclampsia. Further clinical research is needed to clarify the optimal application of rhTM in patients with preeclampsia.

A sustained increase of plasma fibrinogen in sudden sensorineural hearing loss predicts worse outcome independently

ObjectivesA number of etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and has been reported to be associated with fibrinogen. We aimed to determine whether hyperfibrinogenemia is associated with poor outcome and whether a serial change in fibrinogen level is associated with outcome. MethodsTwenty-two patients with ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups classified as improved and non-improved according to improvement of hearing. Blood samples were also collected from patients who visited the emergency room with coronary heart disease (CHD) as the control group. ResultsInitial fibrinogen level was significantly different between the non-improved and improved ISSNHL group (350.63±87.20 vs. 310.71±81.06. The improved ISSNHL group showed a “surge phenomenon”, in which fibrinogen started to decrease at day 5 and increased at day 26. In the non-improved group, fibrinogen remained elevated throughout the course of therapy. ConclusionIt is important to measure not only the initial fibrinogen level but also to monitor its change throughout the course of therapy in order to predict the outcome of ISSNHL.

Relationship between initial fibrinogen level with coagulopathy and mortality in multiple trauma patients

Background: In trauma induced coagulopathy (TIC), low fibrinogen value is often found and plasma fibrinogen reached low value earlier than other parameters of coagulation factors. Initial fibrinogen value is strongly correlated to the injury severity score (ISS) and be an independent predictor of mortality. This study was expected to see the relationship between initial fibrinogen level with coagulopathy and mortality, so it can predict early coagulopathy and can prevent bleeding complications that lead to mortality. Methods: The study was conducted prospectively. The entire examination obtained from patients with multiple trauma. Fibrinogen levels and coagulopathy were taken from the blood laboratory tests in conjunction with other routine examination when patients were admitted to the ER of Hasan Sadikin General Hospital. Outcome parameters were the incidence of coagulopathy and mortality. Statistical analyses were performed to look at the significance of relationships.Results: Of the 25 patients with multiple trauma obtained a majority of 80% were male patients and with the highest incidence mechanism was head trauma as many as 16 people (64%). There were 8 patients (32%) experienced coagulopathy and mortality occurred in 7 patients (28%). Chi square analysis found a significant association between fibrinogen and coagulopathy (p = 0.043), while the association between initial fibrinogen with mortality was not significant (p = 0.341).Conclusions: Initial fibrinogen level is significantly associated with coagulopathy but it cannot predict mortality in patients with multiple trauma. Further study is needed in order to assess the benefit of these results on the management of multiple trauma patients.

Fibrinogen is an independent predictor of mortality in major trauma patients: A five-year statewide cohort study

IntroductionFibrinogen may be reduced following traumatic injury due to loss from haemorrhage, increased consumption and reduced synthesis. In the absence of clinical trials, guidelines for fibrinogen replacement are based on expert opinion and vary internationally. We aimed to determine prevalence and predictors of low fibrinogen on admission in major trauma patients and investigate association of fibrinogen levels with patient outcomes. Patients and methodsData on all major trauma patients (January 2007–July 2011) identified through a prospective statewide trauma registry in Victoria, Australia were linked with laboratory and transfusion data. Major trauma included any of the following: death after injury, injury severity score (ISS) >15, admission to intensive care unit requiring mechanical ventilation, or urgent surgery for intrathoracic, intracranial, intra-abdominal procedures or fixation of pelvic or spinal fractures. Associations between initial fibrinogen level and in-hospital mortality were analysed using multiple logistic regression. ResultsOf 4773 patients identified, 114 (2.4%) had fibrinogen less than 1g/L, 283 (5.9%) 1.0–1.5g/L, 617 (12.9%) 1.6–1.9g/L, 3024 (63.4%) 2–4g/L and 735 (15%) >4g/L. Median fibrinogen was 2.6g/L (interquartile range 2.1–3.4). After adjusting for age, gender, ISS, injury type, pH, temperature, Glasgow Coma Score (GCS), initial international normalised ratio and platelet count, the lowest fibrinogen categories, compared with normal range, were associated with increased in-hospital mortality (adjusted odds ratio [OR] for less than 1g/L 3.28 [95% CI 1.71–6.28, p<0.01], 1–1.5g/L adjusted OR 2.08 [95% CI 1.36–3.16, p<0.01] and 1.6–1.9g/L adjusted OR 1.39 [95% CI 0.97–2.00, p=0.08]). Predictors of initial fibrinogen <1.5g/L were younger age, lower GCS, systolic blood pressure <90mmHg, chest decompression, penetrating injury, ISS >25 and lower pH and temperature. ConclusionsInitial fibrinogen levels less than the normal range are independently associated with higher in-hospital mortality in major trauma patients. Future studies are warranted to investigate whether earlier and/or greater fibrinogen replacement improves clinical outcomes.

Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

AimAll-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.MethodsRetrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.ResultsCompared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001). Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05). After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer) was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma) did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05).ConclusionsUnexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all-trans retinoic acid combining chemotherapy.

Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia.

Background/Aims:This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis.Methods:A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012.Results:A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS).Conclusions:Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS.

Asociación entre el nivel de fibrinógeno y severidad en la hemorragia posparto

ObjectiveTo determine if the level of fibrinogen at the onset of postpartum haemorrhage is associated with bleeding severity and a higher number of complications; to determine outcome-related cut-off points. Materials and methodsSecondary analysis of a cohort study conducted with 79 mothers admitted to the Intensive Care Unit between February 1st, 2012 and January 31st, 2013, with a diagnosis of postpartum haemorrhage, defined as all cases of blood loss greater than 1000mL. Fibrinogen levels were measured at the onset of the postpartum haemorrhage. Fibrinogen values were compared between patients with severe obstetric bleeding and those with mild-to-moderate bleeding, in order to establish the correlation with severity of blood loss and complications. ResultsOverall, 24.1% of the patients showed severe postpartum haemorrhage compared to 75.9% of the patients classified as having mild-to-moderate haemorrhage. There were 12 complications (15.2%), including 9 cases of acute renal injury, 2 cases of disseminated intravascular coagulation, and one death, all of them only in patients with severe obstetric haemorrhage. Regarding the initial fibrinogen value, the AUC-ROC for fibrinogen levels and their relationship with the severity was 0.71, with a cut-off point of <200mg/dL to predict severity (100% positive predictive value). ConclusionThe initial fibrinogen level in obstetric postpartum haemorrhage is a predictor of severity that helps in alerting to the need for treatment in these patients.

Association between fibrinogen levels and the severity of postpartum haemorrhage

ObjectiveTo determine if the level of fibrinogen at the onset of postpartum haemorrhage is associated with bleeding severity and a higher number of complications; to determine outcome-related cut-off points. Materials and methodsSecondary analysis of a cohort study conducted with 79 mothers admitted to the Intensive Care Unit between February 1st, 2012 and January 31st, 2013, with a diagnosis of postpartum haemorrhage, defined as all cases of blood loss greater than 1000mL. Fibrinogen levels were measured at the onset of the postpartum haemorrhage. Fibrinogen values were compared between patients with severe obstetric bleeding and those with mild-to-moderate bleeding, in order to establish the correlation with severity of blood loss and complications. ResultsOverall, 24.1% of the patients showed severe postpartum haemorrhage compared to 75.9% of the patients classified as having mild-to-moderate haemorrhage. There were 12 complications (15.2%), including 9 cases of acute renal injury, 2 cases of disseminated intravascular coagulation, and one death, all of them only in patients with severe obstetric haemorrhage. Regarding the initial fibrinogen value, the AUC-ROC for fibrinogen levels and their relationship with the severity was 0.71, with a cut-off point of <200mg/dL to predict severity (100% positive predictive value). ConclusionThe initial fibrinogen level in obstetric postpartum haemorrhage is a predictor of severity that helps in alerting to the need for treatment in these patients.

Early coagulopathy at hospital admission predicts initial or delayed fibrinogen deficit in severe trauma patients.

Early detection of a fibrinogen deficit in the initial phase of trauma is a determinant for anticipating massive blood loss. Hemostatic impairment should rationally be associated with an overall depletion of clotting factors, leading to early coagulopathy. The main objective of this study was to evaluate whether the severity of coagulopathy at admission could predict an initial and delayed fibrinogen deficit during the initial management of severe trauma patients. All severe trauma patients admitted consecutively to our trauma center between January 2006 and December 2009 were retrospectively reviewed. The results of coagulation tests and plasma fibrinogen levels at admission were studied. Patients were grouped according to severity of coagulopathy at admission: prothrombin time ratio and/or activated partial thromboplastin time ratio of 1.50 or greater, between 1.49 and 1.20, or less than 1.20. Correlation between severity of coagulopathy at admission and initial or delayed fibrinogen deficit (fibrinogen level < 1.5 g/L) within the first 24 hours was established. Of the 663 patients studied, 481 (72%) were male, and the mean (SD) Injury Severity Score (ISS) was 21.3 (17.6). At admission, 105 patients (20%) had severe coagulopathy, 215 (33%) had moderate coagulopathy, and 313 (47%) had no coagulopathy. The number of patients with a fibrinogen level less than 1.5 g/L at admission increased with the severity of coagulopathy: 87%, 29%, and 1%, respectively (p < 0.001). Corresponding rates for an initial fibrinogen level less than 1.0 g/L were 53%, 2%, 0.3%, respectively (p < 0.001). Moreover, severity of coagulopathy at admission was an independent risk factor of the occurrence of fibrinogen deficit within the first 24 hours (p < 0.001). Early coagulopathy at admission in severe trauma patients was strongly associated with a fibrinogen deficit during initial management. In the absence of specific monitoring of fibrinogen, coagulopathy severity helps to guide fibrinogen replacement therapy. Prognostic and epidemiologic study, level III.

CP-073 Use of human fibrinogen in patients at high risk of severe bleeding in a trauma hospital

BackgroundSevere deficiency in human fibrinogen is a cause of massive haemorrhage whose management in emergency situations is the subject of debate.PurposeA prospective, observational study to ascertain how human fibrinogen is...

Cryoprecipitate use in the PROMMTT study

There are few clinical data to guide the use of cryoprecipitate in severely injured trauma patients. Cryoprecipitate is a rich source of fibrinogen and has been associated with improved survival in animal as well as limited human studies. Our objectives were to identify patterns and predictors of cryoprecipitate use and determine whether transfusing cryoprecipitate was associated with improved survival. This secondary analysis of 1,238 of 1,245 PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study patients who had timed transfusion data included 359 (29%) who received cryoprecipitate. For this analysis, one dose of cryoprecipitate was defined as 10 U. Unadjusted predictors of cryoprecipitate use were identified using logistic regression. Multivariable time-dependent Cox models were performed to examine the association of cryoprecipitate on time to in-hospital death. Cryoprecipitate use varied significantly by center, ranging from 7% to 82%. Among patients who received cryoprecipitate, the median number of units infused by 24 hours was 10 (interquartile range, 10-20). The median time from admission to first cryoprecipitate unit was 2.7 hours (interquartile range, 1.7-4.4 hours). Of those who died of a hemorrhagic death within 6 hours of admission, 72% received no cryoprecipitate. Other unadjusted predictors of cryoprecipitate use included Injury Severity Score (ISS), initial fibrinogen levels, base deficit, international normalized ratio, prothrombin time/partial thromboplastin time, hemoglobin, damage-control surgery, and surgical intervention of the chest and abdomen. Cryoprecipitate use was not associated with in-hospital mortality after adjusting for initial pH, initial hemoglobin, emergency department systolic blood pressure, emergency department Glasgow Coma Scale (GCS) score, blood product use, ISS, and center. Ten US Level 1 trauma centers vary greatly in their timing and use of cryoprecipitate in severely injured trauma patients. We could not identify any association of cryoprecipitate use with in-hospital mortality, although most patients did not receive this product. Randomized controlled studies are needed to determine if cryoprecipitate (or fibrinogen concentrates) have a beneficial effect.

Impact of Low Fibrinogen Levels in the Puzzle of Traumainduced Coagulopathy: Is This the Missing Link?

ABSTRACT Background Patients with severe tissue injury and tissue hypoperfusion can present with low fibrinogen levels and signs of hyperfibrinolysis. The role of damage control resuscitation (DCR) in addressing the hyperfibrinolytic aspect of trauma induced coagulopathy (TIC) is unknown. We hypothesize a survival advantage when DCR is used in TIC patients with severe tissue injury and low fibrinogen levels. Materials and methods This is a 2 years prospective observational study of TIC patients who received DCR. TIC was defined as initial base deficit = –6 in combination with ISS = 12. Low fibrinogen was considered when serum level &lt;200 mg/dl. Patients were stratified into those with an injury severity score (ISS) &lt;20, and those with an ISS = 20. Variables analyzed between groups included: initial serum fibrinogen, INR, base deficit, intraoperative FFP: PRBC ratio and mortality. Results Of 67 patients with TIC, 29 (43.2%) had ISS &lt; 20, and 38 (56.7%) an ISS ≥ 20. Mean ISS was 13.9 vs 32.8 (p &lt; 0.0001) for the ISS &lt; 20 group vs the ISS ≥ 20 group respectively. Mean initial fibrinogen levels for the ISS &lt; 20 group vs the ISS ≥ 20 group was 357.4 mg/dl vs 148.5 mg/dl (p = 0.0007). Intraoperative DCR with FFP: PRBC for the ISS &lt; 20 group vs the ISS ≥ 20 group showed no statistical difference: 1 to 1.12 vs 1 to 1.3 (p = 0.12). Overall mortality after controlling for DCR in the ISS &lt; 20 group was 29 and 73% in the ISS ≥ 20 group (p = 0.0007). In a stepwise logistic regression, low fibrinogen levels was associated with mortality, p = 0.01; OR 1.01 (1.23-11.55) with area under the receiver operating characteristic curve of 0.701. The correlation coefficient for ISS vs initial fibrinogen level was –0.5635 (p = 0.0001). Conclusion Overall mortality was significantly increased in patients who had an ISS . 20 with low fibrinogen level despite effective DCR. Given the correlated decrease in fibrinogen levels in patients with severe tissue injury, further investigation regarding potential benefits of antifibrinolytic agents in DCR needs further validation. How to cite this article Duchesne JC, Guidry C, Park TS, Simms E, Hoffman JRH, Bock JM, Wascom J, Barbeau J, Meade P, McSwain NE Jr. Impact of Low Fibrinogen Levels in the Puzzle of Trauma-induced Coagulopathy: Is This the Missing Link? Panam J Trauma Critical Care Emerg Surg 2013;2(2): 74-79.

Significance of Fibrinogen and the D-Dimer Level for Predicting the Risk of Fatal Bleeding in Patients with Acute Promyelocytic Leukemia.

Abstract 3118Poster Board III-55 BackgroundBleeding associated with disseminated intravascular coagulation is an important cause of early mortality in patients with acute promyelocytic leukemia (APL) which shows a favorable prognosis after remission. To date, little has been known regarding which clinical parameters contribute to the development of significant bleeding. MethodsFrom Dec. 1998 to Apr. 2009, patients diagnosed with APL were included in this retrospective analysis. All-transretinoic acid (ATRA) at 45mg/m2 per day and cytotoxic chemotherapy (CTX) were administered. Transfusion of cryoprecipitate (CP) or fresh-frozen plasma (FFP) was considered if a patient's fibrinogen level was below 150mg/dL. The fibrinogen and d-dimer levels were checked regularly until those were normalized. Any significant bleeding which required medical intervention was recorded as a bleeding episode. ResultsNinety patients were included in our retrospective analysis. The male to female ratio was 41: 49. The median patient age was 41 years (range: 15-80). ATRA was administered to all patients except for one, and 79 patients (87.8%) received combined CTX. The complete remission rate was 78.9%, and 15 patients (16.7%) died of bleeding during induction therapy. There were 24 bleeding episodes among 24 patients (26.4%), and 15 of 24 bleeding episodes were fatal. The bleeding site was the brain for 14, lung for one, both for four, and other organs for four patients. In terms of the onset of bleeding, there was bleeding detected on the patient's arrival for five patients, bleeding developing during the first 24 hours after the arrival for five, bleeding during induction therapy for 13, and bleeding after achieving remission for one patient. 'Late bleeding' (bleeding after seven days from the start of CTX) developed in eight patients. Patients who suffered from bleeding differed from those who did not regarding the peripheral blood (PB) platelet count (28.7 vs. 44.9 × 103/mm3, p=0.014), fibrinogen (117.8 vs. 189.7 mg/dL, p=0.001), and d-dimer (51.9 vs. 32.4 μg/mL, p=0.040). The total and fatal bleeding rates differed in the patient subgroups when they were categorized according to the level at diagnosis of the PB platelet count, LDH, fibrinogen, and d-dimer; a low platelet count (< 20 × 103/mm3), high LDH (> x2 of upper normal limit [UNL]), low fibrinogen (< 150 mg/dL), and high d-dimer (°Ã 20 μg/mL) level were all significant risk factors associated with both total and fatal bleeding (Table 1). Patients whose initial fibrinogen level was more than 150 mg/dL and whose d-dimer level was less than 20 μg/mL, did not experience any bleeding episodes during their entire course of treatment. Among the 51 patients whose level of fibrinogen was evaluable for response, those whose level was elevated without transfusion of CP or FFP (0/11, 0%) or those whose initial level was more than 150 mg/dL (1/30, 3.3%), showed a significantly lower 'late bleeding' rate, i.e. p<0.001, compared with those whose level either decreased despite the transfusion (2/6, 33.3%) or without a transfusion (3/4, 75.0%). ConclusionIn this study, the fibrinogen and d-dimer levels at diagnosis of APL were helpful for predicting the development of bleeding episodes in patients with APL. Intensive transfusion of CP to maintain the fibrinogen level at more than 150 mg/dL might be able to significantly decrease the bleeding rate in APL patients.Table 1Difference in total and fatal bleeding risk in the subgroupsPlatelet count (x 103/mm3)LDH ( x UNL)Fibrinogen (mg/dL)D-dimer (μg/mL)< 20>= 20<=2>2<150>=150< 20>= 20Total bleeding43.5%20.9%16.0%51.9%39.1%13.5%0%42.6%(p=0.035)(p=0.002)(p=0.010)(p<0.001)Fatal bleeding40.9%9.0%8.2%37.0%26.7%5.4%0%26.4%(p=0.001)(p=0.004)(p=0.011)(p=0.001) DisclosuresNo relevant conflicts of interest to declare.

Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke

Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome. Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis. Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity. The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

Increased Systemic Inflammation Is a Risk Factor for COPD Exacerbations

COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive factors of acute exacerbations, particularly focusing on systemic inflammation. To determine if an elevated systemic inflammatory status measured at baseline is related to the occurrence of acute exacerbations in patients with COPD. The occurrence of moderate (requiring oral prednisolone) and severe exacerbations (requiring hospitalization) was prospectively recorded over 1 year. At the beginning of the study, lung function values (FEV1, FVC, functional residual capacity, and diffusion capacity of the lung for carbon monoxide [Dlco]) and serum levels of C-reactive protein, fibrinogen, lipopolysaccharide binding protein, tumor necrosis factor (TNF)-alpha, and its soluble receptors (soluble TNF receptors 55 and 75) as markers of systemic inflammation were determined. Two hundred seventy-seven person-years of follow-up were analyzed in the total group of 314 patients: 186 patients were responsible for 411 exacerbations (374 moderate and 37 severe). Multivariate analyses showed that a higher initial fibrinogen level and a lower FEV1 predicted a higher rate of both moderate and severe exacerbations. Additional independent predictors of a severe exacerbation were a higher number of prestudy severe exacerbations and lower Dlco. A higher number of prestudy moderate exacerbations was the only additional independent risk factor for the rate of moderate exacerbations. This study demonstrates that besides lung function impairment systemic inflammation manifested by elevated fibrinogen levels is an independent risk factor for exacerbations of COPD. Attenuation of systemic inflammation may offer new perspectives in the management of COPD patients to reduce the burden of exacerbations.

Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome

Even after the introduction of all-trans retinoic acid (ATRA), early hemorrhagic death remains a major cause of remission induction failure for acute promyelocytic leukemia (APL). To investigate severe hemorrhagic complications during remission induction therapy with respect to incidence, risk factors, and influence on outcome. Results were analyzed for 279 patients enrolled in the APL97 study conducted by the Japan Adult Leukemia Study Group (JALSG). Severe hemorrhage occurred in 18 patients (6.5%). Although most of them were receiving frequent transfusions, the targeted levels of platelet counts (30 x 10(9)/L) and plasma fibrinogen (1.5 g/L) for this study were reached at the day of bleeding in only 71% and 40%, respectively. Nine of them succumbed to an early death, while the remaining nine patients eventually achieved complete remission (CR). The 5-yr event-free survival rate was 68.1% for those who did not suffer severe hemorrhage, and 31.1% for those who did (P < 0.0001). For patients who achieved CR, on the other hand, there was no difference in disease-free survival between patients with and without severe hemorrhage (P = 0.6043). Risk factor analysis identified three pretreatment variables associated with severe hemorrhage: initial fibrinogen level, white blood cell count, and performance status. Additionally, patients with severe hemorrhage were more easily prone to develop retinoic acid syndrome or pneumonia than patients without hemorrhage. These results indicate that fatal hemorrhage represents a major obstacle in curing APL, and that patients with such high-risk features may benefit from more aggressive supportive care.

High initial fibrinogen level is a risk factor for no-reperfusion phenomenon among patients with ST segment elevation myocardial infarction treated with percutaneous coronary intervention

High initial fibrinogen level is a risk factor for no-reperfusion phenomenon among patients with ST segment elevation myocardial infarction treated with percutaneous coronary intervention