Hematology & Oncology Flashcards
This deck covers Chapters 111-115 in Rosens, compromising all of hematology and oncology.
1
Q
Differentiate TTP/HUS from DIC and Liver Infarct
A
- TTP/HUS have normal coags
- DIC has abnormal coags
- Liver infarct has elevated Factor VIII
2
Q
What is thalassemia? What are the types of thalassemia? Is the RDW normal? What might you see on smear?
A
Thalassemia
- Abnormal alpha or beta-globin gene(s)
Workup
- RDW normal
- MCV very low (50s - 60s)
- Target cells and basophilic stippling on smear
Types
- Major: Homozygous B
- Transfusion dependent
- HSM, jaundice, abnormal development, typical facies, premature death
- Patients are transfusion dependent
- Tx: Transfusion + Fe-chelation therapy
- Minor: Heterozygous B
- Elevated HbA2 (alpha/delta) on electrophoresis
- Tx: None necessary
- α-Thalassemia
- Range from asymptomatic carrier to prenatal death
- 4 gene deletion - no α chains, only B = 4γ tetramers / hydrops fetalis
- 3 gene deletion – HbH in adults = 4β tetramers – hang onto oxygen too tightly – poor offloading to tissues (but you still produce SOME α-chains so compatible with life)
3
Q
Provide a differential for normocytic anemia
A
ABCDs
- Acute blood loss
- Bone marrow failure
- Chronic disease
- Destruction (hemolysis)
- Spherocytosis (hereditary)
4
Q
What is the underlying problem in Hemophilia A? How do you dose the treatment?
A
Factor 8 deficiency
- Mild: DDAVP 0.3 mcg/kg (max 20 mcg)
- Moderate: 25 u/kg
- Severe/Life Threat: 50 u/kg
5
Q
List 10 potential organs damaged in Sickle Cell Disease
A
- Brain: strokes
- Retinal hemorrhage, Ischaemic neuropathy
- Lung infarcts
- Spleen: Functional asplenia by age 5
- Heart: CHF
- Skin: ulcers
- Gallstones
- GU: hematuria, priapism
- Skeletal: osteomyelitis, infarct
- Blood: immune deficiency, hemolysis
6
Q
List 6 non-malignant causes of SVC syndrome
A
- Goiter
- Pericardial constriction
- Primary thrombosis
- Idiopathic sclerosing aortitis
- Tuberculous mediastinitis
- Fibrosing mediastinitis (histo + methysergide treatment)
- Arteriosclerotic or (rarely) syphilitic aneurysm
- Nephritic syndrome
- Indwelling CVCs
7
Q
You’re working up a patient for anemia NYD and your lab results come back. MCV is low, low iron, low ferritin, high TIBC. Diagnosis?
A
Iron Deficiency
8
Q
What is von Willebrand’s disease? How do you treat it?
A
Von Willebrand Disease
- Autosomal dominant disorder – common
- vWF is normally involved in PLT adhesion
- vWD leads to factor VIII deficiency, abnormal platelet adhesiveness, and abnormal vascular endothelium
- Similar symptoms to thrombocytopenia rather than hemophilia
Types
- Type 1 (90%) = decrease in vWF
- Type 2 = qualitative issue – 5 subtypes
- Type 3 = same as 1 but severe form – homozygous
Labs
- Platelets normal
- Prolonged BT
- Decreased F8 activity
- INR normal
- aPTT increased
- vWF decreased
Treatment
- Mild/Moderate bleeding
- DDAVP 0.3mcg/kg
- Severe bleeding
- vWF or F8 concentrate 50 U/kg
- Cyro (F8, F13, Fibrinogen, vWF)
- FFP
- TXA
9
Q
List 6 causes of rapid intravascular RBC destruction
A
- DIC and mechanical hemolysis
- Massive burns
- Toxin (Brown recluse spiders/Cobras)
- Infections (Malaria, Clostridium)
- G6PD
- ABO incompatibility
- Cold agglutinin hemolysis (Mycoplasm, EBV)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Immune complex hemolysis
10
Q
List 5 causes of hyperviscosity syndrome
A
- Waldenstrom’s macroglobulinemia (MCC)
- Multiple myeloma
- Cryoglobulinemia
- Leukemias
- Leukemoid reaction
- Polycythemia vera
- Accumulation of abnormal Hb in sickle cell
Blastic phase of CML, chronic granulocytic leukemia
Blast cell crisis of ALL, non-lymphoblastic leukemias
11
Q
You give a hemophilia A patient factor replacement and they’re still bleeding, what likely happened?
A
Antihemophilic factor antibodies post-infusion
Treatment
- Just give more Factor
- Exchange plasmapheresis
- Immunosuppressive therapy
- Prothrombin complexes with activated clotting factors
- Recombinant activated Factor VIIa
12
Q
Describe the pathophysiology and treatment of ITP
A
Immune Thrombocytopenia Purpura
- Autoimmune reaction with IgG against platelets
- Diagnosis of exclusion
Acute ITP
- Children 2-6 yo with a viral prodrome
- Platelets <20
- Self-limited, >90% rate of spontaneous remission
- Tx = supportive. Only give steroids and IVIG to bleeders.
Chronic ITP
- Adults (women > men)
- Gradual, no prodrome
- Platelets 30-100
- Long term mortality low (1%)
- Tx = Prednisone 1 mg/kg + IVIG
13
Q
What are the common signs & symptoms of hypercalcemia in malignant disease?
A
- Neuro: Muscle weakness, fatigue, hyporeflexia, lethargy
- Cardio: Short PR/QT, wide T, heart block, bradycardia
- GI: N/V, constipation
- GU: Polyuria, polydipsia
- Derm: pruritus
14
Q
Name 6 diseases associated with autoimmune hemolytic anemia (AIHA)?
A
Autoimmune Hemolytic Anemia
- RA
- SLE
- PAN
- Malaria
- Syphilis
- Mycoplasm
- Malignancy: CLL/CML, ovarian teratoma
- Ulcerative colitis
15
Q
List 6 drugs commonly implicated in thrombocytopenia
A
- Quinine
- Heparin
- Digoxin
- Sulfonamides
- Phenytoin
- ASA
- Alcohol
- GP IIb-IIIa inhibitors
- Cocaine (IV)
16
Q
How do you reverse heparin?
A
- Protamine 1 mg per:
- 100 units UFH
- 1 mg LMWH
- Give IV over 10-15 minutes
17
Q
Describe the pathophysiology and treatment of HUS
A
Verotoxin-producing bacteria
- >90% cases from E. Coli 0157:H7
- Mycoplasm also implicated
- Childhood illness
- Bloody diarrhea
Treatment
- Fluids, supportive
- Dialysis
- AVOID antibiotics and antimotility agents
- No plasmapheresis in children
TTP/HUS = normal PT/INR/PTT/FDPs/D-dimer/fibrinogen
18
Q
Explain how platelets help hemostasis
A
- Exposed collagen from injury
- vWF binds exposed collagen
- Platelets bind vWF and release ADP and TXA2
* Causes vasoconstriction and aggregation - Plug formation
- Clotting factors bind the plug
19
Q
Explain the pathophysiology of sideroblastic anemia. What are the RBC indices for this disease? What is the treatment?
A
Sideroblastic Anemia
Pathophysiology
- Defect in porphyrin synthesis = impaired Hb synthesis
- Excess Fe in mitochondria of RBC precursor
- Typically a disease of the elderly
- Look for pallor, splenomegaly, microcytic anemia, iron OL
RBC indices
- Increased serum Fe, ferritin & transferrin (TIBC) saturation
Treatment
- Pyridoxine (vitamin B6) 100 mg TID x 1-2 months
- Often need blood transfusions (+ Fe-chelation)
20
Q
List 4 mechanisms of hypercalcemia in cancer
A
Patients with no bone disease (80%)
- Hypercalcemia from tumor-made hormone substances
- Examples: PTHrP, prostaglandins, peptides
Patients with metastatic bone involvement (20%)
- Ca + PO4 release from osteoclasts in the bone
Lymphomas that secrete 1,25(OH)2D
- Calcitriol, the active form of Vitamin D (<1%)
Ectopic hyperparathyroidism (<1%)
21
Q
What is the issue with hemophilia B? How much factor must you give?
A
Hemophilia B
- Factor 9 deficiency
Treatment
- Mild/Moderate = 50 units/kg
- Severe = 100 units/kg (150 units/kg if <15 yo)
22
Q
Describe the pathophysiology and treatment of TTP
A
FATRN
- Fever
- Anemia
- Thrombocytopenia
- Renal Impairment
- Neurological Sequelae
Pathophysiology
- Antibodies to ADAMTS13 – protease that cleaves vWF
- Multimers cause PLT aggregation, thrombosis, and MAHA
- Similar to HUS but TTP has ↑CNS and ↓renal sx
- TTP/HUS = normal PT/INR/PTT/D-dimer/Fibrinogen
Treatment
- Plasmapheresis
- Prednisone (1 mg/kg)
- Heme consult
23
Q
What is paroxysmal nocturnal hemoglobinuria (PNH)? What is the major complication? What intervention can be life-threatening in these patients?
A
Paroxysmal Nocturnal Hemoglobinuria
- Stem cell defect
- Causes abnormal RBC, PMN, and platelet sensitivity to complement
- Chronic hemolysis, hemosiderinuria, decreased WBC, decreased PLT
Complications
- Clotting/DVT
Life-threatening intervention
- Transfusion
- RBC lysis from donor complement
- Can only use washed out packed cells
24
Q
What ABx should be given to a febrile neutropenic patient? List 5 indications to add vancomycin?
A
Pseudomonal coverage
- Ceftazidime
- Cefepime
- Pip-Tazo
- Carbapenem
If they have a PCN allergy give aminoglycoside and fluoroquinolone
Vancomycin Indications
- Shock
- Line
- Mucositis
- MRSA colonized
- Fluoroquinolone prophylaxis
- Blood culture + without speciation
- Pneumonia
- Skin infection
25
List 8 non-neoplastic causes of hypercalcemia
1. Hyperparathyroidism
2. Hyperthyroidism
3. Myxedema
4. Acute adrenal insufficiency
5. Renal insufficiency
6. Drugs (thiazide, diuretics, lithium)
7. Hypervitaminosis A or D
8. Sarcoid
9. Paget's
10. Fractures
11. Idiopathic hypercalcemia of infancy
* Associated with looking like an elf
26
How do you calculate the corrected reticulocyte count? What is a normal corrected reticulocyte count?
**Corrected retic count**
* = [% of retics x %HCT] / 45%
* Normal corrected retic count = 1 – 3%
27
How is DIC treated?
* Treat underlying cause
* Supportive care
* Platelets if \< 50 and bleeding or need surgery
* FFP/Cyro if prolonged PT \>1.5x
* Cyro if fibrinogen \<2.0
* TXA is contraindicated
28
Describe 6 causes of intravascular hemolysis
1. MAHA (TTP/HUS/DIC/HELLP/Malignancy)
2. Valvular stenosis
3. ABO incompatibility
4. Burns
5. Infections (Malaria)
6. Toxins (Nitrates)
7. Environmental (Spider bit)
8. G6PD
29
Define neutropenia. Write out the formula absolute neutrophil count (ANC)
Defined as ANC \< 1500 cells/mm3
* Severe neutropenia
* \<500 cells/mm3
* \<1000 cells/mm3 + predicted to \<500 cells/mm3
ANC = (WBC count) × (%PMNs + %bands)
30
List 6 causes of aplastic anemia
1. Drugs & Chemicals (most common)
2. Viral hepatitis
3. Parvovirus B19
4. Pregnancy
5. Radiation
6. Autoimmune variant
31
List 5 causes of folate deficiency
1. Poor intake
2. Poor uptake (celiac, phenytoin)
3. Inadequate use (blocked by methotrexate or TMP)
4. Increased requirement (pregnant)
5. Increased excretion (dialysis)
32
What are the diagnostic tests for Fe-deficiency anemia? What are the normal values? How are they interpreted?
* HgB low
* MCV low
* RDW high
* TIBC high
* Ferritin low
* Iron low
33
What are the current recommendations for febrile neutropenic cancer patients that you are considering sending home?
* Use the MASCC score to determine risk
* Give antibiotics within 1 hour
* Monitor for 4+ hours
* Rx: Fluoroquinolone + Amox-Clav (Clinda if PCN allergic)
* Return to ED if fever still on Day 3
34
Provide a DDX of Microcytic Anemias
**TAILS**
1. **T**halassemias
2. **A**nemia of chronic disease (late)
3. **I**ron deficiency
4. **L**ead toxicity
5. **S**ideroblastic anemia
35
How is priapism managed in a sickler? What is the name of the complication that can occur if you transfuse them?
* IV fluids
* IV analgesia
* Oxygen
* Dorsal penile ring block (27G at 10 and 2 o'clock)
* 19G inserted into corpus cavernosum --\> aspirate
* May need to inject saline and repeat
* May need phenylephrine
* Urology/Hematology consults
* Exchange transfusion is CONTRAINDICATED
**ASPEN syndrome**
* Association of Sickle cell, Priapism, Exchange transfusion and Neurologic events
36
List 6 causes of leukocytosis
1. Infection
2. Steroids
3. Surgery
4. Trauma
5. Burns
6. Epinephrine
7. Cancers/Lymphomas/Leukemias
8. Pregnancy
9. Ischaemia
37
List 8 causes of DIC
1. Shock
2. Sepsis
3. Hemolysis
4. Malignancy (Blood cancers, solid tumors)
5. Trauma (Multi-trauma, TBI, fat embolism syndrome)
6. Pancreatitis
7. Severe hepatic failure
8. Burns
9. Major surgery
10. PE
11. ECMO
12. Transplant rejection
13. Transfusion reactions
14. Obstetric (Pre-eclampsia, amniotic fluid embolism, intrauterine death, abruption
15. Vascular disorders
38
List 6 risk factors for acute tumour lysis syndrome
1. Dehydration
2. Kidney issues
3. Large tumour burden in the abdomen
4. Recent chemo
5. Elevated LDH at baseline
6. Acidic and concentrated urine
39
What are the diagnostic tests for hemolysis?
1. CBC
2. Peripheral smear
3. PT/INR
4. PTT
5. Fibrinogen
6. D-dimer
7. Haptoglobin
8. LDH
9. Bilirubin
10. Schistocytes (aka Helmet cells)
40
What 5 drugs are associated with hemolysis in G6PD deficiency?
1. Fava Beans
2. TMP-SMX
3. Sulfa
4. Nitrofurantoin
5. Quinine (malaria drugs)
6. ASA
7. Methylene blue
41
How does one diagnose tumour lysis syndrome?
**Cairo and Bishop Criteria**
2+ within 3-7d of chemotherapy:
1. Urate \> 475 mmol/L or 25% increase
2. Potassium \> 6 mEq/L or 25% increase
3. Phosphate \> 1.5 mmol/L or 25% increase
4. Calcium \< 1.75 mmol/L or 25% decrease
Clinical TLS = Lab and 1+ of:
1. Creatinine \>1.5x ULN
2. Cardiac arrhythmia or sudden death
3. Seizure
42
What is the Multinational Association for Supportive Care in Cancer (MASCC) risk index?
**Score for Febrile Neutropenia**
21+ points are considered low-risk (90% resolution in 5d)
* Age \<60 = +2
* Outpatient = +2
* Moderate symptom burden = +3
* No dehydration = +3
* No prior fungal infection = +4
* No COPD = +4
* sBP \>90 = +5
* Asymptomatic/Mild symptoms = +5
43
How do you treat tumour lysis syndrome?
* **Hydration**
* 2L NS bolus
* Infusions as high as 4-5L/day
* Improve GFR
* **Treat Hyperuricemia**
* ****Allopurinol
* Xanthine oxidase inhibitor
* Prevents conversion of nucleic acid to urate
* Dose: 600 – 900 mg/day
* Rasburicase
* Recombinant enzyme urate oxidase
* Converts uric acid --\> allantoin
* Rasburicase affects CURRENT urate
* **Correct electrolytes**
* HyperK treatment as necessary
* Consider hemodialysis
44
What are the diagnostic criteria for Polycythemia Vera?
**Need all of the following:**
1. Hgb \>185 (men), 165 (women)
2. Normal O2 sat \>92%
3. Splenomegaly
**Or two above and one of:**
1. Plt \>400
2. WBC \>12
3. Leuk Alk Phos score \>100
4. B12 \>900 pg/ml
45
Provide a DDx for macrocytic anemia
**FAT RBC**
* **F**etus (pregnancy)
* **A**lcohol
* **T**hyroid (hypo)
* **R**eticulocytosis (active severe hemolysis)
* **B**12 and folate deficiencies
* **C**irrhosis/chronic liver disease
46
What are the 5 indications for hemodialysis in patients with tumour lysis syndrome?
**3-6-600-900**
1. Phos \>3.2
2. K \>6
3. Urate \>590
4. Cr \>880
5. Can't tolerate volume
6. Symptomatic hypocalcemia
47
What are the common biochemical abnormalities seen in TLS?
1. Hyperuricemia
2. Hyperkalemia
3. Hyperphosphatemia
4. Hypocalcemia
5. Hypermagnesemia
48
Outline management of hypercalcemia in malignancy
**Serum Ca \< 3.5 mmol/L**
* Oral rehydration + ambulation
**Serum Ca \> 3.5 mmol/L**
* IV fluid
* Bisphosphonates
* Bind to hydroxyapatite in bone + inhibits dissolution of crystals
* Prevent osteoclast attachment to the bone matrix
* Interfere with osteoclast recruitment
* Dose: 90 mg (pamidronate) over 4 – 24 hours
* Achieves a normal Ca level in a mean of 4 days
* Salmon calcitonin (4 IU/kg)
49
What is DIC? What lab values will you see?
**DIC**
* Consumptive intravascular coagulopathy and thrombocytopenia
* Intravascular fibrin formation
* Microvascular thrombi and organ dysfunction (MAHA)
* Widespread hemorrhage
**Workup**
* Elevated PT/INR/PTT
* Elevated D-dimer
* Low fibrinogen
50
What are the common outpatient management strategies for Sickle Cell Disease?
**Hydroxyurea**
* Induces HbF
* Takes weeks to work
**Bone marrow transplant**
* Only current cure for sickle cell
* Disease-free rates 80-90%
**Hydration**
* D5 ½ NS at 150-200 cc/hr
**Oxygen: (2-4 LPM via NP)**
* Decreases EPO levels & the number of irreversibly sickled cells
**Analgesia**
* NSAIDs
* Opioids
**Blood transfusion**
* May be needed if aplastic or sequestration crisis
* Exchange transfusion for CVA
51
What are 3 admission criteria for non-emergent anemia?
1. Hgb \<80
2. Cardiac Symptoms
3. Outpatient follow up not possible
52
List 5 causes of vitamin B12 deficiency
1. Diet
* Vegetarian, alcoholics
2. Inadequate absorption
* Gastrectomy, pernicious anemia, inflammatory ileum
3. Inadequate Use
* Enzyme deficiency
4. Increased requirement by metabolism
5. Increased Excretion
53
How do you reverse?
* Dabigatran
* Apixaban
* Rivaroxaban
* Warfarin
* Dabigatran: Idarucizumab 5g
* Apixaban: PCC 2000 IU
* Rivaroxaban: PCC 2000 IU
* Warfarin: PCC 2000 IU + Vitamin K 10 mg
54
What is the definition of febrile neutropenia?
**Fever**
* Single reading \>38.3
* \>38.0 for one hour
**Neutropenia**
* ANC \<0.5
* ANC \<1.0 but predicted to be \<0.5 soon
55
What are 6 injuries that are considered life/limb-threatening with respect to dosing Factor in bleeding hemophilia patients?
**Dose Factor VIII at 50 U/kg**
**Dose Factor IX 100 U/kg if \>15yo or 150 U/kg if \<15yo**
1. Head/Neck bleeds
2. Chest/Abdo/Pelvis/Spine bleeds
3. Iliopsoas muscle/hip
4. Massive vaginal bleed
5. Extremity muscle compartments
6. Fractures or Dislocations
7. Any deep laceration
8. Any uncontrolled bleeding
56
What are 4 injuries that are considered moderate/minor with respect to the dosing factor in bleeding hemophilia patients?
1. Nose
2. Mouth/Gums
3. Joint
4. Menorrhagia
5. Abrasions/Superficial lacerations
57
Define an 'acute chest syndrome' in a sickle cell patient. Name 5 treatment priorities.
**Definition**
Acute illness with infiltrate on CXR and one of:
* Fever
* Respiratory symptoms
* Hypoxia
* Chest pain
**Treatment**
1. Oxygen
2. IVF
3. Analgesia
4. Antibiotics (for CAP - incl. atypicals)
5. Exchange transfusion
6. DVTp
58
What are the current platelet transfusion thresholds?
* Non-immune thrombocytopenia = \<10
* Procedures not likely to bleed = \<20
* CVC, I&D
* Significant bleeding = \<50
* Major elective surgery = \<50
* Neuroaxial procedures (LP) = \<50
* Give dose before and check PLT first
* Neuroaxial surgery = \<100
* Intracranial bleed = \<100
* Life-threatening bleed = \<100
* ITP = only if life-threatening bleed
59
List 5 drugs associated with TTP
1. Acyclovir
2. Chemotherapy
3. Quinine
4. Quetiapine
5. Plavix
6. Tacrolimus
7. OCP
