Hematology Flashcards
What is one of the first symptoms in children with sickle cell disease (SCD)?
Sickle Cell Dactylitis
The first pain crisis in about 1/3 of children with SCD is sickle cell dactylitis, a symmetric painful swelling of the hands and feet. Pain crisis is the most common complication of SCD and the most common reason for hospitalization.
A 9-year-old presents with a history of:
- Short stature
- Absent thumbs
- Abnormal radii
- Microcephaly
- Cafe-au-lait spots
- Dark pigmentation
- Renal anomalies
Today he presents with what appears to be aplastic anemia.
What is the most likely diagnosis?
Fanconi’s Anemia
Presents with these classic phenotypical features, but the aplastic anemia does not commonly show up until 8-9 years of age.
- Autosomal recessive
- Presents in the neonatal period with bleeding
- Thrombocytopenia is severe, but the rest of the blood lines are normal.
- There are no megakaryocytes in the bone marrow.
- The newborn has no radii but has normal thumbs.
What syndrome presents with these findings?
Thrombocytopenia with Absent Radii (TAR) Syndrome
TAR syndrome can be differentiated from Fanconi’s and trisomy 18 by the presence of normal thumbs, which are absent in Fanconi’s and trisomy 18. Most survive, and the platelet counts improve spontaneously over time.
- Structural or functional abnormality of cytoskeleton proteins: spectrin, ankyrin, and less commonly band 3, or protein 4.2
- Complications can include cholelithiasis due to bilirubin stones and aplastic crisis from parvovirus infection.
- A positive osmotic fragility test confirms the diagnosis.
What congenital hereditary anemia has these characteristics?
Hereditary Spherocytosis (HS)
HS is an autosomal dominant anemia with the listed characteristics. It is the most common congenital hemolytic anemia in populations of northern European origin.
What is the factor deficiency in Hemophilia A? Hemophilia B?
Factor VIII; Factor IX
The risk of bleeding for Hemophilia A correlates with the serum levels of FVIII. Hemophilia B (Christmas Disease).
Which factor deficiency has a normal PT and a very prolonged PTT, but the patient does not have a clinical bleeding disorder and can even have major surgery without worry of bleeding?
Factor 12 Deficiency
Factor 12 (Hageman factor) deficiency is a rare autosomal recessive disorder. Unlike patients with the other clotting factor deficiencies, those with Factor 12 deficiency are totally asymptomatic.
Which organ produces EPO in the fetus?
Liver
EPO is produced by the liver in the fetus and in early postnatal life. Soon after birth, the kidney takes over producing EPO.
A patient has pre-op testing prior to tonsillectomy. He recently had a viral illness. The activated PTT is prolonged. The PT and platelet count are normal. You perform a mixing study, mixing the patient’s plasma 1:1 with normal plasma. The PTT of the mixed plasma is normal.
Based on these laboratory results, is the patient at risk for bleeding?
Yes
If you do a mixing study and the PTT normalizes, you should suspect a clotting factor deficiency. If the PTT does not normalize with the mixing study, the patient has developed an inhibitor to a clotting factor protein, usually a lupus anticoagulant or Factor 8 inhibitor. Lupus anticoagulant prolongs the PTT but does not cause bleeding. Transient lupus anticoagulants are often identified in children after viral illness.
A 17-year-old boy has the following:
- Asymptomatic firm, nontender, cervical lymph node, 3 × 2 cm in size noticed by his barber
- No other symptoms
He has no cat exposure, and 1 week of cephalexin therapy has not decreased the size of the gland—if anything, it is slightly larger. But he has no new symptoms.
What do you recommend at this point?
Excisional Biopsy of the Node
The is in the age group that is at higher risk for Hodgkin lymphoma. A painless isolated enlarging lymph node with no cat exposure or other risk factors unfortunately raises the possibility of Hodgkin’s. Perform an excisional biopsy of the node.
A 4-year-old girl presents with the following sequence of events:
- Two weeks ago she had a viral infection (cold).
- Now she has the acute onset of bloody nose and noticeable petechial rash.
- Hemoglobin is normal.
- Platelet count is 40,000
- Peripheral smear is normal except for the lack of platelets, and the ones that are seen are large (but not giant) platelets.
Idiopathic (Immune) Thrombocytopenic Purpura (ITP)
ITP is the most common cause of low platelets in children. It occurs because of an immune-mediated destruction of circulating platelets. Treatment is reserved for those with platelets < 20,000, or there is significant skin or mucosal bleeding.
A boy has a suspicious lymph node removed.
What is the classic histologic feature of Hodgkin lymphoma seen on lymph node biopsy?
Reed-Sternberg Cell
The Reed-Sternberg cell is a large cell with multiple or multilobulated nuclei (looks like “owl’s eyes”). Most are of B-cell lineage, but some are also of T-cell lineage.
What is the Japanese term for the collateral formation of vessels in the brain due to previous infarcts?
Moyamoya
Occurs in patients with sickle cell disease and is the collateral formation of vessels due to previous infarcts. Moyamoya means “puff of smoke” which resembles the appearance if the vessels on angiography.
A RDW is likely to be increased or decreased in patients with iron deficiency anemia?
Increased
RDW is increased in iron deficiency and normal patients with thalassemia trait.
- Autosomal recessive (AR)
- Macrothrombocytopenia with giant platelets
- The platelets do not aggregate to ristocetin, but do aggregate in response to ADP, epinephrine, and collagen.
What syndrome presents with these findings?
Bernard-Soulier Syndrome
Bernard-Soulier syndrome is an AR disorder with mild thrombocytopenia and giant, abnormal platelets. Patients have a deficiency of platelet glycoprotein 1b (GP1b) in the platelet membrane, which results in the platelets not being able to aggregate properly. There is severe mucocutaneous bleeding starting in infancy.
A 9-month-old presents with:
- pallor
- irritability
- growth retardation
- hepatosplenomegaly
- jaundice
- “Chipmunk” facies
What is the most likely diagnosis?
Beta Thalassemia Major (Cooley Anemia)
Cooley anemia occurs because there is essentially no beta-globin production. Expansion if the bone marrow space in the facial bones leads to the characteristic “chipmunk” facies.
- Autosomal recessive
- Poor platelet aggregation in response to collagen, epinephrine, and ADP
- Normal platelet counts
- Mucosal bleeding starting in infancy
Name the syndrome with these characteristics.
Glanzmann Thrombasthenia
Glanzmann thrombasthenia is an inherited platelet function disorder that is due to an abnormality in the genes encoding the αIIb-β3 integrin fibrinogen receptor. This results in the inability of platelets to bind fibrinogen and aggregate. Note that patients have normal platelet counts!
An adolescent receives mantle radiation for his Hodgkin lymphoma.
Name a long-term side effect of radiation therapy that affects the heart.
Early-Onset Coronary Artery Disease
Be familiar with the long-term effects of radiation therapy, especially these:
- Growth retardation
- Hypothyroidism
- Early-onset coronary artery disease
- Pulmonary fibrosis
- Increased risk of breast cancer
What is the leading cause of death in adolescents with sickle cell disease?
Acute Chest Syndrome
It is the development if new pulmonary infiltrate with fever, chest pain, tachypnea, and hypoxia. It can progress rapidly to respiratory failure.
A red blood cell transfusion of 10 mL/kg will raise hemoglobin by how much?
2.5-3 g/dL
In RBC transfusions, packed RBCs (PRBCs) are the primary product used; whole blood is rarely used. PRBCs are the product of choice and are ordered according to blood type. A unit is typically a total volume of 250–350 mL of PRBCs reconstituted in plasma.
What congenital hereditary anemia has the following characteristics:
- Due to structural or functional abnormality of cytoskeleton proteins: spectrin, ankyrin, band 3, or protein 4.2
- Complications can include cholelithiasis due to bilirubin stones.
- The osmotic fragility test confirms the diagnosis.
Hereditary Spherocytosis
An autosomal dominant anemia with the characteristics as outlined.
Where is the first site of RBC formation in the fetus?
Yolk Sac
RBC formation in the yolk sac begins at 2 weeks of gestation. By the 8th week, RBC formation shifts to the liver, increases, peaks at 5 months, and then decreases thereafter. At 5 months, the bone marrow takes over and remains the predominant site for RBC production.
Which factor deficiency is associated with a normal PT, PTT, bleeding time, and platelet count, but has severe bleeding problems and scarring with superficial wounds?
Factor XIII Deficiency
It is autosomal recessive and associated with consanguinity. These patients have severe bleeding and severe scarring with superficial wounds, but completely normal routine bleeding tests. The diagnostic test is a euglobulin clot lysis assay - the clot formed in patients who are Factor XIII deficient is abnormally soluble in a 5-molar urea solution.
A 4-year-old girl presents with the following lab findings:
- Iron is low.
- Total iron-binding capacity (TIBC) is high.
- Transferrin saturation is low.
- Ferritin is low.
What is the most likely diagnosis?
Iron Deficiency Anemia
Iron deficiency anemia is the most common anemia in children. It is caused by poor intake, poor absorption, or excess blood loss, with inadequate iron intake being the most common cause.
What is the leading cause of death in adolescents and adults with sickle cell disease (SCD)?
Acute Chest Syndrome (ACS)
ACS is characterized by the development of a new pulmonary infiltrate with fever, chest pain, tachypnea, and/or hypoxia. It can progress rapidly to respiratory failure.
Name the disease:
- Caused by the point mutation in the 6th codon of the beta-globin gene, which is located on the short arm of chromosome 11.
- Adenine is replaced by thymidine, which results in valine being encoded instead of glutamic acid.
Sickle Cell Disease
The most common hemoglobinopathy and is HbS. The average lifespan of an RBC in HbSS disease is only 15-50 days.
- Autosomal recessive (AR) inherited white cell disorder
- Presents at a young age with severe bacterial infection
- Absolute neutrophil count < 200/µL
What syndrome has these characteristics?
Kostmann Syndrome
(Severe Congenital Neutropenia)
Kostmann syndrome is a rare AR disorder. Children with Kostmann syndrome are predisposed to early death and severe bacterial infections. Management includes high doses of granulocyte-colony stimulating factor (G-CSF). Bone marrow transplant is curative.
A 14-year-old girl presents with heavy menstrual flow with her first menses. Workup is done and finds the following:
- PT is normal
- PTT is normal
- Bleeding time is prolonged
- Proportional decrease in biological activity, as measured by the ristocetin cofactor assay (rCoF)
What is the most likely diagnosis?
Von Willebrand Disease
Is usually autosomal dominant with a normal PT and PTT, and a prolonged bleeding time. Expression is variable, but classically, on exams it is seen with heavy menstrual flows in adolescent girls. DDAVP is useful for therapy because it causes a release of vWF and Factor VIII from endothelial cells. For active bleeding, use Factor VIII concentrates.
- Manifests < 2 years of age
- Markedly enlarged spleen
- Modest leukocytosis
- Thrombocytopenia
- Elevated fetal hemoglobin
- Xanthoma
- Café-au-lait spots
- Eczema
- No Philadelphia chromosome
- Monosomy 7 in 30% of patients
Which type of leukemia presents with these findings?
Juvenile Myelomonocytic Leukemia (JMML)
JMML presents as outlined here. There is no blast crisis, but the 5-year survival rate without bone marrow transplant is < 10%. Children with neurofibromatosis Type 1 are at increased risk for JMML.
