Heme/Onc - Week 2 Review - Part 1 Flashcards
Myeloproliferative Disorders - Overall Keys (5)
1) Myeloid Equivelent of Chronic Leukemia
2) Late Adulthood
3) High WBC with Hypercellular Marrow
4) Increased Risk for hyperucricemia + gout (high RBC turnover)
5) Progression to either marrow fibrosis or acute leukemia
Major Classes of Myeloproliferative Disorders (4)
1) CML
2) Polycythemia Vera (PV)
3) Essential Thrombocythemia (ET)
4) Myelofibrosis
Chronic Myeloid Leukemia (CML) - Genetics + Key Facts (3)
Genetics - 9,22 Philadelphia BCR-Abl Translocation
Key Facts
1) Spleenomegaly - Common + indicates risk for AML/ALL Progession
2) Key cells are BASOPHILS + Granulocytes
CML vs. Leukemoid Reaction - 3 Major Keys
Leukimoid Reaction = Acute Infection
CML - Negative Leukocyte Alkaline Phosphate (LAP) Stain —— Positive in Leukimid
CML - Increased Basophils (vs. Neutrophils)
CML - Lots of multilobar granulocytes
Polycythemia Vera - Definition + Cause + Treatment
Description - Neoplastic Disease of Myeloid RBCs (to many RBCs)
Genetics JAX2/STAT5 Mutation
Treatment - Phlebotomy to reduce viscosity
Polycythemia Vera - S/Sx
1) Blurry Vision
2) Venous Thrombosis
3) Flushed Fash
4) Itching After Bathing
Reactive Polycythemia vs. Polycythemia Vera - 2 Keys
Reactive Polycythemia - Response to Hypoxia (E.g. High Altitude)
Reactive Polycythemia = HIgh EPO and Low SaO2
Polycythemia Vera = Low/Normal EPO + Normal SaO2
Essentila Thrombocythemia (ET) - Definition + Genetics + Key Distinguishing Features (3)
Neoplastic Proliferation of platelets
Genetics - JAK2/STAT5 Mutation
Keys
1) Symptoms due to bleeding and clotting
2) Diagnosis of exclusion for platelets > 450,000
3) Giant + Dysfunctional Clonal Platelets (vs. reactive)
Diseases with Target Cells (4)
1`) Hemoglobin C Disease
2) Asplenia
3) Liver Disease
4) Thalasemia
Myelofibrosis - Definition + Genetics + S/Sx (3)
Neoplastic proliferation of Megakaryocytes
Genetics - JAK2 Kinase - Excess PDGF from the Megakaryocytes triggers marrow fibrosis
S/Sx
1) Splenomegally (extramedulary hematopoesis)
2) Increased Bleeding/Thombosis
3) Increased Infection (Spleen can’t keep up)
Myelofibrosis - Histology (3)
Histology - Due to Splenic RBC Production
1) Tear Drop Dacrocytes (from pinches/sheers on early realease)
2) Nucleated RBCs
3) Immature Cells
Normal Bone Marrow - Key Feature
1) Normal Cellularity of Vertebrae never drops below 50% - Femur etc. drop off
Aplastic Anemia - Definition + Key Features (3)
Marked reduction of all three marrow cell lines - error at the common myeloid progenitor level
1) Pancytopenia in the peripherial blood
2) Cellularity < 10%
3) Typically lymphoid + plasma elemnts with few progenitors and no MKs
Aplastic Anemia - Key Clinical Features (4)
1) Low Hb (Anemia - Fatigue)
2) Thrombocytopenia (Easy Bruising/Racoon Eyes + Bleeding)
3) Leukopenia (Infection)
4) Red/Dark Urine (PNH)
Aplastic Anemia - Causes (5) + Treatment (4)
Causes
1) Drugs
2) Radiaiton
3) Viral Infection
4) Chemicals
5) Autoimmune
Treatment
1) Treat Underlying Condition
2) Marrow Transfusion
3) Marrow Stimulation (GM-CSF)
4) Immunosuppresion in T-Cell Idopathic Cases
Aplastic Anemia Causes - Acquired (2) + Chemical (3)
Acquired
1) Loss HSC in the Niche (e.g. loss of CXCR4 or 12)
2) Autoimmune destruction of marrow stem cells
Chemical
1) Benzene
2) Pesticides
3) Heavy Metals
Drug Causes of Aplastic Anemia (4) + Viral Causes (5)
Drugs
1) Chloramphenicol,
2) Carbamazepine
3) Phenytoin
4) Quinine
Viral 1-2) - Hep B/C 3) HIV 4) Parvovirus B19 5) HHV (IN Immunosuppressed Patients)
Paroxysmal Nocturnal Hemoglobinuria (PNH) - Definition + Pathophysiology + Major Complications (2)
Definition - Normocytic Anemia with Intravascular Hemolysis
Pathophysiology - Aquired GPI Defeciency - Can’t hold DAF on the outside of RBCs - No protection against compliment - at night respiratory acidosis triggers compliment which lysis the RBCs - Intravascular hemolysis leads to high Hb in the urine
Major Complications - Iron Deficiency + AML Progression
Paroxysmal Nocturnal Hemoglobinuria (PNH) - Markers (2) + Genetics (1)
Markers - CD55(-) (DAF) and CD59(-) - Missing without GPI
Genetics - PIG-A Gene
Parvovirus B19 - Infection + Importance for Heme Onc + Associated Disease (5)
Infects progenitor red cells and halts erythropoiesis
Major problem for people with pre-existing marrow stress
Associations
1) Fifths Disease (Health Kids)
2) Arthritis
3) Red Cell Aplasia (Immuno-compromised)
4) Hydrops Fetalis
Inherited Bone Failure Syndromes (5)
CLASS
1) Dyskeratosis Congenita (DKC)
2) Fanconi Anemia
3) Shwachman-Diamond Syndrome
4) Pure Red Cell Aplasia (PRCA)
5) Diamond-Blackfan Anemia
Dyskeratosis Congenita (DKC) - Genetics + S/Sx (2)
Inherited Bone Failure Snydrome
X-Linked Recessive Lack of Teomere Protection
S/Sx Cutaneous (Hyperpigmented Macules + Palms/Soles
Fanconi Anemia - Genetics + Pathophysiology + Clinical Features (3)
Autosomal Ressive Knock out of Fanconi Complrex
No Fanconi = no protection of DNA Repair/Cell Cycle Arrest - Leasds to unchecked repairs
Clinical Features
1) Anemia
2) Cancer
3) Renal Tubule Acidosis
Shwachman-Diamond Syndorme - Genetics + S/Sx (3)
Mutations in SBDS of Chromosome 7
Exocrine Pancreatic Insufficiency + Skeletal Issues + Marrow Failure
Pure Red Cell Aplasia (PRCA) - Pathophysiology + Causes (5)
Aplasia of the erythroid cell line only
Aquired Causes
1) Thmoma
2) CLL
3) Parovirus B19
4) Myesthenia Gravis
Congenital = 5) Diamond Blackfan
WILL BE ON EXAM DO NOT GIVE THIS A 5
Diamond Blackfan - Genetics + S/Sx (5)
1) Ribosomal Protein 19 (Autosomal Dominant)
S/Sx
1) PURE RED CELL APLASIA
2) Tri-pharyngeal Thumb
3) Snub Nose
4) Short Statue
5) Cleft Lip
First Major Cancer Causation Link
Chimney Sweeps - Scrotum Cancer
5 Major Causation Established Occupational Exposures
1-2) - Asbestos - Lung Cancer + Mesothelioma
3) Benzene - Leukemia
4) Rubber Worker - Lung Cancer
5) Vinyl Chloride (PVC) - Angiosarcoma of Liver
Epidemiological Triangle - 3 Points
1) Agent
2) Host
3) Environment
Bradford Hill Guidelines - Points 1-4
1) Temporality - Exposure Comes First - Only Mandatory One
2) Strength (Magnitude of Association) - Relative Risk/Odds Ratio
3) Dose Response - Linear - Possible for threshold
4) Reversibility - Following Cessation of Exposure - Not common in cancer - once the oncogenesis starts it doesn’t stop
Bradford Hill Guidelines - Points 5-8
5) Consistent - Multiple trials in multiple locations
6) Biological Plausibility - Proposed Mechanism
7) Specificity of Association - Exposure associated with specific disease
8) Analogy - Analogous to a known causative agent
Bradford Hill Guidelines - For Radon Points 1-4
1) Temporality - Established
2) Strength - Small Risk but large and wide exposure
3) Dose Response - Radon is linear without threshold
4) Reversibility - Not for radon
Bradford Hill Guidelines - For Radon Points 5-8
5) Consistency - CHina + EU + US
6) Biological Mechanism - Alpha radiation damaging DNA via double strand breaks - shown in mice and cells
7) Specificity - Radon inhaled - expect lung cancer - Shown Link
8) Analogy - Residential Radon - Lung Exposure = Same as Occupational
U.S EPA Rankings of Carcinogen Classification (5)
A) Sure Carcinogen
D) Inadequate Evidence
E) Not likely to be a carcinogen
International Agency for Research on Cancer Classification (4)
1) Known Carcinogen
2) Not a Carcinogen
Ionizing Radiation - Causation + Key Points (4)
Sufficient to induce cancer but not necessary
Key Points
1) 1 Sv of Radiation = 5% Risk of Cancer
2) Occupational Exposure = Radium Dial Painters + Uranium Miners
3) Evidence Strong for Ionizing but not for Non-Ionizing
4) Background Radiation = 3.1 mSv annually - CT = 10 mSv
Asbestos - Causation
Sufficient but necessary for lung cancer - Sufficient + necessary for mesothelioma
Shift Work - Causation + Key Points (2)
Mixed Evidence - Probably Human Carcinogen (2A)
1) Discount most negative studies (poor designs)
2) Worst Risk - Breast Cancer (1.5-2X)
Viruses - Causation
Necessary and Sufficient - Hep. B + HPV
Diesel Exhaust - Causation + Key Point
May but sufficient but not necessary (lung cancer)
Key Points
1) IARC - Carcinogenic but hard to split from cigarettes
