Hematology/Oncology Flashcards
B12 deficiency may present with a ________ anemia and ___________ (finding). The most common cause of B12 deficiency is ________, which may be confirmed with a ___________.
macrocytic; peripheral neuropathy
Pernicious anemia; positive intrinsic factor antibody
Iron deficiency is a common cause of _________ anemia. Although usually a benign condition in premenopausal women, it may be related to _________ in men and postmenopausal women.
microcytic
occult GI malignancy
Approach to anemia: 1st 2 steps
1 reticulocyte count (RC) (hi = Red cell destruction and blood loss; low = decreased RBC production)
2 if low RC, measure MCV - Microcytosis: MCV 100 µm3.
Low RC, microcytic anemia DDx (4)
Iron deficiency
Thalassemia
Anemia of chronic disease
Sideroblastic anemia (usually hereditary)
Low RC, macrocytic anemia DDx (8)
B12 (cobalamin) deficiency Folate deficiency Alcohol abuse Liver disease Myelodysplastic syndrome Hypothyroidism, severe Sideroblastic anemia (acquired) Drug effects
Low RC, normocytic anemia DDx (6)
Anemia of chronic disease Anemia of renal failure Aplastic anemia Multiple myeloma Myelophthisis Hypothyroidism
Anemia of chronic disease (ACD) is caused by ________ (2). The three major categories of disease associated with ACD are _________.
iron trapping in the reticuloendothelial system and suppression of erythropoiesis, perhaps mediated by cytokines such as interleukin-1
infection, malignancy, and inflammatory disease (e.g., rheumatoid arthritis)
The characteristic feature of sideroblastic anemia is the presence of ____________, which represents abnormal iron accumulation in the mitochondria.
ringed sideroblasts in the bone marrow
Myelodysplastic syndrome (MDS) is a stem cell disorder characterized by _____________, usually presenting as _________. It occurs most often in the elderly.
an arrest in maturation of all blood cells
a pancytopenia
Myelophthisis refers to __________, usually leading to _________.
It may be secondary to _________ (3).
extensive marrow infiltration that inhibits bone marrow function
a pancytopenia
metastatic carcinoma, leukemia, or chronic infection (e.g., tuberculosis).
Thalassemia is an inherited defect in _________ gene. Mutations result in lack of, or decreased production of, a globin chain. Lack of ___ of the two β genes or ______ of the four α genes leads to ________, usually an asymptomatic microcytic anemia.
either the α-or the β-globin
One, two
the thalassemia trait
Findings seen in marked iron deficiency anemia include: (3)
Atrophic glossitis
Angular cheilitis (scaling at corners of mouth)
Koilonychia (spoon nails)
- Formula for corrected RC
- cutoffs for decreased RBC production vs. hemolysis or blood loss.
Corrected RC = RC × (Patient’s Hematocrit ÷ Expected Hematocrit)
A corrected RC of ≤2% = decreased RBC production; >3% = hemolysis or blood loss.
An anemia that has a dimorphic population has a high ________ (measured value); this can help to distinguishing which two common types of microcytic anemia?
RDW
iron deficiency anemia (high RDW) and thalassemia (low RDW)
Megaloblastic anemia findings on peripheral smear (2)
Hypersegmented PMNs
Ovalocytes
Target cells on peripheral smear are assoc with (3):
Liver disease, thalassemia, hemolysis
Bilobed PMNs on periph smear are assoc with (1):
Myelodysplastic syndrome
Teardrop cells on periph smear are assoc with (1):
Myelophthisis
Schistocytes on periph smear are assoc with (1)
Microangiopathic hemolytic anemia
An elevated RBC count in the presence of a microcytic anemia is suggestive of _________.
thalassemia
All pure microcytic anemias are associated with a low ______ (1) and the most useful initial tests are ___________ (1).
RC
Iron studies
_________ may be elevated with inflammation, so a normal _______ level does not rule out iron deficiency in the presence of chronic disease. However, iron deficiency is extremely uncommon when the ________ level is >150 µg per L. (All the same answer)
Ferritin
Macrocytic anemias are subclassified into those with and without ______________.
impaired deoxyribonucleic acid (DNA) synthesis (megaloblastic anemias = impaired).
Megaloblastic anemias include ________ (3)
B12 deficiency, folate deficiency, and drug effects.
Patients with myelodysplasia often have extremely high ______ levels.
B12
__________ may be elevated in all megaloblastic anemias because of ineffective erythropoiesis.
Lactate dehydrogenase (LDH)
________ is the most common cause of normocytic anemia.
Anemia of chronic disease
Aplastic anemia is characterized by ________(2)
pancytopenia and a zero RC.
The anemia of renal failure may be present in a patient with an estimated glomerular filtration rate (GFR) less than _______.
50
Iron studies: Fe, TIBC, and ferritin levels in each of: Iron deficiency Thalassemia Anemia of chronic disease Sideroblastic anemia
Fe - TIBC - ferritin
Iron deficiency: ↓↑↓
Thalassemia: N N N
Anemia of chronic disease↓↓↑
Sideroblastic anemia ↑ N N/↑
Pernicious anemia is related to the lack of ________ (1)
intrinsic factor (IF)
Syndrome where bacterial overgrowth reduces the B12 available for absorption?
blind intestinal loop syndrome
Schilling test: results which indicate 4 different etiologies
Able to Absorb B12 After Oral Administration of:
- B12 only = Inadequate diet
- B12 and intrinsic factor = Pernicious anemia
- B12 after administration of antibiotics = Blind loop syndrome
- Failure to absorb B12 in all of above tests = malabsorption/ileal disease (eg Crohn’s)
Indications for bone marrow biopsy to determine etiology of anemia: (3)
Pancytopenia (suggesting aplastic anemia or marrow infiltration)
Macrocytic anemia of unknown etiology (to rule out myelodysplasia)
Findings suggestive of sideroblastic anemia or myelophthisis
Hemolysis may be caused by extraerythrocytic factors (usually _________) or intrinsic defects in the RBC (often _______). (Acquired or inherited)
Acquired, inherited
Intravascular hemolysis results in release of hemoglobin, which is quickly bound to the serum protein _________. Next, the hemoglobin-_________ complex is cleared by the reticuloendothelial (RE) system, and the ________ level rapidly falls to low or undetectable levels. Once intravascular hemoglobin overloads the __________ capacity, it is filtered by the kidney and reabsorbed in the proximal tubule. (All the same answer)
These tubular cells are sloughed off into the urine and are detected as urine _________. Finally, when proximal tubular reabsorption is overwhelmed (only in severe hemolysis), _________ can be detected. This is suggested by a positive occult blood reading on urine dipstick, but no ______ are seen on urinalysis.
haptoglobin
hemosiderin
hemoglobinuria
RBCs
Extravascular space (organs) where extravascular hemolysis may occur (2)
Spleen, liver
In extravascular hemolysis, RBCs are removed by the ________ and ____________; therefore, little hemoglobin is released into the bloodstream. Haptoglobin may be ______, and urine hemosiderin and hemoglobinuria are usually ________. (Hi/lo)
Spleen and reticuloendothelial system
Low; not present
Microangiopathic hemolytic anemia (MAHA) DDx (4)
Intravascular; Extraerythrocytic Factors
Disseminated intravascular coagulation (DIC)
Hemolytic uremic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)
Cardiac valve hemolysis
Immune-Mediated Hemolytic Anemia DDx (2 groups)
Extraerythrocytic Factors
Warm antibody (hematologic malignancy, connective tissue disorders, drugs) (extravascular) Cold antibody (lymphoma, mycoplasma, mononucleosis) (intravascular)
Infections causing hemolytic anemia DDx (3)
Extraerythrocytic Factors; Intravascular & Extravascular
Malaria
Babesiosis
Clostridial toxin
Hemolytic anemia assoc with splenomegaly (2)
Extraerythrocytic Factors; Extravascular
Infiltrative diseases
Portal hypertension
DDx Hemolytic anemia due to RBC defects: Hemoglobinopathies (1), Enzyme Defects (2), membrane defects (2)
Hemoglobinopathies (Extravascular)
Sickle cell disease
Enzyme Defects (Intravascular) Pyruvate kinase deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Membrane Defects
Hereditary spherocytosis and elliptocytosis (extravascular)
Paroxysmal nocturnal hemoglobinuria (intravascular)
Sickle cell disease:
- pattern of inheritance?
- A mutation in the ______ hemoglobin chain results in production of hemoglobin ___, which polymerizes in the deoxygenated state and causes red cells to form sickle-shaped cells. This leads to vaso-occlusion in the microvasculature, which causes pain and organ dysfunction.
AR
Beta; S;
G6PD deficiency:
- pattern of inheritance
- G6PD is the enzyme responsible for generation of _______ in the red blood cell, which protects against oxidative stress. Loss of this enzyme leads to oxidation of hemoglobin and hemolysis.
X-linked trait
NADPH
Paroxysmal nocturnal hemoglobinuria (PNH)
- due to Extraerythrocytic Factors or RBC defect?
- acquired or inherited?
- affects which cells?
- Which Gene is mutated?
- result of mutation - why does hemolysis occur?
RBC defect Acquired Stem cell disorder PIG-A Mutation results in lack of a glycosylphosphatidylinositol (GPI) anchor in RBCs, and Lack of certain GPI dependent receptors leads to an increased sensitivity to complement-mediated hemolysis.
Certain drugs are associated with warm-antibody hemolytic anemia: (4)
Methyldopa
Quinine
Sulfonamides
Penicillin
________ often precedes the hemolysis in G6PD deficiency and can be due to __________ (3).
An oxidative stress
infection, ingestion of fava beans, or certain drugs (Sulfonamides, Nitrofurantoin, Methylene blue, Dapsone, Primaquine)
Hemolytic anemia assoc with fever suggests which etiologies? (2)
Presence of an infectious or microangiopathic etiology
The key laboratory features of hemolysis include: (5)
Elevated indirect bilirubin Elevated lactate dehydrogenase (LDH) Increased reticulocyte count Decreased haptoglobin Urine hemosiderin may be present (especially with intravascular hemolysis).
Elevated LDH and indirect bilirubin may be seen in patients with ineffective hematopoiesis (e.g., B12 deficiency) and in hemolytic anemia. What other test tells these two apart?
The reticulocyte count is low in patients with ineffective hematopoiesis
Hemolytic anemia with schistocytes on smear (more than 5 per HPF) indicate which group of pathologies? What other lab finding is most prominent within this group compared to other groups?
Microangiopathic hemolytic anemia (MAHA) - Causes include DIC, HUS, and TTP.
Thrombocytopenia
How to tell Disseminated intravascular coagulation (DIC), Hemolytic uremic syndrome (HUS), and Thrombotic thrombocytopenic purpura (TTP) apart on labs?
PT is elevated in DIC but is normal in TTP and HUS. Renal failure is an important feature of HUS but is also seen in other microangiopathic etiologies.
RBC hemolysis usually results in which cell morphologies? (2)
However, a large number of one of these morphologies is related to two specific pathologies - what are they?
Target cells and spherocytes.
However, large numbers of spherocytes are limited to hereditary spherocytosis and warm-antibody hemolysis.
Elliptocytes (RBC morphology) are seen in ______ (2).
hereditary elliptocytosis and severe iron deficiency
DDX for Intracellular parasites in RBC seen on smear (2)
Malaria
Babesiosis
Once examination of the smear eliminates _________ (3), a Coombs test should be performed.
- indirect vs direct Coombs test?
MAHA, intraerythrocytic infections, and sickle cell
An indirect Coombs’ test looks for an antibody in the patient’s serum that can agglutinate normal RBCs. A direct Coombs’ test is the definitive test for immune-mediated hemolysis, searching for the presence of the antibody directly on the patient’s own RBCs.
A direct Coombs’ test may be further classified by the type of antibody associated with the hemolysis. Most warm-antibody hemolysis is mediated by ______, and therefore _______ will be detected on the RBC surface. Cold-antibody hemolysis is mostly ______ mediated, and therefore ______ will be detected on the cell surface.
IgG; IgG and C3
IgM; only C3 (IgM binds to the RBC and fixes complement at lower temperatures but then dissociates from the RBC)
Test (1) used for Dx in each of the following cases:
- membrane defects (eg hereditary spherocytosis)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- G6PD deficiency
- Sickle cell disease
- Osmotic fragility test (abnormal cells lyse more easily)
- flow cytometry to detect cells deficient in the GPI anchor protein.
- fluorescent spot test, which measures generation of the reduced form of NADPH
- hemoglobin electrophoresis, which demonstrates hemoglobin S.
Drug that may cause a pseudolymphoma syndrome
phenytoin (Dilantin)
DDx adenopathy plus each of the following assoc Sx:
Weight loss, night sweats (3)
Sore throat (2)
Genital lesion (2)
Pets, especially cats (2)
History of travel to the southwestern United States (1) or the midwestern United States (1)
History of IV drug use or high-risk sexual behavior (1)
Weight loss, night sweats (lymphoma, metastatic cancer, tuberculosis)
Sore throat (mononucleosis, pharyngitis)
Genital lesion (syphilis, chancroid)
Pets, especially cats (cat-scratch disease, toxoplasmosis)
History of travel to the southwestern United States (coccidioidomycosis) or the midwestern United States (histoplasmosis)
History of IV drug use or high-risk sexual behavior (HIV)
