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Acute (Childhood) Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by immune-mediated platelet destruction and resultant thrombocytopenia. Two forms of ITP had been described previously: acute ITP that resolves within 6 months and chronic ITP that persists beyond 6 months. Recently, an international working group on ITP has modified these designations to reflect the relatively common occurrence of spontaneous remission in children between 6 months and 1 year…

Other Platelet Abnormalities

There are countless mechanisms for causing platelet abnormalities, many of which are likely yet to be discovered. This chapter is meant to touch on additional platelet abnormalities not completely discussed in other chapters of this book—but is not by any means all inclusive. It is important to note that some platelet abnormalities may incidentally be detected in laboratory assays without an associated manifestation of clinical signs…

Failure to Release and Aspirin-Like Defects

Multiple platelet signaling and synthetic pathways are necessary for the optimal propagation and stabilization of the forming thrombus. Mutations in platelet receptors, signaling proteins, and synthetic pathways have been identified in patients with granule release and aspirin-like defects. Patients with platelet granule release and aspirin-like defects typically have mild mucocutaneous bleeding. Rare patients have been identified with an isolated defect in platelet procoagulant activity. Defects in…

Platelet Storage Granule Defects

Platelets contain two major types of granules, dense and α-granules. Granule contents include numerous factors essential to the normal formation and stabilization of a hemostatic plug. Either a decrease in the number of platelet granules or a defect in their release can result in a bleeding diathesis. Several clinical syndromes are associated with storage granule defects. Bleeding manifestations in patients with storage granule defects are typically…

Glanzmann Thrombasthenia

Glanzmann thrombasthenia (GT) is an autosomal-recessive platelet function disorder in which platelet appearance and platelet number are unaffected. Patients with GT present with platelet-type bleeding, which may be severe, such as purpura, epistaxis, oral mucosal bleeding, menorrhagia, or gastrointestinal bleeding. Pathophysiology The most common genetic cause of GT is mutations in both alleles of one of the genes that encode for the α IIb or β…

Bernard–Soulier Syndrome and Other GPIb-IX-Related Receptor Defects

GPIb-IX is the major platelet receptor for von Willebrand factor (VWF). Normal GPIb-IX function is essential both for normal megakaryocyte/platelet maturation and for normal platelet function, most prominently adhesion. Mutations in GPIb-IX result in a number of different syndromes. Clinical manifestations of these syndromes range from a severe platelet function defect in patients with a homozygous deficiency of one of the molecular components of GPIb-IX, to…

Acquired Neonatal Thrombocytopenia

This chapter will focus on the acquired etiologies of neonatal thrombocytopenia as congenital and alloimmune thrombocytopenias are discussed in Chapter 93, Chapter 94 . Neonatal thrombocytopenia occurs in 1%–2% of healthy term neonates but is common in the neonatal intensive care unit where thrombocytopenia occurs in up to one-third of all admissions. Fetal platelet counts increase during gestation, reaching adult values by the 22nd week. At…

Fetal and Neonatal Alloimmune Thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is characterized by the presence of transient isolated neonatal thrombocytopenia secondary to maternal antibodies against paternally inherited antigens expressed on the fetal platelets. FNAIT is the most common cause of severe thrombocytopenia (<50,000/μL) in term neonates as well as the most common cause of intracranial hemorrhage (ICH). While the incidence varies depending on the definition of thrombocytopenia and in particular…

Congenital Thrombocytopenia

Introduction Inherited thrombocytopenia was once considered a rare disease, but more recent studies using next-generation sequencing (NGS) and genome-wide association studies suggest that the prevalence of inherited or familial thrombocytopenia may be much higher than originally appreciated and that some individuals who were previously thought to have immune thrombocytopenia (ITP) may, in fact, have a defect in platelet or megakaryocyte development. Further characterization and investigation of…

Approach to the Pediatric Patient With a Bleeding Disorder

Basic Considerations for Evaluation of a Pediatric Patient With a Bleeding Disorder Children with bleeding disorders generally present with mild bleeding symptoms including easy bruising, epistaxis, gum bleeding, abnormal clotting tests from presurgical evaluation, or known family history of bleeding disorder. Rarely, they can present with life-threatening bleeding in vital organs or serious postsurgical bleeding. Clinical history is the key to further characterize the bleeding phenotype.…

Overview of the Coagulation System

Hemostasis means stopping blood loss or bleeding. Hemostasis is an orchestrated, balanced, and tightly regulated process. Hemostasis can be subdivided into three sequential processes: primary hemostasis, secondary hemostasis and tertiary hemostasis. In primary hemostasis the interaction of the injured endothelium with von Willebrand factor (VWF) and platelets is crucial for the formation of a platelet plug at the injury site. In secondary hemostasis, the coagulation factors…

Tissue Banking in the Hospital Setting

In many hospitals, management of human tissue, specifically tissue allografts, has been centralized. Centralized tissue services coordinate the supply, dispensing, and accounting of products among numerous clinical services and have an infrastructure to efficiently receive, process, store, issue, and manage products. Tissue Suppliers Tissue suppliers aseptically recover tissue for transplantation from deceased human donors. Suppliers then process and store the recovered tissue. Some of the suppliers…

Quality and Regulatory Issues in Cellular Therapy

Cellular therapy is the use of viable cells and tissues for the treatment of disease. Modern cell-based therapies include regenerative medicine, which is the process of replacing or regenerating human cells, tissues, or organs to restore or establish normal function. With these advances, a need existed to incorporate quality systems and regulatory oversight. While the basics of quality and quality systems are the same for blood…

Adverse Events Associated With Hematopoietic Progenitor Cell Product Infusion

Adverse events associated with hematopoietic progenitor cell (HPC) product infusion can vary depending on the type of product infused ( Table 88.1 ). The Center for Disease Control National Health Safety Network provides a Biovigilance Component Hemovigilance Module Surveillance Protocol that provides definitions for blood transfusion reactions. Similarly, the Circular of Information for the Use of Cellular Therapy Products also provides descriptions of the known side…

T-Cell Immune Therapies

Cellular therapies designed to modulate or enhance immune responses are gaining acceptance as viable treatments for a variety of diseases, most notably in the oncology field. Some therapies such as granulocyte infusion have been a tool in transfusion medicine for more than 40 years, while novel therapies such as chimeric antigen receptor (CAR) T cells have only very recently been licensed for clinical use. This chapter…

Regenerative Medicine

Regenerative medicine is a multidisciplinary field focused on repair, replacement and/or regeneration of diseased cells or organs, or in many cases on protecting vulnerable diseased cells from death. Stem cell (SC) therapies are at the core of many regenerative therapies, although most SC therapies are still at the stage of clinical trial testing. Growth of the field is highlighted in the clinicaltrials.gov registry, which contains >6000…

Cord Blood Banking

Cord blood (CB), the blood remaining in the placenta and umbilical cord after birth is rich in hematopoietic stem cells (HSCs) and can be used for bone marrow reconstitution of patients undergoing myeloablative or non-myeloablative therapy that do not have matched related donors. CB is also being evaluated for tissue repair and regeneration. CB banking refers to the systematic procurement, processing, testing, and storage of CB…

Hematopoietic Progenitor Cell Products Derived From Bone Marrow and Peripheral Blood

Hematopoietic stem cells (HSCs) are blood-forming multipotent stem cells that produce all blood cell lineages and maintain hematopoiesis. Hematopoiesis occurs in bone marrow (BM), but a small number of HSCs circulate in peripheral blood. Like other stem cells, HSCs have the capacity of self-renewal by means of asynchronous cell division, which produces an identical daughter stem cell and another cell, the progeny of which become terminally…

Overview of Cellular Therapy

Cellular therapy is the use of viable cells and tissues for the treatment of disease. Cell and tissue donors can be autologous, syngeneic, or allogeneic. Current good tissue and manufacturing practices must be followed to prevent the introduction, transmission and spread of communicable diseases. Both require donor qualification, controlled environments, use of sterile supplies and reagents, and assays to ensure the purity and potency of products.…

Therapeutic Phlebotomy

Therapeutic phlebotomy entails the removal of blood to treat diseases in which decreasing red blood cell (RBC) mass, hematocrit, and blood viscosity, or inducing iron restriction, enabling management of disease-associated symptoms and complications. Standardized indications for therapeutic phlebotomy for each disease are currently unavailable. Therefore, specific regimens are individually tailored to patient’s needs. Therapeutic phlebotomy is a clinical procedure commonly used to treat diseases associated either…