Hematology and Oncology Flashcards
1
Q
RBC lacks
A
Nucleus and organelles
2
Q
RBC source of energy
A
Glucose → 90% used in glycolysis, 10% used in HMP shunt
3
Q
Compare anisocytosis and poikilocytosis
A
Anisocytosis → varying sizes
Poikilocytosis → varying shapes
4
Q
Granules stored in platelets
A
Dense granules → ADP, Ca2+
Alpha granules → vWF, fibrinogen, fibronectin
5
Q
Granulocytes
A
Neutrophils, eosinophils, basophils
6
Q
Mononuclear cells
A
Monocytes, lymphocytes
7
Q
Granules stored in neutrophils
A
Specific granules → leukocyte alkaline phosphatase (LAP), collagenase, lysozyme, lactoferrin
Azurophilic granules → lysosomes, proteinases, acid phosphatase, myeloperoxidase, β-glucuronidase
8
Q
Neutrophilic chemotactic agents
A
- C5a
- IL-8
- LTB4
- Kallikrein
- Platelet-activating factor
9
Q
Macrophages are an important component in the formation of what
A
Granulomas
10
Q
Lipid A from bacterial LPS binds what to initiate septic shock
A
CD14 on macrophages
11
Q
Causes of eosinophilia
A
- Neoplasia
- Asthma
- Allergic processes
- Chronic adrenal insufficiency
- Parasites (invasive)
“NAACP”
12
Q
Eosinophils produce
A
- Histaminase
- Major basic protein (a helminthotoxin)
13
Q
Granules in basophils contain
A
- Heparin (anticoagulant)
- Histamine (vasodilatory)
- Leukotrienes are synthesized and released on demand
14
Q
Degranulation of mast cells leads to release of
A
- Histamine
- Heparin
- Tryptase
- Eosinophil chemotactic factors
Mast cells contain basophilic granules, just like basophils
15
Q
What cells originate from the same precursor as basophils
A
Mast cells
16
Q
Where are plasma cells found
A
Found in bone marrow and normally do not circulate in peripheral blood
17
Q
Where does fetal erythropoiesis occur
A
- Yolk sac (3-8 weeks)
- Liver (6 weeks - birth)
- Spleen (10-28 weeks)
- Bone marrow (18 weeks to adult)
“Young Liver Synthesizes Blood”
18
Q
Migration pattern for hemoglobin
A
Furthest from cathode (-)
Normal adult (AA) → Normal newborn (AF) → Sickle cell trait (AS) → Sickle cell disease (SS) → HbC train (AC) → Hb C disease (CC) → Hb SC disease (SC)
“A Fat Santa Claus”
19
Q
Anticoagulant with greatest efficacy against factors Xa and IIa
A
Factor Xa → LMWH
Factor IIa (thrombin) → heparin
20
Q
Enzyme responsible for reducing vitamin K
A
Epoxide reductase
21
Q
vWF protects and carries which factor
A
VIII
22
Q
Antithrombin inhibits activated forms of which factors
A
II, VII, IX, X, XI, XII
23
Q
What are the principal targets of antithrombin
A
Thrombin and factor Xa
24
Q
How do protein C and S work as anticoagulants
A
Protein C → Activated Protein C
- via Thrombin-thrombomodulin complex in endothelial cells
Activated Protein C + Protein S → Cleaves and inactivates Va, VIIIa
25
Describe primary hemostasis
INJURY→ endothelial damage → transient vasoconstriction via neural stimulation reflex and endothelin (released from damaged cell)
EXPOSURE → vWF binds to exposed collagen; vWF is from Weibel-Palade bodies of endothelial cells and α - granules of platelets
ADHESION → platelets bind vWF via GpIb receptor at the site of injury only (specific) → platelets undergo conformational changes → platelets release ADP and Ca2+ (necessary for coagulation cascade) and TXA2 → ADP helps platelets adhere to endothelium
ACTIVATION → ADP binding to receptor induces GpIIb/IIIa expression at platelet surface
AGGREGATION → fibrinogen binds GpIIb/IIIa receptors and links platelets
26
Pro-aggregation factors
- TXA2 (released by platelets)
- ↓ blood flow
- ↑ platelet aggregation
27
Anti-aggregation factors
- PGI2 and NO (released by endothelial cells)
- ↑ blood flow
- ↓ platelet aggregation
28
Mechanism of ristocetin
- Activates vWF to bind GpIb
| - Failure of agglutination with ristocetin assay occurs in von Willebrand disease and Bernard-Soulier syndrome
29
Acanthocyte
- Liver disease
| - Abetalipoproteinemia (states of cholesterol dysregulation)
30
Basophilic stipiling
- Lead poisoning
- Sideroblastic anemias
- Myelodysplastic syndromes
31
Dacrocyte
Bone marrow infiltration (eg myelofibrosis, osteopetrosis)
32
Degmacyte
G6PD deficiency
33
Echinocyte
- End-stage renal disease
- Liver disease
- Pyruvate kinase deficiency
Different from acanthocyte; its projections are more uniform and smaller
34
Elliptocyte
- Hereditary elliptocytosis (usually asymptomatic)
| - Caused by mutation in genes encoding RBC membrane proteins (eg spectrin)
35
Macro-ovalocyte
- Megaloblastic anemia (also, hypersegmented PMNs)
| - Marrow failure
36
Ringed sideroblast
- Sideroblastic anemia
| - Excess iron in mitochondria
37
Schistocyte
- DIC
- TTP/HUS
- Mechanical hemolysis (eg heart valve prosthesis)
Examples include "helmet cells"
38
Sickle cell
Sickle cell anemia
Sickling occurs with dehydration, deoxygenation and at high altitude
39
Spherocyte
- Hereditary spherocytosis
| - Drug and infection induced hemolytic anemia
40
Target cell
- HbC
- Asplenia
- Liver disease
- Thalassemia
"HALT"
41
Heinz bodies
G6PD deficiency
Oxidation of Hb-SH groups to -S-S- → Hb precipitation (Heinz bodies) with subsequent phagocytic damage to RBC membrane → degmacyte ("bite cell")
42
Howell-Jolly bodies
- Seen in patients with functional hyposplenia or asplenia
- Basophlic nuclear remnants found in RBCs
- Howell-Jolly bodies are normally removed from RBCs by splenic macrophages
43
How does lead poisoning cause basophilic stippling
Inhibits rRNA degradation → RBCs retain aggregates of rRNA (basophilic stippling)
44
Symptoms of lead poisoning
- Lead Lines on gingivae (Burton lines) and on metaphyses of long bones on x-ray
- Encephalopathy and Erythrocyte basophilic stippling
- Abdominal colic and sideroblastic Anemia
- Drops - wrist and foot drop
"LEAD"
45
Treatment of lead poisoning
- Dimercaprol and EDTA are 1st line of treatment
| - Succimer used for chelation for kids ("it SUCks to be a kid who eats lead")
46
Causes of sideroblastic anemia
- Defect in heme synthesis due to X linked defect in ALA synthase gene
- CAUSES: genetic, acquired (myelodysplastic syndromes), and reversible (alcohol is most common, also lead, B6 deficiency, copper deficiency, isoniazid)
47
Treatment of sideroblastic anemia
Pyridoxine (B6, cofactor for ALA synthase)
48
Orotic aciduria
- Inability to convert orotic acid → UMP (de novo pyrimidine synthesis pathyway) because of defect in UMP synthase
- AR
- Present in children as failure to thrive, developmental delay and megaloblastic anemia refractory to folate and B12
- NO hyperammonemia (vs ornithine transcarbamylase deficiency → ↑ orotic acid with hyperammonemia)
- Orotic acid found in urine
- TREATMENT: UMP to bypass mutated enzyme
49
Diamond-Blackfan anemia
- Rapid-onset anemia within 1st year of life due to intrinsic defect in erythroid progenitor cells
- ↑ % HbF (but ↓ total Hb)
- Presents with short stature, craniofacial abnormalities, and upper extremity malformations (triphalangeal thumbs)
50
Nonmegaloblastic macrocytic anemia
- Macrocytic anemia in which DNA synthesis is unimpaired
- RBC macrocytosis without hypersegmented neutrophils
- Causes include alcoholism and liver disease
51
Intravascular hemolysis findings
- ↓ haptoglobin
- ↑ LDH
- Schistocytes and ↑ reticulocytes on blood smear
- Characteristic hemoglobinuria, hemosiderinuria, and urobilinogen in urine
- May also seen ↑ unconjugated bilirubin
- Causes include mechanical hemolysis (eg prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias
52
Extravascular hemolysis findings
- Macrophages in sleep clear RBCs
- Spherocytes in peripheral smear
- ↑ LDH
- NO hemoglobinuria/hemosiderinuria
- ↑ unconjugated bilirubin (can cause jaundice)
- Can present with urobilinogen in urine
53
Pathogenesis of anemia of chronic disease
Inflammation → ↑ hepcidin (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron tranport) → ↓ release of iron from macrophages and ↓ iron absorption from gut
54
Treatment of anemia of chronic disease in the case of chronic kidney disease
Erythropoietin
55
Causes of aplastic anemia
Caused by failure or destruction of myeloid stem cells due to:
- Radiation and drugs → benzene, chloramphenicol, alkylating agents, antimetabolites
- Viral agents → parvovirus B19, EBV, HIV, hepatitis viruses
- Fanconi anemia → DNA repair defect with NHEJ causing bone marrow failure as well as short stature, ↑ incidence of tumors/leukemias, cafe-au-lait spots, thumb/radial defects
- Idiopathic (immune mediated, primary stem cell defect), may follow acute hepatitis
56
Presentation of hereditary spherocytosis
- Splenomegaly
| - Aplastic crisis (parvovirus B19 infection)
57
Hereditary spherocytosis - intravascular or extravascular hemolysis
Extravascular hemolysis
58
Presentation of G6PD deficiency
- Back pain
| - Hemoglobinuria a few days after oxidant stress
59
Inheritance pattern of G6PD deficiency
X linked recessive
60
G6PD deficiency - intavascular or extravascular hemolysis
Both
61
Pyruvate kinase deficiency
- AR
- Defect in pyruvate kinase → ↓ ATP → rigid RBCs → extravascular hemolysis
- Hemolytic anemia in a newborn
62
Hb C disease - intravascular or extravascular hemolysis
Extravascular
63
What does the blood smear show for Hb C disease homozygotes
Blood smear shows hemoglobin crystals inside RBCs and target cells
64
Triad of paroxysmal nocturnal hemoglobinuria
- Coombs (-) hemolytic anemia
- Pancytopenia
- Venous thrombosis
65
Cause of paroxysmal nocturnal hemoglobinuria
Acquired mutation in a hematopoietic stem cell. ↑ incidence of acute leukemias.
66
Paroxysmal nocturnal hemoglobinuria - intravascular or extravascular hemolysis
Intravascular
67
Treatment of paroxysmal nocturnal hemoglobinuria
Eculizumab → terminal complement inhibitor
68
Sickle cell anemia - intravascular or extravascular hemolysis
Both
69
Treatment of sickle cell anemia
Hydroxyurea and hydration
70
Compare microangiopathic and macroangiopathic anemia
Microangiopathic → RBCs are damaged when passing through obstructed or narrowed vessel lumina; seen in DIC, TTP/HUS, SLE, and malignant hypertension
Macroangiopathic → prosthetic heart valves and aortic stenosis may also cause hemolytic anemia secondary to mechanical destruction of RBCs
Schistocytes are seen on peripheral blood smear for both
71
Iron deficiency anemia lab values
- ↓ serum iron (primary)
- ↑ TIBC
- ↓ ferritin
- ↓ % transferrin saturation
72
Chronic disease lab values
- ↓ serum iron
- ↓ TIBC
- ↑ ferritin (primary)
73
Hemochromatosis lab values
- ↑ serum iron (primary)
- ↓ TIBC
- ↑ ferritin
- ↑↑ % transferrin saturation
74
Pregnancy/OCP use
- ↑ TIBC (primary)
| - ↓ % transferrin saturaiton
75
Why do corticosteroids cause neutrophilia despite causing eosinopenia and lymphopenia
Corticosteroids ↓ activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation. In contrast, corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes
76
Causes of neutropenia
- Sepsis/post-infection
- Drugs (including chemotherapy)
- Aplastic anemia
- SLE
- Radiation
77
Causes of lymphopenia
- HIV
- DiGeorge syndrome
- SCID
- SLE
- Corticosteroids
- Radiation
- Sepsis
- Postoperative
78
Causes of eosinopenia
- Cushing syndrome
| - Corticosteroids
79
Left shift
- ↑ neutrophil precursors, such as band cells and metamyelocytes, in peripheral blood
- Usually seen with neutrophilia in the acute response to infection or inflammation
- Called LEUKOERYTHROBLASTIC REACTION when left shift is seen with immature RBCs → occurs with severe anemia (physiologic response) or marrow response (eg fibrosis, tumor taking up space in marrow)
80
Lead poisoning
- Affected enzymes → ferrochelatase, ALA dehydratase
- Accumulated substrates → protoporphyrin, ALA (blood)
Presentation:
- Microcytic anemia (basophilic stippling), GI, kidney disease
- Children → exposure to lead paint → mental deterioration
- Adults → environmental exposure (eg batteries, ammunition) → headache, memory loss, demyelination
81
Acute intermittent porphyria
- Affected enzyme → porphobilinogen deaminase
- Accumulated substrates → porphobilinogen, ALA, corphobilinogen (urine)
Presentation (5 Ps):
- Painful abdomen
- Port wine-colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs (eg cytochrome P450 inducers), alcohol, starvation
Treatment → glucose and heme, which inhibit ALA synthase
82
Porphyria cutanea tarda
- Affected enzyme → uroporphyrinogen decarboxylase
- Accumulated substrate → uroporphyrin (tea-colored urine)
Presentation:
- Blistering cutaneous photosensitivity
- Most common porphyria
83
Iron poisoning
- Cell death due to peroxidation of membrane lipids
- Symptoms → N/V, gastric bleeding, lethargy, scarring leading to GI obstruction
- Treatment → chelation and dialysis → IV deferoxamine, oral deferasirox
84
PT tests function of what
- Common and extrinsic pathway
| - Factors I, II, V, VII, and X
85
PTT tests function of what
- Common and intrinsic pathway
| - All factors except VII and XIII
86
PT and PTT in vitamin K deficiency
↑ PT, ↑ PTT
87
Bernard-Soulier syndrome
- -/↓ platelet count
- ↑ BT
- Defect in platelet plug formation
- ↓ GpIb → defect in platelet-to-vWF adhesion
- Large platelets
88
Glanzmann thrombasthenia
- - platelet count
- ↑ BT
- Defect in platelet plug formation
- ↓ GpIIb/IIIa → defect in platelet-to-platelet aggregation
- Labs: blood smear shows no platelet clumping
89
Hemolytic-uremic syndrome
- ↓ platelet count
- ↑ BT
- Characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure
- Typical HUS seen in children, accompanied by diarrhea and commonly caused by Shiga-toxin producing E coli (STEC)
- HUS in adults does NOT present with diarrhea, STEC infection is NOT required
- Same spectrum as TTP, with a similar clinical presentation and same initial treatment of plasmapheresis
90
Immune thrombocytopenia
- ↓ platelet count
- ↑ BT
- Anti-GpIIb/IIIa antibodies → splenic macrophage consumption of platelet-antibody complex
- Commonly due to viral illness
- Labs: ↑ megakaryocytes on bone marrow biopsy
- Treatment: steroids, IVIG, splenectomy for refractory ITP
91
Thrombotic thombocytopenic purpura
- ↓ platelet count
- ↑ BT
- Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) → ↓ degradation of vWF multimers
- Pathogenesis: ↑ large vWF multimers → ↑ platelet adehesion → ↑ platelet aggregation and thrombosis
- Labs: schistocytes, ↑ LDH
- Symptoms: pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia
- Treatment: plasmapheresis, steroids
92
von Willebrand disease
- - platelet count
- ↑ BT
- - PT
- -/↑ PTT
- Intrinsic pathway coagulation defect: ↓ vWF → ↑ PTT (vWF acts to carry/ protect factor VIII)
- Defect in platelet plug formation: ↓ vWF → defect in platelet-to-vWF adhesion
- AD
- Mild but most common inherited bleeding disorder
- No platelet aggregation with ristocetin cofactor assay
- Treatment: desmopressin (releases vWF stored in endothelium)
93
Disseminated intravascular coagulation
- ↓ platelet count
- ↑ BT
- ↑ PT
- ↑ PTT
- Widespread activation of clotting → deficiency in clotting factors → bleeding state
- Causes: Sepsis (gram -), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion ("STOP Making New Thrombi")
- Labs: schistocytes, ↑ fibrin degradation products (D dimers), ↓ fibrinogen, ↓ factors V and VIII
94
Antithrombin deficiency
- Inherited deficiency of antithrombin → has no direct effect on the PT, PTT or thrombin time but diminitshes the increase in PTT following heparin administration
- Can also be acquired: renal failure/ nephrotic syndrome → antithrombin loss in urine → ↓ inhibition of factors IIa and Xa
95
Factor V Leiden
- Production of mutant factor V (G → A DNA point mutation → Arg506Gln mutation near the cleavage site) that is resistant to degradation by activated protein C
- Most common cause of inherited hypercoagulability in Caucasians
- Complications include DVT, cerebral vein thromboses, recurrent pregnancy loss
96
Protein C or S deficiency
- ↓ ability to inactivate factor Va and VIIIa
- ↑ risk of thrombotic skin necrosis with hemorrhage after administration of warfarin
- If this occurs, think protein C deficiency
- "Together protein C Cancels and protein S Stops Coagulation"
97
Prothrombin gene mutation
Mutation in 3' untranslated region → ↑ production of prothrombin → ↑ plasma levels and venous clots
98
Packed RBCs
- ↑ Hb and O2 carrying capacity
| - Clinical use → acute blood loss, severe anemia
99
Platelets
- ↑ platelet count (↑ by approximately 5000/mm3/unit)
| - Clinical use → stop significant bleeding (thrombocytopenia, qualitative platelet defects)
100
Fresh frozen plasma
- ↑ coagulation factor levels
| - Clinical use → DIC, cirrhosis, immediate warfarin reversal
101
Cryoprecipitate
- Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
- Clinical use → coagulation factor deficiencies involving fibrinogen and factor VIII
102
Risks of blood transfusions
- Infection transmission (low)
- Transfusion reactions
- Iron overload (may lead to secondary hemochromatosis)
- Hypocalcemia (citrate is a Ca2+ chelator)
- Hyperkalemia (RBCs may lyse in old blood units)
103
Compare Hodgkin and Non-Hodgkin lymphomas
Hodgkin:
- Localized, single group of nodes
- Contiguous spread (stage is strongest predictor of prognosis)
- Many patients have a relatively good prognosis
- Characterized by Reed-Sternberg cells
- Bimodal distribution → young adulthood and >55 years; more common in men except for nodular sclerosing type
- Associated with EBV
- Constitutional ("B") signs/symptoms": low grade fever, night sweats, weight loss
Non-Hodgkin:
- Multiple lymph nodes involved
- Extranodal involvement common
- Noncontiguous spread
- Majority involve B cells; a few are of T cell lineage
- Can occur in children and adults
- May be associated with HIV and autoimmune diseases
- May present with constitutional signs/symptoms
104
Primary central nervous system lymphoma
- Non-Hodgkin lymphoma
- Neoplasm of mature B cells
- Occurs in adults
- Most commonly associated with HIV/AIDS
- Considered an AIDS-defining illness
- Variable presentation: confusion, memory loss, seizures
- Mass lesion(s) on MRI, needs to be distinguished from toxoplasmosis via CSF analysis or other lab tests
105
Waldenstrom macroglobulinemia
- M spike = IgM
- Hyperviscosity syndrome (eg blurred vision, Raynaud phenomenon)
- No CRAB findings
106
Monoclonal gammopathy of undetermined significance (MGUS)
- Monoclonal expansion of plasma cells
- Asymptomatic
- May lead to multiple myeloma
- No CRAB findings
- Patients with MGUS develop multiple myeloma at a rate of 1-2% per year
107
Myelodysplastic syndromes
- Stem-cell disorders involving ineffective hematopoiesis → defects in cell maturation of all nonlymphoid lineages
- Caused by de novo mutation or environmental exposures (eg radiation, benzene, chemotherapy)
- Risk of transformation to AML
108
Pseudo-Pelger-Huet anomaly
- Neutrophils with bilobed nuclei
- Typically seen after chemotherapy
- Myelodysplastic syndrome
109
Lukemia cutis
Lukemic cell infiltration of skin
110
Rare leukemias present with
Normal/ ↓ WBCs
111
Lymphoid neoplasm associated with autoimmune hemolytic anemia
Chronic lymphocytic leukemia/ small lymphocytic lymphoma
112
Richter transformation
SLL/CLL transformation into an aggressive lymphoma, most commonly diffuse large B cell lymphoma
113
Patients with hairy cell leukemia generally present with
Massive splenomegaly
114
Treatment of hairy cell leukemia
- Cladribine
| - Pentostatin
115
Are dendritic/Langerhans cells of Langerhans cell histiocytosis functional
Cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation
116
Presentation of polycythemia vera
- Erythromelalgia → severe, burning pain and red-blue coloration due to episodic blood clots in vessels of the extremities
- Itching after hot shower
- These symptoms respond to aspirin
117
Relative polycythemia
- ↓ plasma volume
- - RBC mass
- - O2 saturation
- - EPO
- Associated with dehydration and burns
118
Appropriate absolute polycythemia
- - plasma volume
- ↑ RBC mass
- ↓ O2 saturation
- ↑ EPO levels
- Associated with lung disease, congenital heat disease, and high altitude
119
Inappropriate absolute polycythemia
- - plasma volume
- ↑ RBC mass
- - O2 saturation
- ↑ EPO
- Associated with malignancy (eg renal cell carcinoma, hepatocellular carcinoma), hydronephrosis
- Due to ectopic EPO secretion
120
Polycythemia vera
- ↑ plasma volume
- ↑↑ RBC mass
- - O2 saturation
- ↓ EPO (due to negative feedback)
