Fibrinogen Replacement Underutilization in ECMO

Background: Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for critically ill children and adults. Hematologic complications, such as hemorrhage and thrombosis, are the major complications in ECMO. The contact of blood with the tubing of the circuit, lines, blood pump, and oxygenator all contribute to the process. Most patients require anticoagulation while on ECMO. According to the international summary of Extracorporeal Life Support Organization (ELSO) registry in 2017, patients on ECMO consist of 69% neonate and pediatric patients (Neo 44.8%, Peds 24.1%, Adult 31.1%). Contributors to the risk of bleeding include excessive heparin use for systemic anticoagulation, consumption of coagulation factors, low fibrinogen levels, thrombocytopenia, platelet dysfunction, and hyperfibrinolysis, among others. This gives the appearance of a consumptive coagulopathy, the hallmark of which is hypofibrinogenemia. Fibrinogen replacement is most efficiently done with cryoprecipitate (cryo) or fibrinogen concentrate, while fresh frozen plasma (FFP) has a low and variable fibrinogen content. Cryo and FFP may contribute to volume expansion and have other prothrombotic factors which could contribute to thrombotic complications. We performed a retrospective analysis of pediatric and adult patients who presented for ECMO to evaluate management of low fibrinogen and bleeding and thrombotic complications. Methods: Data was reviewed for 11 adult and 12 pediatric consecutive patients who received ECMO prior to June 1st, 2019. Time on ECMO (hours), type of ECMO, indication, presence of bleeding or thrombotic complications during ECMO, and use of therapeutic anticoagulation was collected. Laboratory data included platelet counts, hemoglobin, fibrinogen activity, antithrombin activity, prothrombin time, and partial thromboplastin time. Transfusion data was also collected for amount of packed red blood cells (PRBC), platelets, FFP, and cryo transfused. Data were analyzed to evaluate when fibrinogen was low and if cryo was given. According to our institutional guideline, the fibrinogen activity goal is >100 mg/dL and >200 mg/dL if bleeding. Bleeding and/or clotting complications were also noted. Data: There were 24 runs of ECMO evaluated (11 adults, 12 children), including VA and VV, lasting from 65-1343 hours. One child had 2 runs of ECMO. The majority were VA (13/24; 54%) with 33% (8/24) VV and 13% (3/24) combined VA/VV (all occurred in children). Therapeutic anticoagulation was given in 17/24 (71%) overall, but 92% (12/13) of pediatric cases. Bleeding and/or clotting complicated 17 (71%) runs. Overall, bleeding occurred in 13 (54%) runs and thrombosis in 12 (50%). Of these events, 8 (33%) runs had both bleeding and thrombosis. Bleeding occurred in 8/11 (73%) adults and 5/12 (42%) children. Bleeding and/or thrombus occurred more often with longer ECMO runs, but affected all runs longer than 250 hours (12/24, 50%). While on ECMO, the fibrinogen activity was below 100 mg/dL at some point in 11/24 (46%) of runs. Of those 11, only 6 (55%) received cryo in response to the fibrinogen activity. Cryo was more likely to be given if both a low fibrinogen and bleeding were present. Even with bleeding episodes and fibrinogen activities <200 mg/dL, cryo was not given in the majority of cases (70% adults, 40% children), but FFP was given preferentially. Conclusions: Almost half (45%) of the patients evaluated had low fibrinogen levels at some point while on ECMO. Despite cryoprecipitate being standard replacement at our institution for low fibrinogen, only 55% of those patients received cryo in response to the low level. Therefore, 21% (5/24) of all cases were not specifically treated for their low fibrinogen value. Bleeding and/or thrombotic complications are common with ECMO. Further study to determine if fibrinogen replacement or lack thereof contributes to these complications and guide management of fibrinogen deficiency in ECMO patients is warranted. Figure Disclosures No relevant conflicts of interest to declare.

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Platelet consumption during neonatal extracorporeal life support (ECLS)

Perfusion ◽

10.1177/026765919200700106 ◽

1992 ◽

Vol 7 (1) ◽

pp. 27-33 ◽

Cited By ~ 9

Author(s):

Franz B Plötz ◽

Walter R Wildevuur ◽

Charles RH Wildevuur ◽

Ralph E Delius ◽

Robert H Bartlett

Keyword(s):

Blood Loss ◽

Life Support ◽

Extracorporeal Life Support ◽

Fresh Frozen Plasma ◽

Entire Period ◽

Bleeding Complications ◽

Wound Drainage ◽

Packed Red Blood Cells ◽

Neck Wound ◽

Fresh Frozen

This paper reports the results of a retrospective study of blood use and blood loss in 40 neonates during extracorporeal life support (ECLS). Immediately after onset of bypass 39±2.5ml platelets, 59.4±6.5ml packed red blood cells (PRBC) and 15.0±5.4ml fresh frozen plasma (FFP) per patient were needed. The average daily amount given per patient was 49.0±3.0ml of platelets and 48.0±3.4ml and 9.6±3.9ml of PRBC and FFP respectively. The 10 patients who had bleeding complications received 50.0±6.3ml/day of platelets compared to 49.0±3.4ml in the other patients. The majority of blood loss during the entire period of ECLS was from samples, averaging 43.0 ± 1.5ml/day. Neck wound drainage, 6.7±2.5ml/day per patient, lasted for the entire period.

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A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures

Neurosurgery ◽

10.1093/neuros/nyx327 ◽

2017 ◽

Vol 82 (6) ◽

pp. 877-886 ◽

Cited By ~ 6

Author(s):

Prateek Agarwal ◽

Kalil G Abdullah ◽

Ashwin G Ramayya ◽

Nikhil R Nayak ◽

Timothy H Lucas

Keyword(s):

Propensity Score ◽

Intracranial Hemorrhage ◽

Fresh Frozen Plasma ◽

Neurosurgical Procedures ◽

Thrombotic Complication ◽

Propensity Score Matching Analysis ◽

Therapeutic Anticoagulation ◽

Fresh Frozen ◽

Thrombotic Complications ◽

Frozen Plasma

AbstractBACKGROUNDReversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP).OBJECTIVETo compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center.METHODSSixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status.RESULTSThrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias.CONCLUSIONIn this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures.

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Prothrombin Complex Concentrate Is Safe and Effective for Achieving Hemostasis in the Setting of Urgent Surgery for Patients Treated with Direct Xa Inhibitors

Blood ◽

10.1182/blood-2018-99-117378 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2541-2541

Author(s):

Merav Barzilai ◽

Ilya Kirgner ◽

Arza Steimatzky ◽

Dalit Salzer Gotler ◽

Yulia Belnick ◽

...

Keyword(s):

Prothrombin Complex Concentrate ◽

Conflicts Of Interest ◽

Reversal Agent ◽

Safety Measures ◽

Packed Red Blood Cells ◽

Urgent Surgery ◽

Limited Experience ◽

Tertiary Hospitals ◽

Thrombotic Complications ◽

Hemoglobin Drop

Abstract Introduction: Patients treated with direct Xa inhibitors may require an urgent surgery. A reversal agent for Xa inhibitors was recently approved for major bleeding but not prior to urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is a common practice; however, it is based on limited experience in healthy volunteers. Objective: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery/procecdure and evaluate its efficacy and safety. Methods: A retrospective study in two tertiary hospitals. Bleeding was evaluated by surgical reports, hemoglobin drop and use of packed red blood cells or additional PCC during 48h. Safety measures were thrombotic complications and 30-day mortality. Results: Sixty-two patients, aged 80.7±9, received PCC prior to urgent invasive procedures ;39 (63%) received apixaban and 23( 37%) rivaroxaban. Ninety percent of them received anticoagulation due to atrial fibrillation. Most urgent procedures were abdominal surgery (61%), orthopedic surgery (13%) or transhepatic cholecystostomy insertion (10%). Mean dose of PCC was 26.6±8 U/kg. Fourteen patients (23%) received 1 gram of tranexamic acid. Bleeding was reported by surgeons in 3(5%) patients and no patient required additional PCC. Sixteen (26%) patients received packed cells (median 1 unit, range 1-5). Thirty day mortality and thrombosis were 13(21%) and 2(3%) respectively. Cause of death was related to the primary disease or sepsis. No patient died due to bleeding/thrombosis. Conclusions: PCC is safe and effective for the reversal of Xa inhibitors prior to an urgent surgery/procedure. Disclosures No relevant conflicts of interest to declare.

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Hemolytic Intravascular Anemia (HIA) Microangiopathic-Like and Deep Venous Thrombosis (DVT) Due to Ozone Exposure: Case Report

Blood ◽

10.1182/blood.v118.21.5278.5278 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5278-5278

Author(s):

Luis Fernando Cortázar-Benítez ◽

Pablo Vargas Viveros ◽

Alfredo Aiza Alvarez ◽

Rafael Hurtado Monroy

Keyword(s):

Conflicts Of Interest ◽

Laboratory Data ◽

Peripheral Blood Smear ◽

Fresh Frozen Plasma ◽

Ozone Exposure ◽

Fresh Frozen ◽

The Right ◽

Glucose 6 Phosphate Dehydrogenase ◽

Frozen Plasma

Abstract Abstract 5278 HIA due to ozone exposure on patients with glucose 6 phosphate dehydrogenase deficiency (G6PDd) is extremely rare. The purpose of this report is to describe in detail a case of HIA and DVT on a woman without G6PDd, with a successful treatment with fresh frozen plasma (FFP) transfusion and Thrombolysis. The patient is a 36 years old woman, that 3 months before she was diagnosed with multiple sclerosis (MS) because paresthesias in the fingers of her left foot and she received treatment with blood ozone exposure (at unknown dose) in 3 sessions each week for 3 months. The patient attended to our center with severe anemic syndrome during the last 2 weeks and disabling pain of her left leg of 12 hours of evolution. Physical examination showed pale ++++, jaundice ++, functional systolic murmur grade IV, without adenomegaly or splenomegaly, increasing volume, induration, erythema and intense pain from the ankle to the popliteal space of her left leg. The urine was dark. Laboratory data were haemoglobin 5 g/dL, hematocrit 17%, reticulocytes 62%, and platelets 281×109/L. Peripheral blood smear showed esquistocytes +++ and spherocytes ++, suggesting intravascular hemolysis. Total bilirrubin 2.99mg/dL, direct bilirubin 0.57, and LDH 750 U/L. Doppler ultrasound: obstruction of the deep and superficial venous system of tibial, peroneal and left popliteal veins. Four red cells units were transfused and FFP transfusion was started every 6 hours, anticoagulation with enoxaparina sodium (1mg/Kg/day) and thrombolysis with rhTPA 100 mg for 3 hours infusion. The patient successfully improved with increase and maintenance of hemoglobin, decrease of the reticulocytes count and evident clinical improvement of her left leg. She was in-hospital for 8 days at the end of which was achieved ambulation, Doppler showed remission of DVT. The association between exposure to ozone and HIA has not been informed in the absence of G6PD deficiency, and today, little is known of the ideal treatment. Though plasmapheresis is the treatment of choice in a HIA, the presence of DVT and be in a period appropriate for thrombolysis, determined the use of FFP transfusion as the main treatment. The right clinical evolution observed in the treatment of our patient gave her solving clinical problems. Ozone has been widely used for a variety of off-label purposes. In vitro experiments had demonstrated hemolysis with ozone concentration > 30 mcg/mL, therefore this case must represent an important alert for those ozone users, however the mechanism of hemolysis because ozone exposure remains to be elucidated. Disclosures: No relevant conflicts of interest to declare.

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Associated Risk of Recombinant Activated Factor VIIa Application

The Heart Surgery Forum ◽

10.1532/hsf98.20121127 ◽

2013 ◽

Vol 16 (3) ◽

pp. 132

Author(s):

Arndt-Holger Kiessling ◽

Janine Nitsch ◽

Ulrich Strouhal ◽

Angela Kornberger ◽

Andreas Zierer ◽

...

Keyword(s):

Factor Viia ◽

Therapeutic Option ◽

Treatment Algorithm ◽

Fresh Frozen Plasma ◽

Severe Bleeding ◽

Acute Bleeding ◽

Packed Red Blood Cells ◽

Fresh Frozen ◽

Thrombotic Complications ◽

Ischemic Attack

Background: The recombinant human coagulation FVIIa was approved for the treatment of bleeding in hemophilia patients. The reports of a good hemostatic effect were followed by studies and applications without a regulatory extension of the therapeutic indication (off-label use). The aim of this retrospective study is the evaluation of thromboembolic adverse events and side effects in a large cohort of patients with FVIIa therapy.Methods: In the period from January 2009 to March 2011, a total of 143/2453 (5.8%) cardiac surgical patients (69% male; age 67 � 11 years; 39% thoracic aorta) were treated with different doses (mean, 6.1 mg; range, 1 to 27.2 mg) of factor VIIa. The administration of FVIIa was seen as a last therapeutic option and administered at the end of the treatment algorithm for severe bleeding.Results: Due to an acute bleeding situation in 143 patients, 7.9 � 5.8 units of packed red blood cells, 9.5 � 6.1 units of fresh frozen plasma, 1740 � 1860 IU PPSB (Prothrombin-Proconvertin-Stuart Factor-Antihemophilic Factor B), 5.6 � 4 g fibrinogen, and 7.9 � 7.6 units of platelets were administered. A re-thoracotomy was necessary, despite maximal procoagulant therapy, in 55% of patients. The in-hospital mortality was 36% (51/2453 = 2%). Thrombotic complications occurred with a frequency of 16% (mesenteric infarction, n = 9; stroke/transient ischemic attack, n = 3; myocardial infarction, n = 3; other, n = 8).Conclusion: The proof of direct causality of the events in relation to the administration of FVIIa is difficult because the temporal and therapeutic relationships with concomitant vasoconstrictive and procoagulant therapies were not obvious. However, there remains a suspicion that a higher rate of mesenteric infarctions may be provoked by the administration of FVIIa.

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Outcomes of extracorporeal life support for respiratory failure in children with primary immunodeficiencies

Perfusion ◽

10.1177/02676591211033946 ◽

2021 ◽

pp. 026765912110339

Author(s):

Brandon Michael Henry ◽

Alexis L Benscoter ◽

Maria Helena Santos de Oliveira ◽

Jens Vikse ◽

Tanya Perry ◽

...

Keyword(s):

Respiratory Failure ◽

Life Support ◽

Extracorporeal Life Support ◽

Discharge Rate ◽

Rescue Therapy ◽

Survival Rates ◽

Pulmonary Complications ◽

Primary Immunodeficiencies ◽

Critically Ill Children ◽

Cardiac Complications

Objective: Extracorporeal Membrane Oxygenation (ECMO) may serve as a life-saving rescue therapy in critically ill children with respiratory failure. While survival rates of ECMO in children with secondary immunodeficiency is considered relatively poor, survival rates in children with primary immunodeficiencies (PID) has yet to be thoroughly investigated. Design: Retrospective analysis of prospectively collected data from children (29 days–18 years old). PID patients were identified by using International Classification of Diseases (ICD) codes. Setting: Data were retrieved from Extracorporeal Life Support Organization Registry (1989–2018). Interventions: ECMO for a pulmonary support indication. The survival-to-discharge rate was calculated and factors influencing outcomes were compared between survivors and non-survivors. Measurements and main results: A total of 73 eligible ECMO runs were included. The survival-to-discharge rate in pediatric PID patients was 45.2%. No differences were noted in survival based on type of immunodeficiency (p = 0.42) or decade of support (p = 0.98). There was no difference in the rate of pre-ECMO infection in survivors versus non-survivors (p = 0.69). The survival-to-discharge rate in patients with a culture positive infection during the ECMO run was 45.0% versus 45.3% in those with no infection (p = 0.98). In multivariate analysis, only cardiac complications (OR 5.09, 95% CI: 1.15–22.53), pulmonary complications (OR: 13.00, 95% CI: 1.20–141.25), and neurologic complications (OR: 9.86, 95% CI: 1.64–59.21) were independently associated with increased mortality. Conclusion: Children with a PID who require extracorporeal life support due to respiratory failure have a reasonable chance of survival and should be considered candidates for ECMO. The presence of a pre-ECMO infection should not be considered an ECMO contraindication.

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Extracorporeal life support in pediatric patients

Patologiya krovoobrashcheniya i kardiokhirurgiya ◽

10.21688/1681-3472-2018-4-35-47 ◽

2018 ◽

Vol 22 (4) ◽

pp. 35

Author(s):

I. A. Kornilov

Keyword(s):

Conflict Of Interest ◽

Life Support ◽

Extracorporeal Life Support ◽

Pediatric Intensive Care ◽

Careful Consideration ◽

Critically Ill Children ◽

Multicenter Studies ◽

Clinical Indications ◽

Life Saving ◽

Patient Selection Criteria

Extracorporeal life support (ECLS) or extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for critically ill children with high mortality, cardiac and/or respiratory failure refractory to conventional intensive treatment. In the last decade, the use of ECLS in pediatric intensive care has rapidly grown. The clinical indications and contraindications for ECLS have changed dramatically. The given review describes the fundamentals of ECMO technology, main clinical indications for ECLS and outcomes of ECMO in neonates and children. ECMO has become the standard for treatment of refractory acute heart failure, cardiac arrest, severe acute respiratory distress syndrome against the background of a decreasing number of contraindications. Although ECMO may be used nowadays to support even smaller babies and those with far more serious pathologies, careful consideration of the risk factors and probable outcomes is very important for decision to initiate and continue ECMO. The use and management of ECLS widely varies between clinics. Further multicenter studies are required to optimize patient selection criteria, cannulation and ECMO management, to reduce the number of complications and to analyze the quality of life of patients after ECMO and the cost effectiveness.Received 2 December 2018. Revised 14 December 2018. Accepted 14 December 2018.Funding: The study did not have sponsorship.Conflict of interest: Author declares no conflict of interest.

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Management of Major Bleeding Caused By Rivaroxaban and the Use of Desmopressin

Blood ◽

10.1182/blood.v124.21.5099.5099 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5099-5099

Author(s):

Ahmad Jajeh

Keyword(s):

Major Bleeding ◽

Large Scale ◽

Conflicts Of Interest ◽

Factor Xa ◽

Fresh Frozen Plasma ◽

Thrombin Time ◽

Gi Bleeding ◽

Complex Product ◽

Packed Red Blood Cells ◽

Treatment And Prevention

Abstract Rivaroxaban is a new anticoagulant that is substituted for Coumadin on a large scale in the treatment and prevention of Deep Vein Thrombosis DVT and Pulmonary Embolism PE. It is an oral agent that inhibits Factor Xa. The most attractive attribute of this new anticogulant is the lack of monitoring PT/INR. However, out of many cases put on Rivaroxaban a few reports of major and threatening bleed that could be fatal. Particularly, the the GI bleeding. Unfortunately, no set standard antidote or management is available when such catastrophic bleeds happen. This abstract present our experience with three major bleeding cases that presented with massive GI bleeding. Two are associated with peptic ulcer upon Upper GI endoscopy. Two males and one female age 60, 71 (males) and 71 (female). The first two patients were treated with Prothrombin complex product. The female patient presented with sever anemia of 4 grams of Hb with hematemesis and bright red blood per rectum. The Prothrombin complex product was not readly available . She was given multipe doses of Fresh Frozen Plasma FFP and multiple units of packed red blood cells. She was also given a product Profilnine which contains Factor II, IX and VII. Patient's coagulation profile of PTT, PT and Thrombin time were corrected. However, she continue to have bright blood per NG suction. Upon receiving D-DAVP Desmopressin 0.3 micrograms per Kg she stopped bleeding and EGD was done later with sclerosing treatment of gastric ulcer and ligation. Patient was given later a small dose of Prothrombine complex when was available since the last dose of Rivaroxaban was given less than 13 hours from her presentation to the hospital. All of the mentioned patients had prolongation of PT/INR/PTT at presentation. Thrombin time was monitored in all of them. All patients had survived the magor GI bleeding. D-DAVP were given to all of them. In conclusion D-DAVP Desmopressin should be considered as an adjuvant drug in patient presentong with major GI bleeding secondary to Rivaroxaban. Disclosures No relevant conflicts of interest to declare.

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Development of a Novel Fluid Management System for Accurate Continuous Hemofiltration in Extracorporeal Membrane Oxygenation

ASME 2007 2nd Frontiers in Biomedical Devices ◽

10.1115/biomed2007-38062 ◽

2007 ◽

Cited By ~ 1

Author(s):

Lakshmi P. Dasi ◽

Philippe Sucosky ◽

Stephen Goldman ◽

Mathew Paden ◽

James Fortenberry ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Neonatal Intensive Care ◽

Life Support ◽

Extracorporeal Life Support ◽

Fluid Management ◽

Volume Overload ◽

Critically Ill Children ◽

Continuous Hemofiltration ◽

Membrane Oxygenation ◽

Life Saving

Failure of the cardiac or respiratory system is a common problem in the pediatric and neonatal intensive care unit. When conventional management fails to improve the child’s condition, extracorporeal life support such as extracorporeal membrane oxygenation (ECMO) can serve to provide life-saving temporary heart and lung support [1]. Renal failure often complicates care of these critically ill children on ECMO, leading to accumulation of fluid and volume overload that can worsen their heart and lung disease. Restrictive fluid management has been demonstrated to improve patient outcomes in acute lung injury.

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