Hematology

Question 1

What are the symptoms of anemia?

Answer 1

there is a progression from dyspnea and fatigue to lightheadedness, syncope, and chest pain

Question 2

Whaat is cryoprecipitate?

Answer 2

a blood product used to replace fibrinogen and provides high amounts of clotting factors

Question 3

When do we transfuse platelets?

Answer 3

• less than 10K in an asymptomatic patient

- less than 50K in a bleeding patient

Question 4

Describe the etiology, symptoms, labs, and treatment of iron deficiency anemia.

Answer 4

• most often due to chronic blood loss or dietary deficiency, particularly with unsupplemented breast milk
• presents with koilonychia, pica, and anemia
• labs demonstrate a microcytic anemia with low ferritin, high TIBC, low saturation, and low serum iron; RDW is elevated
• treat with iron replacement

Question 5

Describe the pathogenesis and labs suggestive of anemia of chronic disease.

Answer 5

• chronic inflammation upregulates IL-6 and thus hepcidin, which lowers iron availability
• presents with a microcytic anemia, increased ferritin, reduced TIBC, low serum iron, and low % saturation

Question 6

Compare the iron studies for iron deficiency anemia and anemia of chronic disease.

Answer 6

• IDA: low serum iron, low ferritin, elevated TIBC, low % sat
• AOCD: low serum iron, high ferritin, low TIBC, low % sat

Question 7

Describe the pathophysiology, etiology, and labs consistent with sideroblastic anemia.

Answer 7

• a defect in protoporphyrin synthesis that results in formation of ringed sideroblasts present on blood smear
• causes include X-linked defect in ALA synthase, alcohol’s suppressive effect on bone marrow, lead poisoning, and isoniazid or vitamin B6 deficiency
• labs demonstrate a microcytic anemia with iron overload and sideroblastic rings, which are iron-laden mitochondria around the nuclei

Question 8

What is the difference between sideroblastic anemia and porphyria?

Answer 8

both are defects in heme synthesis, but porphyrias do not present with ringed sideroblasts on blood smear

Question 9

What is the difference between a ringed sideroblast and basophilic stippling?

Answer 9

• ringed sideroblasts are caused by iron-lade mitochondria and seen in the bone marrow for sideroblastic anemias
• basophilic stippling is an aggregation of residual ribosomes seen in sideroblastic anemias and thalassemias but on a peripheral smear

Question 10

Target cells on a peripheral smear are indicative of what diseases?

Answer 10

HALT:

• HbC
• Asplenia
• Liver disease
• Thalassemia

Question 11

Describe the of pathophysiology, labs, and diagnosis of alpha-thalassemia.

Answer 11

• due to a deletion of one or more alpha-globin genes, which produces a microcytic anemia
• 1 is asymptomatic, 2 produces a mild anemia, 3 produces HbH (B4 tetrads), and 4 produces HbBarts (y4 tetrads) with hydrops fetalis and in utero death
• importantly, 3 deletions is the only microcytic anemia that is associated with an increased reticulocyte and erythrocyte count
• diagnosis is made with hemoglobin electrophoresis and genetic testing

Question 12

Describe the pathophysiology and labs of B-thalassemia minor.

Answer 12

• a microcytic anemia caused by the deletion of one beta-globin gene, typically in Mediterraneans or Africans
• labs demonstrate a microcytic anemia, elevated HbA2 and HbF levels, and target cells

Question 13

Describe the pathophysiology, presentation, lab findings, and treatment of B-thalassemia major.

Answer 13

• a microcytic anemia caused by the mutation of two beta-globing genes, which results in unpaired alpha chains
• these alpha chains damage RBC membranes, contributing to ineffective hematopoiesis and extravascular hemolysis
• presents with hepatosplenomegaly and crew cut sign after birth since HbF is protective
• labs demonstrate a microcytic anemia, elevated HbA2 and HbF levels, and target cells
• requires chronic transfusions

Question 14

What are the etiologies and common features of all megaloblastic anemias?

Answer 14

• caused by folate or B12 deficiency, orotic acuduria, and Diamond-Blackfan anemia
• all are caused by impaired DNA synthesis
• they all present with macrocytic anemia, hyper-segmented neutrophils, and glossitis

Question 15

Describe the pathophysiology and presentation of Diamond-Blackfan anemia.

Answer 15

• a megaloblastic anemia with rapid-onset in the first year of life
• due to an intrinsic defect in erythroid progenitor cells
• presents with elevated HbF, short stature, craniofacial abnormalities, and upper extremity malformations (e.g. triphalangeal thumbs)

Question 16

Describe the etiology, pathophysiology, and labs consistent with folate deficiency anemia.

Answer 16

• commonly due to dietary deficiency or the use of folate antagonists like methotrexate
• impaired DNA synthesis leads to a megaloblastic, macrocytic anemia
• labs demonstrate an elevated homocysteine level but normal MMA level

Question 17

Describe the etiology, pathophysiology, and labs consistent with B12 deficiency anemia.

Answer 17

• due to dietary deficiency, pernicious anemia, pancreatic insufficiency, any damage to the terminal ileum, and occasionally metformin use
• impaired DNA synthesis leads to a megaloblastic, macrocytic anemia as well as posterior column dysfunction
• labs reveal elevated homocysteine and methylmalonic acid

Question 18

Describe the pathogenesis, presentation, diagnosis, and treatment of sickle cell disease.

Answer 18

• an autosomal recessive Glu to Val mutation in the beta chain leads to sickling, particularly with hypoxia, dehydration, fever, and cold temperatures
• leads to predominately extravascular hemolysis but some intravascular hemolysis as well
• presents with bilirubin gallstones, infection following autosplenectomy, osteomyelitis from Salmonella, stroke, avascular necrosis, and renal papillary necrosis
• the best initial test is a peripheral smear while the most accurate is hemoglobin electrophoresis
• treat with oxygen, hydration, and analgesia PRN; chronic folic acid replacement; early pneumococcal and meningococcal vaccination; hydroxyuria; daily penicillin prophylaxis; and ceftriaxone or fluoroquinolones for fever

Question 19

What preventative care is indicated for patients with sickle cell disease?

Answer 19

• hydroxyurea to increase HbF
• daily oral penicillin prophylaxis to decrease the risk of S. pneumoniae sepsis
• daily folic acid
• the PCV23 polysaccharide vaccine at 2 and 5 years old; MCV at 2 with a booster 3-5 years later
• serial transcranial Doppler ultrasound beginning at 2 years of age to identify those are risk for stroke

Question 20

Describe the pathogenesis, presentation, labs, diagnosis, and treatment of hereditary spherocytosis.

Answer 20

• a cytoskeleton defect leads to an abnormal shape and loss of flexibility, which causes extravascular hemolysis in the spleen
• presents the symptoms of extravascular hemolytic anemia: splenomegaly, gallstones, and jaundice
• labs demonstrate microcytosis, elevated MCHC, elevated RDW, and a negative Coombs test
• the most accurate test is eosin-5-maleimide flow cytometry which is more accurate than osmotic fragility
• treat with folate replacement and splenectomy

Question 21

Describe the pathophysiology, etiology, diagnosis, and treatment of autoimmune hemolysis.

Answer 21

• IgG binds RBCs in the central body at warm temperatures and induce an extravascular hemolysis, leaving spherocytes
• associated with SLE, CLL, penicillin, and cephalosporins
• labs show an elevated MCHC and, in contrast to hereditary spherocytosis, a positive Coombs test
• treat with steroids, IVIG, rituximab, and splenectomy

Question 22

Describe the pathogenesis, etiology, diagnosis, and treatment of cold agglutinin disease.

Answer 22

• due to IgM antibodies that bind RBCs and fix complement at cold temperatures in the extremities, producing extravascular hemolysis and spherocytes
• due to EBV, Waldenstrom macroglobulinemia, and Mycoplasma pneumoniae
• a direct Coombs test is positive only for complement and the cold agglutinin titer is most accurate
• treat with rituximab and plasmapheresis (steroids and splenectomy don’t help)

Question 23

Describe the pathogenesis, etiology, and diagnosis of G6PDH deficiency.

Answer 23

• due to an X-linked recessive mutation inhibiting production of glutathione reductase
• infection, dapsone, quinidine, sulfa drugs, primaquine, nitrofurantoin, and fava beans then induce hemolysis
• the best initial test is blood smear for Heinz bodies and bite cells; the most accurate is a G6PDH level months after the acute episode
• treatment is avoidance

Question 24

What are Heinz bodies?

Answer 24

hemoglobin precipitants seen on the periphery of blood cells in those with G6PDH deficiency and eventually removed, forming bite cells

Question 25

Describe the pathogenesis, presentation, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria.

Answer 25

• CD55, CD59, or PIGA deficiency, which lead to over activation of the complement system, intravascular hemolysis, and thrombosis
• presents with pancytopenia, hematuria, and thrombosis
• may be complicated by iron deficiency anemia or AML
• the diagnosis is made with flow cytometry
• treat with steroids, eculizumab, and HSCT

Question 26

Describe the pathophysiology, presentation, diagnosis, and treatment of polycythemia vera.

Answer 26

• a proliferation of mature myeloid cells, particularly erythrocytes but also granulocytes and platelets, due to a JAK2 mutation
• presents with hyperviscosity symptoms including headache, blurry vision, flushing, venous thrombosis, and itching after bathing
• labs demonstrate normal oxygen levels and an appropriately depressed EPO
• treat with phlebotomy, aspirin, hydroxyurea, allopurinol and rasburicase, and ruxolitinib, a JAK inhibitor

Question 27

Describe the pathophysiology, presentation, and treatment of essential thrombocytosis.

Answer 27

• a proliferation of mature myeloid cells, particularly platelets, due to a JAK2 mutation
• symptoms are derived from the increased risk of bleeding and/or thrombosis
• very few complications (no risk of malignancy or hyperuricemia) but if treatment is needed, the initial therapy is hydroxyurea

Question 28

What are acute leukemias?

Answer 28

• those characterized by the accumulation of >20% blasts in the bone marrow, which crowds out normal hematopoiesis
• causes thrombocytopenia, anemia and neutropenia but a high white count as blasts enter circulation
• tends to present with infection due to the loss of functioning white blood cells

Question 29

Describe the pathophysiology, presentation, feared complication, and treatment of acute promyelocytic leukemia.

Answer 29

• a subtype of AML characterized by a t(15;17) translocation which disrupts the retinoic acid receptor (RAR)
• presents with signs of pancytopenia including bleeding and infection despite a normal or elevated WBC
• a risk for DIC given the presence of Auer rods
• treat with ATRA which causes the blasts to mature and die off

Question 30

Chronic Myelogenous Leukemia

Answer 30

• a proliferation of mature myeloid cells, particularly granulocytes, due to a t(9;22) mutation creating a BCR-ABL fusion protein with excess tyrosine kinase activity
• classically presents with basophilia and pruritus, splenomegaly, and a high WBC
• treat with imatinib (aka Gleevec), which binds and blocks the ATP-binding domain of the fusion protein