Final Flashcards
1
Q
Where can you see neutrophilia
A
CML, leukemia, sickle cell
Secondary disosrders: infection, inflammation, smoking, stress, asplenia and medications (corticosteroids lithium and exogenous growth factors), CSF secreting tumors (bronchogenic carcinoma)
2
Q
How do neutrophils change with infection
A
Increase in marginated pool, decrease in circulating, increase in tissue
3
Q
How do neutrophils change with epi
A
Increased circulating pool, decreased marginated pool, decreased in tissue
4
Q
How do neutrophils change with steroids
A
Equal circulating and marginated pool
5
Q
How does leukocyte adhesion deficiency affect neutrophils
A
Increase in circulating pool, low marginated pool, low in tissues
6
Q
What are causes of acute vs chronic neutrophilia
A
Acute: physical stimuli, emotional stimuli, infection (localized or systemic, bacterial, mycotic, rickettsial, some viral), inflammation or necrosis (burns, trauma, gout, vasculitis), drugs
Chronic: heme disorders (chronic hemolysis, asplenia*, myeloproliferative disorders), endocrine disorders (thyroid storm, ACTH overproduction), drugs, malignancy (gastric or bronchogenic), inflammation and infection
7
Q
What is the workflow for evaluation of neutrophilia
A
Repeat counts; if persistent examine smear for leukocrythroblastosis -> if yes, BM exam for tumor, granulomas, CML; if no -> look for signs of fever or infection -> if no, serological for AID, peripheral blood for BCR-ABL and JAK2, potential drugs, smoking
8
Q
What are the causes of eosinophilia
A
Parasite infections (trichinella), allergic rhinitis, atopic dermatitis, urticaria, fungal allergy, asthma, meds (abx, NSAIDs, antipsychotics), bronchiectasis/cardiac failure
9
Q
What should basophilia always trigger evaluation for
A
CML and PV
10
Q
What drugs cause neutropenia
A
Cephalosporins, clindamycin, gentamicin, sulfonamides, tetracyclines, vancomycin, carbamazepine, mephenytoin, phenytoin, anti depressants (amitriptylene), H2 blockers (ranitidine), antimalarials, antithyroid, CV drugs (hydralazine, captopril, propranolol), diuretics (thiazides), antipsychotics (chlorpromazine), allopurinol
11
Q
What is the suggested workup for neutropenia
A
If fever and ANC <500 give abx; if new -> see if isolated or pancytopenia -> if isolated do BM exam, if pan measure B12; if BM exam reveals abnormal cytogenetics, myelodysplasic, if LGL by flow then LGL if normal then idiopathic; if not new see if FH -> check for ELANE mutation (cyclic neutropenia)
12
Q
What is lymphopenia
A
Lymphocyte count <1500
13
Q
What are the causes of lymphopenia
A
Congenital immunodeficiency diseases (SCID, CVID, ATM, wiskott-Aldrich), aplastic anemia, infections, iatrogenic (chemo, glucocorticoids)
14
Q
What is monocytopenia seen in
A
Hairy cell leukemia even in absence of hair cells on smear, do flow cytometry for markers (CD11c and CD103)
15
Q
What conditions have low hemoglobin but normal hematocrit
A
Thalassemia
16
Q
What is the definition of anemia
A
Hemoglobin <12 in females and <13 in males
17
Q
How do you calculate mea corpuscular hemoglobin and mean corpuscular hemoglobin concentration
A
MCH: hemoglobin/red cell count
MCHC: hemoglobin/hct
18
Q
What does increased reticulocyte count suggest in terms of anemia
A
Either blood loss or response to therapy; low reticulocyte count indicates iron deficiency or folate/b1 efficiency or low. EPO
19
Q
What are acanthocytes associated with
A
Liver disease
20
Q
What are echinocytes associated with
A
End stage renal dz
21
Q
What is the evaluation of someone with anemia
A
Look at reticulocyte count; if high and bleeding, due to blood loss, if high and no bleeding do a smear - if schistocytes (microangiopathy), spherocytes (hereditary spherocytosis or warm abs), sickle cell, bite cells (G6PD), target (thalassemia), inclusions (malaria); if reticulocyte count low do peripheral smear - if microcytic (iron def, thalassemia, sideroblastic), normocytic (aplasia, marrow infiltration, Renal dz, inflammation, chronic dz), if macrocytic (B12 def, folate def, Myelodysplasia, drug toxicity, alcohol)
22
Q
What is the treatment for aplastic anemia
A
Offer HSC transplant for <40; if not eligible, immunosuppressive therapy with antithymocyte globulin and cyclosporine
23
Q
What drugs can cause microcytic anemia
A
Alcohol, lead, chloramphenicol, isoniazid - via reducing heme synthesis
24
Q
What is pagophagia
A
Craving for ice seen with iron deficiency
25
Why is ferritin not useful in diagnosing inflammation related anemia
Ferritin is an acute phase reactant
26
Where is intramedullary hemolysis seen
Thalassemia
27
What is characteristic of methemoglobinuria
Contains ferric ions which causes pO2 values higher than expected in relation to percent oxygen saturation
28
What drugs should not be used in patients with G6PD deficiency
Dapsone, methylene blue, nitrofurantoin, phenylhydrazine, primaquine, sulfamethoxazole, sulfapyridine
29
What is nonmegaloblastic macrocytosis associated with
Liver disease
30
What does inflammation do to erythropoeisis
Decreases it; hepcidin increases which decreases iron
31
What do you treat babies who test positive for sickle cell with
5 years of prophylactic penicillin (or macrolide if allergy)
32
What are the risks assoc with sickle cell trait
Sudden death with extreme exercise
33
What is the anemia seen with sickle cell
Normocytic normochromic; increased reticulocyte count; if microcytic suggests sickle cell beta thalassemia or coninherited alpha thalassemia
34
What kind of murmur can be caused by anemia
Systolic
35
What are the effects of hydroxyurea
Increases HbF, lowers neutrophils, hydrates erythrocytes, macrocytosis, lower reticulocyte count
36
When should exchange transfusions be used in sickle cell
To manage acute complications; reduces iron overload (rather than transfusion)
37
What are ACE inhibitors used for in sickle cell
Prevent kidney dz by lowering intraglomerular pressure; also lowers protein excretion (used in patients with sickle cell and albuminuria even in abscence of HTN)
38
What vitamins supplement must be given to sickle cell patient
Folic acid
39
What drugs are linked to ITP
Quinidine, rifampin, TMP-SMX, phenytoin, gold
40
What screening is required for all patients with ITP
HIV
41
What is the treatment for ITP
Glucocorticoids and IV immune globulin
42
If there are schistocytes on a peripheral blood smear, can ITP be a diagnosis
No; will be TTP, DIC or HELLP; when measuring platelets make sure to exclude clumpin
43
What should be administered if patient has HIT
Direct thrombin inhibitors (lepirudin or argatroban)
44
What is the 4T score for diagnosis of HIT
-thrombocytopenia:2 points (platelet count fall >50%), 1 point (platelet count fall 30-50% or nadir 10k-19k)), 0 points (platelet fall <30% or nadir <10,000)
-timing of fall: onset btw 5-10 das 2 points, onset after 10 days 1 point, <4 days 0 points
-thrombosis: new thrombosis, skin necrosis 2 points, progressive or recurrent thrombosis, nonnecrotizing skin lesions 1 point, no thrombosis 0 points
-other causes for thrombocytopenia: none 2 points, possible 1 point, definite 0 points
Score 0-3: low probability, 4-5 intermediate, 6-8 high
45
Should you transfuse platelets in untreated TTP-HUS
No; associated with stroke and acute kidney injury
46
What is the treatment for essential thrombocythemia
If <60 with no hx of thromboembolic event, and platelet count <1 million follow without therapy; those not in this category treated with hydroxyurea and low dose aspirin (if need greater platelet reaction, give pegylated IFN-alpha or anagrelide)
47
What are causes of reactive thrombocytosis
Iron deficiency, inflammation, cancer, infection
48
What is the Ann Arbor staging system for lymphoma
- stage I: involvement of single LN region or single extranodal organ
- stage II: involvement of 2 or more LN regions or lymphatic structures on same side of diaphragm; or involvement of limited contiguous extranodal sites (IIE)
- STage III: involvement of LN regions or lymphoid structures on both sides of the diaphragm (if involves spleen IIIS)
- Stage IV: diffuse or disseminated involvement of one or more extranodal Organs with or without LN involvement
49
What should patients with HL receive before starting treatment
EKG and pulm function; women should receive fertility preservation counseling
50
What are prognostic risk factors for HL therapy
Increased ESR, male, >40, stage IV dz, bulky mediastinal LAD
51
What is the treatment for Hodgkin
ABVD
52
What is patient management after treatment of HL
For first 3 years, seen every 3-6 months; in 4th and 5th year every 6 months and annually thereafter
53
What should be included in follow up for HL survivors
CBC, thyroid function, annual infuenza shot if received bleomycin or chest radiation; breast cancer screening beginning 8-10 years post radiation or at age 40
54
What should all patients with NHL be tested for
HIV and hep C
55
What is the prognosis of 8;21 AML
Good in adults, poor in kids; RUNX1/AML1 gene
56
What is the abnormality seen in AMML
Inversion 16 or translocation 16;16; abnormal eosinophils with large and irregular basophilic granules and positivity for chloroacetate esterase; KIT mutation confers poor prognosis; RUNX1/CBFB
57
Where is translocations involving 11q seen
Acute monocytic leukemia ; poor prognosis unless have 9;11 mutation; involves KMTA/MLL
58
What are the most common mutations seen in AML
FLT3(most common in APL and AML with normal karyotype) - assoc with poor prognosis
NPM1 - favorable
CEBPA - favorable
59
What is the standard chemo induction for AML
3 days of daunorubicin or idarubicin, and 7 days of continuous infusion of cytarabine; can cause tumor lysis syndrome; if neutropenic fever, give abx, if persists, give antifungals
60
What is the definition of remission for AML
Normalized blood counts, <5% BM blasts, normalization of karytoype
61
what are the treatments for AML and ALL
- AML: induction = 3+7 anthracyclin and ara-c; consolidation: high dose ara-c (HDAC); maintenance: promyelocytic leukemia only - ATRA
- ALL: induction - vincristine/prednisone + others; consolidation: multiple agents plus CNS prophylaxis (MTX or ara-c), maintenance: 6MP and MTX
62
What is IKZF1 alterations seen in
ALL with Ph chrom; poor prognosis
63
What are the 2 groups of ALL with hyperdiploidy
A group with 1-4 extra chrom (47-50) and more commonly more than 50 chrom - more common in kids (X, 21, 10, 14, 17,18, 4, 6); gain of 5 and 17q is poor prognosis; 4 10 17 good prognosis
64
What is the 1;19 translocation seen in
Kids with B cell ALL; CD10, CD19, CD34-, CD9
65
What is 8;14 seen in besides burkitt
Mature B cell ALL: high incidence of CNS involvement or abndominal LN involvement
66
What is the follow up for CML
1-2 weeks during initiation of imatinib; once stable blood counts, every month
67
What is the Rai staging system for CLL
Stage 0 - asymptomatic with lymphocytosis
Stage I: lymphocytosis with LAD
Stage II: lymphocytosis, LAD and HSM
Stage III: anemia
Stage IV: thrombocytopenia ; last 2 have mean survival of <2 years
68
What is the Binet staging system for CLL
Based on # of LN sites involved
Stage A: fewer than 3 sites
Stage B:3 or more sites - survival of 7 years
Stage C: anemia or thrombocytopenia; survival < 2 years
69
What can complicate CLL
Prone to autoimmune disease development; autoimmune thrombocytopenia or hemolytic anemia
70
What are the markers for hairy cell
CD22, 25, 103; also express tartrate resistant acid phosphatase
71
What is the treatment for hairy cell leukemia
Splenectomy; cladribine and deoxycoformycin; chemo refractory responds to vemurafenib (BRAF inhibitor)
72
What drugs can cause myelodysplastic syndromes
```
Alkylating agents (busulfan, nitrosurea, procarbazine) - latency 5-7 years
Topoisomerase inhibitors: 2 year latency
```
73
What alterations are seen in myelodysplastic syndromes
Euploidy mostly; loss of 5,7, 20 or trisomy 8
74
What mutation is seen specifically in MDS (not AML)
SF3B1 (RNA splicing machinery) - favorable outcome
75
What causes diamond Blackfan anemia
5q deletion
76
What is the treatment for MDS
If asymptomatic, nothing; if anemic, transfusion, azacitidine(hypomethylating agent) can prolong survival and delay time of formation to leukemia - give to patients with poor prognosis and symptomatic
77
What is lenalidomide used for
Thalidomide derivative; reversing anemia in MDS with 5q deletion; side effect: mylosuppresion and increased risk of thrombosis
78
What treatment can be given for MDS in patients with HLA-DR15
ATG, cyclosporine and anti-CD52 mab (alemtuzumab)
79
What is primary myelofibrosis
Proliferation of dysplastic megakaryocytes that produce factors that stimulate collagen formation leading to BM fibrosis
80
What mutations are seen in primary myelofibrosis
JAK2, MPL (thrombopoietin receptor), CAL
81
What factors are overproduced in primary myelofibrosis
TGFeta, tissue inhibitors of metalloproteinases; osteoprotegrin (osteoclasts inhibitor)
82
What can the extramedullary hematopoeisis of primary myelofibrosis cause
Ascites, portal or intracranial HTN, intestinal or ureteral obstrution, pericardial tamponade, spinal cord compression, skin nodules
83
What is the treatment for primary myelofibrosis
No definitive therapy; danazol used for anemia; hydroxyurea to control splenomegaly; allopurinol to control hyperuricemia; IFN alpha in early dz; ruxolitinib imrpvoes sx and prolongs survival (JAK2 inhibitor)
84
What is significant about the pruritis seen with PCV
Worsens after a warm bath
85
What is the treatment for PCV
Phlebotomy weekly (want Hb <15);if >60 or prior thrombosis - give hydroxyurea; also manage stroke risk ie: tobacco cessation, management of lipids, and BP control
86
What is does the evaluation of MM begin with
Serum protein electrophoresis and urine protein electrophoresis on 24 hr urine sample
87
What is the most common CBC abnormality seen in MM
Normochromic anemia
88
Do you do bone scans for MM
No - use conventional radiography instead
89
What is used to determine prognosis of MM
Beta 2 microglobin level and serum lactate DH level
90
What are markers of poor prognosis of MM
Chrom 13 deletion, elevated B2, hypoalbuminemia and >50% plasma cells on BM aspirate
91
What is the staging for MM
Stage I: low B2 and normal albumin
| Stage III B2 >5.5 poor prognosis
92
When can you not give HSC transplant for people with MM
If progressive kidney dz, decompensated cirrhosis, and class III or IV heart failure
93
What is the initiation treatment for HSC as a treatment for MM
High dose dexamethasone and thalidomide *require prophylaxis treatment for DVT with spirit, low molecular weight heparin or warfarin
94
What should be given to prevent complications of MM
Pneumococcal and influenza vaccine, TMP SMX to prevent pneumocystis pneumonia; acyclovir if receiving bortezomib; bisphosphonates to all patients (pamidronate or zoledronate)but limited to 2 years
95
What do MM patients with back pain need
MRI to rule out spinal cord compression
96
What mutations are seen in WM
MYD88, CXCR4, ARID1A, CD79
97
What are the markers for WM
IgM, CD19, CD20 and CD22 positive; CD10 and CD23 neg
98
What is the presence of CXCR4 associated with
Higher BM dz burden and higher incidence of hyperviscosity
99
What is the treatment for WM
Plasmapharesis; ibrutinib in patients with sx - targets bruton tyrosine kinase; can also use rituximab, bendamustine, cyclophosphamide, or bortezomib
100
What is POEMS syndrome
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes
101
What is the diagnostic criteria for POEMS
All of the following must be met:
Polyneuropathy, monoclonal plasma cell proliferative disorder, any one off the following (sclerotic bone lesions, castelman’s dz, elevated VEGF), any one off the following (organomegaly -HSM or LAD, extravascular volume overload, endocrinopathy, skin Changes, papilldema, or thrombocytosis/polycythemia)
102
What is gamma heavy chain dz
Franklin dz; LAD, ever, anemia, malaise, HSM, and weakness, *palatal edema resulting from involvement of waldeyer’s ring; reacts with anti-IgG but not antilight chain; die of infection; usually rapid downhill course
103
What is alpha heavy chain dz
Seligmann dz; most common heavy chain dz; related to Mediterranean lymphoma (where intestinal parasites are common); infilatration of lymphocytes in lamia propria of small intestine; no hyperviscosity; no light chains; present with chronic diarrhea, weight loss, and malabsorption mesenteric and paraaortic LAD; IPSID assoc with campylobacter
104
What is mu heavy chain dz
Subset of CLL; presence of vacuoles in malignant lymphocytes; diagnosis required ultracentrifugation or gel filtration to confirm nonreactivity of paraprotein with light chain;; treated same as CLL
105
What is AA amyloid
Composed of acute phase reactant protein serum amyloid A - occurs chronic inflammation or infection (secondary amyloidosis)
106
What tissue should you test to confirm diagnosis of systemic amyloidosis
Abdominal fat
107
How does renal amyloidosis manifest
Proteinuria and hypoalbuminemia, secondary hypercholesterolemia, hypertriglyceridemia, edema, anasarca
108
What is the leading cause of death of amyloidosis
Cardiac failure
109
What is raccoon eye sign indicative of
AL amyloidosis
110
How do you treat AL amyloidosis
Dexamethasone, high dose melphalan followed by HSC transplant
111
How do you manage nephrotic syndrome caused by amyloidosis
Diuretics, supportive stockings, albumin
112
What meds are contraindicated in amyloidosis
Beta blockers digitalis and calcium channel blockers
113
What activates secondary Hemostasis
Tissue factor binding Factor VII
114
What can measure increased bleeding time as a result of liver dz
Levels of fibrinogen, fibrinogen degradation products and D dimmer
115
What can cause prolonged PT
Warfarin, factor VII deficiency, vitamin K def, liver dz
116
What can cause a prolonged PTT
Heparin; lupus anticoagulant, vWD, factor VIII, IX, XI, XII def
117
What can cause prolonged PT and PTT
Heparin, warfarin, DIC, liver dz, factor V or X, prothrombin, or fibrinogen def
118
What can cause increased thrombin time
Heparin, direct thrombin inhibitor, factor Xa inbhitor, fibrin degradation product
119
At what platelet level does spontaneous bleeding occur
<10k
120
What are the factor Xa inhibitors
Fondaparinux, rivaroxaban, apixaban
121
What are the direct thrombin inhibitors
Argatroban, lepirudin, dabigatran
122
What coagulapathies will cause an increase in PT/INR
Liver dz, vit K def DIC
123
What is a cause of acquired inhibitors of clotting factors
Phenytoin, sulfa drugs, penicillin, malignancy, autoimmune disorders; present with tissue hematomas but not hemarthrosis
124
What does IV vitamin K in crease the risk of
Anaphylaxis use FFP if need urgent correction
125
What do you manage INR in patients taking vitamin K antagonists
Withhold drug if <5; if >5 but <9 add oral vit K; if >9 use FFP or recombinant factor VII
126
What can you do to reverse direct thrombin inhibitors
Fluid and blood products if bleeding moderately; can use hemodialysis; severe bleeding use prothrombin complex concentrations or factor VII
127
How do you reverse factor Xa inhibitors
Bleeding - discontinue; hemodialysis does NOT work; give PCC or recombinant factor VII
128
What is the most common infection associated with DIC
Gram negative sepsis
129
What does factor V Leiden mutation cause
Protein C resistance (cant inactivate 5 and 8)
130
How is protein C deficiency inherited
AR; causes warfarin induced skin necrosis
131
How is protein S inherited
AD; cofactor to protein C so also leads to less protein C activity (increased fibrin)
132
What is the inheritance pattern of antithrombin deficiency
AD *suspect if clot does not respond to heparin
133
What factors does antithrombin decrease the production of
XII, XI, X, IX and II
134
What causes hyperhomocystinuria
Inherited mutation in MTHFR
135
What is the most common form of acquired thrombophilia
Antiphospholipid ab syndrome
136
What can cause acquired hyperhomocysteinemia
B6, B12, and folate deficiency
137
Should you screen children under 15 for thrombophilia if they are asymptomatic
No
138
What are the factors that suggest an increased risk for inherited thrombophilia
Thrombosis <50 years old, hx of recurrent thrombosis, first degree relatives with thrombosis, unusual site of thrombosis (mesenteric, splenic, portal, hepatic, cerebral, UE), thrombotic event during pregnancy or postpartum, thrombotic event while taking OCP, hx of recurrent pregnancy loss
139
What can artificially decrease protein C and S levels
Warfarin
140
When should yo discontinue anticoagulation in patients heterozygous for factor V Leiden or prothrombin G20210A mutation
3-6 months; extend therapy only if cancer, persistently elevated anticardiolipin abs, or antithrombin deficiency
141
Has vitamin B or folic acid helped with VTEs in hyperhomocystinemia
Nope
142
What are unna boots
Compressive dressings treated with agents to decrease edema and promote healing of ulcers caused by venous stasis
143
What is the Wells score
Prediction of DVT
144
What test should patients with low clinical likelihood of DVT undergo
D dimer (negative will rule out DVT); if D dimer is positive then do US Doppler
145
What is unique to lymphedema
Toe edema
146
How do you treat DVT
Unfractionated or low molecular weight heparin (outpatient); long term with warfarin - overlap with heparin for 5 days and until INR has reached therapeutic range (2-3) for 2 measurements taken 24 hrs apart *treamtent for min of 3 months
147
What is the only test that can exclude PE
Totally normal V/Q
148
Do V/Q scans use contrast
No
149
What is the Wells criteria for DVT
- active cancer: point
- bedridden >3 days or major surgery within 4 weeks:1 point
- calf swelling >3cm: 1 point
- collateral superficial veins:1 point
- entire leg swollen: point
- localized tenderness along deep venous system: 1 point
- pitting edema confined to sx leg: 1 point
- paralysis of LE: 1 point
- previous DVT: 1 point
- alternative diagnosis to DVT as likely or more likely: -2
150
What do scores from the Wells criteria indicate
0 or lower: d-dimer testing; negative means no DVT and no further testing; if positive -> US
- 1-2: moderate risk; do high sensitivity d-dimer; neg rules out DVT; positive -> US
- 3 or higher suggest DVT is likely
151
What lifestyle habit can cause neutrophilia
Smoking
152
When is pain in LN after drinking beer reported
Hodgkin
153
Radiation can cause all Leukemias except .....
CLL
154
What is sweet’s syndrome
Aka acute febrile neutrophilic dermatitis; cutaneous manifestation of AML; bx demonstrates myeloblasts in dermis; treatment is management of AML
155
Where is gingival hypertrophy seen
M4 and M5 variants of AML
156
What are the physiologic responses to anemia
Increased CO, shunting of blood to vital tissues, increased concentration of 2,3 DPG in RBCs (shifts to right - affinity for oxygen reduced)
157
How do you calculate MCHC
Hgb/Hct
158
What is the cutoff for microcytic, normocytic Nd mcrocytic anemia
Micro <2.5th percentile
| Macro >97.5 percentile
159
What is the cutoff for MCHC (hypo or hyper)
Hypo <32; hyper >35
160
What are the causes of anemia in the neonate
- blood loss
- Immune hemolytic anemia (pos direct Coombs, indirect bilirubin, normocytic anemia, elevated reticulocyte count)
- congenital hemolytic anemia: G6PD def(Heinz bodies and bite cells), pyruvate kinase def (spur cells)
- congenital infection: *parvovirus
- diamond Blackfan syndrome: macrocytic anemia with low reticulocyte count; congenital pure red cell aplasia (increased apoptosis of precursors)
- fanconi anemia: macrocytic, reticulocytopenia, thrombocytopenia, leukopenia; *most common form of inherited aplastic anemia; progresses to pancytopenia
161
What are the causes of anemia in infancy and toddlers
- iron deficiency anemia; target cells; microscopic loss in blood due to milk
- chronic infection: normocytic; low transferrin; Ferritin can be elevated
- blood loss
- disorder of Hb structure: thalassemia (low mentzer index - MCV/RBC count if >13 iron def <13 thalassemia, Hb, basophilic stippling); sickle cell
- RBC enzyme defects
- acquired hemolytic anemia
- transient eythroblastopenia of childhood
- *lead poisoning - microcytic hypochromic; basophilic stippling
162
What are the causes o anemia in late childhood and adolescence
- iron deficiency
| - chronic dz
163
What does normal reticulocyte count rule out
Fanconi, diamond Blackfan syndrome, congenital infections
164
What history would suggest transient erythroblastopenia of childhood
Recent viral infection
165
Where do you see Howell jolly bodies
Hereditary spherocytosis; AD
166
What are the most common types of pediatric cancers
0-14: leukemia
| 15-19: lymphoma
167
What are B sx
Fever >39, weight loss >10% body weight over 6 months, drenching night sweats
168
What should any patient with suspected HL undergo before LN biopsy
Chest radiography to rule out mediastinal mass
169
What can increase a child’s risk for NHL
SCID
Wiskott-Aldrich syndrome: X linked recessive; recurrent Sino pulm infections and ear infections, severe atopic dermatitis, bleeding secondary to thrombocytopenia
Ataxia telangiectasia
Bloom syndrome
170
What are the subtypes of NHL in kids
Burkitt, lymphoblastic, diffuse large B cell, anaplastic large cell
171
What does survival of pediatric NHL depend on
Pathological subtype, tumor burden (reflected by serum LDH), presence or absence of CNS dz and sites of met spread
172
What is the definition of LAD
LN that are abnormal in number, size or consistency
173
Where are common spots for LAD
Cervical, supraclavicular, axillary , inguinal
174
What is considered an enlarged LN
> 2cm
175
What does the quality of the LN tell you about your diagnosis
- tender, warm, red, fluctuant: lymphadenitis
- soft, mobile, smooth: benign
- firm and rubbery: lymphoma
- fixed and matted: malignancy or TB
176
When should you biopsy LN in a kid
If nodes never get better after watchful waiting, if after 4-6 weeks of abx nodes don’t improve, right away if supraclavicular nodes consistent with malignancy are palpated
177
How do you treat MRSA
Bactrim, clindamycin, vancomycin
178
How do you treat cat scratch dz
Azithromycin, TMP-SMX, rifampin, ciprofloxin
179
What are the manifestations of cat scratch dz
Visceral involvement, parinaud’s syndrome (conjunctivitis, preauricular adenitis, conjunctival granuloma), neuroretinits, encephalopathy, transverse myelitis, radiculitis, cerebellar ataxia
180
What tumors are seen in each area of the mediastinum
Anterior: thymoma, teratoma, lymphoma
Middle: LN from met or granuloma, pleuropericardial and bronchogenic cysts
Posterior: neurogenic tumors, meningocele, esophageal lesions, gastroenteric cyst
181
What do neuroblastomas produce
Catcholamines; check urine VMA and HVA
182
What is WAGR
Wilms tumor, Aniridia, genital anomalies, mental retardation
183
What is beckith wiedeman syndrome
Enlargement of body organs, macroglossia, hemi hypertrophy, ompalocole, WT2 mutation; increased risk of wilms tumor
184
How does wilms tumor present
Large ab mass, hematuria, pain in ab, intestinal obstrution, HTN, pulm met
185
How do you calculate ANC
%neutrophils + %bands x WBC / 100
186
What is the definition of neutropenia
ANC <1500; severe if <500
187
What is severe congenital neutropenia (kostmann syndrome)
Life threatening pyogenic infections; defect in myeloid dif; AR; ANC <200 since birth increased risk of AML ELA-2 mutation
188
What is cyclic neutropenia
Cyclic fever, oral ulcers, gingivitis, periodontal dz, recurrent bacterial infections; AD; ANC <200 for 3-7 days every 3 weeks; ELA-2 mutation; no increased risk for malignancy
189
What is schwachman-diamond syndrome
Triad: neutropenia, exocrine pancreases insufficiency, skeletal abnormalities; defects in neutrophil migration; AR; low serum trypsinogen, elevated fecal at, rib cage abnormalities, short stature, SBDS mutation increase risk for myelodysplastic syndrome or leukemia
190
What is fanconi anemia
Bone marrow failure syndrome; GU and skeletal abnormalities, increased chromosome fragility; neutropenia
191
What is leukocyte adhesion deficiency
Delayed separation of umbilical cord (>3 weeks); recurrent bacterial and fungal infections without pus; poor wound healing, periodontal dz; AR
192
What is hyper-IgE or job syndrome
Severe eczema, bacterial infections of skin and lung; defect in chemotaxis, eosinophilia
193
What is chronic granulomatous dz
Recurrent purulent infections with fungal or bacterial catalase positive organisms; cant generate superoxide; diagnosed with nitroblue tetrazolium test; X linked
194
What viruses cause neutropenia
HIV, parvovirus, EBV, CMV, influenza
195
What is the most common cause of neutropenia in infancy and childhood
Primary autoimmune neutropenia
196
What platelet count would impair primary Hemostasis
<75 k
197
What platelet count would lead to spontaneous bleeding
<50k
198
What platelet count can cause significant bleeding
<20k
199
What platelet count could cause life threatening hemorrhage
<10k
200
What are the most common causes of fetal and neonatal thrombocytopenia
Alloimmune, congenital infection, aneuploidy, autoimmune, placental insufficiency, perinatal asphyxia, DIC
201
What are the destructive thrombocytopenias
- primary platelet consumption syndromes: idiopathic thrombocytopenia purpura
- immunologic: HUS
- nonimmunologic: TTP
- combined platelet and fibrinogen consumption syndromes: DIC, Kassabach-Merritt
- specific to neonate: HELLP
202
What are the impaired or ineffective production of platelet causes of thrombocytopenia in kids
- congenital and hereditary disorders: TAR syndrome, fanconi aplastic anemia
- primary hematologic processes: Wiskott-Aldrich syndrome
- acquired: marrow infiltrative process, nutritional deficiency
203
What would you think of for a child with petechiae, thrombocytopenia but otherwise normal CBC
Meds, portal HTN, early aplastic process like fanconi anemia; kids would be sick with increased platelet destruction
204
What should you think of in a kid with eczema, recurrent infections and small platelets
Wiskott aldrich
205
What is the most common cause of isolated thrombocytopenia in otherwise well children
Acute ITP
206
Do we treat acute ITP
Not usually; but can with IVIG, prednisone or anti-D immunoglobulin in RH-
207
What is kasabach Merritt syndrome
Thrombocytopenia and hypofibrinogenemia secondary to hemangiomas and intravascular coagulation
208
What are the lab finings in typical ITP
Normal WBC, normal reticulocyte count, normal RBC, negative Coombs
209
What are the proteins involved in HIV
- 2 positive ssRNA held tougher by P7
- enclosed by capsid P24
- RNA genome consists of 9 genes: gag, pol, env most important in making structural proteins for new virus particles
210
What does the HIV capsid contain
Reverse transcriptase, integrate, protease
211
How can HIV cause autoimmunity
Result of disordered cell immune function or B lymphocyte dysfunction; ie thrombocytopenia
212
What are examples of allergic hypersensitivity reactions seen in AIDS
Eosinophilic pustular folliculitis (itchy red bump syndrome), increased hypersensitivity reaction to meds - fever and sunburn like rash with TMP-SMX
213
What infections are seen at a CD4 count >500
Bacterial, TB, herpes simplex, herpes zoster, vagina candidiasis, hairy leukoplakia, kaposi
214
What infections are seen at a CD4 count <200
Pneumocystosis, toxoplasmosis, cryptococcus, coccidiodes, cryptosporidosis, miliary TB, kaposi
215
What infections are seen at a CD4 count <50
MAC, histoplasmosis, CMV retinitis, CNS lymphoma
216
What do you see at CD4 <100
Cryptococcal, esophageal candidiasis, toxoplasmosis
217
What is the testing for HIV
Immunoassay for HIV ab with test for p24 Ag; no western blot; positive result of HIV ab followed with testing of sample with HIV ab differentiation which confirms diagnosis BUT IF NEGATIVE, test with NAAT - if positive, then HIV, if neg initial test was false positive
218
How often are CD4 counts measured
Every 3-6 months; if drops <200 start pneumocystis prophylactic therapy; if <100 MAC prophylaxis
219
What tests the level of viral replication
HIV viral load
220
How do you diagnosis pneumocystis
Chest XR; diffuse or perihilar infiltrates; don’t usually have pleural effusions (more bacterial, TB or kaposi); definitive diagnosis with wright-giemsa stain or fluorescence ab; bronchoalveolar lavage - if negative sputum but suspect pneumocystis
221
What lab findings are consistent with pneumocystis pneumonia
Elevated LDH, serum beta glucan (more sensitive and specific), *if see normal diffusing capacity of CO or no interstitial lung dz, pneumocystis unlikely*, pneumothoraces (cystic appearing areas)
222
What is the most common cause of pulm dz in HIV patients
Community acquired pneumonia
223
What will you se on CT in toxoplasmosis
Subcortical lesions with predilection for basal ganglia
224
What is the test for cryptococcal meningitis
Latex agglutination test of serum that detects CRAG
225
What is a normal PT time
10-13; assesses extrinsic; factors II, V, VII, X and fibrinogen; *prolonged in warfarin or dicoumarol
226
What is a normal PTT
25-40; tests factors VIII, IX, XI, XII prolonged in patients on heparin
227
How do you treat vWD
Cryoprecipitate; DDAVP
228
What can cause defects in platelet function
Uremia: impaired platelet adhesion
Dsproteinemias: interference with membrane function
Autoimmune
229
What is prolonged with vit k deficiency
PT
230
What is the defect in hereditary hemorrhagic telangiectasia
Endoglin; epistaxis most common symptom
231
What is the clinical presentation of antithrombin III def
Variable from min sx to death from recurrrent PE;recurrent DVT, leg ulcers, etc; treat with prophylaxis anticoagulant and high doses of heparin if have DVT; replacement of anti thrombin III available if dont respond to heparin
232
What does protein C do
Inactivate factor V and VIII
233
How do you treat protein C and S def
Warfarin ***but most common cause of hypercoagulble state from def of these proteins is initiation of warfarin - depleted. Earlier than th other factors resulting in increase coagulation
234
What is the treatment for factor V Leiden
If no prior episodes, monitor, DVT prophylaxis and risk reduction
Prior episodes life long anticoagulation
235
What are associated features of antiphospholipd ab syndrome
Connective tissue dz; prolonged PTT that fails to correct with mixing studies
236
How do you diagnose antiphospholipid ab syndrome
Prolonged PTT not corrected with mixing studies, neutralization of inhibitor with excess phospholipid; *dilute Russell viper venom time (DRVVT) may be more specific
237
What is the treatment for antiphospholipid ab syndrome
No benefit if no hx of thromboembolic dz; with a hx, lifelong anticoauglation BUT NEED multiple positive tests over a 3-12month period; during pregnancy treat with SC heparin; hydroxychloroquine can help with APS and SLE
238
What do you do for pseudothrombocytopenia
Repeat CBC in heparin or citrate tube
239
What drugs can cause thrombocytopenia
Loop diuretics, H2 blockers, digoxin and abx
240
What is liskers sign
Pain with percussion of anteriomedial tibia
241
What is lowenergs sign
BP cuff applied to mid calf; pain when inflated to 80
242
What drugs can cause hypercoagulability
Tamoxifen, bevacizumab, thalidomide and lenalidomide
243
What conditions can affect d dimer levels
DVT/PE, stroke, age, malignancy, pregnancy, recent surgery, DIC, cocaine, connective tissue dz, hemodialysis
244
What is the management of acute DVT or PE
Anticoagulate for 3 months then reassess
245
How do you anticoagulate cancer patients
Low molecular weight heparin. (Enoxaparin)
246
What are the cytogenic of myelodysplasias
Partial or total loss of chrom 5 or 7; inv 16, trisomy 8
247
What lab abnormalities can you see with mylodysplasias
Elevated LDH, sometimes iron overload (increased serum ferritin, serum iron and TIBC normal)
248
Which myelodysplastic syndrome has the lowest risk of conversion to AML
Refractory anemia with rings sideroblastic
249
What is the treatment for B6 def
Replace for 6 months then repeat marrow; if no improvement patient has pyridoxine resistant sideroblastic anemia
250
What are adverse prognostic features of myelodysplasias
Marrow blasts >5%, platelets <100,000, Hb <10, neutrophils <2500, age >60, *monosomy 7, hypodiploidy, multiple abnormalities
*5q deletion is favorable and responds to lenalidomide
251
How do you treat iron overload in patients with myelodysplasias
Desferrioxamine or deferasirox
252
At what EPO level should you not administer EPO
If serum EPO >500
253
What can androgens be used to treat
Myelodysplasias
254
Are corticosteroids used to treat myelodysplasias
NO
255
What is low/intermediate therapy for myelodysplasias
Hypomethylating agents: azacitidine, decitabine
| Lenalidomide: angiogenesis inhibitor for 5q deletion only
256
What is high intensity therapy for myelodysplasias
AML induction style treatment
| HSC transplant: if <60
257
What will you see with myelofibrosis
Massive splenomegaly **Triad = leukoerythroblastic anemia, poikilocytosis and splenomegaly
258
What is the most common cause of death in myelofibrosis
Overwhelming infection
259
What can ruxolitinib be used to treat
Myelofibrosis; JAK inhibitor
260
What are the labs of polycythemia Vera
Increased RBC, nucleated RBCs, elevated LAP, increased WBC or platelet counts
261
What is the cause of death in polycythemia Vera
Progressive fibrosis - spent phase
262
What could be on your differentials for polycythemia Vera
Hemoconcentration, pulm dz (smokers erythrocytosis), EPO producing tumors (RCC, neuroendocrine), hemoglobinopathy, living at high altitude (low FiO2)
263
What is the definition of neutropenic fever
Temp >101.4 with ANC,500
264
What agents cause neutropenic fever
Indwelling venous catheters - staph aureus and epidermidis, klebsilla
Fungal: candida, aspergillus, pneumocystis and toxoplasma
265
What should you NOT do if a patient has neutropenic fever
No rectal exams
266
What is the primary prophylaxis of neutropenic fever
-if <500 for >7 days; levofloxacin and ciprofloxacin; fluconazole (but no activity against aspergillus) so use echinocandins (caspofungin, micafungin, anidulafungin) but only IV
267
What is secondary prophylaxis for neutropenic fever
Prevents RECURRENT infection; for patients with hx of prior fungal infection; voriconazole first line for aspergillus but cant give with cytarabine or fludarabine - severe neurotoxicity with vincristine so give 1 week prior to chemo and then start after chemo again; if continued during chemo amphotericin B or echinocandins can be used
268
What is empiric therapy for neutropenic fever
When suspected neutropenic fever is occuring; IV abx given until ANC >1000 then switch to oral abx only if patient is afebrile and tolerating meals without emesis
*IV: piperacillin + tazobactam, carbapnm, ceftazidime, cefepime
269
How do you adjust empiric abx based on specific data
If have cellulitis or pneumonia - vanc or linezolid
Gram neg: add aminoglycoside
Ab sx or suspected c diff: metronidazole
270
What are the outpatient oral regimes for empiric treatment for neutropenic fever
Ciprofloxacin + amoxicillin/clavulanic acid
Empiric antifungal should be added if persistent or recurrent fever does not resolve after 5 days - give caspofungin
271
What is low risk post op patient
<40 no risk factors; minor surgery
272
What are the intermediate risk factors
Non ambulatory, active infection, active malignancy, non orthopedic surgery, history of VTE, stroke, CVC or PICC, IBD, prior immobilization pre op, obesity, age >50, OCP, hypercoagulability, nephrotic syndrome, burns, cellulitis, varicose veins, paresis, systolic heart failure ,COPD
273
What agents can be used for post op antioagulation
LMWH (enoxaparin), fondaparinux, DOACs, warfarin
274
When do you use LMWH
Most critical care patients, many surgical patients (4 weeks in ab/pelvic cancer surgery), orthopedic patients (twice daily 10 day min), bariatric surgery (twice daily)
275
When do we use fondaparinux
Orthopedic patients (10 day min)
276
When do we use rivaroxaban or apixaban (DOAC)
Orthopedic patients s/p THA o TKA for 12 days (knee) and 35 days for hip
277
When do we use dabigatran (DOAC) direct thrombin inhibitor
Cleared by kidney so use for THA only if CrCl >30 ml/min.
278
When do we use warfarin
Goal: INR 2.5; administer to orthopedics patients for 10 days; if high risk and THA, TKA or hip fracture, up to 1 month
