Risk Of Transfusion-associated Circulatory Overload Research Articles

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

Continuous Platelet Infusion Is an Effective Alternative to Conventional Transfusion in Reducing Platelet Transfusions in Critically Ill Pediatric Patients with Refractory Thrombocytopenia

Background: Thrombocytopenia is often seen in critically ill children and platelet transfusions are needed to prevent or treat bleeding. However, some patients can exhibit platelet refractoriness (PR), characterized as a suboptimal rise in platelet count after platelet transfusion resulting in increased platelet transfusion to maintain the desired platelet target. Repeat platelet transfusions can increase the risk of transfusion-associated circulatory overload (TACO), allergic transfusion reaction and human leukocyte antigen (HLA) alloimmunization. To reduce the total platelet requirement and maintain platelet target, continuous platelet infusion (CPI), which involves transfusion of small volumes of platelets over an extended period of time, is utilized. However, data comparing the total platelet usage between CPI and conventional platelet transfusion (CPT) in critically ill children with PR are lacking. Objectives: Compare total platelet usage per day and peak platelet count between CPI and CPT in pediatric patients with PR. Methods: A retrospective cohort study was performed on all children who received CPI from February 2014 through December 2021 at a tertiary pediatric hospital. CPI was defined as: 1) for children weighing ≤35kg, transfusion of 5ml/kg apheresis platelets over 4 hours every 4-8 hours or 2) for children weighing >35kg, transfusion of 0.5 unit of apheresis platelet over 4 hours every 4-8 hours. Data collection included patient demographics, reason for admission, and bleeding history. A two-tailed paired sample t-test was used to compare platelet count trough and peak, and total platelet volume transfused per day, between CPT (before initiating CPI or pre-CPI) and during CPI (CPI). A P<0.05 was defined as statistically significant. This study was approved by the Institutional Review Board. Results: Sixteen children with PR received CPI with demographics summarized in Table 1. Median age at time of study was 6.1 years (IQR: 0.4-14). Patients were initiated on CPI by the Transfusion Medicine service due to suspected PR. All patients were admitted to the intensive care unit (ICU) when CPI was initiated. Prior to CPI, 10 (62.5%) children had bleeding symptoms, including 6 major bleeds (intracranial hemorrhage) and 4 clinically relevant non-major bleeds (1 post-surgical, 1 pulmonary, 1 mucocutaneous, and 1 gastrointestinal bleeding event). There was a no difference in the mean platelet trough with CPI (m= 20x109/L, s= 16.2) versus pre-CPI (m= 26x109/L, s= 22.4), (t(15) =-1.705, P=0.109). There was no difference in the platelet peak in the pre-CPI (m= 80x109/L, s= 44.6) versus CPI (m= 98x109/L, s= 56.1), (t(15) =-1.185, P=0.254). There was a statistically significant difference in the mean total volume of transfused platelets per day in patients receiving CPT, pre-CPI (m= 158.4 mL/day, s= 68.5) versus CPI (m= 132.6 mL/day, s= 67.1); there was less volume infused daily when patients received CPI (t(15) =2.530, p=0.023). Overall, both transfusion strategies achieved a similar platelet peak, but the CPI required significantly less platelet transfusion by volume per day compared to CPT (Figure 1). Conclusion: Our study demonstrated that those on CPI received a statistically significantly lower volume of platelet transfusion per day compared to CPT to maintain similar platelet counts. While a small sample size and wide variation in platelet counts likely limited the comparison of platelet peak and trough values, there was a trend towards higher platelet counts with CPI. This study suggests that CPI should be considered as alternative to CPT in critically ill children with PR, especially those at risk of TACO. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Conceptual Framework for Evaluating Patients Who May Need Red Cell Transfusion

Blood transfusion is an extremely common procedure that may be associated with significant risks, and orders for transfusion are common targets for “Choosing Wisely” Campaigns. Evaluating a patient for the need for red blood cells (RBCs) transfusion is not always a simple process. Although several guidelines are published to aid in determining which patients need a transfusion of RBCs, the decision can be complicated and must be individualized. Guidelines are frequently updated based on current published literature, but several elements must always be considered during patient evaluation for the possible need for RBC transfusion. We suggest using the acronym HOPES 2 C as a reminder of these elements (Hemoglobin level, Onset of anemia, Patient view, Extremes of age, Symptoms, Cause of anemia, and Co-morbidities).Hemoglobin level must always be taken into account when evaluating a patient for the need for RBC transfusion. Many randomized clinical trials (RCTs) have shown that following a restrictive transfusion strategy (avoiding transfusion until Hb reaches 7 or 8 g/dL) is either equal or superior when compared with a liberal transfusion strategy (transfusion for Hb of 9-10 g/dL). The lower the hemoglobin, the more likely the patient will require a transfusion.Onset of anemia: Patients with chronic anemia rarely require rapid transfusion, allowing time for investigation and provision of other effective treatments, such as iron or B12. These patients are also at increased risk of transfusion-associated circulatory overload. On the other hand, most patients with acute blood loss will require transfusion as part of resuscitation efforts.Patient view: Patient caremust be guided by the individual patient's values and preferences.Extremes of age: Patients at extremes of age (newborns and geriatric patients) may require different transfusion thresholds. This point needs further evaluation through RCTs.Symptoms: The presence of hypotension, tachycardia, and end-organ dysfunction secondary to anemia indicate the need for transfusion.Cause: Patients with anemia must not be transfused without an attempt to understand the cause of anemia. History, physical examination, and laboratory tests must be reviewed to evaluate for cause of anemia that may be correctable through effective alternatives to transfusions, such as iron or B12.Co-morbidities: Patients with acute coronary syndrome or other diseases affecting oxygen delivery may need special consideration at the time of assessment. RCTs were published about a number of these settings, such as acute coronary syndrome, but further evidence is awaited for others.It must be emphasized that this conceptual framework does not apply to patients with thalassemia and hemoglobinopathies, as care of these patients must follow disease-specific guidelines.We hope that this conceptual framework helps physicians capture all assessment elements of a patient who may need a blood transfusion. We expect that this will reduce unnecessary transfusions while maintaining patient safety and quality of care. DisclosuresNo relevant conflicts of interest to declare.

Scalp Swelling and Headache in a 12-year-old Boy

1. Kathryn Westphal, MD* 2. Respicius Bakalemwa, MD† 3. Elizabeth Groothuis, MD, MPH* 1. *Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 2. †Department of Pediatrics, Bugando Medical Centre, Mwanza, Tanzania A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma. On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of …

Left heart dimensions in anemic cats and dogs before and after blood transfusion.

BackgroundWhether anemic cats and dogs with increased left heart dimensions are at higher risk of transfusion‐associated circulatory overload, and the effect of blood transfusion on left heart dimensions in naturally occurring anemia is unknown.Hypothesis/objectivesTo evaluate the effect of blood transfusion on left heart dimensions in clinically relevant anemia.AnimalsTwenty dogs and 20 cats presenting to a university veterinary teaching hospital.MethodsIn this prospective observational study, anemic dogs and cats requiring blood transfusion were included. Packed cell volume (PCV), total solids, and echocardiography were performed before and within 24 hours of blood transfusion. Signalment, bodyweight, disease process, transfusion duration and volume, and prior treatments were recorded. Nonparametric statistics were reported as median [range]. Post hoc Bonferroni correction set significance at P < .006.ResultsAfter transfusion, PCV increased in cats (12% [6–16] to 18% [10‐33], P = .001) and dogs (14% [7–24] to 25% [9‐37], P = .001), heart rate decreased in dogs (104 bpm [86‐166] to 87 bpm [56‐138], P < .001), and fractional shortening decreased in cats (57.1% [36.0‐84.7] to 41.0% [28.1‐69.6], P = .002) and dogs (33.79% [19.33‐62.79] to 31.89% [19.06‐51.47], P = .006). Left ventricular internal diameter in systole increased in cats (6.5 mm [2.7‐9.8] to 7.9 mm [5.3‐11.1], P = .001). Normalized left ventricular internal diameter in diastole (1.48 [1.25‐1.79] to 1.57 [1.33‐2.00], P = .001) and systole (0.87 [0.58‐1.19] to 1.00 [0.74‐1.36], P = .001) increased in dogs. Incidence of volume overload did not differ before (14/20 cats, 70%; 9/20 dogs, 45%) or after (12/20 cats, 60%; 11/20 dogs, 55%) transfusion (P = .64).Conclusions and clinical importanceBlood transfusion is well tolerated when signs of volume overload are present before transfusion.

The Fares Study: A Multicenter, Randomized, Active-Control, Pragmatic, Phase 2 Pilot Study Comparing Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgical Patients

Introduction: Coagulopathic bleeding is a frequent complication of cardiac surgery and can lead to excessive blood loss, blood product transfusion, and bleeding-related complications. Hemostatic management in bleeding surgical patients is evolving towards targeted therapy with purified products undergoing pathogen reduction technology. Unlike frozen plasma (FP), purified prothrombin complex concentrates (PCCs) do not require ABO blood type matching or thawing, are pathogen-reduced, and are associated with a lower risk of transfusion-associated circulatory overload and transfusion-related acute lung injury. The FARES study will compare the efficacy and safety of PCC (Octaplex; Octapharma) versus FP in bleeding cardiac surgical patients with confirmed or suspected coagulopathy. Preliminary non-randomized studies suggest PCC may be superior to plasma for management of bleeding after cardiac surgery. Methods: The randomized, active-control, single-blinded, pragmatic, investigator-initiated, Phase 2 FARES pilot study will enrolled 120 bleeding adult cardiac surgery patients requiring coagulation factor replacement from two hospitals to achieve 100 treated patients. The study outline is shown in Figure 1. Patients were randomized to PCC or FP, with two weight-based doses, for management of bleeding where coagulation factor deficiency is known or suspected (patients over 50 kg were transfused either 2000 IU of PCC or 4 units of plasma; patients under 50 kg were transfused 1500 IU of PCC or 3 units of plasma). Required second doses will be given according to randomization group allocation, but all patients will receive FP for their third and any subsequent doses. The primary endpoint is hemostatic effectiveness and transfusion requirements. Adverse events will be recorded from the beginning of surgery. Results: The study commenced in September of 2019 and completed enrollment of the last patient in June of 2020. Results were monitored and overseen by the Independent Data and Safety Monitoring Committee. The database will be locked in August 2020 after 28 day follow-up is complete for all patients. Statistical analysis plan is complete. The results will inform a definitive, pragmatic, multi-center trial to determine if PCCs can replace plasma for the management of coagulopathy in the bleeding cardiac surgery patient. Conclusions: This study will determine the feasibility, and inform the design and primary outcome parameter, of a definitive Phase 3 trial comparing the efficacy and safety of PCC versus FP in bleeding cardiac surgical patients requiring coagulation factor replacement. The pilot study results will also be used in sample size calculations and to aid detection of any safety issues. Disclosures Karkouti: Octapharma: Research Funding; Canadian blood services: Research Funding. Callum:Canadian Blood Services: Research Funding; Octapharma: Research Funding. OffLabel Disclosure: Coagulation factor replacement with Prothrmobin Complex Concentrates (off-label in the USA and on label in Canada/Europe)

Transfusion-associated circulatory overload risk mitigation: survey on hospital policies for compliance with AABB Standard 5.9.17.

AABB Standards for Blood Banks and Transfusion Services require accredited institutions to have a policy for handling requests for blood components on patients clinically identified as being at high risk for transfusion-associated circulatory overload (TACO; Standard 5.19.7, 31st edition). This survey elucidated how AABB accredited hospital transfusion services/blood banks around the world are complying with this Standard. A link to a Web-based survey in English was e-mailed under the auspice of the AABB to each AABB accredited hospital transfusion service/blood bank (n = 851) asking for details on how their institution is complying with this Standard and for general information on any TACO risk mitigation strategies in place. Of the 290 responses received (34% response rate), 282 met the criteria for analysis. There were 174 of 282 (62%) respondents who indicated that their institution has a formal policy for complying with the Standard, and 108 of 282 (38%) who indicated that their institution does not have a formal policy. A diverse range of policies and practices were in place at the institutions with and without a formal policy ranging from writing advice/recommendations in the charts of patients at increased risk of TACO, promulgating policies from the transfusion service/blood bank or institution itself that would reduce the risk, or using decision support tools to provide education about reducing the risk of TACO. Many but not all AABB accredited institutions have policies to comply with the TACO risk mitigation Standard. However, the vast majority conduct activities that could mitigate risk for TACO.

AGA Clinical Practice Update: Coagulation in Cirrhosis.

This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. BEST PRACTICE ADVICE 1: Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. BEST PRACTICE ADVICE 2: In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction-induced coagulation abnormalities. BEST PRACTICE ADVICE 3: Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. BEST PRACTICE ADVICE 4: The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. BEST PRACTICE ADVICE 5: Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. BEST PRACTICE ADVICE 6: The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. BEST PRACTICE ADVICE 7: The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. BEST PRACTICE ADVICE 8: Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. BEST PRACTICE ADVICE 9: Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. BEST PRACTICE ADVICE 10: Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). BEST PRACTICE ADVICE 11: Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. BEST PRACTICE ADVICE 12: Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease.

Cardiac stress biomarkers after red blood cell transfusion in patients at risk for transfusion-associated circulatory overload: a prospective observational study.

Transfusion-associated circulatory overload (TACO) is a leading cause of serious reactions. In regard to TACO, little is known regarding biomarkers as a predictor, their most informative timing, or thresholds of significance or differentiation from other reactions. In this study of inpatients at risk for TACO (age ≥ 50 years) receiving 1 red blood cell unit, cardiac biomarkers, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and high-sensitivity troponin were measured at baseline, 6 to 12 hours (except troponin) posttransfusion, and 18 to 24 hours posttransfusion. Primary outcome was a critical increase in biomarkers (>1.5-fold increase and supranormal) at 18 to 24 hours. Fifty-one patients were analyzed; 29% had cardiovascular disease, 73% had one or more cardiac risk factors, and 50% took cardiac or antihypertensive therapies. Although eight (16%) developed an increase in systolic pressure of at least 30 mmHg and four (8%) reported dyspnea and/or cough, none had TACO. At baseline, BNP level was more than 100 ng/L in 59% and NT-proBNP was more than 300 pg/mL in 83%. A total of 25% had a BNP critical increase, 33% had a NT-proBNP critical increase, and 2% had a troponin critical increase at 18 to 24 hours. Overall, 38% had at least one biomarker critical increase and NT-proBNP/BNP concordance was 84%. An increase in the NT-proBNP (>1.5-fold increase and >300 pg/mL) at 18 to 24 hours was the commonest biomarker change. An increase of the NT-proBNP at 18 to 24 hours may be the preferred surrogate marker for identifying a patient experiencing physiologic difficulty in handling the volume challenge. Larger studies are needed to clarify the risk of TACO for a given pretransfusion biomarker profile and the correlation between TACO and increase in biomarkers after transfusion.

Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. Case-control study. Four tertiary care hospitals. We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. None. Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

An order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion-associated circulatory overload.

There are few studies of quality interventions to mitigate the risk of transfusion-associated circulatory overload (TACO). Our aim was to reduce TACO risk in patients admitted to internal medicine at our hospital, by addressing gaps in transfusion practice. A 3-month baseline audit of red blood cell (RBC) transfusion orders was conducted. An intervention consisting of a transfusion order set and physician checklist was developed and implemented based on identified gaps, followed by a 3-month post-intervention audit. Compliance with appropriateness criteria for RBC transfusion was ascertained, along with documentation of transfusion rate, diuretic usage and consent. A total of 97 transfusion orders from 68 inpatients and 95 orders from 62 inpatients were audited in the baseline and post-intervention groups, respectively. Compliance with appropriateness criteria was similar pre- and post-intervention (87 versus 85%, P = 0·81). Specification of transfusion rate improved (84 versus 98%, P < 0·01), and diuretics were appropriately ordered more frequently for patients with TACO risk factors (37 versus 64%, P < 0·01). Timing of diuretics shifted from between or post-transfusion to pre-transfusion (35 versus 86%, P < 0·01), without increases in hypokalemia or acute kidney injury. No case of TACO was observed during the study. Documentation of specific risks discussed during consent discussion improved (4 versus 23%, P < 0·01). A checklist and order set are tools that can improve the quality of transfusion orders by increasing the judicious use of pre-transfusion diuretics and augmenting the specification of transfusion rate. These interventions could be adapted to electronic order formats to improve transfusion safety.

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.

経口抗凝固療法に関連する二大合併症（頭蓋内出血，血栓症／血栓弁）の治療，及び併発時の管理

Warfarinによる経口抗凝固薬療法には，効果不足に起因する血栓性合併症と，効果過剰に起因する出血性合併症という双方のリスクが伴う．後者の中で特に重大な合併症である頭蓋内出血の死亡率は50％を超える．予後改善には早急かつ完全なWarfarin拮抗が必須である．新鮮凍結血漿が第一選択だが，Vitamin K依存性凝固因子の含有量が製剤間で異なり必要量が一概に予測できない，拮抗に時間を要する，容量負荷が大きいという側面を有する．緊急時には血液凝固第IX因子複合体が有用だが，適応外使用である．Warfarin拮抗の際には同時に血栓塞栓症の予防も念頭に置かなければならず，特に機械弁挿入患者では完全な止血を確認後，早期からヘパリンを併用し，発症1～2週間でWarfarin再開を考慮する．また機械弁不全をみた場合，血栓溶解療法を行うか否かには血栓弁とパンヌスの鑑別が重要である．さらに頭蓋内出血既往例が血栓弁を生じた場合，血栓溶解療法は禁忌に準じると考えるべきである．

Risk Factors and Outcomes in Transfusion-associated Circulatory Overload

BackgroundTransfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. MethodsUsing a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic (Rochester, Minn) hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression, and survival and length of stay were analyzed using proportional hazard models. ResultsTransfusion-associated circulatory overload was associated with chronic renal failure (OR 27.0; 95% CI, 5.2-143), a past history of heart failure (OR 6.6; 95% CI, 2.1-21), hemorrhagic shock (OR 113; 95% CI, 14.1-903), number of blood products transfused (OR 1.11 per unit; 95% CI, 1.01-1.22), and fluid balance per hour (OR 9.4 per liter; 95% CI, 3.1-28). Patients with transfusion-associated circulatory overload had significantly increased in-hospital mortality (hazard ratio 3.20; 95% CI, 1.23-8.10) after controlling for Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score, and longer hospital and intensive care unit lengths of stay. ConclusionsThe risk of transfusion-associated circulatory overload increases with the number of blood products administered and a positive fluid balance, and in patients with pre-existing heart failure and chronic renal failure. These data, if replicated, could be used to construct predictive algorithms for transfusion-associated circulatory overload, and subsequent modifications of transfusion practice might prevent morbidity and mortality associated with this complication.

Red blood cell transfusion in pediatric patients with severe chronic anemia: How slow is necessary?

Historic practice recommends slow transfusion for children with chronic anemia and hemoglobin less than 5.0 g/dl due to the theoretical risk of transfusion-associated circulatory overload (TACO). In our pediatric intensive care unit (PICU), we have been utilizing a more liberal transfusion practice in patients without underlying cardiopulmonary disease, and a faster transfusion rate appears safe in this population. Rate of transfusion must be based on multiple factors including convenience, timeliness of procedures and transport to an appropriate care facility, risk of alloimmunization and wastage of blood, stress for the family, and need for PICU monitoring.