Minimizing surgical blood loss at cesarean hysterectomy for placenta previa with evidence of placenta increta or placenta percreta: the state of play in 2020.

The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of the internal iliac arteries. With incremental gains in surgical expertise, described in 5 steps in this review, our teams have witnessed a steady decline in surgical blood loss. Nevertheless, a subset of women has the most severe form of placenta accreta spectrum, namely placenta previa-percreta. Such women are at risk of major hemorrhage during surgery from vessels arising outside the territories of the internal iliac arteries. These additional blood supplies, mostly from the external iliac arteries, pose significant risks of major blood loss even in experienced hands. To address this risk, some centers, principally in China, have adopted an approach of routinely placing an infrarenal aortic balloon, with both impressively low rates of blood loss and an ability to conserve the uterus by resecting the placenta with the affected portion of the uterine wall. We review these literature developments in the context of safely performing elective cesarean hysterectomy for placenta previa-percreta, the most severe placenta accreta spectrum disorder.

Blood Products in the Management of Abnormal Placentation.

A critical tool in the successful management of patients with abnormal placentation is an established massive transfusion protocol designed to rapidly deliver blood products in obstetrical and surgical hemorrhage. Spurred by trauma research and an understanding of consumptive coagulopathy, the past 2 decades have seen a shift in volume resuscitation from an empiric, crystalloid-based method to balanced, targeted transfusion therapy. The present article reviews patient blood management in abnormal placentation, beginning with optimizing the patient's status in the antenatal period to the laboratory assessment and transfusion strategy for blood products at the time of hemorrhage.

A randomized controlled pilot study of VO2 max testing: a potential model for measuring relative in vivo efficacy of different red blood cell products.

BACKGROUND: Randomized trials, for example, RECESS, comparing "young" (median, 7-day) versus "middle-aged" (median, 28-day) red blood cells (RBCs), showed no difference in outcome. These data are important; however, they do not inform us about the safety and effectiveness of the oldest RBCs, which some patients receive. It may not be feasible to conduct a clinical trial randomizing patients to receive the oldest blood. Therefore, we propose strenuous exercise (VO2 max testing) as a model to study the relative efficacy to increase oxygen delivery to tissue of different RBC products, for example, extremes of storage duration. STUDY DESIGN AND METHODS: In this pilot study, eight healthy subjects had 2 units of leukoreduced RBCs collected by apheresis in AS-3 using standard methods. Subjects were randomized to receive both (2) units of their autologous RBCs at either 7 or 42 days after blood collection. VO2 max testing on a cycle ergometer was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). This design avoids confounding effects on intravascular volume from the 2-unit blood transfusion. The primary outcome was the difference in VO2 max between Friday and Monday (delta VO2 max). RESULTS: VO2 max increased more in the 7-day RBC arm (8.7 ± 6.9% vs. 1.9 ± 6.5%, p = 0.202 for comparison between arms). Exercise duration (seconds) increased in the 7-day RBC arm (8.4 ± 1.7%) but actually decreased in the 42-day arm (-2.6 ± 3.6%, p = 0.002). CONCLUSIONS: This pilot study suggests that VO2 max testing has potential as a rigorous and quantitative in vivo functional assay of RBC function. Our preliminary results suggest that 42-day RBCs are inferior to 7-day RBCs at delivering oxygen to tissues.

Management of Coagulopathy in Postpartum Hemorrhage.

The purpose of this article is to review the use of blood products and hemostatic agents in the management of coagulopathy at the time of postpartum hemorrhage. Blood product administration strategies are broadly reviewed, including the role of the blood bank, the role of massive transfusion protocols, the role of laboratory monitoring, and the role of anesthesia management. Aspects of patient blood management are discussed. The concept refers to an evidence-based, comprehensive, multidisciplinary approach to optimizing the care of patients who might need transfusion and includes measures to avoid or minimize transfusion such as preoperative anemia management, cell salvage, and the use of hemostatic medication to reduce bleeding. The contributions of individual blood components-red blood cells, plasma, cryoprecipitate, and platelets-are described. Current data regarding the complementary role of hemostatic agents-antifibrinolytic agents and clotting factor concentrates-are presented. Two developments in blood component pathogen reduction are introduced.

Comparison of the Trends in Risk Factors and Management of Severe Postpartum Hemorrhage Years 2000-2004 Versus 2005-2008.

OBJECTIVE: To compare trends in the etiology and management of severe postpartum hemorrhage (PPH) during 2 time periods: 2000-2004 (Period 1) versus 2005-2008 (Period 2). STUDY DESIGN: Medical records with a diagnosis of PPH were identified by ICD-9 codes for immediate, third-stage, delayed, and secondary. PPH and post- partum coagulation defect. Subjects having a PPH within 24 hours of delivery who also received blood component therapy (defined as severe PPH) during Period 1 were compared with those from Period 2. RESULTS: There were 109 and 119 cases identified from Periods 1 and 2, respectively. Uterine atony was the most common cause of severe PPH during both time periods. In the second time period women with severe PPH had a lower mean hematocrit (p<0.05), a greater mean BMI (p<0.05), and more induced labor (p<0.01) as compared to the first time period. A greater proportion of the women in the second time period received misoprostol (p<0.0001) and platelets (p<0.05). The proportions of other therapies and surgical interventions remained unchanged, as did the ultimate outcomes. CONCLUSION: At a single large institution over the course of a 9-year period the management of severe PPH changed to include a greater utilization of misoprostol and platelet therapy.

Autologous platelet-rich plasma: evidence for clinical use.

PURPOSE OF REVIEW: Autologous platelet-rich plasma (aPRP) is growing in popularity as a therapy to augment wound healing, speed the recovery from muscle and joint injuries, and enhance recovery after surgical repair. High-profile athletes treated with aPRP have increased the demand from the general population. Yet, evidence to support the use of aPRP in most clinical settings is weak, because of poorly controlled clinical trials. RECENT FINDINGS: Preparations of aPRP vary by platelet count, leukocyte content, and degree of platelet activation. Nonetheless, these heterogeneous preparations are used in trials to assess the efficacy of aPRP treatment. SUMMARY: Despite weak evidence, the use of aPRP continues to grow. High-quality randomized controlled trials are needed to validate or repudiate the potential efficacy of aPRP. Standards for aPRP preparation and quality should be created.

The use of autologous platelet-rich plasma in the orthopedic setting.

BACKGROUND: Autologous platelet-rich plasma (aPRP) is widely used with orthopedic patients to help treat injuries to tendons, cartilage, ligaments, and muscle. A comprehensive review of the literature was conducted to evaluate aPRP's efficacy and compare available methods. In addition, the production and administration of aPRP were explored. STUDY DESIGN AND METHODS: A literature search was performed. Randomized controlled clinical trials (RCTs) in orthopedic procedures on adult patients were included and assessed for methodologic quality. The main outcomes were pain relief, increase in function, structural integrity, and "healing" based on various validated scales. RESULTS: Twelve RCTs and one controlled cohort were included (four lateral epicondylitis, two chronic Achilles tendinopathy, two anterior cruciate ligament injury, and five rotator cuff injuries). Four trials reported some benefit from aPRP versus controls while eight trials found no benefit from aPRP applications versus control. One study had too many patients withdraw from the control arm for acceptable data interpretation. All protocols used a different aPRP formulation or method of delivery or application. CONCLUSIONS: Despite its popularity, there are no standardized criteria that define aPRP. Different techniques yield wide variability in terms of platelet count and concentration. These variations make it difficult to compare clinical trials that use aPRP or draw conclusions concerning its clinical efficacy in orthopedic procedures. Blood bankers have experience in the production of standardized blood components. This expertise may be used to develop and implement protocols for the production and administration of aPRP, as well as quality control measures.

Reduced use of allogeneic platelets through high-yield perioperative autologous plateletpheresis and reinfusion.

BACKGROUND: Intraoperative autologous platelet (PLT) collection as part of a multimodal blood conservation program carries a Class IIa recommendation from the Societies of Thoracic Surgeons and Cardiovascular Anesthesiologists, but achieving a suitable PLT yield limits its application. A novel, autologous, intraoperative, high-yield plateletpheresis collection program was established and retrospectively analyzed to identify potential improvements over previously reported plateletpheresis protocols. STUDY DESIGN AND M-ETHODS: Targeting complex cardiothoracic surgery patients without recent anti-PLT agents, thrombocytopenia, or severe anemia, the program aimed to achieve a PLT yield of at least one standard apheresis unit (3.0 × 10(11) ) within 60 to 90 minutes and using an automated plateletpheresis device (Trima, Terumo BCT). Anesthetized and invasively monitored patients underwent plateletpheresis via a large-bore, indwelling central line placed for the surgery. Collection-related data for quality control purposes and subsequent PLT transfusion requirements were analyzed and reported. RESULTS: Forty-two patients donated autologous PLTs between 2011 and 2012. PLT yield was 4.5 (3.9-5.0) × 10(11) , which significantly exceeds previously reported yields, and procedure duration was 53.2 (48.4-57.9) minutes. As anticipated, postcollection PLT count decreased from 268 (242-293) × 10(9) to 182 (163-201) × 10(9) /L; hypocalcemia was minimized by infusion of 1 g of CaCl2 . Autologous PLT yield was inversely correlated with allogeneic PLT use, and avoidance of allogeneic PLT transfusion was increased when the autologous yield was the equivalent of 2 or more apheresis units. CONCLUSION: High-yield, intraoperative autologous PLT collection is achievable using an automated plateletpheresis device. Initial experience shows a reduction in reliance on allogeneic PLTs for complex cardiothoracic surgery.

Medical advances in the treatment of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Recent advances in the management of severe bleeding for trauma patients may provide insight into PPH management, but must be applied with caution considering the significant differences between trauma and obstetric patients. In this review, we summarized evidence for current management strategies for patients with major obstetric hemorrhage, including (1) rapid laboratory assessment of coagulopathy, (2) early transfusion of plasma and high plasma-to-red blood cell transfusion ratios in massive PPH, and (3) use of tranexamic acid and fibrinogen concentrates in the setting of PPH complicated by coagulopathy.

Impact of transfusion of autologous 7- versus 42-day-old AS-3 red blood cells on tissue oxygenation and the microcirculation in healthy volunteers.

BACKGROUND: Stored red blood cells (RBCs) accumulate biochemical and biophysical changes. Maximum storage duration is based on acceptable in vitro characteristics and 24-hour survival, but not RBC function. Relatively little is known about the impact of RBC storage duration on oxygenation and the microcirculation. STUDY DESIGN AND METHODS: Eight healthy subjects donated a double RBC apheresis, which were prestorage leukoreduced and processed in AS-3. Subjects were transfused 1 unit of RBCs at 7 and 42 days after blood collection. Measurements of percentage of tissue oxygenation in the thenar eminence muscle (StO2) and brain (SctO2) were recorded with Food and Drug Administration-cleared noninvasive devices. Sublingual microvascular blood flow (microcirculatory flow index [MFI]) was quantified before and after RBC transfusion using a video microscope. Raw electronic data for all measurements were analyzed by a blinded observer at a core laboratory. RESULTS: The only pre- versus posttransfusion change observed in measurements of SctO2, StO2, or MFI was a very small increase in SctO2, from 70.4 to 71.8 (means, p=0.032) at 7 days. There was no significant difference in the amount of pre-post change at 7 days versus 42 days for any of the measures. CONCLUSION: Transfusion of 1 unit of 42-day-stored RBCs to healthy subjects has no overt detrimental effect on tissue oxygenation or the microcirculation assessed by clinically available monitors.

Postpartum hemorrhage: when uterotonics and sutures fail.

Systemic bleeding at the time of postpartum hemorrhage (PPH) is usually the result of coagulopathy that has developed acutely as a result of massive hemorrhage after uterotonics and sutures have failed. Occasionally, the patient has a preexisting coagulopathy, but more often, coagulopathy arises acutely as the result of massive hemorrhage, which is usually related to obstetrical and less often surgical bleeding. Despite being able to identify risk factors for PPH in the antenatal and intrapartum period, the majority of women who ultimately develop PPH do not have any such factors and every pregnancy is at risk. The coagulopathy associated with massive PPH may be due to hemodilution, failure of liver synthetic function as occurs with acute liver failure of pregnancy, or disseminated intravascular coagulation (DIC). There are no data from clinical trials to help guide management of transfusion in PPH, although the management of blood component therapy in severe PPH is similar to that in other massive hemorrhage. Standard practice is to replace fibrinogen to maintain a level of ≥ 100 mg/dL, yet recent evidence suggests that the level of fibrinogen needed to prevent PPH is at least 400 mg/dL. Recombinant activated factor VIIa (rFVIIa) has been used in the management of severe PPH unresponsive to blood component therapy. Coagulation laboratory evaluation may be useful in guiding hemostatic management during massive PPH, but for the results to be useful, they must be rapidly available and provide information that would not be available from clinical assessment alone. The hematologist or hemostasis expert has the opportunity to make the difference between life and death for the patient experiencing massive PPH.

Report of a young girl with MYH9 mutation and review of the literature.

MYH9 mutations cause the inherited macro-thrombocytopenic syndromes of May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, and Epstein syndrome, collectively referred to as MYH9-related disease. We present the case of a girl with MYH9-related disease whose diagnosis was facilitated by platelet electron microscopy and MYH9 sequencing. We discuss our patient's clinical presentation, now with 12 years of follow-up. We also discuss management and her possible prognosis given her specific MYH9 mutation.

How I investigate acquired megaloblastic anemia.

In this review of megaloblastic anemia (MA), an overview of vitamin B12 and folate body requirements, biochemical pathways, and laboratory testing strategies will be provided. However, the focus of this review is the classic and unique features of MA in blood and bone marrow. Acquired MA is a benign disorder for many, but can be detrimental for some. The clinical presentation can vary considerably, and the spectrum of symptoms and signs is diverse and quite broad. Prompt recognition and therapy are critical to prevent potential irreversible damage and clinical sequelae, especially in patients with vitamin B12 deficiency. A delay in diagnosis of vitamin B12 deficiency can result in significant neurologic sequelae that may not fully resolve with treatment, including in neonates and young infants. The blood and bone marrow features in MA can closely mimic thrombocytopenic purpura, myelodysplasia, and other myeloid neoplasms. Both pancytopenia and normal MCV at presentation are common in MA and raise unique challenges for the diagnostician. Partially treated MA is also a significant diagnostic "trap". MA is highly responsive to treatment, and patients tend to improve rapidly upon treatment initiation. However, the broad range of clinical and hematologic features makes the rapid, successful diagnosis of MA a unique challenge for the hematopathologist. Even in the era of state-of-the-art laboratory testing, a high suspicion is required.

Storage age of transfused platelets and outcomes after cardiac surgery.

BACKGROUND: The relationship between duration of platelet (PLT) storage, currently limited to 5days, and surgical outcomes has not been established. We tested the hypothesis that PLT storage age was associated with adverse outcomes. STUDY DESIGN AND METHODS: A retrospective cohort of aortocoronary bypass (CABG) surgery patients from January 1996 to January 2005 receiving one or more PLT transfusions was selected for study. The composite primary ("short-term") outcome was 30-day mortality or prolonged hospital stay. Secondary outcomes included complications and survival to annual follow-up. Multivariable logistic regression models and Cox proportional hazards regression analysis evaluated the association between PLT storage age and outcomes, expressed as an odds ratio (OR) or hazard ratio with 95% confidence intervals (CIs), respectively. RESULTS: PLT transfusion was administered to 3272 of 10,275 CABG patients and 2578 received units of known storage age, which ranged between 2 and 5days (median, 4days; 25th percentile, 3days; 75th percentile, 5 days). The mortality rate for the 1637 patients receiving a single plateletpheresis transfusion was 3.8%, while 21.6% experienced a prolonged hospital stay or death. After adjusting for the number of PLT and red blood cell (RBC) units transfused, RBC storage age, and preoperative mortality risk, there was no association between PLT storage age and short-term outcome (OR, 1.01; 95% CI, 0.90-1.14), survival (hazard ratio [HR], 1.04; 95% CI, 0.96-1.13), or postoperative infections. CONCLUSIONS: PLT storage age was not associated with adverse short-term outcomes, decreased long-term survival, or infections after cardiac surgery.

Use of Fetal Hemoglobin Quantitation for Rh-Positive Pregnant Females: A National Survey and Review of the Literature.

CONTEXT.­: The Kleihauer-Betke (KB) test is validated for estimating the dose of Rh immune globulin needed for Rh-negative pregnant females. However, some clinicians are also ordering the test for Rh-positive women. The degree to which this practice occurs is unknown. OBJECTIVE.­: To evaluate the number of laboratories that perform the KB test on Rh-positive pregnant women, and to establish current ordering practices for this indication. DESIGN.­: We added 9 supplemental questions regarding KB test use for fetomaternal hemorrhage to the 2016 College of American Pathologists proficiency test survey. We also reviewed the available literature regarding the diagnostic utility of the KB test for Rh-positive women. RESULTS.­: A total of 1578 surveys were evaluated and revealed that 52% (824) of respondents perform these tests for Rh-positive women, and more than 50% (440 of 819; 53.7%) of these laboratories report that the results for Rh-positive women are treated as important or very important. CONCLUSIONS.­: The KB test is commonly used for Rh-positive women, and the information obtained from the test is considered as urgent and important. However, the available literature in support of this practice is still nonconclusive.

Transfusion Management of Obstetric Hemorrhage.

Obstetric hemorrhage is one of the leading, as well as one of the most treatable, causes of maternal morbidity and mortality worldwide. As obstetric hemorrhage often occurs in patients without risk factors, there is virtually unanimous agreement from obstetric professional societies to establish obstetric hemorrhage protocols in anticipation of these emergencies. These protocols involve multidisciplinary teams in which the transfusion service plays an essential and vital role. This manuscript will examine the epidemiology of obstetric hemorrhage, risk factors that may be present, and recommendations for these protocols, with a focus on massive transfusion protocols, laboratory testing, cell salvage and use of pharmacologic adjuvant therapy including tranexamic acid and factor concentrates.