What is physiological anemia of infancy?
As the fetus develops, the erythropoietin levels rise, with the highest levels occurring in the final trimester. Erythropoiesis is directly driven by erythropoietin, and as a consequence, a significant portion of the red blood cell mass is produced in the final trimester of pregnancy. Upon birth, blood oxygen levels suddenly increase with the onset of breathing, closure of the ductus arteriosus, and transition of the newborn from the relatively hypoxic environment of the amniotic sac to oxygen-rich room air. Renal oxygen tension sensors detect this sudden rise in oxygen levels, and in response, downregulate hypoxia-inducible factors, which in turn, downregulate the production of erythropoietin. This results in a slowly decreasing hemoglobin for several weeks after birth, known as the physiologic nadir of infancy. In full-term infants, the hemoglobin typically reaches a nadir of approximately 11 g/dL (110 g/L) at 8 to 12 weeks after birth.
Other factors that can lead to anemia in the neonatal period include phlebotomy for frequent blood tests in sick neonates, a reduced lifespan for the red blood cells, and iron depletion.
A number of factors in the vignette suggest that the drop in hemoglobin is not caused by hemolysis. These include the low reticulocyte count, negative direct antibody test, and the normal direct and indirect bilirubin levels. Therefore, maternal-fetal ABO incompatibility, maternal-fetal Rh incompatibility, and red blood cell membrane defects are incorrect responses. As discussed, the rapid increase in blood oxygen levels at birth result in a drop in erythropoietin levels after birth, causing a gradual drop in hemoglobin.

What is x-linked recessive?
The prolonged bleeding after circumcision in the newborn in the vignette suggests a congenital bleeding disorder. The formation of a functional clot requires 2 components, fibrin and platelets. Fibrin is the end-product of the coagulation cascade. The absence of any of the coagulation cascade factors can result in failure to form a clot and is associated with a prolonged prothrombin time (PT) or partial thromboplastin time (PTT). Prothrombin time and PTT are effective measures of the functionality and presence of the components of coagulation cascade, except for the conversion of fibrinogen to fibrin. The patient’s prolonged PTT suggests an absence or dysfunction of a factor in the coagulation cascade. The gene for factor VIII is found on the X chromosome and is the subject of frequent spontaneous mutations. The deficiency of factor VIII is known as hemophilia A. Given that the child is male and therefore subject to X-linked disorders, factor VIII deficiency is the most likely diagnosis.
Factor XIII is responsible for clot stabilization. Since it plays a role after the formation of a clot, an absence of factor XIII would not prolong the PT or PTT; those are measures of the time to clot formation, not clot stabilization

What is flow cytometry?
Flow cytometry maps the surface antigens on cells. The cells are incubated with antibodies to surface markers that are conjugated to fluorochromes. After incubation, the cells are drawn in a single file through the flow cytometer in which various lasers hit the cells. If the wavelength of light emitted by the laser excites the fluorochrome conjugated to the antibody, a different wavelength of light is emitted by the fluorochrome that can be detected by the flow cytometer. If that second wavelength is detected, then the targeted surface marker is present on the cell. Acute lymphoblastic leukemia and AML have markedly different patterns of surface markers, making flow cytometry an effective way to rapidly and accurately distinguish between the two. Flow cytometry can also be used to distinguish between different subtypes of ALL, including B and T cell.

What is Strep pneum sepsis?
The patient in the vignette has presented with signs and symptoms of sepsis, including fever, tachycardia, hypotension, and rigors. It is critical to rapidly recognize sepsis because it can quickly result in disseminated intravascular coagulation and death. Every fever in a child with sickle cell disease should be considered an emergency and treated as bacteremia until proven otherwise. A blood culture should be performed with a complete blood cell count and reticulocyte count, and a broad-spectrum antibiotic (typically a third-generation cephalosporin) should be administered as quickly as possible. Streptococcus pneumoniae is the most frequent causative agent of sepsis in patients with sickle cell disease. Prophylactic daily penicillin in children up to 5 years of age and the use of pneumococcal vaccines have been two of the most significant medical advances for reducing the morbidity and mortality of sickle cell disease. It is important to recognize that even patients who have been taking prophylactic penicillin and have received pneumococcal vaccines can still experience pneumococcal sepsis.

What is vit B12 def anemia?
The differential diagnosis of macrocytic anemia in children includes vitamin B12 deficiency, folate deficiency, and bone marrow failure. Folate deficiency is most often dietary, typically in children whose diets rely heavily on goat milk. When vitamin B12 (also called cobalamin) is consumed, it attaches to haptocorrin and travels to the duodenum, where it is hydrolyzed and released from the haptocorrin. The free vitamin B12 then binds to gastric intrinsic factor and travels to the ileum. It is then absorbed in the ileum, enters the blood stream, and binds to transcobalamin. Vitamin B12 deficiency in pediatrics most often occurs either because of an absence of the terminal ileum (where B12 is absorbed), or because of a deficiency of intrinsic factor. The deficiency of intrinsic factor and subsequent vitamin B12 deficiency is called pernicious anemia. Congenital pernicious anemia occurs when there is a genetic defect resulting in hypofunctional or absent intrinsic factor. Pernicious anemia in adolescents typically results from gastric atrophy and achlorhydria caused by antibodies to the parietal cell and intrinsic factor. Left untreated, vitamin B12 deficiency results in a macrocytic anemia, in addition to neurologic symptoms including paresthesias, ataxia, and gait abnormalities, as a result of posterior and lateral spinal column degeneration. Vitamin B12 deficiency can be treated with the parenteral administration of vitamin B12.
The patient in the vignette has a medical history remarkable for autoimmunity, suggesting that her macrocytic anemia also has an autoimmune origin. Thus, it is likely that her macrocytic anemia is caused by autoimmune damage to the gastric parietal cells.

What is Glanzmann's thrombasthenia?
The clinical findings seen in the girl in the vignette suggest a congenital bleeding disorder. Of note, she has had unusual bleeding since birth, repeated mucosal bleeding (such as gum bleeding while tooth brushing), palpable bruising, and petechiae. The normal prothrombin time (PT), partial thromboplastin time (PTT), and platelet number effectively rule out disorders of the coagulation cascade or platelet number. It is therefore likely that this girl has a disorder of platelet function. In platelet function disorders, platelets are present, but cannot activate to effectively form a clot. The most common congenital platelet function disorders are Bernard-Soulier syndrome (a disorder of platelet adhesion) and Glanzmann thrombasthenia (a disorder of platelet aggregation). The most appropriate management for life-threatening bleeding in a child with a known or suspected platelet function disorder is to transfuse functional platelets.
In VWD: VWF level and/or activity decreased with abnormal ristocetin aggregation
In Bernard-soulier's disease,defect in GP IB, mild thrombocytopenia with large platelets and abnormal ristocetin test seen
in Glaanzman, genetic GPIIb/3a deficiency with normal ristocetin test seen

What is Tumor lysis syndrome?
PKU C
High( Phosphate, Potassium and Urine acid)
Low Ca
Treat with allopurinol, hyperhydration, alkalinization of urine

What are hepatoblastoma and nephroblastoma?
The infant in the vignette has global macrosomia (95th percentile for height and weight), macroglossia, and hemihyperplasia (an enlarged left side of the body and face). This presentation suggests an overgrowth syndrome such as Beckwith-Wiedemann syndrome (BWS). Beckwith-Wiedemann syndrome is caused by genetic or epigenetic abnormalities involving chromosome 11p15. Affected children have an increased risk of cancer through age 7 to 8 years, with embryonal tumor types such as hepatoblastoma and nephroblastoma (Wilms tumor) most commonly reported. Given that these embryonal solid tumors have a higher rate of cure when identified at an earlier stage, screening for these tumors in patients with BWS is appropriate. Screening recommendations typically include serum a-fetoprotein measurements every 3 months until age 4 years to screen for hepatoblastoma and complete abdominal ultrasonography every 3 months through age 7 to 8 years to screen for Wilms tumor

What is iron overload?
The 2 primary components of hemoglobin that can be deficient are iron or the globin protein. Hemoglobin A, the normal adult variant, consists of 2 β-globin chains and 2 α-globin chains, with the β-globin gene located on chromosome 11 and the α-globin gene on chromosome 16. Mutations resulting in reduced production of either α-globin or β-globin result in various thalassemia phenotypes and present with a microcytic anemia. The child in the vignette has a severe microcytic anemia and his hemoglobin electrophoresis pattern shows the absence of hemoglobin A (α2 β2), with only hemoglobin A2 (α2 δ2) and F (α2 γ2) present. This means that he has 2 dysfunctional β-globin genes, and therefore has β-thalassemia major. The most appropriate management of thalassemia major is chronic blood transfusions, typically every 3 to 4 weeks, to maintain a hemoglobin greater than 10 g/dL (100 g/L). With each transfusion of packed red blood cells (PRBC) comes a large iron load (each mL of PRBC delivers 0.75 mg of iron). The human body has no mechanism for eliminating excess iron, so iron accumulates with each transfusion. Patients with thalassemia who are treated with frequent transfusions are therefore at high risk for complications associated with iron overload.
The complications associated with chronic iron overload include endocrinopathies such as hypothyroidism, diabetes, hypogonadism, cardiomyopathy, and liver failure. Iron overload can be managed or even prevented through the use of aggressive chelation therapy. The most commonly used chelator is deferasirox, an oral, once a day medication. Some patients are unable to be adequately chelated with deferasirox and require the subcutaneous or intravenous administration of deferoxamine to maintain iron balance. The gold standard for assessing iron overload is liver biopsy, although newer techniques using specially calibrated magnetic resonance imaging are increasingly used.

What is immune thrombocytopenic purpura?
Conservative
observation
indication
in patients with a platelet count > 30,000/μL and no bleeding
Medical
corticosteroids
indication
initial treatment for patients with a platelet count < 30,000/μL
intravenous immunoglobulins (IVIG)
indication
for patients with a platelet count < 30,000/μL who have contraindications to corticosteroids, are refractory to corticosteroid treatment, or are bleeding or have a high risk of bleeding that will need a rapid increase in platelet count
Operative
splenectomy
indication
second-line treatment for patients with refractory ITP

What are anthracyclines?

What is leucoreduced blood product?
The infusion of even small numbers of granulocytes can lead to the release of pro-inflammatory cytokines, thereby increasing the risk of a febrile transfusion reaction. In order to reduce this risk, granulocytes are removed from blood products at the time of initial processing or immediately prior to transfusion via filtration, a process called leukodepletion. For the girl in the vignette, leukodepletion of the red blood cells (RBC) prior to transfusion would have had the greatest likelihood of reducing her risk of fever.
Although granulocytes are removed through filtration, many lymphocytes are the size of RBC and are therefore not as effectively removed by filtration. While RBCs are typed by ABO typing, they are not human leukocyte antigen typed or matched to the recipient, and lymphocytes infused with a transfused product may recognize the recipient as foreign. In immune compromised hosts, the host immune system is unable to clear the infused donor lymphocytes, which may then undergo expansion in response to recognition of a foreign antigen and cause a severe, typically fatal, graft-versus-host reaction. In immune competent hosts, this does not occur, as the host immune system recognizes the donor lymphocytes as foreign and successfully eliminates them. Irradiation of blood products prior to transfusion renders donor lymphocytes replication incompetent, eliminating the threat of transfusion-associated graft-versus-host disease.

The girl in the vignette has splenic sequestration. It is critical to rapidly recognize this event, as it can quickly result in very severe anemia and death. This sickle cell–related crisis occurs when sickling in the vasculature of the spleen entraps red blood cells, resulting in rapid splenic engorgement and a severe, potentially life-threatening anemia. Splenic sequestration is most common in children younger than 5 years, but can occur at any age. It typically presents, as in the child in the vignette, with signs of severe anemia (tachycardia, pallor, and fussiness), thrombocytopenia, and a palpable spleen. Fever may be present. One of the most effective interventions for reducing mortality in young children with sickle cell disease has been teaching parents to palpate for a spleen in their child daily. Splenic sequestration associated with sickle cell disease should be treated with a transfusion of packed red blood cells. If the anemia is very severe, the transfusion should be given slowly, over several hours, and typically in aliquots of 5 to 7 mL/kg. This approach avoids further cardiac stress. In addition, the spleen will eventually “release” the entrapped red blood cells, leading to a rapid rise in hemoglobin; if too much blood was transfused when this occurs, the child can experience a hyperviscous state.

What is hemolytic uremic syndrome?
The hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. It is one of the main causes of acute kidney injury in children. Although all pediatric cases exhibit the classic triad of findings that define HUS.
Important etiological factors include Shiga toxin-producing Escherichia coli (STEC) infections which is responsible for 90% of pediatric cases. S.pneum and S. dysenteriae also implicated along with other non-infectious causes

What is neuroblastoma?
The term neuroblastoma is commonly used to refer to a spectrum of neuroblastic tumors (including neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) that arise from primitive sympathetic ganglion cells and, like paragangliomas and pheochromocytomas, have the capacity to synthesize and secrete catecholamines.

What is CGD?
While frequent bacterial infections as described in the vignette could represent a clinical manifestation of severe neutropenia, such as that seen in severe congenital or cyclic neutropenia, the complete blood cell count reported has a normal number of neutrophils. Thus, consideration must be given to neutrophil dysfunction. The most common disorder of neutrophil function is chronic granulomatous disease (CGD), a defect caused by a failure to produce oxygen radicals to kill phagocytosed microorganisms. The gold standard for diagnosing and initial management of CGD is testing the phagocyte oxidative burst by flow cytometry and initiating prophylaxis with trimethoprim and sulfamethoxazole.
Chronic granulomatous disease is a genetic disorder that can be transmitted by X-linked or autosomal recessive inheritance. The X-linked form is by far the most common and is caused by a mutation in the CYBB gene that results in a dysfunctional gp91 protein. The most common autosomal form of CGD is caused by a mutation in the NCF1 gene on chromosome 7, resulting in a dysfunctional p47 protein. Chronic granulomatous disease most often presents with recurrent abscesses, most frequently caused by Staphylococcus aureus. It can also present with invasive fungal infections, usually with Aspergillus species.

What is autoimmune hemolytic anemia?
Autoimmune hemolytic anemia (AIHA) is a true hematologic emergency. Rapid diagnosis and initiation of therapy can be life-saving. The adolescent girl in the vignette presents with signs and symptoms that strongly suggest AIHA. In particular, her tachycardia, fatigue, and exercise intolerance are likely due to hypoxemia of an acute onset. The laboratory results show a severe, normocytic anemia with a marked reticulocytosis, suggesting a destructive process rather than a red blood cell (RBC) production failure. The reticulocyte count increases as the renal oxygen tension sensors detect a drop in oxygen-carrying capacity caused by the anemia. In response, they upregulate hypoxia-inducible factors, which in turn upregulate the production of erythropoietin, driving erythropoiesis.
The most appropriate next steps in her care would be to order a direct antibody test (DAT) and begin emergent management. The DAT will be positive if there are circulating antibody-coated RBCs. It is important to note that in instances of brisk hemolysis from AIHA, the antibody-coated cells may be destroyed so quickly that the DAT is paradoxically negative. Management of severe, life-threatening AIHA requires the emergent transfusion of a “least-incompatible” unit of packed RBCs, rapid initiation of immune suppression with corticosteroids, and ultimately identification of the autoantibody. The blood bank will perform compatibility testing on a number of units of packed RBC to determine which is least likely to be hemolyzed by the offending antibody

Wiskott-Aldrich syndrome: TIE
Thrombocytopenia
Immunodeficency
Eczema

What is Shwachman-Diamond syndrome?
Shwachman-Diamond syndrome (SDS) is an autosomal recessive syndrome that generally presents in infancy with bone marrow failure, particularly neutropenia, and exocrine pancreatic dysfunction. Approximately 90 percent of patients have homozygous or compound heterozygous mutation of the Shwachman-Bodian-Diamond syndrome (SBDS) gene. Additional manifestations include frequent infections, hepatic or cardiac abnormalities, neurocognitive deficits, other congenital anomalies, and an increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)