Evaluation of effect of scheduled fresh frozen plasma on ECMO circuit life: A randomized pilot trial
BACKGROUND Factor consumption is common during ECMO complicating the balance of pro and anticoagulation factors. This study sought to determine whether transfusion of coagulation factors using fresh frozen plasma (FFP) increased ECMO circuit life and decreased blood product transfusion. Secondly, it analyzed the association between FFP transfusion and hemorrhagic and thrombotic complications. STUDY DESIGN AND METHODS Thirty-one pediatric ECMO patients between October 2013 and January 2016 at a quaternary care institution were included. Patients were randomized to FFP every 48 hours or usual care. The primary outcome was ECMO circuit change. Secondary outcomes included blood product transfusion, survival to decannulation, hemorrhagic and thrombotic complications, and ECMO costs. RESULTS Median (interquartile range [IQR]) number of circuit changes was 0 (0, 1). No difference was seen in percent days without a circuit change between intervention and control group, P = .53. Intervention group patients received median platelets of 15.5 mL/kg/d IQR (3.7, 26.8) vs 24.8 mL/kg/d (12.2, 30.8) for the control group (P = .16), and median packed red blood cells (pRBC) of 7.7 mL/kg/d (3.3, 16.3) vs 5.9 mL/kg/d (3.4, 18.7) for the control group, P = .60. FFP transfusions were similar with 10.2 mL/kg/d (5.0, 13.9) in the intervention group vs 8.8 (2.5, 17.7) for the control group, P = .98. CONCLUSION In this pilot randomized study, scheduled FFP did not increase circuit life. There was no difference in blood product transfusion of platelets, pRBCs, and FFP between groups. Further studies are needed to examine the association of scheduled FFP with blood product transfusion.
A study of effectiveness of fresh frozen plasma in organophosphorous compound poisoning in reducing length of Intensive Care Unit stay and in reducing need for tracheostomy
Anesthesia, Essays and Researches. 2016;10((2)):268-72.
BACKGROUND The main stay of treatment in organophophosphorous [OP] poisoning is with atropine, oximes and supportive therapy. Despite the therapy, no improvement in mortality and morbidity. Fresh frozen plasma [FFP] a source of serum cholinesterase act as bio-scavenger to neutralise organophosphate toxins to improve the patients out come. METHODS The prospective study was conducted in 80 patients with acute OP poisoning. Patients with moderate to severe grade of OP poisoning with serum cholinesterase level <1000 IU/L were included in the study. Study group received atropine and oximes along with FFP given as 4 units first day, 3units on 2(nd) day, 2 units on 3(rd) day. Control group was given atropine and oximes only. Serum cholinesterase enzymes level, consumption of atropine per day, number of days on ventilator, length of ICU stay, and need for tracheostomy were assessed. RESULTS There was a significant increase in the serum cholinesterase levels after FFP infusion in the study group in comparison to the control group. Mean duration of Intensive Care Unit [ICU] stay was 8.35+/-4.3 in the study group and 12.45+/-4.13 in the control group. 06 patients in the control group succumbed whereas there were no fatalities in the study group. CONCLUSION Daily reducing dose of FFP therapy for 3 consecutive days has beneficial effect in acute OP poisoning by increasing serum cholinesterase enzymes in blood with reduction in total dose of atropine consumption per day. It also reduces the ICU stay with zero mortality in OP poisoning.
Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME)
BACKGROUND Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion-related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP. STUDY DESIGN AND METHODS A multicenter randomized open-label trial with blinded endpoint evaluation was performed in critically ill patients with a prolonged international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a central venous catheter, percutaneous tracheostomy, chest tube, or abscess drainage were eligible. Patients with clinically overt bleeding, thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients were randomly assigned to omitting or administering a prophylactic transfusion of FFP (12mL/kg). Outcomes were occurrence of postprocedural bleeding complications, INR correction, and occurrence of lung injury. RESULTS Due to slow inclusion, the trial was stopped before the predefined target enrollment was reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP transfusion. Incidence of bleeding did not differ between groups, with a total of one major and 13 minor bleedings (p=0.08 for noninferiority). FFP transfusion resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No differences in lung injury scores were observed. CONCLUSION In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not.Copyright 2014 AABB.
What is known?
Audits continue to document that a common reason for transfusion of plasma is to non-bleeding critically ill patients with laboratory measures of abnormal coagulopathy and prior to invasive procedures. Although the broader observational literature argues against benefit for this practice, evidence from randomized controlled trials is very limited.
What did this paper set out to examine?
This paper describes a multi-centred randomized open-label trial in adult critically ill patients to determine whether FFP transfusion could be safely omitted prior to invasive procedures. The patients admitted to critical care were prospectively screened between 2010 and 2013 for prolongation of the INR. Patients fulfilling the inclusion criteria were randomly assigned to receive or not to receive a single dose of 12mg of FFP prior to defined invasive procedures which included insertion of a central venous catheter, for thoracocentesis, percutaneous tracheostomy, drainage of abscess or fluid collection. The primary outcome of the study was procedure related bleeding occurring within 24 hours after the procedure. Bleeding was assessed using a tool previously validated and published in the critically ill population. For this tool, major bleeding was defined if bleeding accompanied by any of the following; a decrease in Hb by more that 2g/dL in the absence of another course of bleeding, transfusion of two or more units of red cells without an increase in Hb, a decrease in systolic blood pressure by more that 20mmHg, an increase in heart rate or wound related bleeding requiring specific intervention.
What did they show?
Due to slow patient accrual the trial was stopped before the predefined target enrolment was reached which was indicated to be a sample size in each arm of 198 patients. 81 patients were randomly assigned, 42 FFP and 41 to no FFP transfusion. The incidence of bleeding did not differ between the two study group arms. One major bleed was reported but although this event rate was consistent with the prediction of the researchers, the lower event rate was considered too small to complete a planned inferiority analysis. There were 13 minor bleeds recorded but there is some uncertainty about these numbers given that the clinical significance of these events is unclear. It was also noted that transfusion resulted in a reduction of INR to less than 1.5 in 54% of the transfused patients. No differences were reported in lung injuries scores between the arms.
What are the implications for practice and for future work?
The researchers are to be commended for attempting to address a clinical important research question: that of the role of plasma transfusion prior to invasive procedures in critically ill patients. Unfortunately the trial failed to recruit to target and the findings are not able to provide the level of evidence required to refute a clinical role for plasma in this setting. There is a need for research to address the best diagnostic tests as well as the optimal role of plasma or other pro-haemostatic coagulation factors. Arguably another lesson from this trial is the value of pilot trials ahead of a larger trial which might, for example, identify issues with recruitment.
Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy
Journal of Thrombosis & Haemostasis. 2015;13((6)):989-97.
BACKGROUND 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. OBJECTIVES 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. METHODS 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). RESULTS 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. CONCLUSION In non-bleeding critically ill patients with a coagulopathy, FFP transfusion failed to induce a more procoagulant state.Copyright Â© 2015 International Society on Thrombosis and Haemostasis. RN 0 (Biomarkers). ES 1538-7836 IL 1538-7836
Plasma transfusion strategies for critically ill patients
Cochrane Database of Systematic Reviews. 2013;12:CD010654.
BACKGROUND Although plasma transfusions are frequently prescribed for critically ill patients, most clinical uses of plasma are not supported by evidence. Plasma transfusions do not seem to correct mild coagulation abnormalities based on international normalised ratio (INR) testing, but they seem to be independently associated with worse clinical outcomes in non-massively bleeding patients. Current recommendations on plasma transfusion strategies advocate limiting plasma transfusions to patients who are actively bleeding or who are at risk of bleeding and concomitantly have moderately abnormal coagulation tests. OBJECTIVES To determine whether use of a restrictive versus a liberal plasma transfusion threshold affects mortality or morbidity in critically ill patients, and to assess the clinical effects of different plasma transfusion thresholds in critically ill patients. SEARCH METHODS A search for studies was run on 15 August 2013. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE(R) Ovid, MEDLINE(R) Ovid In-Process & Other Non-Indexed Citations, MEDLINE(R) Ovid Daily and OLDMEDLINE(R) Ovid, EMBASE Classic + EMBASE (Ovid SP), reference lists, related websites and trial registries and checked lists of references. SELECTION CRITERIA Randomised clinical trials that assessed the effects of two plasma transfusion strategies, using a restrictive and a liberal threshold of at least one coagulation test, in critically ill participants. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed trial quality using the standard methods of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS Of 843 references identified by our search, none of the trials satisfied our predefined inclusion criteria. No studies are included in this review. AUTHORS' CONCLUSIONS This review highlights the lack of evidence that is available to guide plasma transfusions in critically ill patients. Randomised controlled trials are needed to determine the appropriate plasma transfusion strategy in critically ill patients.
Transfusion of fresh frozen plasma in non-bleeding ICU patients--TOPIC trial: study protocol for a randomized controlled trial
BACKGROUND Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure. METHODS A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay. DISCUSSION The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure. TRIAL REGISTRATION Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909.
Antithrombin III in comparison with fresh frozen plasma in patients with disseminated intravascular coagulation accompanied by antithrombin III deficiency
ISTH Congress. 2007;: Abstract No. P-T-666.
Comparison of the diuretic effect of furosemide mixed with human albumin or fresh frozen plasma for patients with hypoalbuminemia in the intensive care unit
Journal of Nephrology. 2006;19((5):):621-7.
BACKGROUND Diuretics are commonly used in the intensive care unit (ICU) for patients with fluid over-loading. Hypoalbuminemia is a major cause of diuretic resistance. Albumin mixed with furosemide can promote diuresis and sodium excretion in patients with hypoalbuminemia. The purpose of this study is to compare the diuretic effect of furosemide (FU) mixed with human albumin (HA) or fresh frozen plasma (FFP) in ICU patients with hy-poalbuminemia. METHODS Patients with fluid overloading and hypoalbuminemia who needed diuretic treatment were enrolled and were divided into 2 groups: the first group having clearance of creatinine (CCr) >20 ml/min, and the second group having CCr < or = 20 ml/min. FU (60 mg) mixed with HA (HA group), 60 mg FU mixed with FFP (FFP group) and water (placebo group) were given intravenously to these patients for 60 minutes in random order on the first, third and fifth day. After drug administration, 8-hour urine was collected, and urine amount and urinary sodium excretion were checked. RESULTS Both the HA group and the FFP group had significantly higher urinary volume and sodium excretion than the placebo group in the patients with CCr >20 ml/min or CCr < or = 20 ml/min (p < 0. 01). In the patients with CCr >20 ml/min, there was no difference in the amount of urine excretion and cumulative urinary sodium excretion between the HA group and FFP group. In the patients with CCr < or =ml;20 ml/min, the HA group had a significantly higher urine output and urinary sodium excretion than the FFP group (p < 0. 05). CONCLUSIONS In ICU patients, 60 mg FU mixed with HA or FFP has a similar diuretic effect in patients with CCr >20 ml/min. FFP is an effective alternative choice for improving diuresis for ICU patients with hypoalbuminemia. In patients with CCr < or = 20 ml/min, albumin mixed with 60 mg FU has a superior diuretic effect compared with FFP mixed with FU.
A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?
BACKGROUND Transfusion-related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double-blind, crossover study. STUDY DESIGN AND METHODS Intensive care patients, judged to need at least 2 units of plasma, were randomly assigned to receive a unit of control plasma and, 4 hours later, a plasma unit from a multiparous donor (> or = 3 live births) or to receive the plasma units in opposite order. The patients were closely monitored, and body temperature, blood pressure, and heart rate were recorded. Blood samples for analysis of blood gases, TNFalpha, IL-1 receptor antagonist, soluble E selectin, and C3d complement factor were collected at least on four occasions (before and after the transfusion of each unit). RESULTS Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFalpha concentrations than transfusion of control plasma. The mean arterial pressure increased significantly after the transfusion of control plasma, whereas plasma from multiparous donors had no effect on it. Five posttransfusion reactions were observed in 100 patients, in four cases after the transfusion of plasma from multiparous donors. CONCLUSION Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients.
Prevention of intraventricular haemorrhage by fresh frozen plasma
Archives of Disease in Childhood. 1985;60((8):):710-3.
Seventy three preterm infants weighing less than 1500 g or less than 32 weeks' gestation, or both, were allocated randomly to treatment (fresh frozen plasma 10 ml/kg on admission and at 24 hours of age) or control groups. Fifteen (41%) out of 37 control patients sustained intraventricular haemorrhage compared with five (14%) of 36 patients receiving treatment (X2 = 5.24, P = 0.022). No difference was found in coagulation factors measured at birth or at 48 hours of age in both groups. Fresh frozen plasma appears to have a beneficial effect in the prevention of intraventricular haemorrhage.