ABSTRACT
ABSTRACT: The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development. It is crucial that end users be aware of the differences between CPGs and other forms of clinical advice and that producers and publishers of these resources use clear and unambiguous terminology to facilitate their distinction. The objective of this article is to highlight the similarities and differences between ASH CPGs and other forms of ASH clinical advice and discuss the implications of these differences for end users.
Subject(s)
Hematology , Practice Guidelines as Topic , Humans , Hematology/standards , Societies, Medical , United StatesABSTRACT
Gender dysphoria or gender incongruence is defined as "persons that are not satisfied with their designated gender" [1]. The awareness and evidence-based treatment options available to this population have grown immensely over the last two decades. Protocols now include an Endocrine Society Clinical Practice Guideline [1] as well as the World Professional Association of Transgender Health Standards of Care (WPATH SOC) [2]. Hematologic manifestations, most notably thrombosis, are one of the most recognized adverse reactions to the hormones used for gender-affirming care. Therefore, hematologists are frequently consulted prior to initiation of hormonal therapy to help guide safe treatment. This review will focus on the scientific evidence related to hemostatic considerations for various gender-affirming therapies and serve as a resource to assist in medical decision-making among providers and patients.
Subject(s)
Hemostatics , Transgender Persons , Humans , Hemostatics/adverse effects , Gender Identity , Delivery of Health CareABSTRACT
Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.
Subject(s)
Erythroblastosis, Fetal , Immunoglobulins, Intravenous , Blood Group Incompatibility , Erythroblastosis, Fetal/drug therapy , Exchange Transfusion, Whole Blood , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant, Newborn , PhototherapyABSTRACT
Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 × 103/µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.
Subject(s)
Hematologic Tests , Societies, Medical , Child , Erythrocyte Transfusion , Hematologic Tests/methods , Hemostasis , Humans , United StatesABSTRACT
BACKGROUND: Early hepatic artery thrombosis (HAT) after liver transplantation is a serious complication that frequently results in graft loss and the need for retransplantation. Although studies have reported on various operative and endovascular treatment approaches, pharmacologic strategies for the prevention or management of HAT are not well defined. Patients with blood clotting disorders, those with a contraindication to heparin, and those who have previously developed HAT represent unique challenges in management. METHODS: We present the case of a 9-month-old male with a hypercoagulable state who developed early HAT after two liver transplants, despite the use of postoperative therapeutic heparin infusion. RESULTS AND CONCLUSION: The patient successfully underwent a third liver transplant using intraoperative and postoperative bivalirudin infusion, a direct thrombin inhibitor. Rotational thromboelastometry (ROTEM) was used to guide anticoagulation and blood product administration in the perioperative period. At 1.5 years post-transplant, the patient has good graft function with patent hepatic vasculature. This case demonstrates the innovative use of bivalirudin anticoagulant therapy and viscoelastic methodologies to improve outcomes in hypercoagulable liver transplant recipients.
Subject(s)
Antithrombins/therapeutic use , Hepatic Artery , Liver Transplantation , Peptide Fragments/therapeutic use , Postoperative Complications/prevention & control , Thrombosis/prevention & control , Hirudins , Humans , Infant , Male , Ornithine Carbamoyltransferase Deficiency Disease/complications , Recombinant Proteins/therapeutic useABSTRACT
Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count 10 × 103 /µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.
Subject(s)
Hematologic Tests , Child , Erythrocyte Transfusion , Hemostasis , Humans , Iron Deficiencies , Societies, Medical , United StatesABSTRACT
BACKGROUND: Prompt resuscitation with plasma and other blood products reduces trauma-related morbidity and mortality. Standard storage and preparation techniques for frozen plasma limit its utility in the pre-hospital setting. Plasma can be dehydrated using hot air (spray-dried plasma), stored at room temperature and rehydrated quickly for use. The spray-dry process decreases high-molecular-weight multimers of von Willebrand factor compared with conventional plasma. The objective of this study was to compare platelet adhesion and thrombus formation in a microfluidic perfusion assay facilitated by spray-dried compared with frozen plasma using a non-inferiority design. STUDY DESIGN AND METHODS: Whole blood was centrifuged to obtain red cell concentrate, and a platelet pellet that was suspended in either spray-dried or frozen plasma to create recombined whole blood. Platelets were fluorescently labelled, and samples were flowed through a collagen-coated microchannel. Surface area coverage by platelets and thrombi was analysed and compared between each spray-dried and frozen plasma pair. RESULTS: Compared with whole blood samples containing frozen plasma, samples with spray-dried plasma had similar surface area coverage of platelets and thrombi after 180 s of flow. Even when diluted with von Willebrand factor-free plasma, there was no reduction thrombus formation. CONCLUSION: Spray-dried plasma is not inferior in supporting haemostasis compared with fresh frozen plasma in a paired analysis. It offers advantages with respect to portability and ease of preparation over frozen plasma in the pre-hospital setting. This study supports development of clinical studies to evaluate the efficacy and safety of spray-dried plasma in trauma patients.
Subject(s)
Blood Preservation/methods , Cryopreservation/methods , Microfluidics/methods , Spray Drying , Thrombosis/blood , Blood Platelets/metabolism , Blood Preservation/adverse effects , Collagen/metabolism , Hemostasis , Humans , Thrombosis/etiology , von Willebrand Factor/metabolismSubject(s)
Base Sequence , Exons , Protein C , Purpura Fulminans , Sequence Deletion , Amino Acid Substitution , Blood Coagulation Tests , Child, Preschool , Female , Humans , Infant, Newborn , Protein C/genetics , Protein C/metabolism , Purpura Fulminans/blood , Purpura Fulminans/genetics , Purpura Fulminans/pathology , Purpura Fulminans/therapyABSTRACT
OBJECTIVE: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds. PURPOSE: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.
Subject(s)
Cautery , Endoscopy/methods , Epistaxis/therapy , Ligation , Quality Improvement , Vasoconstrictor Agents/therapeutic use , Epistaxis/diagnosis , Epistaxis/prevention & control , Hemostatics/therapeutic use , Humans , Nasal Surgical Procedures/methods , Patient Acuity , Patient Education as Topic/methods , Risk Factors , Tampons, Surgical , Telangiectasia, Hereditary Hemorrhagic/diagnosisABSTRACT
OBJECTIVE: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the great majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds. PURPOSE: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It will focus on nosebleeds that commonly present to clinicians with phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients, patients with hemorrhagic telangiectasia syndrome (HHT) and patients taking medications that inhibit coagulation and/or platelet function, are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the working group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based upon their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include 1 or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome (HHT). (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation about examination of the nasal cavity and nasopharynx using nasal endoscopy was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.
Subject(s)
Epistaxis/epidemiology , Epistaxis/therapy , Nasal Surgical Procedures/methods , Practice Guidelines as Topic , Quality Improvement , Conservative Treatment/methods , Epistaxis/diagnosis , Evidence-Based Medicine , Guideline Adherence , Humans , Incidence , Ligation/methods , Quality of Life , Recurrence , Risk Assessment , Severity of Illness Index , Treatment OutcomeABSTRACT
Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet count and to excessive bleeding in neonatal CPB surgery. Platelet counts and platelet P-selectin exposure in response to agonist stimulation were measured at four times before, during, and after CPB surgery in neonates with normal versus excessive levels of postsurgical bleeding. Relative to baseline, platelet counts were reduced in patients while on CPB, as was platelet activation by the thromboxane A2 analog U46619, thrombin receptor activating peptide (TRAP), and collagen-related peptide (CRP). Platelet activation by adenosine diphosphate (ADP) was instead reduced after platelet transfusion. We provide evidence that thrombocytopenia is a likely contributor to CPB-associated defects in platelet responsiveness to U46619 and TRAP, CPB-induced collagen receptor downregulation likely contributes to defective platelet responsiveness to CRP, and platelet transfusion may contribute to defective platelet responses to ADP. Platelet transfusion restored to baseline levels platelet counts and responsiveness to all agonists except ADP but did not prevent excessive bleeding in all patients. We conclude that platelet count and function defects are characteristic of neonatal CPB surgery and that platelet transfusion corrects these defects. However, since CPB-associated coagulopathy is multifactorial, platelet transfusion alone is insufficient to treat bleeding events in all patients. Therefore, platelet transfusion must be combined with treatment of other factors that contribute to the coagulopathy to prevent excessive bleeding.
Subject(s)
Blood Platelets/physiology , Cardiopulmonary Bypass , Extracorporeal Circulation , Heart Defects, Congenital/surgery , Platelet Transfusion/methods , Postoperative Hemorrhage/prevention & control , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Adenosine Diphosphate/metabolism , Cells, Cultured , Female , Humans , Infant, Newborn , Male , Platelet Activation , Platelet Count , Platelet Function TestsABSTRACT
BACKGROUND: Neonates undergoing cardiopulmonary bypass (CPB) surgery to correct congenital heart defects often experience excessive bleeding. Exposure of blood to artificial materials during CPB may activate coagulation, complement and inflammatory pathways. In addition, the surgical stress placed on the haemostatic system may result in cross-activation of other plasma proteolytic cascades, which could further complicate physiological responses to the surgical procedure and post-operative recovery. Plasma protease inhibitors undergo distinct conformational changes upon interaction with proteases, and, thereby, can serve as endogenous biosensors to identify activation of the different proteolytic cascades. We tested the hypothesis that changes in the concentration and conformation of protease inhibitors regulating plasma proteolytic cascades during neonatal CPB are associated with post-operative bleeding. PATIENTS AND METHODS: Plasma samples from 44 neonates were obtained at four time points across the surgical procedure. Anti-thrombin, antitrypsin, anti-chymotrypsin, anti-plasmin, C1-inhibitor and tissue factor pathway inhibitor (TFPI) concentrations and conformations were evaluated by enzyme-linked immunosorbent assay, transverse urea gradient gel electrophoresis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS/CONCLUSION: The most striking changes were observed following heparin administration and were associated with the appearance of inactive forms of anti-thrombin and an increase in the plasma concentration of TFPI. Changes in anti-thrombin and TFPI remained evident throughout surgery and into the post-operative period but were not different between patients with or without post-operative bleeding. The concentration of antitrypsin decreased across surgery, but there was no significant accumulation of inactive conformations of any inhibitor besides anti-thrombin, indicating that widespread cross-activation of other plasma proteolytic cascades by coagulation proteases did not occur.
Subject(s)
Anticoagulants/blood , Blood Coagulation/drug effects , Cardiopulmonary Bypass , Heparin/therapeutic use , Lipoproteins/blood , Female , Hemorrhage/etiology , Humans , Infant, Newborn , Male , Peptide Hydrolases/blood , Plasma/metabolism , Postoperative Complications , Protein Binding , Thrombin/metabolismABSTRACT
BACKGROUND: Thrombocytopenia and hypofibrinogenemia during neonatal cardiopulmonary bypass (CPB) contribute to bleeding and morbidity. Rotational thromboelastometry (ROTEM) is a viscoelastic assay with a rapid turnaround time. Data validating ROTEM during neonatal cardiac surgery remain limited. This study examined perioperative hemostatic trends in neonates treated with standardized platelet and cryoprecipitate transfusion during CPB. We hypothesized that ROTEM would predict thrombocytopenia, hypofibrinogenemia, and the correction thereof. METHODS: Forty-four neonates undergoing CPB were included in this prospective observational study. Blood samples were obtained at Baseline, On CPB, Post-CPB, and Postoperative. The ROTEM analysis included extrinsically activated (Extem) and fibrinogen-specific (Fibtem) assays. Platelet-specific thromboelastometry (Pltem) values were calculated. Platelet and cryoprecipitate transfusion was initiated prior to termination of CPB. RESULTS: Platelet count and Extem amplitude decreased significantly On CPB ( P < .0001), increased significantly Post-CPB ( P < .0001), and Postoperative values were not significantly different from Baseline. Extem amplitude at 10 minutes (A10) > 46.5 mm (AUC = 0.941) and Pltem A10 > 37.5 mm [area under curve (AUC) = 0.960] predicted platelet count > 100 × 103/µL, and they highly correlated with platelet count ( R = 0.89 and R = 0.90, respectively). Fibrinogen concentration and Fibtem amplitude decreased significantly On CPB ( P ≤ .0001) and normalized after cryoprecipitate transfusion. Fibtem A10 > 9.5 mm predicted fibrinogen >200 mg/dL (AUC = 0.817), but it correlated less well with fibrinogen concentration ( R = 0.65). CONCLUSIONS: ROTEM analysis during neonatal cardiac surgery is sensitive and specific for thrombocytopenia and hypofibrinogenemia, identifying deficits within 10 minutes. Platelet and cryoprecipitate transfusion during neonatal CPB normalizes platelet count, fibrinogen level, and ROTEM amplitudes.
Subject(s)
Afibrinogenemia/diagnosis , Cardiopulmonary Bypass , Intraoperative Care/methods , Intraoperative Complications/diagnosis , Thrombelastography/methods , Thrombocytopenia/diagnosis , Afibrinogenemia/etiology , Female , Humans , Infant, Newborn , Male , Prospective Studies , Sensitivity and Specificity , Thrombocytopenia/etiologyABSTRACT
OBJECTIVE: To derive and validate an objective definition of postoperative bleeding in neonates and infants undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Using a retrospective cohort of 124 infants and neonates, we included published bleeding definitions and cumulative chest tube output over different postoperative periods (eg, 2, 12, or 24 hours after intensive care unit admission) in a classification and regression tree model to determine chest tube output volumes that were associated with red blood cell transfusions and surgical re-exploration for bleeding in the first 24 hours after intensive care unit admission. After the definition of excessive bleeding was determined, it was validated via a prospective cohort of 77 infants and neonates. RESULTS: Excessive bleeding was defined as ≥7 mL/kg/h for ≥2 consecutive hours in the first 12 postoperative hours and/or ≥84 mL/kg total for the first 24 postoperative hours and/or surgical re-exploration for bleeding or cardiac tamponade physiology in the first 24 postoperative hours. Excessive bleeding was associated with longer length of hospital stay, increased 30-day readmission rate, and increased transfusions in the postoperative period. CONCLUSIONS: The proposed standard definition of excessive bleeding is based on readily obtained objective data and relates to important early clinical outcomes. Application and validation by other institutions will help determine the extent to which our specialty should consider this definition for both clinical investigation and quality improvement initiatives.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Cardiopulmonary Bypass/adverse effects , Postoperative Hemorrhage/classification , Terminology as Topic , Age Factors , Cardiac Surgical Procedures/mortality , Cardiopulmonary Bypass/mortality , Chest Tubes , Drainage/instrumentation , Erythrocyte Transfusion , Female , Hospital Mortality , Humans , Infant , Infant, Newborn , Length of Stay , Male , Patient Readmission , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/mortality , Postoperative Hemorrhage/therapy , Prospective Studies , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence-based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom thrombocytopenia is common. Their unique physiology and associated complications make the risks and benefits of platelet transfusions difficult to understand. The goal of this review was to highlight research areas that need to be addressed to better understand the risks and benefits of platelet transfusions in neonates. Specifically, it will be important to identify neonates at risk of bleeding who would benefit from a platelet transfusion and to determine whether platelet transfusions either abrogate or exacerbate common neonatal complications such as sepsis, chronic lung disease, necrotizing enterocolitis, and retinopathy of prematurity.
Subject(s)
Platelet Count , Platelet Transfusion , Thrombocytopenia/therapy , Blood Platelets , Blood Transfusion/methods , Hematology/methods , Hematology/trends , Hemorrhage/etiology , Hemostasis , Humans , Infant, Newborn , Infant, Premature , Intensive Care Units, Neonatal , Neovascularization, Pathologic , Platelet Transfusion/adverse effects , Risk FactorsABSTRACT
Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.