- Email: [email protected]
Retrospective analysis of transfusion outcomes in pregnant patients at a tertiary obstetric center
International Journal of Obstetric Anesthesia (2009) 18, 302–308 0959-289X/$ - see front matter c 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2009.02.005
ORIGINAL ARTICLE
www.obstetanesthesia.com
Retrospective analysis of transfusion outcomes in pregnant patients at a tertiary obstetric center A.J. Butwick, P. Aleshi, M. Fontaine, E.T. Riley L.T. Goodnough *
Departments of Anesthesiology and Pathology, Stanford University School of Medicine, Stanford, California, USA ABSTRACT Background: The decision to use red blood cell transfusion and/or blood products (fresh frozen plasma, platelets, cryoprecipitate) to manage obstetric hemorrhage or treat postpartum anemia is often made empirically by physicians. We performed a retrospective study to review transfusion outcomes in pregnant and postpartum patients at a large obstetric center. Methods: A retrospective, observational study was performed of obstetric in-patients who received red blood cell transfusion and/ or blood products over a one-year period. Data abstracted included transfusion data, pre-transfusion hemoglobin (Hb) and lowest recorded (nadir) Hb, and maternal and neonatal outcomes. Results: During the study period, 74 patients received transfusion therapy (1.4%). Pre-transfusion and nadir Hb values were 7.6 g/ dL and 7.0 g/dL respectively. Median [IQR] total red blood cells transfused were 2 units [2 -3], with 41 (55%) patients receiving 1-2 units. Based on chart review, no specific indications for transfusion were identified in 25 patients (34%), and 13 patients (18%) had undetected postpartum anemia (Hb values <8.2 g/dL) at least 24 h after delivery. Conclusion: More formal assessment and documentation of the etiologic factors associated with transfusion management in pregnant patients is advised. In addition, the identification and management of undetected postpartum anemia is underappreciated. c 2009 Elsevier Ltd. All rights reserved.
Keywords: Transfusion; Pregnancy; Anesthesia; Hemorrhage
Introduction Obstetric hemorrhage is the second most common cause of pregnancy-related death in the USA with a maternal mortality rate of 2 per 100 000 live births.1 During acute obstetric hemorrhage, obstetric care providers are often primarily involved in decision making on transfusion management. Laboratory assessments of hematocrit and hemoglobin concentration require time for laboratory processing, and are often reviewed retrospectively to assess the efficacy of empirical transfusion management in the setting of ongoing blood loss. Previous studies using simulated scenarios have suggested that there is marked variability among physicians in accuracy of estimating blood loss during obstetric hemorrhage,2 and in physician attitudes to blood transfusion for patients undergoing cesarean Accepted February 2009 This study was presented in part at the Society of Obstetric Anesthesia and Perinatology (SOAP) 40th Annual Meeting, April 2008, Chicago. Correspondence to: Dr. Alexander Butwick, Department of Anesthesiology (MC: 5640), 300 Pasteur Drive, Stanford University School of Medicine, Stanford, California 94305, USA. Tel.: +1 650 736 8513; fax: +1 650 725 8544. E-mail address: [email protected]
delivery.3 Furthermore, the incidence of red blood cell (RBC) transfusion after vaginal delivery and cesarean delivery can vary (<1% and 1-7% respectively).4,5 The aim of this retrospective study was to review transfusion outcomes and the indications for transfusion in obstetric patients receiving RBC transfusion at a large tertiary obstetric center.
Methods After gaining institutional review board approval, a retrospective chart review was performed of obstetric patients who received blood transfusions (RBC and/or blood products) between September 2006 and August 2007, at Lucille Packard Children’s Hospital. This is a university hospital and tertiary obstetric center with >5000 deliveries per year. Study investigators used the hospital’s computerized perinatal database to source data on all obstetric patients who received a transfusion of blood products (RBC, fresh frozen plasma, platelets, cryoprecipitate) during the study period. Blood transfusions administered to obstetric in-patients in the antepartum, peripartum and postpartum periods were included. Two fellowship-trained obstetric anesthesiolo-
A.J. Butwick et al. gists (PA, AB) independently reviewed individual patient medical records and laboratory data. Study investigators also reviewed the transfusion database from the transfusion service in the department of pathology. Based on chart review, data extracted included details of transfusion triggers, specific transfusion data, estimated blood loss (EBL) and maternal and neonatal outcomes. Blood loss is normally estimated by the obstetrician for patients undergoing vaginal delivery, and by mutual agreement between obstetrician and anesthesiologist for patients undergoing cesarean delivery. Laboratory values recorded included: baseline hemoglobin (Hb), the last recorded Hb before transfusion (pre-transfusion Hb), lowest recorded Hb during the study period (nadir Hb), Hb before discharge, and coagulation data (peak international normalized ratio (INR) and activated partial thromplastin time (APTT) values, lowest fibrinogen values). Baseline Hb values are routinely obtained at the time of admission to our labor and delivery unit for all patients admitted in labor or for induction of labor, or within 24 h before elective cesarean delivery. Sub analysis of patients receiving transfusion therapy was also performed, including etiology of hemorrhage requiring transfusion and timing of laboratory assessments of Hb following delivery. The use of a ‘massive transfusion protocol’ (MTP), which provides emergency RBC (6 units), plasma (4 units) and platelets (one unit) for managing severe unanticipated obstetric hemorrhage at our institution, was also assessed. Details of the MTP have been previously described.6 Descriptive statistics were used to summarize demographic, obstetric and transfusion data. Data are expressed as mean (standard deviation), median [interquartile range] and numbers or percentages as appropriate. Normal distribution was determined using QQ plots and the Kolmogorov-Smirnov test. Regression analysis was performed to assess the relationship between EBL and total RBC transfusion using Pearson correlation coefficient. SPSS version 16.0 (Chicago, IL) and Microsoft Excel were used for data entry and analysis; P < 0.05 was considered statistically significant.
Results During the study period, there were 5432 deliveries (4004 vaginal deliveries, 1428 cesarean deliveries) at Lucille Packard Children’s Hospital, and 74 patients received transfusion therapy (transfusion rate: 1.4%). Patient demographic and obstetric data are shown in Table 1. Eight patients in the study cohort had multiple gestations. Blood transfusions were administered to three patients (4.1%) in the antepartum period: (two intrauterine deaths, one uterine rupture), and 65 patients (87.8%) in the postpartum period. Six patients (8.1%) received transfusions in both ante- and postpar-
303 tum periods: (two placenta previa, one hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, one coagulopathy, one antepartum anemia and postpartum uterine atony, one Ex-utero intrapartum treatment (EXIT). Modes of delivery are shown in Table 1. Fortyseven patients undergoing cesarean delivery (15 elective, 32 non-elective) received transfusions, one patient receiving transfusion therapy required a dilatation and evacuation for an intrauterine death at 19 weeks of gestation, and one patient required cesarean delivery with an EXIT procedure (Table 1). The indications for transfusion are shown in Table 2. Six patients (19%) received emergency-release, uncrossmatched RBC transfusions (two cesarean delivery with abnormal placentation, two uterine atony following cesarean delivery, one uterine atony following vaginal delivery, one HELLP syndrome with instrumental delivery). The MTP was activated for all six patients receiving uncrossmatched blood. Hematologic and transfusion data are shown in Table 3. The number of patients receiving RBC transfusion and the amount used is displayed in Fig. 1. The majority (80%) of patients with no etiology associated with transfusion received 1-2 RBC units (one patient: one RBC unit, 19 patients: 2 RBC units). Three patients had Hb values P8 g/dL before transfusion. Estimated blood Table 1 Patient demographic and obstetric data in patients receiving transfusion (n = 74) Age (years) Race Caucasian Hispanic Pacific-Asian Other Unknown African-American Parity Body mass index (kg/m2) Gestational age (weeks) Obstetric disease None Preeclampsia / HELLP syndrome Placenta previa Multiple gestation Gestational diabetes Placental abruption Fibroids / previous myomectomy Intrauterine death Polyhydramnios Mode of delivery Cesarean delivery Spontaneous vaginal delivery Instrumental delivery Dilatation and evacuation EXIT procedure Data are mean (SD), median [interquartile range], n (%). EXIT: Ex-utero intrapartum treatment.
31.5 (6.5) 19 (25.7%) 29 (39.2%) 17 (23%) 5 (6.8%) 3 (4.1%) 1 (1.4%) 0 [0-1] 29.3 (5.4) 38 [33-39] 32 (43.2%) 13 (17.6%) 9 (12.2%) 8 (10.8%) 4 (5.4%) 2 (2.7%) 2 (2.7%) 2 (2.7%) 1 (1.4%) 47 (63.5%) 22 (29.7%) 3 (4.1%) 1 (1.4%) 1 (1.4%)
304 Table 2
Obstetric anesthesia and transfusion outcomes Indications for transfusion
No indication noted Uterine atony Abnormal placentation Coagulation disturbance / DIC / HELLP syndrome Genital tract lacerations Retained placenta Uterine rupture Wound seroma / hematoma
25 (33.8%) 18 (24.3%) 9 (12.2%) 8 (10.8%) 5 5 2 2
(6.8%) (6.8%) (2.7%) (2.7%)
Data are n (%). DIC: disseminated intravascular coagulation.
loss was significantly associated with the total number of RBC units transfused (R2: 0.4; P < 0.001). Based on chart review, 52 patients (70%) received RBC transfusion in the postpartum period following Hb assessment. Red blood cells were transfused to 39 patients in the first 24 h postpartum, 7 patients between 24-48 h and 6 patients >72 h following delivery. Subanalysis of the 13 patients transfused P24 h following delivery revealed that the pre-transfusion Hb values were 68.2 g/dL in all cases, with the nadir and pretransfusion values being identical in 12/13 patients. Based on chart review, 25 patients (34%) did not have documented indications for transfusion therapy. Hemoglobin values before transfusion were reviewed and 13 patients (18%) received RBC transfusions with pre-transfusion and nadir Hb values >8 g/dL: one patient: one unit, eight patients: 2 units, one patient: 3 units, three patients P4 units. Coagulation values (peak INR and APTT values; lowest fibrinogen values) and blood product usage are displayed in Table 4. Blood products (FFP ± platelets ± cryoprecipitate) were administered in 11/57 patients (19%) receiving 63 RBC units and 13/17 patients (77%) receiving P4 RBC units. No patients received anti-fibrinolytic therapy (epsilon aminocaproic acid, tranexamic acid), pro-hemostatic agents (recombinant factor VIIa), DDAVP or oral/parenteral iron therapy during the study period. Intraoperative cell salvage was used for one Jehovah’s Witness patient who experienced postpartum hemorrhage secondary to refractory uterine atony during non-elective cesarean delivery. Eight patients received transfusion of blood products
Table 3 (n = 74)
Hematologic parameters in transfused patents
Baseline hemoglobin (g/dL) Pre-transfusion hemoglobin (g/dL) Nadir hemoglobin (g/dL) Estimated blood loss (mL) Total red blood cells transfused (units) Hemoglobin before hospital discharge (g/dL)
11.4 (1.7) 7.6 (2.2) 7.0 (1.6) 1200 [800-2000] 2 [2-3] 9.1 [8.4-9.9]
Data are mean (SD), median [interquartile range], n (%).
Fig. 1 Total number of patients within the study cohort receiving red blood cell transfusions (0, 1-2, 3-4, 5-6, P7 units). RBC: red blood cell.
without RBC transfusion during in-hospital admission, including one immune thrombocytopenic purpura, three HELLP syndrome, one postpartum hemorrhage and coagulopathy (Jehovah’s Witness), one chorioamnionitis and suspected coagulation disturbance, one acute liver failure secondary to hepatitis B reactivation and one acute fatty liver of pregnancy). Maternal arterial acid-base values were reviewed, and the lowest recorded arterial pH and the highest recorded base deficit are shown in Table 4. Seventeen patients (23%) in the study cohort required intensive care, and no in-hospital maternal deaths were recorded. Neonatal outcomes as assessed by Apgar scores and neonatal intensive care unit (ICU) transfers were recorded. Median [IQR] Apgar scores were 7 [7-9] and 9 [9-9] at 1 and 5 min respectively, and 25 babies required transfer to the neonatal ICU following delivery.
Discussion In this retrospective study, the overall transfusion rate for obstetric in-patients at a tertiary obstetric center was 1.4%, 3.3% for all cesarean deliveries and 0.6% for all vaginal deliveries. Based on chart review, no specific indications for transfusion were identified in over a third of patients receiving transfusion, with the majority of patients receiving 1-2 RBC units without specific indications (80%). Our transfusion rate in obstetric patients is within the range previously reported by other institutions (0.0032%);7–12 the wide variability in transfusion rates is probably related to heterogeneity in patient populations and different transfusion practices between institutions. Most patients (63%) in our study cohort who required
A.J. Butwick et al.
305
Table 4 Coagulation laboratory values, blood product usage and arterial acid-base balance Highest INR (n = 22) Highest APTT (s) (n = 22) Lowest fibrinogen (mg/dL) (n = 28) Fresh frozen plasma (units) 0 1 2 3 P4 Platelets (units) 0 1 P2 Cryoprecipitate (pool) 0 P1 Lowest recorded arterial pH (n = 21) Highest base deficit (mEq/L) (n = 20)
1.2 [1.1-1.4] 31.6 [31.6-38.8] 303 (132) 54 (73%) 3 (4.1%) 9 (12.2%) 1 (1.4%) 7 (9.6%) 62 (83.8%) 8 (10.8%) 4 (5.5%) 69 (93.2%) 5 (6.8%) 7.32 [7.28-7.37] 8.3 [7.8-10.6]
Data are mean (SD), median [interquartile range], n (%). INR: international normalized ratio; APTT: activated partial thromboplastin time; FFP: fresh frozen plasma.
transfusion underwent cesarean delivery. This is consistent with previous studies that showed higher incidences of postpartum anemia requiring RBC transfusion following cesarean delivery compared with vaginal delivery (1-7% vs. <1% respectively).4 The differences in transfusion rates reflect the higher EBL values in the first 24 h postpartum in patients undergoing cesarean delivery compared with vaginal delivery,4 and higher incidences of postpartum hemorrhage (6.4% vs. 3.9% respectively).13,14 In our study, higher rates of transfusion were observed in patients requiring non-elective compared with elective cesarean delivery, which corroborates previous studies reporting that labor increases the risk of uterine atony and subsequent post-partum hemorrhage.13,15 The etiologic factors associated with transfusion (notably uterine atony and abnormal placentation) are consistent with results from studies assessing risk factors associated with postpartum hemorrhage.5,8,13,16 However, absent or insufficient documentation associated with etiology was found in 34% of patients in our study. The lack of adequate documentation to assess the appropriateness of transfusion has been similarly reported by Friedman et al. and Audet et al. in non-obstetric patients, with 49% and 32% of RBC transfusions respectively being associated with suboptimal chart documentation.17,18 The costs and risks associated with transfusion merit better justification for its use in an obstetric setting, although differences in physician training and attitudes can contribute towards inconsistent transfusion practices.3,19 These factors may also have contributed towards the differences in recognition and management of postpartum anemia by different physicians in our study. Inappropriate blood transfusion
practices can be reduced by introducing guidelines, educational sessions and reminder systems.20 At our institution, we have introduced simulation teaching and more robust guidelines (Fig. 2) to improve transfusion practice for obstetric patients. Postpartum anemia may be under-recognized, as 17% of patients in our cohort had Hb <8.2 g/dL at least 24 h after delivery. Underestimation of blood loss, as well as hemodilution during the peripartum period, may have contributed to the delay in recognition of postpartum anemia for these patients. A previous study using clinical reconstructions simulating obstetric hemorrhage reported that obstetric health care providers tended to underestimate blood loss, but also observed that anesthesiologists were better at estimating blood loss than were other professional groups.2 Although acute isovolemic anemia does not necessitate transfusion, previous authors have speculated that RBC transfusion may be useful to alleviate associated symptoms (such as shortness of breath, palpitations, fatigue) for postpartum patients.21 There is also increasing interest in the use of non-transfusion therapies such as oral/parenteral iron and erythropoietin, with evidence suggesting that combination therapy of erythropoietin and iron is more effective in treating postpartum anemia than iron therapy alone.22,23 However, our institution has not formally implemented the use of non-transfusion therapies for managing postpartum anemia. A previous retrospective study reported that 32% of RBC transfusions given to peripartum women were ‘‘inappropriate’’; this was described in a number of ways: over-transfusion to treat symptomatic anemia, patients with ongoing bleeding, stable vital signs and Hb >7 g/dL and asymptomatic anemia.12 As in our study, 18% of patients had pre-transfusion and nadir Hb values >8 g/dL, based on chart review the indications for transfusion for these cases were unclear. However, it is likely that some of these patients received transfusion therapy during ongoing bleeding, which limits the interpretation of laboratory values, or had evidence of symptomatic anemia. Therefore the retrospective nature of our study limits the identification of patients receiving ‘‘inappropriate’’ transfusions. Variations in the severity of hemorrhage, as well as different transfusion practices between physicians, may explain the different transfusion outcomes in our study.4 Guidelines have been published by the American Society of Anesthesiologists (ASA),24 the British Society for Standards in Haematology25 and the Development Task Force of the College of American Pathologists26 recommending that RBC transfusion is indicated for Hb values between 6 and 7 g/dL. However, a survey of transfusion practice of members of the ASA confirmed that 46% of anesthesiologists would transfuse based on the medical condition and age of the patient, clinical assessment and hemodynamic status during
306
Obstetric anesthesia and transfusion outcomes
Fig. 2 Suggested guidelines for transfusion management in obstetric patients. ABG: Arterial Blood Gas; CBC: Complete Blood Count; CVP: Central Venous Pressure; EBL: Estimated Blood Loss; FFP: Fresh Frozen Plasma; Hb: Hemoglobin; HDU: High Dependency Unit; ICU: Intensive Care Unit; IV: Intravenous; PLTS: Platelets; PT: Prothrombin Time; PTT: Partial Thromboplastin Time; Rh: Rhesus; RBC: Red Blood Cells.
the intraoperative period.27 Therefore physicians are likely to rely upon the clinical indications for transfusion decision-making in the setting of acute or severe obstetric hemorrhage such as maternal intravascular volume, the rate and magnitude of blood loss, and evidence of organ hypoperfusion. The use of laboratory Hb values (specific transfusion triggers) is important, but can cause delay due to transport and laboratory processing of blood samples. Blood product administration (FFP ± platelets ± cryoprecipitate) was higher in patients receiving P4 RBC units. In addition, median coagulation values (APTT, INR, fibrinogen) for the study cohort were within normal limits. The pathophysiology of coagulopathy in massively transfused patients undergoing surgery is multifactorial (including hypofibrinogenemia, thrombocytopenia, coagulation factor deficiencies, tissue trauma, hypothermia and hemodilution).28 Charbit et al. reported that coagulation is disturbed early in patients presenting with severe post-partum hemorrhage, and that low fibrinogen values (<2 g/dL) may predict severity of bleeding.29 Fibrinogen deficit is likely to oc-
cur early in massive surgical bleeding following plasma-poor RBC transfusion and infusion of colloids to maintain intravascular volume.28 Metabolic acidosis can often occur following massive blood transfusion, and has also been shown to be a risk factor for developing coagulopathy.30 Our institution does not provide obstetric highdependency facilities on the labor and delivery unit, which probably contributed to the relatively high rate (25%) of patients receiving transfusion who required transfer to ICU. Previous studies have reported a low but variable incidence of requirement for ICU admission (approximately 2-4 patients /1000 deliveries) in developed countries, with postpartum hemorrhage one of the commonest causes of admission.31 It is likely that the incidence of neonatal ICU admission is related to pre-term delivery, with 49% patients in our cohort at <37 weeks of gestation. Previous studies investigating perinatal outcomes observed high incidences of pre-term delivery in patients with placenta previa (16% in patients <34 weeks)32 and accreta (10% in patients <37 weeks).33
A.J. Butwick et al. We acknowledge that there are several limitations with our study. The study design is based on institutional data, which limits how data on transfusion practice may be extrapolated to other units. Furthermore, the retrospective nature of the study does not control for unrecognized differences in physician practice. We did not assess data for quality of life outcome measures in this study, therefore it is unclear whether obstetric hemorrhage affects duration of hospitalization. A previous study has shown that duration of in-patient admission is not affected by the transfusion of 1-2 RBC units in the post-partum period.34 There is currently no consensus with regard to the timing of transfusion for obstetric patients, especially during the peripartum period. The timing and urgency of transfusion are often determined by the patient’s physiological state and the presence of ongoing bleeding. Furthermore, there are no recommendations for investigating post-partum anemia following successful management of obstetric hemorrhage. If bleeding has resolved and the patient is hemodynamically stable, we recommend that a complete blood count be performed in all obstetric patients with EBL values P1000 mL within 2 h following delivery (Fig. 2). Lower EBL thresholds may be considered if patients have evidence of antepartum anemia. Further studies are needed to assess maternal outcome associated with unrecognized post-partum anemia, as well as the health and cost implications of different transfusion practices in obstetric patients.
References 1. Chang J, Elam-Evans LD, Berg CJ et al. Pregnancy-related mortality surveillance–United States, 1991–1999. MMWR Surveill Summ 2003;52:1–8. 2. Bose P, Regan F, Paterson-Brown S. Improving the accuracy of estimated blood loss at obstetric haemorrhage using clinical reconstructions. BJOG 2006;113:919–24. 3. Matot I, Einav S, Goodman S, Zeldin A, Weissman C, Elchalal U. A survey of physicians’ attitudes toward blood transfusion in patients undergoing cesarean section. Am J Obstet Gynecol 2004;190:462–7. 4. Jansen AJ, van Rhenen DJ, Steegers EA, Duvekot JJ. Postpartum hemorrhage and transfusion of blood and blood components. Obstet Gynecol Surv 2005;60:663–71. 5. Rouse DJ, MacPherson C, Landon M et al. Blood transfusion and cesarean delivery. Obstet Gynecol 2006;108:891–7. 6. Burtelow M, Riley E, Druzin M, Fontaine M, Viele M, Goodnough LT. How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol. Transfusion 2007;47:1564–72. 7. Burrows LJ, Meyn LA, Weber AM. Maternal morbidity associated with vaginal versus cesarean delivery. Obstet Gynecol 2004;103:907–12. 8. Reyal F, Sibony O, Oury JF, Luton D, Bang J, Blot P. Criteria for transfusion in severe postpartum hemorrhage: analysis of practice and risk factors. Eur J Obstet Gynecol Reprod Biol 2004;112:61–4. 9. Klapholz H. Blood transfusion in contemporary obstetric practice. Obstet Gynecol 1990;75:940–3.
307 10. Naef 3rd RW, Washburne JF, Martin RW, Magann EF, Scanlon Jr PH, Morrison JC. Hemorrhage associated with cesarean delivery: when is transfusion needed? J Perinatol 1995;15:32–5. 11. Sherman SJ, Greenspoon JS, Nelson JM, Paul RH. Obstetric hemorrhage and blood utilization. J Reprod Med 1993;38:929–34. 12. Silverman JA, Barrett J, Callum JL. The appropriateness of red blood cell transfusions in the peripartum patient. Obstet Gynecol 2004;104:1000–4. 13. Combs CA, Murphy EL, Laros Jr RK. Factors associated with hemorrhage in cesarean deliveries. Obstet Gynecol 1991;77:77–82. 14. Combs CA, Murphy EL, Laros Jr RK. Factors associated with postpartum hemorrhage with vaginal birth. Obstet Gynecol 1991;77:69–76. 15. Kamani AA, McMorland GH, Wadsworth LD. Utilization of red blood cell transfusion in an obstetric setting. Am J Obstet Gynecol 1988;159:1177–81. 16. Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18:149–54. 17. Friedman MT, Ebrahim A. Adequacy of physician documentation of red blood cell transfusion and correlation with assessment of transfusion appropriateness. Arch Pathol Lab Med 2006;130: 474–9. 18. Audet AM, Goodnough LT, Parvin CA. Evaluating the appropriateness of red blood cell transfusions: the limitations of retrospective medical record reviews. Int J Qual Health Care 1996;8:41–9. 19. Transfusion medicine. First of two parts–blood transfusion. N Engl J Med 1999;340:438–47. 20. Tinmouth A, Macdougall L, Fergusson D et al. Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians’ transfusion practices. Arch Intern Med 2005;165:845–52. 21. Asakura Y, Kato N, Sato Y, Mizutani M, Fujiwara Y, Komatsu T. The attitude towards red blood cell transfusion for bleeding at childbirth in women. Acta Anaesthesiol Scand 2007;51:1402–3. 22. Breymann C, Richter C, Huttner C, Huch R, Huch A. Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with postpartum anaemia and blunted erythropoiesis. Eur J Clin Invest 2000;30:154–61. 23. Breymann C, Zimmermann R, Huch R, Huch A. Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia. Eur J Clin Invest 1996;26:123–30. 24. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology 2006;105:198–208. 25. Murphy MF, Wallington TB, Kelsey P et al. Guidelines for the clinical use of red cell transfusions. Br J Haematol 2001;113: 24–31. 26. Simon TL, Alverson DC, AuBuchon J et al. Practice parameter for the use of red blood cell transfusions: developed by the Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med 1998;122:130–8. 27. Nuttall GA, Stehling LC, Beighley CM, Faust RJ. Current transfusion practices of members of the American Society of Anesthesiologists: a survey. Anesthesiology 2003;99:1433–43. 28. Hardy JF, De Moerloose P, Samama M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anesth 2004;51:293–310. 29. Charbit B, Mandelbrot L, Samain E et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007;5:266–73. 30. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch B, Galloway B. Predicting life-threatening coagulopathy in the
308 massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma 1997;42:857–61. 31. Zeeman GG. Obstetric critical care: a blueprint for improved outcomes. Crit Care Med 2006;34:S208–14. 32. Zlatnik MG, Cheng YW, Norton ME, Thiet MP, Caughey AB. Placenta previa and the risk of preterm delivery. J Matern Fetal Neonatal Med 2007;20:719–23.
Obstetric anesthesia and transfusion outcomes 33. Gielchinsky Y, Mankuta D, Rojansky N, Laufer N, Gielchinsky I, Ezra Y. Perinatal outcome of pregnancies complicated by placenta accreta. Obstet Gynecol 2004;104:527–30. 34. Palo R, Ahonen J, Salo H, Salmenpera M, Krusius T, Maki T. Transfusion of red blood cells: no impact on length of hospital stay in moderately anaemic parturients. Acta Anaesthesiol Scand 2007;51:565–9.
ORIGINAL ARTICLE
www.obstetanesthesia.com
Retrospective analysis of transfusion outcomes in pregnant patients at a tertiary obstetric center A.J. Butwick, P. Aleshi, M. Fontaine, E.T. Riley L.T. Goodnough *
Departments of Anesthesiology and Pathology, Stanford University School of Medicine, Stanford, California, USA ABSTRACT Background: The decision to use red blood cell transfusion and/or blood products (fresh frozen plasma, platelets, cryoprecipitate) to manage obstetric hemorrhage or treat postpartum anemia is often made empirically by physicians. We performed a retrospective study to review transfusion outcomes in pregnant and postpartum patients at a large obstetric center. Methods: A retrospective, observational study was performed of obstetric in-patients who received red blood cell transfusion and/ or blood products over a one-year period. Data abstracted included transfusion data, pre-transfusion hemoglobin (Hb) and lowest recorded (nadir) Hb, and maternal and neonatal outcomes. Results: During the study period, 74 patients received transfusion therapy (1.4%). Pre-transfusion and nadir Hb values were 7.6 g/ dL and 7.0 g/dL respectively. Median [IQR] total red blood cells transfused were 2 units [2 -3], with 41 (55%) patients receiving 1-2 units. Based on chart review, no specific indications for transfusion were identified in 25 patients (34%), and 13 patients (18%) had undetected postpartum anemia (Hb values <8.2 g/dL) at least 24 h after delivery. Conclusion: More formal assessment and documentation of the etiologic factors associated with transfusion management in pregnant patients is advised. In addition, the identification and management of undetected postpartum anemia is underappreciated. c 2009 Elsevier Ltd. All rights reserved.
Keywords: Transfusion; Pregnancy; Anesthesia; Hemorrhage
Introduction Obstetric hemorrhage is the second most common cause of pregnancy-related death in the USA with a maternal mortality rate of 2 per 100 000 live births.1 During acute obstetric hemorrhage, obstetric care providers are often primarily involved in decision making on transfusion management. Laboratory assessments of hematocrit and hemoglobin concentration require time for laboratory processing, and are often reviewed retrospectively to assess the efficacy of empirical transfusion management in the setting of ongoing blood loss. Previous studies using simulated scenarios have suggested that there is marked variability among physicians in accuracy of estimating blood loss during obstetric hemorrhage,2 and in physician attitudes to blood transfusion for patients undergoing cesarean Accepted February 2009 This study was presented in part at the Society of Obstetric Anesthesia and Perinatology (SOAP) 40th Annual Meeting, April 2008, Chicago. Correspondence to: Dr. Alexander Butwick, Department of Anesthesiology (MC: 5640), 300 Pasteur Drive, Stanford University School of Medicine, Stanford, California 94305, USA. Tel.: +1 650 736 8513; fax: +1 650 725 8544. E-mail address: [email protected]
delivery.3 Furthermore, the incidence of red blood cell (RBC) transfusion after vaginal delivery and cesarean delivery can vary (<1% and 1-7% respectively).4,5 The aim of this retrospective study was to review transfusion outcomes and the indications for transfusion in obstetric patients receiving RBC transfusion at a large tertiary obstetric center.
Methods After gaining institutional review board approval, a retrospective chart review was performed of obstetric patients who received blood transfusions (RBC and/or blood products) between September 2006 and August 2007, at Lucille Packard Children’s Hospital. This is a university hospital and tertiary obstetric center with >5000 deliveries per year. Study investigators used the hospital’s computerized perinatal database to source data on all obstetric patients who received a transfusion of blood products (RBC, fresh frozen plasma, platelets, cryoprecipitate) during the study period. Blood transfusions administered to obstetric in-patients in the antepartum, peripartum and postpartum periods were included. Two fellowship-trained obstetric anesthesiolo-
A.J. Butwick et al. gists (PA, AB) independently reviewed individual patient medical records and laboratory data. Study investigators also reviewed the transfusion database from the transfusion service in the department of pathology. Based on chart review, data extracted included details of transfusion triggers, specific transfusion data, estimated blood loss (EBL) and maternal and neonatal outcomes. Blood loss is normally estimated by the obstetrician for patients undergoing vaginal delivery, and by mutual agreement between obstetrician and anesthesiologist for patients undergoing cesarean delivery. Laboratory values recorded included: baseline hemoglobin (Hb), the last recorded Hb before transfusion (pre-transfusion Hb), lowest recorded Hb during the study period (nadir Hb), Hb before discharge, and coagulation data (peak international normalized ratio (INR) and activated partial thromplastin time (APTT) values, lowest fibrinogen values). Baseline Hb values are routinely obtained at the time of admission to our labor and delivery unit for all patients admitted in labor or for induction of labor, or within 24 h before elective cesarean delivery. Sub analysis of patients receiving transfusion therapy was also performed, including etiology of hemorrhage requiring transfusion and timing of laboratory assessments of Hb following delivery. The use of a ‘massive transfusion protocol’ (MTP), which provides emergency RBC (6 units), plasma (4 units) and platelets (one unit) for managing severe unanticipated obstetric hemorrhage at our institution, was also assessed. Details of the MTP have been previously described.6 Descriptive statistics were used to summarize demographic, obstetric and transfusion data. Data are expressed as mean (standard deviation), median [interquartile range] and numbers or percentages as appropriate. Normal distribution was determined using QQ plots and the Kolmogorov-Smirnov test. Regression analysis was performed to assess the relationship between EBL and total RBC transfusion using Pearson correlation coefficient. SPSS version 16.0 (Chicago, IL) and Microsoft Excel were used for data entry and analysis; P < 0.05 was considered statistically significant.
Results During the study period, there were 5432 deliveries (4004 vaginal deliveries, 1428 cesarean deliveries) at Lucille Packard Children’s Hospital, and 74 patients received transfusion therapy (transfusion rate: 1.4%). Patient demographic and obstetric data are shown in Table 1. Eight patients in the study cohort had multiple gestations. Blood transfusions were administered to three patients (4.1%) in the antepartum period: (two intrauterine deaths, one uterine rupture), and 65 patients (87.8%) in the postpartum period. Six patients (8.1%) received transfusions in both ante- and postpar-
303 tum periods: (two placenta previa, one hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, one coagulopathy, one antepartum anemia and postpartum uterine atony, one Ex-utero intrapartum treatment (EXIT). Modes of delivery are shown in Table 1. Fortyseven patients undergoing cesarean delivery (15 elective, 32 non-elective) received transfusions, one patient receiving transfusion therapy required a dilatation and evacuation for an intrauterine death at 19 weeks of gestation, and one patient required cesarean delivery with an EXIT procedure (Table 1). The indications for transfusion are shown in Table 2. Six patients (19%) received emergency-release, uncrossmatched RBC transfusions (two cesarean delivery with abnormal placentation, two uterine atony following cesarean delivery, one uterine atony following vaginal delivery, one HELLP syndrome with instrumental delivery). The MTP was activated for all six patients receiving uncrossmatched blood. Hematologic and transfusion data are shown in Table 3. The number of patients receiving RBC transfusion and the amount used is displayed in Fig. 1. The majority (80%) of patients with no etiology associated with transfusion received 1-2 RBC units (one patient: one RBC unit, 19 patients: 2 RBC units). Three patients had Hb values P8 g/dL before transfusion. Estimated blood Table 1 Patient demographic and obstetric data in patients receiving transfusion (n = 74) Age (years) Race Caucasian Hispanic Pacific-Asian Other Unknown African-American Parity Body mass index (kg/m2) Gestational age (weeks) Obstetric disease None Preeclampsia / HELLP syndrome Placenta previa Multiple gestation Gestational diabetes Placental abruption Fibroids / previous myomectomy Intrauterine death Polyhydramnios Mode of delivery Cesarean delivery Spontaneous vaginal delivery Instrumental delivery Dilatation and evacuation EXIT procedure Data are mean (SD), median [interquartile range], n (%). EXIT: Ex-utero intrapartum treatment.
31.5 (6.5) 19 (25.7%) 29 (39.2%) 17 (23%) 5 (6.8%) 3 (4.1%) 1 (1.4%) 0 [0-1] 29.3 (5.4) 38 [33-39] 32 (43.2%) 13 (17.6%) 9 (12.2%) 8 (10.8%) 4 (5.4%) 2 (2.7%) 2 (2.7%) 2 (2.7%) 1 (1.4%) 47 (63.5%) 22 (29.7%) 3 (4.1%) 1 (1.4%) 1 (1.4%)
304 Table 2
Obstetric anesthesia and transfusion outcomes Indications for transfusion
No indication noted Uterine atony Abnormal placentation Coagulation disturbance / DIC / HELLP syndrome Genital tract lacerations Retained placenta Uterine rupture Wound seroma / hematoma
25 (33.8%) 18 (24.3%) 9 (12.2%) 8 (10.8%) 5 5 2 2
(6.8%) (6.8%) (2.7%) (2.7%)
Data are n (%). DIC: disseminated intravascular coagulation.
loss was significantly associated with the total number of RBC units transfused (R2: 0.4; P < 0.001). Based on chart review, 52 patients (70%) received RBC transfusion in the postpartum period following Hb assessment. Red blood cells were transfused to 39 patients in the first 24 h postpartum, 7 patients between 24-48 h and 6 patients >72 h following delivery. Subanalysis of the 13 patients transfused P24 h following delivery revealed that the pre-transfusion Hb values were 68.2 g/dL in all cases, with the nadir and pretransfusion values being identical in 12/13 patients. Based on chart review, 25 patients (34%) did not have documented indications for transfusion therapy. Hemoglobin values before transfusion were reviewed and 13 patients (18%) received RBC transfusions with pre-transfusion and nadir Hb values >8 g/dL: one patient: one unit, eight patients: 2 units, one patient: 3 units, three patients P4 units. Coagulation values (peak INR and APTT values; lowest fibrinogen values) and blood product usage are displayed in Table 4. Blood products (FFP ± platelets ± cryoprecipitate) were administered in 11/57 patients (19%) receiving 63 RBC units and 13/17 patients (77%) receiving P4 RBC units. No patients received anti-fibrinolytic therapy (epsilon aminocaproic acid, tranexamic acid), pro-hemostatic agents (recombinant factor VIIa), DDAVP or oral/parenteral iron therapy during the study period. Intraoperative cell salvage was used for one Jehovah’s Witness patient who experienced postpartum hemorrhage secondary to refractory uterine atony during non-elective cesarean delivery. Eight patients received transfusion of blood products
Table 3 (n = 74)
Hematologic parameters in transfused patents
Baseline hemoglobin (g/dL) Pre-transfusion hemoglobin (g/dL) Nadir hemoglobin (g/dL) Estimated blood loss (mL) Total red blood cells transfused (units) Hemoglobin before hospital discharge (g/dL)
11.4 (1.7) 7.6 (2.2) 7.0 (1.6) 1200 [800-2000] 2 [2-3] 9.1 [8.4-9.9]
Data are mean (SD), median [interquartile range], n (%).
Fig. 1 Total number of patients within the study cohort receiving red blood cell transfusions (0, 1-2, 3-4, 5-6, P7 units). RBC: red blood cell.
without RBC transfusion during in-hospital admission, including one immune thrombocytopenic purpura, three HELLP syndrome, one postpartum hemorrhage and coagulopathy (Jehovah’s Witness), one chorioamnionitis and suspected coagulation disturbance, one acute liver failure secondary to hepatitis B reactivation and one acute fatty liver of pregnancy). Maternal arterial acid-base values were reviewed, and the lowest recorded arterial pH and the highest recorded base deficit are shown in Table 4. Seventeen patients (23%) in the study cohort required intensive care, and no in-hospital maternal deaths were recorded. Neonatal outcomes as assessed by Apgar scores and neonatal intensive care unit (ICU) transfers were recorded. Median [IQR] Apgar scores were 7 [7-9] and 9 [9-9] at 1 and 5 min respectively, and 25 babies required transfer to the neonatal ICU following delivery.
Discussion In this retrospective study, the overall transfusion rate for obstetric in-patients at a tertiary obstetric center was 1.4%, 3.3% for all cesarean deliveries and 0.6% for all vaginal deliveries. Based on chart review, no specific indications for transfusion were identified in over a third of patients receiving transfusion, with the majority of patients receiving 1-2 RBC units without specific indications (80%). Our transfusion rate in obstetric patients is within the range previously reported by other institutions (0.0032%);7–12 the wide variability in transfusion rates is probably related to heterogeneity in patient populations and different transfusion practices between institutions. Most patients (63%) in our study cohort who required
A.J. Butwick et al.
305
Table 4 Coagulation laboratory values, blood product usage and arterial acid-base balance Highest INR (n = 22) Highest APTT (s) (n = 22) Lowest fibrinogen (mg/dL) (n = 28) Fresh frozen plasma (units) 0 1 2 3 P4 Platelets (units) 0 1 P2 Cryoprecipitate (pool) 0 P1 Lowest recorded arterial pH (n = 21) Highest base deficit (mEq/L) (n = 20)
1.2 [1.1-1.4] 31.6 [31.6-38.8] 303 (132) 54 (73%) 3 (4.1%) 9 (12.2%) 1 (1.4%) 7 (9.6%) 62 (83.8%) 8 (10.8%) 4 (5.5%) 69 (93.2%) 5 (6.8%) 7.32 [7.28-7.37] 8.3 [7.8-10.6]
Data are mean (SD), median [interquartile range], n (%). INR: international normalized ratio; APTT: activated partial thromboplastin time; FFP: fresh frozen plasma.
transfusion underwent cesarean delivery. This is consistent with previous studies that showed higher incidences of postpartum anemia requiring RBC transfusion following cesarean delivery compared with vaginal delivery (1-7% vs. <1% respectively).4 The differences in transfusion rates reflect the higher EBL values in the first 24 h postpartum in patients undergoing cesarean delivery compared with vaginal delivery,4 and higher incidences of postpartum hemorrhage (6.4% vs. 3.9% respectively).13,14 In our study, higher rates of transfusion were observed in patients requiring non-elective compared with elective cesarean delivery, which corroborates previous studies reporting that labor increases the risk of uterine atony and subsequent post-partum hemorrhage.13,15 The etiologic factors associated with transfusion (notably uterine atony and abnormal placentation) are consistent with results from studies assessing risk factors associated with postpartum hemorrhage.5,8,13,16 However, absent or insufficient documentation associated with etiology was found in 34% of patients in our study. The lack of adequate documentation to assess the appropriateness of transfusion has been similarly reported by Friedman et al. and Audet et al. in non-obstetric patients, with 49% and 32% of RBC transfusions respectively being associated with suboptimal chart documentation.17,18 The costs and risks associated with transfusion merit better justification for its use in an obstetric setting, although differences in physician training and attitudes can contribute towards inconsistent transfusion practices.3,19 These factors may also have contributed towards the differences in recognition and management of postpartum anemia by different physicians in our study. Inappropriate blood transfusion
practices can be reduced by introducing guidelines, educational sessions and reminder systems.20 At our institution, we have introduced simulation teaching and more robust guidelines (Fig. 2) to improve transfusion practice for obstetric patients. Postpartum anemia may be under-recognized, as 17% of patients in our cohort had Hb <8.2 g/dL at least 24 h after delivery. Underestimation of blood loss, as well as hemodilution during the peripartum period, may have contributed to the delay in recognition of postpartum anemia for these patients. A previous study using clinical reconstructions simulating obstetric hemorrhage reported that obstetric health care providers tended to underestimate blood loss, but also observed that anesthesiologists were better at estimating blood loss than were other professional groups.2 Although acute isovolemic anemia does not necessitate transfusion, previous authors have speculated that RBC transfusion may be useful to alleviate associated symptoms (such as shortness of breath, palpitations, fatigue) for postpartum patients.21 There is also increasing interest in the use of non-transfusion therapies such as oral/parenteral iron and erythropoietin, with evidence suggesting that combination therapy of erythropoietin and iron is more effective in treating postpartum anemia than iron therapy alone.22,23 However, our institution has not formally implemented the use of non-transfusion therapies for managing postpartum anemia. A previous retrospective study reported that 32% of RBC transfusions given to peripartum women were ‘‘inappropriate’’; this was described in a number of ways: over-transfusion to treat symptomatic anemia, patients with ongoing bleeding, stable vital signs and Hb >7 g/dL and asymptomatic anemia.12 As in our study, 18% of patients had pre-transfusion and nadir Hb values >8 g/dL, based on chart review the indications for transfusion for these cases were unclear. However, it is likely that some of these patients received transfusion therapy during ongoing bleeding, which limits the interpretation of laboratory values, or had evidence of symptomatic anemia. Therefore the retrospective nature of our study limits the identification of patients receiving ‘‘inappropriate’’ transfusions. Variations in the severity of hemorrhage, as well as different transfusion practices between physicians, may explain the different transfusion outcomes in our study.4 Guidelines have been published by the American Society of Anesthesiologists (ASA),24 the British Society for Standards in Haematology25 and the Development Task Force of the College of American Pathologists26 recommending that RBC transfusion is indicated for Hb values between 6 and 7 g/dL. However, a survey of transfusion practice of members of the ASA confirmed that 46% of anesthesiologists would transfuse based on the medical condition and age of the patient, clinical assessment and hemodynamic status during
306
Obstetric anesthesia and transfusion outcomes
Fig. 2 Suggested guidelines for transfusion management in obstetric patients. ABG: Arterial Blood Gas; CBC: Complete Blood Count; CVP: Central Venous Pressure; EBL: Estimated Blood Loss; FFP: Fresh Frozen Plasma; Hb: Hemoglobin; HDU: High Dependency Unit; ICU: Intensive Care Unit; IV: Intravenous; PLTS: Platelets; PT: Prothrombin Time; PTT: Partial Thromboplastin Time; Rh: Rhesus; RBC: Red Blood Cells.
the intraoperative period.27 Therefore physicians are likely to rely upon the clinical indications for transfusion decision-making in the setting of acute or severe obstetric hemorrhage such as maternal intravascular volume, the rate and magnitude of blood loss, and evidence of organ hypoperfusion. The use of laboratory Hb values (specific transfusion triggers) is important, but can cause delay due to transport and laboratory processing of blood samples. Blood product administration (FFP ± platelets ± cryoprecipitate) was higher in patients receiving P4 RBC units. In addition, median coagulation values (APTT, INR, fibrinogen) for the study cohort were within normal limits. The pathophysiology of coagulopathy in massively transfused patients undergoing surgery is multifactorial (including hypofibrinogenemia, thrombocytopenia, coagulation factor deficiencies, tissue trauma, hypothermia and hemodilution).28 Charbit et al. reported that coagulation is disturbed early in patients presenting with severe post-partum hemorrhage, and that low fibrinogen values (<2 g/dL) may predict severity of bleeding.29 Fibrinogen deficit is likely to oc-
cur early in massive surgical bleeding following plasma-poor RBC transfusion and infusion of colloids to maintain intravascular volume.28 Metabolic acidosis can often occur following massive blood transfusion, and has also been shown to be a risk factor for developing coagulopathy.30 Our institution does not provide obstetric highdependency facilities on the labor and delivery unit, which probably contributed to the relatively high rate (25%) of patients receiving transfusion who required transfer to ICU. Previous studies have reported a low but variable incidence of requirement for ICU admission (approximately 2-4 patients /1000 deliveries) in developed countries, with postpartum hemorrhage one of the commonest causes of admission.31 It is likely that the incidence of neonatal ICU admission is related to pre-term delivery, with 49% patients in our cohort at <37 weeks of gestation. Previous studies investigating perinatal outcomes observed high incidences of pre-term delivery in patients with placenta previa (16% in patients <34 weeks)32 and accreta (10% in patients <37 weeks).33
A.J. Butwick et al. We acknowledge that there are several limitations with our study. The study design is based on institutional data, which limits how data on transfusion practice may be extrapolated to other units. Furthermore, the retrospective nature of the study does not control for unrecognized differences in physician practice. We did not assess data for quality of life outcome measures in this study, therefore it is unclear whether obstetric hemorrhage affects duration of hospitalization. A previous study has shown that duration of in-patient admission is not affected by the transfusion of 1-2 RBC units in the post-partum period.34 There is currently no consensus with regard to the timing of transfusion for obstetric patients, especially during the peripartum period. The timing and urgency of transfusion are often determined by the patient’s physiological state and the presence of ongoing bleeding. Furthermore, there are no recommendations for investigating post-partum anemia following successful management of obstetric hemorrhage. If bleeding has resolved and the patient is hemodynamically stable, we recommend that a complete blood count be performed in all obstetric patients with EBL values P1000 mL within 2 h following delivery (Fig. 2). Lower EBL thresholds may be considered if patients have evidence of antepartum anemia. Further studies are needed to assess maternal outcome associated with unrecognized post-partum anemia, as well as the health and cost implications of different transfusion practices in obstetric patients.
References 1. Chang J, Elam-Evans LD, Berg CJ et al. Pregnancy-related mortality surveillance–United States, 1991–1999. MMWR Surveill Summ 2003;52:1–8. 2. Bose P, Regan F, Paterson-Brown S. Improving the accuracy of estimated blood loss at obstetric haemorrhage using clinical reconstructions. BJOG 2006;113:919–24. 3. Matot I, Einav S, Goodman S, Zeldin A, Weissman C, Elchalal U. A survey of physicians’ attitudes toward blood transfusion in patients undergoing cesarean section. Am J Obstet Gynecol 2004;190:462–7. 4. Jansen AJ, van Rhenen DJ, Steegers EA, Duvekot JJ. Postpartum hemorrhage and transfusion of blood and blood components. Obstet Gynecol Surv 2005;60:663–71. 5. Rouse DJ, MacPherson C, Landon M et al. Blood transfusion and cesarean delivery. Obstet Gynecol 2006;108:891–7. 6. Burtelow M, Riley E, Druzin M, Fontaine M, Viele M, Goodnough LT. How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol. Transfusion 2007;47:1564–72. 7. Burrows LJ, Meyn LA, Weber AM. Maternal morbidity associated with vaginal versus cesarean delivery. Obstet Gynecol 2004;103:907–12. 8. Reyal F, Sibony O, Oury JF, Luton D, Bang J, Blot P. Criteria for transfusion in severe postpartum hemorrhage: analysis of practice and risk factors. Eur J Obstet Gynecol Reprod Biol 2004;112:61–4. 9. Klapholz H. Blood transfusion in contemporary obstetric practice. Obstet Gynecol 1990;75:940–3.
307 10. Naef 3rd RW, Washburne JF, Martin RW, Magann EF, Scanlon Jr PH, Morrison JC. Hemorrhage associated with cesarean delivery: when is transfusion needed? J Perinatol 1995;15:32–5. 11. Sherman SJ, Greenspoon JS, Nelson JM, Paul RH. Obstetric hemorrhage and blood utilization. J Reprod Med 1993;38:929–34. 12. Silverman JA, Barrett J, Callum JL. The appropriateness of red blood cell transfusions in the peripartum patient. Obstet Gynecol 2004;104:1000–4. 13. Combs CA, Murphy EL, Laros Jr RK. Factors associated with hemorrhage in cesarean deliveries. Obstet Gynecol 1991;77:77–82. 14. Combs CA, Murphy EL, Laros Jr RK. Factors associated with postpartum hemorrhage with vaginal birth. Obstet Gynecol 1991;77:69–76. 15. Kamani AA, McMorland GH, Wadsworth LD. Utilization of red blood cell transfusion in an obstetric setting. Am J Obstet Gynecol 1988;159:1177–81. 16. Sheiner E, Sarid L, Levy A, Seidman DS, Hallak M. Obstetric risk factors and outcome of pregnancies complicated with early postpartum hemorrhage: a population-based study. J Matern Fetal Neonatal Med 2005;18:149–54. 17. Friedman MT, Ebrahim A. Adequacy of physician documentation of red blood cell transfusion and correlation with assessment of transfusion appropriateness. Arch Pathol Lab Med 2006;130: 474–9. 18. Audet AM, Goodnough LT, Parvin CA. Evaluating the appropriateness of red blood cell transfusions: the limitations of retrospective medical record reviews. Int J Qual Health Care 1996;8:41–9. 19. Transfusion medicine. First of two parts–blood transfusion. N Engl J Med 1999;340:438–47. 20. Tinmouth A, Macdougall L, Fergusson D et al. Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians’ transfusion practices. Arch Intern Med 2005;165:845–52. 21. Asakura Y, Kato N, Sato Y, Mizutani M, Fujiwara Y, Komatsu T. The attitude towards red blood cell transfusion for bleeding at childbirth in women. Acta Anaesthesiol Scand 2007;51:1402–3. 22. Breymann C, Richter C, Huttner C, Huch R, Huch A. Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with postpartum anaemia and blunted erythropoiesis. Eur J Clin Invest 2000;30:154–61. 23. Breymann C, Zimmermann R, Huch R, Huch A. Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia. Eur J Clin Invest 1996;26:123–30. 24. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology 2006;105:198–208. 25. Murphy MF, Wallington TB, Kelsey P et al. Guidelines for the clinical use of red cell transfusions. Br J Haematol 2001;113: 24–31. 26. Simon TL, Alverson DC, AuBuchon J et al. Practice parameter for the use of red blood cell transfusions: developed by the Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med 1998;122:130–8. 27. Nuttall GA, Stehling LC, Beighley CM, Faust RJ. Current transfusion practices of members of the American Society of Anesthesiologists: a survey. Anesthesiology 2003;99:1433–43. 28. Hardy JF, De Moerloose P, Samama M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anesth 2004;51:293–310. 29. Charbit B, Mandelbrot L, Samain E et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007;5:266–73. 30. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch B, Galloway B. Predicting life-threatening coagulopathy in the
308 massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma 1997;42:857–61. 31. Zeeman GG. Obstetric critical care: a blueprint for improved outcomes. Crit Care Med 2006;34:S208–14. 32. Zlatnik MG, Cheng YW, Norton ME, Thiet MP, Caughey AB. Placenta previa and the risk of preterm delivery. J Matern Fetal Neonatal Med 2007;20:719–23.
Obstetric anesthesia and transfusion outcomes 33. Gielchinsky Y, Mankuta D, Rojansky N, Laufer N, Gielchinsky I, Ezra Y. Perinatal outcome of pregnancies complicated by placenta accreta. Obstet Gynecol 2004;104:527–30. 34. Palo R, Ahonen J, Salo H, Salmenpera M, Krusius T, Maki T. Transfusion of red blood cells: no impact on length of hospital stay in moderately anaemic parturients. Acta Anaesthesiol Scand 2007;51:565–9.