Hematology and Oncology Flashcards
1
Q
alpha thalessemia
A
- pathophysiology
- hemoglobin A is a tetramer of 4 globin chains
- one pair of alpha (α) globin chains
- one pair of beta (β) globin chains
- alpha and beta globins coded in pairs on each chromosome
- alpha thalassemia
- Anemia caused by lack of alpha globin chains
- disease expression depends on number of alpha thalassemia globin chains expressed
- Symptomatic in utero since fetal Hgb is α 2 γ 2
- hemoglobin A is a tetramer of 4 globin chains
2
Q
beta thalassemia pathophysiology
A
- pathophysiology
- beta thalassemia
- due to impaired production of beta globin chains
- relative excess of alpha globin chains
- excess alpha globin is toxic & forms precipitates in cell
- RBCs are destroyed prematurely
- typically presents between 4 and 12 months of life, as normal hemoglobin (α 2 β 2) replaces fetal Hgb (α 2 γ 2)
- beta thalassemia
- types of beta thalassemia
- β o – absent production of beta globin
- β + – decreased production of beta globin
- beta thalassemia major (β o β o or β o β +)
- beta thalassemia minor (β β o or β β +)
- beta thalassemia intermedia (β + β +)
3
Q
diagnostic testing for thalassemia
A
- Laboratory – Remember: Many Small Red Blood Cells
- Microcytic anemia
- Higher RBC count than iron deficiency anemia
- Mentzer index <12.5
- Low reticulocyte count
- There may be signs of hemolysis
- Definitive diagnosis with hemoglobin electrophoresis and genetic testing.
4
Q
beta thalassemia clinical manifestations and treatment
A
- clinical manifestations are of chronic hemolytic anemia and ineffective erythropoiesis
- beta thalassemia minor
- anemia
- beta thalassemia major
- skeletal changes (extramedullary hematopoiesis)
- expansion of bone marrow cavities of all bones
- osteopenia
- pathologic fractures
- splenomegaly
- hemochromatosis from chronic transfusion dependence
- endocrine, cardiac and metabolic abnormalities
- cardiopulmonary complications
- aplastic crises
- skeletal changes (extramedullary hematopoiesis)
- treatment
- beta thalassemia major
- chronic transfusions
- suppresses abnormal erythropoiesis
- diminishes abnormally high iron absorption
- management of iron overload from chronic transfusion therapy
- iron chelation
- chronic transfusions
- beta thalassemia major
5
Q
sickle cell disease epidemiology and physiology
A
- epidemiology and physiology
- 1 in 500 African-Americans (~1 in 5,000 in all U.S. people)
- hemoglobin S
- single amino acid substitution
- protective against malaria
- creates an abnormal hemoglobin tetramer
- 2 alpha chains & 2 beta S chains
- poorly soluble when deoxygenated
- cells form a sickle shape
- hemoglobin crystallizes and forms gel
- causes microvasculature occlusion
- surrounding tissue infarcts
- single amino acid substitution
6
Q
sickle cell disease manifestations
A
- disease manifestations vary
- most severe
- sickle cell disease – homozygous for Hgb S
- moderate severity
- Hgb SC – heterozygous for Hgb S with hemoglobin C
- Hgb S β0thal – heterozygous for Hgb S with beta (β0) thalassemia
- less severe
- Hgb S β+thal – heterozygous for Hgb S with (β+) thalassemia
- sickle cell trait (heterozygous Hgb S with normal Hgb A)
- most severe
- major clinical manifestations
- hemolytic anemia
- dactylitis (common presentation in infancy)
- acute vaso-occlusive crisis
- acute chest syndrome*
- functional asplenia
- susceptible to infections by four months of age
- bacteremia
- meningitis
- bacterial pneumonia
- osteomyelitis (Salmonella, as well as usual organisms)
- splenic infarction typically by 2 to 4 years of age
- susceptible to infections by four months of age
- major clinical manifestations
- psychosocial (chronic pain, recurrent hospital stays)
- cerebrovascular events (stroke)
- bone complications
- infarction
- osteonecrosis of femoral and humeral head
- hepatobiliary disease (cholelithiasis, hemosiderosis, hepatitis C)
- priapism
7
Q
sickle cell disease: acute chest syndrome
A
- Acute Chest Syndrome: A vaso-occlusive event in the lungs
- Most common cause of death in SCD
- Diagnosis:
- New pulmonary infiltrate
- AND one of the following
- Chest pain
- Temp >38.5
- Tachypnea, wheezing, cough, increased work of breathing
- Hypoxemia
- Recognize early and treat with O2, fluids, pain medication, transfusion, antibiotics, bronchodilators
8
Q
sickle cell disease treatment
A
- treatment addresses need to create red cell volume
- folate
- iron
- treatment for acute severe anemia
- supportive care, red cell transfusions
- hydroxyurea
- promotes Hgb F production
- chronic transfusion therapy
- with chelation for iron overload
- stem cell transplant – can be curative
9
Q
G6PD deficiency epidemiology and signs and symptoms
A
- epidemiology and pathophysiology
- Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency-seen most frequently in people of Asian, African, and Mediterranean ancestry
- X-linked – usually males – runs in families
- Defective enzyme leads to inability to handle oxidant stress leads to hemolysis when oxidant stresses are high and RBC survival is low
- signs and symptoms
- generally asymptomatic
- during oxidant stress
- red cell turnover
- pallor
- jaundice
- hemoglobinuria or bilirubinuria (dark urine)
- during oxidant stress
-
neonate
- hyperbilirubinemia
- generally asymptomatic
10
Q
G6PD deficiency laboratory findings and treatment
A
- laboratory findings (when to suspect)
- with oxidant stress
- hemolysis (causing anemia)
- “bite” cells, schistocytes, spherocytes
- elevated reticulocyte count
- Heinz bodies (sulfhemoglobin precipitates)
- hemolysis (causing anemia)
- without oxidant stress
- normal hematocrit, reticulocyte count & smear
- with oxidant stress
- laboratory diagnosis
- measurement of levels of G6PD in erythrocytes
- best tested when not in acute episode of hemolysis
- most deficient cells have already ruptured, leaving behind only young cells with high G6PD levels
- treatment
- currently no enzyme replacement therapy
- removal of oxidant stress – mainstay is prevention
- transfusion in severe hemolysis
- renal protection from products of hemolysis
- prevention
- NO fava beans
- avoid sulfonamide drugs and nitrofurantoin
- avoid naphthalene (moth balls)
- monitor for hemolysis during times of metabolic stress/infection
- usually self-limited but RBC transfusions may be needed in cases of cardiovascular compromise (a rare event)
- G6PD IS tested for with newborn screening, must consider obtaining G6PD enzyme levels in any patient with hyperbilirubinemia who requires phototherapy and is refractory to treatment
11
Q
autoimmune hemolytic anemia
A
- usually acute and self-limited, following a viral infection or infection with Mycoplasma)
- rarely a feature of a chronic autoimmune disease (lupus, lymphoproliferative disorder, etc.)
- drugs may also induce an autoimmune hemolysis
- phenomenon causes lots of positive direct Coombs’ tests but rarely causes anemia
- signs and symptoms
- pallor
- jaundice
- fatigue
- dark urine
- splenomegaly
- laboratory
- CBC
- normochromic, normocytic anemia
- usually with elevated reticulocyte count, sometimes with nucleated RBCs
- Elevated total and indirect hyperbilirubinemia
- elevated LDH, haptoglobin, & urinary urobilinogen
- evidence of intravascular hemolysis
- hemoglobinuria
- positive Coombs test
- CBC
- classification and treatment
- ≥ 80% of children with AIHA recover spontaneously
- IVIG
- corticosteroids
- transfusion
- cessation of causative drug, if any
12
Q
Immune (idiopathic) thrombocytopenic purpura - ITP
A
- most common bleeding disorder in childhood
- typically follows viral infection by 1-4 weeks
- frequent in children 2-5 years of age
- clinical manifestations
- abrupt onset
- petechiae, purpura, bruising & epistaxis
- adenopathy and splenomegaly are unusual (happens but not frequently)
- laboratory
- thrombocytopenia, often profound (10k/µL)
- bone marrow biopsy (only performed if necessary to rule out leukemia or aplastic anemia) reveals increase in megakaryocyte number
- anti-platelet antibodies
- Treatment – often in conjunction with a hematologist
- most cases (>30k platelet count) – observation only
- Other available treatments:
- IVIG
- corticosteroids
- IV anti-D (rho immune globulin)
- in refractory or severe cases
- splenectomy
- repeat dosing of IVIG or high dose corticosteroids
13
Q
Hemophilia
A
- Bleeding disorder due to the lack of a coagulation factor.
- Hemophilia A- Factor VIII deficiency
- X-linked recessive – almost entirely seen on males
- 1 in 5000 males
- Hemophilia B- Factor IX deficiency
- X-linked recessive
- Presentation
- Most children with hemophilia present within the first 1.5 years of life with bruising, hemarthrosis, oral bleeding or bleeding after surgeries – including circumcision.
- Treatment
- Factor replacement. Amount and periodicity is dependent upon severity of disease.
- Patients should not take medications that can increase bleeding risk: aspirin, NSAIDS
14
Q
von Willebrands disease
A
- von Willebrand factor is important in initial clot formation.
- Deficiency in this factor is the most common inherited bleeding disorder.
- Presentation
- Easy bruising
- Skin bleeding
- Mucosal bleeding
- Heavy menstrual bleeding
15
Q
cancer in children
A
- 1% of all new U.S. cancers occur in children
- neuroblastoma & retinoblastoma peak in 1st 2 years
- ALL peaks between ages 2 and 5 years
- osteosarcoma peaks during adolescence
- Hodgkin disease peaks in late adolescence
- most common symptoms of malignancy in children are fatigue, anorexia, malaise, pain and fever
- benign tumors (hamartomas, germ cell tumors, hemangiomas, bone cysts, mesoblastic nephromas) are relatively common in children
