Dose Of Fresh Frozen Plasma Research Articles

EFFECT OF EDUCATION FOR THE CLINICAL USAGE OF FRESH FROZEN PLASMA

Abstract Introduction/Objective Plasma is generally transfused to replenish coagulation factors to stop bleeding. It is processed as “Fresh Frozen Plasma” (FFP), wherein units are frozen within 8 hours of collection from the donor for storage, and thawed in a 30-37 C water bath before usage. The Association for the Advancement of Blood & Biotherapies (AABB) recommends a dose of 15 ml/kg plasma in adults, and one unit of FFP is 200-250 ml in volume. Plasma units are recommended to be transfused within 6 hours at a rate of 2-3 ml/kg/hour. At Danbury Hospital, Connecticut, there has been a tendency of clinicians to order only one unit of FFP, however, the recommended dose is at least two units. The exact incidence of one unit of FFP usage was not well known before the initiation of this study. This retrospective study aimed to focus on the incidence of the administration of single unit FFP and estimate the effect of education to clinicians regarding the recommended dosage of FFP. Methods/Case Report Inappropriate quantity was defined as the administration of only 1 FFP dose given more than 6 hours from any other FFP dose(s), either before or after. The study included all patient cases with orders of fresh frozen plasma at Danbury Hospital, Connecticut, from Dec 1, 2020 to April 30, 2022. Patients under 18 years of age were excluded from the study. Education was provided continuously during the time period through telephone calls. Data was gathered both from blood bank records and the electronic medical record system. Trend analysis was performed on the incidence of recommended versus inappropriate dosage over the time period. Results (if a Case Study enter NA) 94 patients were given FFP at Danbury Hospital, Connecticut, from Dec 1, 2020 to April 30, 2022. There were 49 instances of an inappropriate dose of FFP given more than 6 hours from any other FFP dose(s), resulting in a rate of 0.52 instances of inappropriate doses per patient. The rate of inappropriate doses of FFP per patient was 0.53 during the first half of the time period studied, and 0.52 during the second half. There was no significant trend in the rate of FFP doses per patient during the time period (P value: 0.9998). Conclusion We did not find a statistically significant change in the fresh frozen plasma (FFP) orders at our institution despite the education of clinicians by telephone contact. A robust systematic education of clinicians with digital order entry forms to actively motivate clinicians for at least two units may be required to result in a significant change in clinician practice.

Futility of fresh frozen plasma in the correction of coagulopathy prior to image-guided drainage of infected collections: Results from a prospective case–control study

Abstract BACKGROUND: Fresh frozen plasma (FFP) is frequently used as prophylactic hemostatic therapy for correction of periprocedural coagulopathy. This practice is frequently based on the assumption that deranged international normalized ratio (INR) predicts the risk of periprocedural bleeding and that FFP transfusion is effective in mitigating the procedure-associated bleeding risks. There is limited evidence to support both these assumptions in the context of image-guided drainage of infected collections. AIMS: The study aimed to analyze the efficacy of weight-based standard FFP dose for correction of infection-associated coagulopathy in patients with clinicoradiologically diagnosed infected collections planned for image-guided drainage. MATERIALS AND METHODS: In this prospective case–control study, 229 patients with clinicoradiologically diagnosed infected abdominal collection(s) planned to undergo image-guided drainage were included. Cases and controls were defined as patients with baseline INR >1.2–3 (in the absence of any other bleeding diathesis) and INR ≤1.2, respectively. Cases received 10–15 mL/kg of FFP before drainage. Costs and time delays in drainage among the two groups, efficacy of plasma transfusion in the correction of coagulopathy, incidence of transfusion reactions, bleeding complications, and inhospital mortality were analyzed. RESULTS: There were 117 cases and 112 controls. A total of 445 FFP units were utilized. The median (interquartile range) time required from diagnosis of collection to the procedure was 25.3 (20.8–40.3) hours among cases and 16.4 (8.7–20.1) hours among controls (P < 0.001). FFP transfusion resulted in INR normalization (≤1.2) only in 7.9% of cases (n = 9). Among the 81 cases who had pretransfusion INR ≥1.5, INR improved to ≤1.5 in 49 (60.4%) patients. There was an average of 2.9% decrease in INR per unit of FFP transfused. No bleeding complications were noted in patients undergoing drainage despite a persistent deranged INR (>1.5) postplasma transfusion. Transfusion reactions occurred in 17/117 (14.5%) patients. There were no deaths among the controls while five patients died among the cases. CONCLUSION: Prophylactic FFP transfusion for infection-associated coagulopathy leads to a significant delay in lifesaving drainage procedures. Minority of patients attain normalization of INR with FFP transfusion.

Effect of Phytonadione on Correction of Coagulopathy in Pediatric Patients With Septic Shock.

The purpose of this study was to evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC). The primary objective was to identify the number of patients with an international normalized ratio (INR), defined as ≤1.2, following phytonadione. Secondary objectives were to compare patients who achieved a normalized INR versus those with INR >1.2 and to determine factors associated with a normalized INR. A retrospective study of children <18 years of age receiving phytonadione from October 1, 2013, to August 31, 2020, with a diagnosis of septic shock, were included. Data collection included demographics, phytonadione regimen, INR values, Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality III (PRISM III) scores, fresh frozen plasma (FFP) and cryoprecipitate use. A logistic regression model and generalized linear model were used to explore factors associated with a normalized INR and evaluate phytonadione dosing. Data for initial phytonadione course for 156 patients were evaluated. Sixty-six (42.3%) patients had a normalized INR. Most patients (n = 145; 92.9%) received ≤3 phytonadione doses, with the largest reduction in INR occurring after the second dose. In the logistic regression model, baseline INR, FFP, cryoprecipitate, vasopressors, PIM2, PRISM III, or cumulative phytonadione dose were not associated with achieving a normalized INR. Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy.

Laparoscopic hepatectomy for hepatocellular carcinoma in a patient with congenital factor V deficiency: a case report

BackgroundFactor V (FV) deficiency is an extremely rare disease, with an incidence of 1 in 1 million. The bleeding symptoms are mild, and the prognosis is good; however, the safety of surgical treatment is unclear, because there are few available reports. Herein, we report a case of hepatocellular carcinoma with congenital FV deficiency in a patient who safely underwent laparoscopic hepatectomy.Case presentationA 79-year-old man, diagnosed with hepatocellular carcinoma of liver segment 5, with type C cirrhosis and sustained virological response visited our hospital. He had congenital FV deficiency, and blood tests showed coagulation deficiencies with an FV activity of < 2.6%, prothrombin time activity of 11%, and activated partial thromboplastin time of 100.3 s. Surgery and radiofrequency ablation were considered for treatment. Since the tumor was in contact with the Glissonean pedicle 5 + 6, surgery was judged to be superior from the viewpoint of safety and curability. After discussing the safety of the surgery with a hematologist, it was determined that the operation could be performed safely by transfusing sufficient fresh frozen plasma (FFP). Laparoscopic hepatic segment 5 + 6 subsegmental resection was performed with FFP transfusion, fluid restriction, airway pressure control, and central venous pressure reduction to control the bleeding. Bleeding was minimized during the transection of the liver parenchyma and no bleeding tendency was observed. The operative time was 445 min, and the amount of intraoperative bleeding was 171 mL. No complications, such as postoperative bleeding, were observed, and the patient was discharged on the eighth postoperative day.ConclusionsLiver surgery can be performed safely in FV-deficient patients with strict coagulation capacity monitoring and appropriate transfusion of FFP. Preoperative evaluation of cardiac function to determine tolerance to high doses of FFP and ingenuity of surgery and intraoperative management to minimize blood loss are important.

Term Infant with Bilateral Parenchymal Brain Hemorrhages.

Term Infant with Bilateral Parenchymal Brain Hemorrhages.

1110 The Use of Four-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma in Patients With Cirrhosis

INTRODUCTION: Cirrhotic patients (pts) are at increased risk for bleeding due to alterations in hemostasis. Fresh frozen plasma (FFP) is the most common agent used for reversal of coagulopathy. However, four-factor prothrombin complex concentrate (4F-PCC) usage has increased as it has a lower infusion volume and shorter administration time. The objective of this study was to evaluate the efficacy of 4F-PCC compared to FFP in correcting INR for treatment and prophylaxis of bleeding in pts with cirrhosis undergoing urgent procedures. METHODS: A retrospective chart review of cirrhotic pts who received at least one dose of 4F-PCC or FFP during the defined study period of January 2016 through March 2019 was performed. Pts were identified in the Allscripts EMR. Cirrhosis was identified by the presence of one or more of seven pre-determined diagnostic codes. Pts were excluded if they received both agents within 24 hours or had no documented INRs. Data collected included: age, sex, race, etiology of liver disease, baseline anticoagulant and antiplatelet use, reversal agent administered, baseline and subsequent INR values,, thromboembolic events, mortality, and length of stay (LOS). All data was recorded confidentially and de-identified. The primary outcome was time to INR reversal, defined as an INR of less than 1.5 ULN. Secondary outcomes included thromboembolic event occurrence, all-cause mortality and hospital length of stay. Appropriate statistical analysis was performed. RESULTS: 39 pts were included in the study with 43 reversal agents administered, 29 FFP and 14 4F-PCC. There was no statistical difference in baseline characteristics between groups. A majority of pts had Child’s C cirrhosis. Reversal of INR was observed in 4 FFP pts (14%), and 8 4F-PCC pts (57%). The median time to reversal in the 4F-PCC group was 267.5 minutes (P = 0.035). The reduction in INR from baseline to nadir was 0.5 units (20.5%) in the FFP group and 1.2 units (44%) in the 4F-PCC group (P &lt; 0.001). There was no observed thromboembolic events and mortality rates did not differ between groups (44% vs 30%, P = 0.70). Mean hospital (LOS) was 20.7 days in the FFP group and 12.8 days in the 4F-PCC group (P = 0.67). CONCLUSION: 4F-PCC was associated with significantly 1) improved time to INR reversal, 2)improved extent of INR correction and 3)decreased hospital LOS compared to FFP. Cirrhotic pts with an abnormal INR who present with bleeding may benefit from the administration of 4F-PCC prior to procedural intervention.

Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation

The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients. Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion. FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5. FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases. Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

A Rare Case of Congenital Factor X Mild Deficiency Presenting as Life-Threatening Hemorrhagic Shock in a Neonate

Abstract Introduction Congenital factor X deficiency is one of rarest bleeding disorders, occurring in 1 out of 1 million births. Its rarity limits its consideration in newborns presenting with hemodynamic instability. It is autosomal recessive and seen frequently in the consanguineous population. Patients with factor X deficiency are classified into three groups, based on factor X activity level: severe (&lt;1%), moderate (1%-4%), and mild (6%-10%). Severe deficiency presents with bleeding diathesis early in life. Methods A 3-day-old male newborn, delivered at term via spontaneous vaginal delivery, presented in a well-baby clinic for a routine bilirubin check. Family history was negative for bleeding disorder or consanguinity. Nurse noted persistent blood oozing at heel stick site and oral, nasal, and umbilical stump bleeding. The patient immediately developed respiratory distress and shock. Sepsis, vitamin K deficiency, and congenital metabolic syndrome were considered. Liver function, WBC count, and other chemistry were normal, and cultures were negative. Hemoglobin was low and platelet count was elevated. PT (30.3 seconds) and aPTT (53.3 seconds) were both prolonged. Mixing patient’s sample with normal plasma corrected PT (13.1 seconds) and aPTT (25.7 seconds), indicating a factor deficiency. Results Coagulation factor assays revealed normal levels of factors VII, VIII, IX, and II. Factor X activity (12.9%) was low. The patient’s condition improved after multiple pRBC and plasma transfusions. He was placed on a daily 25-mL/kg dose of fresh-frozen plasma, which maintained his PT at 17.6 to 19.1 seconds and aPTT at 34.1 to 48.0 seconds. Factor X level increased to 20% after plasma transfusion. Conclusion Congenital bleeding disorder should be considered for neonates presenting with bleeding and shock. Factor X deficiency is suspected when both PT and aPTT are prolonged and corrected with mixing studies. Although factor levels of 10% to 40% are considered adequate for hemostasis, our patient with 12% factor X activity presented with a life-threatening bleeding event.

Contemporary Reversal of Oral Anticoagulation in Intracerebral Hemorrhage.

Author(s): Bower, Matthew M; Sweidan, Alexander J; Shafie, Mohammad; Atallah, Steven; Groysman, Leonid I; Yu, Wengui

Preponderant use of fresh-frozen plasma in children despite weaker evidence

BACKGROUND: Considering the higher use of fresh-frozen plasma (FFP) in our hospital, we desired to determine the pattern, prevalence, and potential complications of its utilization in new-born and children with the primary aim to observe its effect on the conventional coagulation screening (CCS) parameters. SUBJECTS AND METHODS: Patients' demographics, clinical indications, and pre- and posttransfusion CCS parameters such as the prothrombin time, the international normalized ratio (INR), and partial thromboplastin time were observed over a period of 10 months. Any improvement observed in the laboratory parameters after FFP transfusion was noted. RESULTS: We studied 433 episodes, where 499 FFP units were utilized in 184 patients. Mean age in years was 6 ± 0.16 (new-born to 17). Diagnoses-wise majority had diffuse intravascular coagulation with sepsis 25% (46/184) followed by febrile illness 23% (42/184). Around 46% (84/184) patients had bleeding episodes of which four had known family history of bleeding (three factors IX and one factor XI deficiency). Mean doses of FFP utilized (mL/kg) in children and infants were 12.6 ± 6.3 (n = 297 episodes) and 14.4 ± 6.3 (n = 136 episodes), respectively (P = 0.006). Mean change in INR in the cohort with deranged coagulation parameters against the overtly bleeding cohort was 0.85 versus 0.40 (P = 0.006). CONCLUSION: The study elicits minimal evidence in correcting the coagulation parameters, especially in the infants, whenever FFP was transfused prophylactically. Joint-decision making of the pediatricians and transfusion medicine physician would promote judicious use in children.

Human Plasminogen Replacement Therapy Vs. Best Supportive Care in Patients with Congenital Plasminogen Deficiency: A Comparison of Health Care Resource Use over a 48-Week Period

Background: Congenital plasminogen deficiency (CPD), is an ultra-rare autosomal recessive disorder that causes severe and debilitating clinical sequelae. Clinical signs are characterized by ligneous conjunctivitis, gingivitis, otitis media, impaired wound healing and even hydrocephalus. Current disease management includes surgery and systemic/topical therapies, but successful clinical responses are few and recurrences are typically rapid. Intravenous (IV) human plasminogen is a new treatment for CPD currently undergoing regulatory review in the United States. A recent clinical trial demonstrated that regular infusions of plasminogen IV (every 2 to 4 days) induced near complete and long term durable responses in affected patients. The current study compared overall health care resource use required to manage clinical manifestations of CPD for patients treated with human plasminogen in the clinical trial relative to a historical control group.Methods: The registration trial database was used to extract health care resource data in CPD patients (n=14) who received human plasminogen IV therapy throughout a 48-week period. Total health care resource use was compared to a control sample consisting of CPD patients (n=16) who did not receive human plasminogen IV and were managed with only best supportive care (BSC) over a one year period from the date of diagnosis. Health care resource extraction consisted of topical and systemic therapies such as fresh frozen plasma (FFP), clinic visits, surgical interventions and hospital admissions related to CPD.Results: A total of 16 patients who received BSC in either the United States (n=3), Spain (n=3) and Turkey (n=10) were identified and formed the control group. Over a 12-month assessment period, there were 304 clinic visits and 65 days of hospitalization for CPD related complications. IV FFP was given to 12 of 16 (75%) patients, which translated to 246 individual FFP doses administered (dose range = 5 to 15 mg/kg) over 12 months. Furthermore, there were 54 eye surgeries performed on the 16 control patients to remove ligneous membranes. In contrast, none of the 14 patients treated with plasminogen IV required surgical interventions, hospital admissions or FFP infusions over the 48-week treatment period (p < 0.001). There were also significant reductions in all types of supportive therapy in the human plasminogen treated patients relative to their utilization at baseline (p < 0.05).Conclusions: Human plasminogen replacement therapy was able to significantly offset health care resource use compared to patients receiving BSC only. Patients in the trial were also able to incorporate IV human plasminogen therapy into their weekly routine, with administrations often performed at home. DisclosuresDranitsaris:Prometic Life Sciences Inc.: Consultancy. Dorward:Prometic Life Sciences Inc.: Employment.

Transfusion of Fresh Frozen Plasma in Critically Ill Patients: Effective or Useless?

BACKGROUND:Fresh frozen plasma (FFP) is widely used in critically ill patients to correct the deficiency of coagulation factors or increased INR.AIM:In the present study we aimed to evaluate the outcome of the freshly frozen plasma use as prophylaxis in ICU patients before an invasive procedure.METHODS:The study was conducted at Central Anaesthesiology and Intensive Care Service UHCT “Mother Theresa”, Tirana. 136 patients were enrolled with coagulopathy with no bleeding before the invasive procedure, from June 2016 to December 2016. A group of 75 patients underwent a median volume of 12.5 ml/kg FFP given, and 61 had no transfusion. Data were collected on demographics, the severity of illness measured by APACHE III scores, INR, medication use, hemodynamic data.RESULTS:From 136 patients with coagulopathy with no bleeding who underwent planned invasive interventions, 75 [55%] received FFP, vs 61 [45%] p = 0.04 who did not receive. Overall, the median FFP dose was 12.5 ml kg-1. Median INR level in FFP and non-FFP groups was respectively 3.1 (1.9-4.8) and 3.5 (1.8-5.2). INR was corrected in 24 of 75 (32%) of those who received a transfusion. The frequency of minor bleeding episodes was 9.3% in transfused patients vs 4.9% in the non-transfused group. Patients who developed an onset of acute lung injury were more frequent in the FFP group. No allergic transfusion complications were observed. Also, the median length of hospital stay [LOS] was 3.05 days vs 2.91 days and mortality rate 8.2% vs 6.5% with no significant difference between two groups.CONCLUSIONS:Freshly frozen plasma transfusions are often unnecessarily administered during an inadequate correction of the deficiencies of coagulation factors. When comparing a liberal FFP transfusion strategy vs restrictive other clinical trials are required to asses which one is the best to adopt in intensive care settings.

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).

Fresh Frozen Plasma Transfusion Ameliorates INR and aPTT but Does Not Increase Thrombomodulin-Corrected Thrombin Generation in Patients with Cirrhosis

▪Introduction: In vitro studies have shown that transfusion of fresh frozen plasma (FFP) has limited efficacy in correcting coagulopathy in cirrhosis. This study aims to assess the effect of FFP transfusion on endogenous thrombin potential (ETP) in patients with cirrhosis with abnormal coagulation test results. Methods: Using a stringent protocol for control of pre-analytic variables, blood samples were collected before and up to 8 hours after FFP transfusion. All samples were tested for INR, aPTT and ETP. The ETP assay was performed in platelet-poor plasma, using an automated fluorometer (CAT, Netherlands), using the technique developed by Hemker and modified by Tripodi. ETP was defined as the area under ROC curve and results were expressed as the ratio of ETP with thrombomodulin addition to ETP without (used to mimic in vivo conditions when patients are transfused). Results: 42 patients were included (male n=28; Child-B n= 11; Child-C n=31). Patients underwent FFP transfusion prior to high-risk invasive procedures (n=25), for treatment of bleeding (n=10) or for both reasons (n=6). The mean dose of FFP was 11.3 ml/kg (95% CI 9.16 - 20.46). After transfusion, INR decreased from 2.6±1,4 to 2.09±0.5 (p<0.0001) and aPTT from 1.47±0.5 to 1.27±0.26 (p<0.0001). At baseline, normal or above normal values of ETP ratio (³0.66) were found in 37 (88%) patients, and mean values remained largely unchanged after FFP transfusion (0.75±0.22; median 0.82 before to 0.76±0.16; median 0.81 after transfusion; p=0.56). The results for INR, aPTT and ETP are shown in figure 1. During the one-week follow-up period, 4 patients (9,5%) had acute reactions to transfusion, including fluid overload and allergic reactions. Of the 31 patients that underwent invasive procedures, four had severe bleeding. Discussion: FFP transfusion at standard doses ameliorated INR and aPTT, but did not increase thrombin generation corrected by thrombomodulin. That might be explained by the fact the former tests detect only 5% of the amount of thrombin generated. Besides, they are performed without the addition of thrombomodulin, an endothelial protein with anticoagulant effects, to which patients with cirrhosis have shown to be resistant. Patients were exposed to the risks of transfusions, without a clear benefit in the improvement in thrombin generation and decreasing the risk of bleeding. Our results call into question the common use of INR and aPTT for guiding the transfusion policy of FFP when treating coagulopathy in cirrhosis.Figure 1: Results showing comparison before and after FFP transfusionfor (A) INR, (B) aPTT and (C) ETP ratio with and without thrombomodulin. DisclosuresNo relevant conflicts of interest to declare.

Effects of a Standard Dose of Fresh Frozen Plasma on Various Elevations in the International Normalized Ratio

Effects of a Standard Dose of Fresh Frozen Plasma on Various Elevations in the International Normalized Ratio

Dose‐associated pulmonary complication rates after fresh frozen plasma administration for warfarin reversal

ESSENTIALS: Fresh frozen plasma (FFP) may be associated with a dose-based risk of pulmonary complications. Patients received FFP for warfarin reversal at a large academic hospital over a 3-year period. Almost 20% developed pulmonary complications, and the risk was highest after > 3 units of FFP. The risk of pulmonary complications remained significant in multivariable analysis. Fresh frozen plasma (FFP) is often administered to reverse warfarin anticoagulation. Administration has been associated with pulmonary complications, but it is unclear whether this risk is dose-related. Aims We sought to characterize the incidence and dose relationship of pulmonary complications, including transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI), after FFP administration for warfarin reversal. We performed a structured retrospective review of patients who received FFP for warfarin reversal in the emergency department (ED) of an academic tertiary-care hospital over a 3-year period. Logistic regression was used to explore the relationship between FFP dose and risk of pulmonary events. Two hundred and fifty-one patients met the inclusion criteria. Overall, 49 patients (20%) developed pulmonary complications, including 30 (12%) with TACO, two (1%) with TRALI, and 17 (7%) with pulmonary edema not meeting the criteria for TACO. Pulmonary complications were significantly more frequent in those who received > 3 units of FFP (34.0% versus 15.6%, 95% confidence interval for risk difference 7.9%-8.9%). After stratification by subtype of complication, only the risk of TACO was statistically significant (28.3% versus 7.6%, 95% confidence interval for risk difference 8.2%-16.6%). In multivariable analysis controlling for age, sex, initial systolic blood pressure, and intravenous fluids given in the ED, > 3 units of FFP remained a significant risk factor for pulmonary complications (odds ratio 2.49, 95% confidence interval 1.21-5.13). Almost 20% of patients who received FFP for warfarin reversal developed pulmonary complications, primarily TACO, and this risk increased with > 3 units of FFP. Clinicians should be aware of and prepared to manage these complications.

Comparison between Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) for the Urgent Reversal of Warfarin in Patients with Mechanical Heart Valves in a Tertiary Care Cardiac Center.

Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.

Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy

Coagulopathy has a high prevalence in critically ill patients. An increased International Normalized Ratio (INR) is a common trigger to transfuse fresh frozen plasma (FFP), even in the absence of bleeding. Therefore, FFP is frequently administered to these patients. However, the efficacy of FFP in correcting hemostatic disorders in non-bleeding recipients has been questioned. To assess whether INR prolongation parallels changes in the results of other tests investigating hemostasis, and to evaluate the coagulant effects of a fixed dose of FFP in non-bleeding critically ill patients with a coagulopathy. Markers of coagulation, individual factor levels and levels of natural anticoagulants were measured. Also, thrombin generation and thromboelastometry (ROTEM) assays were performed before and after FFP transfusion (12 mL kg(-1) ) to 38 non-bleeding critically ill patients with an increased INR (1.5-3.0). At baseline, levels of factor II, FV, FVII, protein C, protein S and antithrombin were reduced, and thrombin generation was impaired. ROTEM variables were within reference ranges, except for a prolonged INTEM clot formation time. FFP transfusion increased the levels of coagulation factors (FII, 34% [interquartile range (IQR) 26-46] before vs. 44% [IQR 38-52] after; FV, 48% [IQR 28-76] before vs. 58% [IQR 44-90] after; and FVII, 25% [IQR 16-38] before vs. 37% [IQR 28-55] after), and the levels of anticoagulant proteins. Thrombin generation was unaffected by FFP transfusion (endogenous thrombin potential, 72% [IQR 51-88] before vs. 71% [IQR 42-89] after), whereas ROTEM EXTEM clotting time and maximum clot firmness slightly improved in response to FFP. In non-bleeding critically ill patients with a coagulopathy, FFP transfusion failed to induce a more procoagulant state.

The Effect of Fresh Frozen Plasma Transfusion on International Normalized Ratio in Emergency Department Patients

BackgroundThere are few studies researching the effect of fresh frozen plasma (FFP) transfusion on international normalized ratio (INR) in patients with coagulation abnormality. ObjectiveThis study's aim was to determine the effect of FFP transfusion on INR as calculated pretransfusion. In addition, patients were grouped according to pretransfusion INR to determine the improvement in INR per unit of FFP. MethodsAdult patients who had been admitted to our Emergency Department (ED) with coagulation abnormality and received an FFP transfusion, and had pre- and posttransfusion coagulation tests performed, were included in the study. Patients were categorized into five groups according to their pretransfusion INR levels. Improvement in INR per unit of FFP-transfused values (Δ INR 1 unit FFP) was determined for each group. ResultsEighty-seven patients were entered into the study, and were administered a total of 199 units of FFP. Δ INR 1 unit FFP value was 0.03 ± 0.13 for patients whose pretransfusion INR level was under 2; 0.77 ± 0.47 for those between 2 and 5; 2.14 ± 0.63 for those between 5 and 9; 3.34 ± 0.89 for those between 9 and 12; and 4.63 ± 1.99 for those over 12. A very strong positive correlation was found between pretransfusion INR and Δ INR 1 unit FFP (p < 0.001, r = 0.957). ConclusionA significant improvement in INR was observed in patients with higher pretransfusion INR. While determining FFP dose for patients admitted to the ED due to coagulation defect, pretransfusion INR value should be taken into account.

Misdiagnosis of Alpha-1 Antitrypsin Phenotype in an Infant with CMV Infection and Liver Failure

A 4-month-old female with a history of neonatal cholestasis was initially evaluated with jaundice, ascites, coagulopathy, and worsening aminotransferase levels. At 5 weeks of age, her parents had noticed ‘‘yellowing’’ of her eyes and skin accompanied by a slightly more pale appearance of her regularly yellow-colored stools. Initially, she was noted to have conjugated hyperbilirubinemia, with total bilirubin 6.5 and conjugated 4.5, aspartate aminotransferase (AST) 163, alanine aminotransferase (ALT) 103, and elevated alkaline phosphatase. Liver ultrasound was normal. A percutaneous liver biopsy, obtained due to her continued unexplained cholestasis, was reported as showing possible large duct obstruction and bile duct proliferation, suggestive of extrahepatic biliary atresia. A subsequent endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiogram showed no anatomic abnormalities in the intrahepatic and extra hepatic biliary system, inconsistent with the diagnosis of biliary atresia (Fig. 1). During her hospital admission, a serum alpha-1 antitrypsin (A1AT) concentration was 34 mg/dl (normal 100–250 mg/dl), with A1AT MZ phenotype reported. Her conjugated hyperbilirubinemia improved slightly, and her liver numbers stabilized. She was discharged home with a close follow-up outpatient appointment in the pediatric gastroenterology clinic. The remainder of her evaluation for neonatal cholestasis, including an echocardiogram and ophthalmology examination for Alagille’s syndrome, was negative. Infectious studies were negative as well. Hepatosplenomegaly or ascites were not detected by physical examination, with reassuring and age-appropriate biometrics noted. Ongoing outpatient medical care revealed elevated cytomegalovirus (CMV) IgM titers (0.97). Due to persistent cholestasis, a repeat A1AT serum concentration was low level at 32 mg/dl, although a repeat ELISA was now reported as the Z phenotype consistent with the ZZ genotype. Due to conflicting tests of mutant serum A1AT proteins, her liver biopsy was re-analyzed with intrahepatic positive periodic acid–schiff stain (PAS) granules now reported, consistent with the diagnosis of A1AT deficiency (Fig. 2). Concomitantly, CMV viremia was confirmed with an elevated CMV polymerase chain reaction (PCR) assay of 12,800. In the clinic, she exhibited significantly increased abdominal distension and marked ascites. Her bilirubin (total 8.8 mg/dl; conjugated 5.3 mg/dl) and aminotransferases (AST/ALT 500/309 units/l) were elevated. Additionally, a significant coagulopathy was noted with an international normalized ratio (INR) of 2.2 and low fibrinogen of 88. Hyponatremia (119 mg/dl) and metabolic acidosis were also present. She did not have any changes in her mental status, and her venous ammonia concentration was mildly elevated to 68 lmol/l. She was admitted to Lucile Packard Children’s Hospital at Stanford for correction of her electrolyte abnormalities and coagulopathy. She was treated with ganciclovir for CMV viremia. During her first 48 h in the hospital, despite the use of IV phytonadione, her hepatic synthetic liver function deteriorated rapidly, with daily doses of fresh-frozen plasma required to treat her coagulopathy. Due to her P. Arias (&) J. Kerner M. Christofferson W. Berquist K. T. Park Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Lucile Packard Children’s Hospital, Stanford University Medical Center, 750 Welch Road, Suite 116, Palo Alto, CA 94304, USA e-mail: parias@stanford.edu