Exam 2 Flashcards
1
Q
Prothrombin Time (PT)
A
Assesses the extrinsic system. Normal: 10-13 sec.
Prolonged in deficiencies of Factors II, V, IVV, X, fibrinogen, patients taking warfarin or dicoumarol
2
Q
Partial Thromboplastin Time (PTT)
A
Assesses the intrinsic system. Normal 25-40 sec.
Prolonged in deficiencies of Factors VIII, IX, XI, XII, patients on heparin
3
Q
Thrombin Time (TT)
A
Assesses for deficiency or abnormalities in fibrinogen
4
Q
Platelet Aggregation Studies
A
Assist in diagnosis of vWF disease, storage pool disease, Bernard-Soulier syndrome
5
Q
What is the most likely cause of petechiae and thrombocytopenia?
A
Medications
6
Q
DIC
A
Med/surg/obstetrical complication. Initial thrombosis as intrinsic/extrinsic coagulation systems activated. Depletion of platelets and clotting factors leads to bleeding
7
Q
Treatment of DIC
A
Treat the underlying disorder! Supportive care
Heparin only with overt thrombosis
8
Q
TTP
A
Generalized disorder of microcirculation; TTP, microangiopathic hemolytic anemia, fluctuating neurological signs, renal dysfunction, and febrility
9
Q
HUS
A
MAHA + Thrombocytopenia (<50K) + fever + neurologic symptoms + RENAL FAILURE
10
Q
Signs/Symptoms of TTP
A
Microangiopathic anemia - shistocytes, helmet cells
Pathologic lesion - hyaline thrombi occluding capillaries
11
Q
2 major forms of TTP
A
- Hereditary - ADAMTS13 gene mutation
2. Acquired - autoAbs directed at ADAMTS13
12
Q
Treatment of TTP
A
Treat underlying disorder.
Plasmapharesis is life saving in almost all cases
13
Q
von Willebrand disease
A
Spectrum of diseases with decreased platelet adhesion to vascular endothelium (mediated by vWF).
Decreased/absent production of vWF
14
Q
Results of platelet aggregation tests in von Willebrand Disease
A
Abnormal - espeically to ristocetin
15
Q
Treatment for von Willebrand disease
A
DDAVP (desmopressin) - type I, release of vWF from endothelium
Cryoprecipitate - type 2 and 3, replaces vWF
16
Q
Glanzmann’s thrombasthenia
A
Inherited (AR) qualitative platelet disorder
Absence of platelet Gp IIb/IIIa receptor
17
Q
Bernard-Soulier syndrome
A
Inherited (AR) qualitative platelet disorder
Absence of platelet Gp Ib-IX-V receptor
18
Q
Result of platelet aggregation studies for Glanzmann’s thrombasthenia
A
Restocetin is present, but all other aggregation studies are absent
19
Q
Result of platelet aggregation studies for Bernard-Soulier syndrome
A
Restocetin is ABSENT, all other aggregation studies normal
20
Q
Platelet Storage Pool Disorder (SPD)
A
Autosomal dominant qualitative platelet disorder
Mild bleeding
21
Q
Hermansky-Pudlak syndrome
A
Inherited disorder of granule formation
22
Q
Treatment of severe platelet dysfunction
A
Platelet transfusion
23
Q
Reasons for acquired disorders of platelet function
A
Medications, uremia, cardiopulm bypass, myelodysplastic or myeloproliferative syndromes
24
Q
Hemophilia A
A
X-linked recessive trait, deficiency of Factor VIII
Risk of bleeding corresponds to degree of deficiency
Mild, Moderate, or Severe
25
Clinical features of Hemophilia A
Easy bleeding/bruising, hematomas, frequent hemarthroses
26
Hemophilia B
Decreased serum Factor IX
| Similar inheritance, course, clinical features as A
27
Deficiency of vitamin K-dependent factors
Features: bleeding/hemorrhage, prolonged PT, deficiency of factors II, VII, IX, X, Proteins C and S
28
Hereditary Hemorrhagic Telangiectasia AKA
| Osler-Weber-Rend syndrome
AD inheritance, gene defect in endoglin (c9)
Caused by thinning of vessel walls with telangiectatic formations, AV malformations, and aneurysmal dilations throughout the body
29
Clinical features of Hereditary Hemorrhagic Telangiectasia
Benign clinical course, recurrent bleeds frequent
30
Treatment of Hereditary Hemorrhagic Telangiectasia
Surgery and laser photoablation
31
Anti-Thrombin III Deficiency (AT-III)
Clinical: recurrent LE thrombophlebitis and DVT, venous insufficiency, chronic leg ulcers
Significantly increased DVT risk in pregnancy
32
How do you diagnose AT-III Deficiency
Diminished levels of AT-III in serum (<50% activity)
33
Treatment of AT-III Deficiency
Prophylactic tx with anticoagulants, patients with DVT should receive heparin
34
Deficiency of Protein C and S
Protein C-inactivates factors V and VIII
| Protein S-cofactor for protein C
35
Treatment of Protein C and S
Warfarin
36
Factor V Leiden mutation
Abnormality of factor V at binding site for activated protein C
37
Treatment of Factor V Leiden mutation and Prothrombin 20210
No prior episodes: monitor; DVT prophylaxis
| Prior episodes: consider lifelong anticoagulation
38
Prothrombin 20210
G-A mutation resulting in increased activity for prothrombin and inability to deactivate prothrombin
HIGH risk throbosis
39
Antiphospholipid Syndrome
Circulating antibodies to phospholipid
| Associated with: anticardiolipin antibody syndrome, lupus anticoagulant, false positive VDRL Ab syndrome
40
Features of Antiphospholipid syndrome
Thromboembolic phenomena, miscarriage, thrombocytopenia, cerebral ischemia and recurrent stroke, UBO
CT disease, prolonged PTT that fails to correct with mixing studies, valvular heart disease, CAD
41
Diagnosis of Antiphospholipid syndrome
1. Prolonged PTT
2. Lack of correction in mixing studies
3. Neutralization of inhibitor with excess phospholipid
42
Test specific for lupus anticoagulant
DRVVT
43
Treatment of Antiphospholipid syndrome
No benefit of tx if no hx thromboembolic dz
Hx of dz: lifelong anticoagulation
Hydroxychloroquine-thromboembolism reduction in patients with APS, SLE
44
How to exclude pseudothrombocytopenia
Repeat CBC with heparin or citrate tube
45
Erythromelalgia
Vasomotor changes that occur in patients with essential thrombocythemia, may be accompanied by burning pain
Treatment: daily baby ASA
46
Common drug causes of lowered platelet count?
Loop diuretics, H2 blockers, digoxin, Abx
47
Acute ITP
ISOLATED thrombocytopenia in absence of underlying causes - children otherwise appear well
Peak incidence 2-5 yrs
48
Difference between Acute and Chronic ITP
```
Acute = up to 6 months
Chronic = greater than 6 months
```
49
Treatment of Acute ITP?
Generally - no tx alters natural history of dz
| Some treat - prednisone, IVIG, anti-D Ig
50
Red Flags in Peds and what do they mean?
Red flags: constitutional sx, hx disease with low platelets, dietary hx suggestive of deficiency, exposure to meds assoc with low platelets, PE findings other than bleeding
These red flags r/o ITP
51
Chronic ITP
Sx last longer than 6 mos; generally benign and mostly otherwise well
Does not require aggresive drug tx
Platelet counts 30-80K
Can attend school and participate EXCEPT CONTACT SPORTS
52
Treatment of chronic ITP
Only cure is splenectomy, but this is approached cautiously
53
Myelodysplastic syndrome
Disorder of pluripotential stem cell leading to ineffective hematopoiesis
54
Clinical features of myelodysplastic syndromes
Pancytopenia with hyperplastic marrow, potential risk for development of acute leukemia
55
Etiology of myelodysplastic syndromes
Radiation, petrochemical exposure, chemotherapy
56
Cytogenetic markers of myelodysplastic syndromes
Partial loss of long arm chromosome 5 or 7
Inv(16)
Trisomy 8
57
Laboratory abnormalities in myelodysplasia
Elevated LDH, serum ferritin
| Normal serum Fe, TIBC
58
Most common causes of pancytopenia
Hypersplenism, aplastic anemia, myelodysplasia
59
Prognosis and adverse prognostic features in myelodysplasias
Poor prognosis
Features: more than 5% marrow blasts, platelet count lower than 100k, Hb lower than 10g/dl, neutrophils lower than 25k, age greater than 60 yrs
60
Favorable prognostic feature in myelodysplasias
5q syndrome - beneficial response to lenalidomide
61
Treatment of myelodysplasia
Supportive - avoid medications that damage marrow, aggressive treatment of infection, transfuse PRBCs if symptomatic, transfuse platelets for bleeding or surgery propylaxis, monitor for iron overload
EPO, androgens
62
Low/Intermediate intensity therapy
Hypomethylating agets, lenalidomide for 5q syndrome
63
High intensity therapy
AML induction treatment, stem cell transplantation
64
Myelofibrosis
Primary myeloproliferative d/o characterized by marrow fibrosis and extramedullary hematopoiesis
65
Triad of symptoms in myelofibrosis
Leukoerythroblastic anemia, poikilocytosis, splenomegaly
66
Disease course of myelofibrosis
Chronic but progressive, patient may be asymptomatic for years; progressive pancytopenia and organomegaly indicate development to later stage of disease
67
Treatment for myelofibrosis
Observation if patient asymptomatic
Otherwise, treat with BMT
Splenomgaly?
Allogenic stem cell transplant the only cure
68
Neutropenic fever
Temp above 38.5 C (101.4 F) with ANC <500
69
Most common pathogens associated with neutropenic fever
Bacteria: S. aureus, S. epidermis, Klebsiella
Fungi: CANDIDA, Aspergillus, Pneumocystis, Toxo
70
What should you NOT do in a pt with severe neutropenia/neutropenic fever?
Rectal exam/genitourinary exams
71
Primary Prophylaxis for pts at risk for neutropenic fever
Antibacterial: Fluoroquinolones (floxacins) to target P. aeruginosa and gram - bacilli
Antifungal: Fluconazole (candida) or echinocandins (-fungins) for more broad coverage
72
Secondary Prophylaxis for pts with history of fungal infection or high infection risk
Voriconazole: 1st line for Aspergillus
73
Adverse effects of Fluoroquinolones
Prolonged QT interval, tendon rupture, increased risk C. diff infection
74
Contraindications with Voriconazole?
DON'T GIVE with: cytarabine, fludarabine, vincristine
75
Inpatient Empiric IV Antibiotics
Piperacillin + tazobactam
Carbapenem
Ceftazidime
Cefepime
76
Empiric IV antibiotic for cellulitis or pneumonia
Vancomycin or linezolid
77
Empiric IV antibiotic for gram negative bacteremia
Add aminoglycoside (ex: gentamicin)
78
Empiric IV antibiotic for C. difficile
Metronidazole
79
Empiric antifungal and when do you add it?
Caspofungin; add if fever does not resolve after 5 days of abx tx
80
Non-antibiotic/anti-fungal considerations for neutropenic fever
Adequate hydration
| G-CSF (Filgrastim)
81
Most common cancer in adolescents?
Lymphoma
82
Most common malignancy of age group 15-19?
Hodgkin's lymphoma
83
What cells are pathognomic for Hodgkin's lymphoma?
Reed-Sternberg cells
84
What are the B symptoms?
| Why are they significant?
Sx: unexplained fever, weight loss more than 10% body weight over 6 months, drenching night sweats
Importance: Staging HL
85
1st diagnostic test for patient with persistent unexplained LAD without obvious underlying infection process?
CXR! THEN - LN biopsy
86
Which neoplasm responsible for 60% lymphomas in children/adolescents?
Non-Hodgkin's lymphoma
87
Name the syndrome - X-linked recessive d/o with recurrent sinopulmonary and ear infections, severe atopic dermatitis, and bleeding d/t thrombocytopenia
Wiscott-Aldrich syndrome
88
Burkitt Lymphoma
Sporadic type - abdominal mass, Endemic - head/neck
| + Involvment of bone marrow or CNS
89
Factors that affect prognosis of Non-Hodgkin's lymphoma
Localized disease: 90-100% survival
Advanced disease: 60-95% survival
Depends on pathologic subtype, tumor burden at dx (serum LDH), CNS disease, metastasis
90
Neoplasm that constitutes 97% of all childhood leukemias
Acute leukemia
91
Chromosomal abnormality that is highly associated with ALL and AML (at less than 3 y/o)
Trisomy 21
92
Which way does the O2 dissociation curve shift in anemia?
RIGHT
93
MCV
Mean Corpuscular Volume. Mean value of individual RBC volume in sample; measured by automated blood counters
94
MCHC
Mean Corpuscular Hgb Concentration. Index = Hgb/Hct
| Grams of Hgb per 100 mL RBCs
95
MCH
Average content (mass, weight) of Hgb per RBC
96
RDW
Red cell Distribution Width; quantitative measure of variability of RBC sizes in sample (anisocytosis)
97
Specific features of intravascular hemolysis
Hemoglobinuria, hemoglobiemia, hemosiderinuria
98
Specific features of extravascular hemolysis
SPLENOMEGALY, anemia, jaundice
99
Specific feature in sequestration
BLEEDING
100
What is the meaning of a low-normal reticulocyte count?
Inadequate bone marrow response to anemia
101
Main causes of MICROCYTIC anemia?
Iron deficiency, Lead intoxication, thalassemias
102
Physiologic nadir of hemoglobin in infants?
At 2-3 months of age. Hgb=9-11, Hct=28-35%
103
Isoimmunization
Neonatal cause of anemia d/t ABO or Rh incompatibility
104
Test results associated with isoimmunization
+ Direct Coomb's, increased indirect bilirubin, normocytic anemia, increased reticulocyte count
105
Heinz bodies and Bite cells are seen with what deficiency?
G6PD Deficiency
106
Most likely viral cause of neonatal anemia?
PARVOVIRUS
107
Diamond-Blackfan syndrome
CONGENITAL PURE RED CELL APLASIA-congenital macrocytic anemia with decreased reticulocytes; d/t apoptosis of erythroid precursors
108
Fanconi Anemia
Macrocytic anemia, leads to PANCYTOPENIA
109
Primary cause of iron deficiency anemia in toddlers?
Inadequate dietary intake - heavy milk drinkers
110
Disorder of Hgb structure/synthesis
Causes microcytic anemia, decreased RDW; LOW MENTZER INDEX IN THALASSEMIA
111
Lead poisoning risk factors
Young age, houses built before 1970s, contaminated soil, pica
112
Features of anemia associated with lead poisoning
Microcytic anemia, peripheral smear may show basophilic stippling
113
Calculate Absolute Neutrophil Count (ANC)
((% neutrophils + % bands) x (WBC)/100)
114
ANC in Neutropenia? Define mild, moderate, and severe neutropenia in terms of ANC
Neutropenia: ANC < 1500
Mild: ANC is 1000-1500
Moderate: ANC is 500-1000
Severe: ANC is less than 500
115
Severe Congenital Neutropenia (Kostmann Syndrome)
Autosomal recessive, d/t impaired myeloid differentiation caused by mutational arrest of neutrophil precursors
Life-threatening pyogenic infx in infancy
Increased risk of AML
116
Cyclic Neutropenia
Autosomal dominant, defect in stem cell regulation leads to defective maturation
Cyclic fever, oral ulcers, gingivitis, periodontal disease, recurrent bacterial infx, NO increased risk of malignancy
117
Schwann-Diamond Syndrome
Autosomal recessive, Neutropenia + defects in neutrophil mobility, migration, chemotaxis
Triad: 1. Neutropenia, 2. Exocrine pancreas insufficiency, 3. Skeletal abnormalities
Increased risk for myelodysplastic syndrome/leukemia
118
Fanconi Anemia
"Classic" congenital neutropenic disorder
Bone marrow failure, GU+skeletal abnormalities, increased chromosome fragility, autosomal recessive
Presents 1-10 yrs of age
119
Leukocyte Adhesion Deficiency
Very rare, autosomal recessive disorder
Delayed separation of umbilical cord (>3 wks), recurrent and severe bacterial/fungal infx w/o pus
Neutrophils have diminished adhesion to surfaces
120
Chronic Granulomatous Disease
X-linked recessive, 1:250000
Recurrent purulent infx w/ fungal or bacterial catalase + organisms, usually starts in infancy, granulomas
Defective oxidative metabolism, no generation of superoxide - good prognosis
121
Infection Associated Neutropenia
Viral cause w/in 2-3 days of illness to 1 week after
| MOST common: Parvovirus B19 - Fifth's disease with "slapped cheek appearance" after 1-2 weeks
122
Acquired Neutrophil Disorders
Due to cytotoxic agents (chemo), Vit B12 deficiency
123
Causes of leukocytosis
Reactive due to infection
Chronic inflammation (autoimmune disorders)
Oncologic process
Seizure
124
Most common trisomy associated with defective maturation or proliferation of myeloid cells
TRISOMY 21 - DOWN SYNDROME
125
Acute vs. Chronic Leukemia in terms of cell types
Acute: proliferation of immature blast cells
Chronic: proliferation of mature appearing cells
126
Toxins and drugs associated with development of leukemia (specify type)
1. Benzene - AML
2. Chemotherapy (alkylators) - treatment related AML
3. Radiation - all leukemias EXCEPT CLL
4. Viruses - HTLV-1 in T cell lymphoma
5. Hereditary disease
6. Myelodysplastic syndromes
127
Most common diseases associated with pancytopenia and macrocytosis?
Myelodysplastic syndrome or early AML
128
Most common chromosomal aberration (pathognomonic) in CML
Philadelphia chromosome t(9;22) = BCR-ABL fusion gene
129
Compare clinical presentation of acute vs. chronic leukemia
Acute: rapid onset and course
Chronic: slow onset, chronic course
130
Most common symptom/complaint of patients with acute leukemias (esp ALL)
Bone pain
131
Sweet's Syndrome
Acute Febrile Neutrophilic Dermatosis (AFND)
| Cutaneous manifestation of AML (myeloblasts in dermis)
132
Auer rods
Purple rods seen in cytoplasm of patients with AML (most commonly APL)
133
Oral manifestation in M4 and M5 variants of AML?
Gingival hypertrophy
134
In what setting are smudge cells seen?
CLL (multiple are seen)
135
Describe findings of affected lymph nodes in a lymphoma
Rubbery, non-tender
136
Associated with pain in lymph nodes after beer drinking?
Hodgkin's lymphoma
137
Richter's syndrome
Patients with pre-existing CLL develop DLBCL
138
B symptoms
Fever, drenching night sweats, 10% weight loss in previous 6 months - Paraneoplastic, worse px
139
Top DDx for patients with cervical LAD
Infection, lymphoma, unusual disorders (Kikuchi)
140
What kind of patients at high risk for primary CNS lymphoma?
IMMUNOSUPPRESSED (HIV, organ transplant, etc)
141
Major cause of neutrophilia and neutropenia?
Drugs
142
Major causes of neutropenia in patients?
Medications, Nutritional deficiences, Sequestration
143
Waldenstrom's Macroglobulinemia
Malignancy of lymphoplasmacytoid cells secreting IgM.
Major clinical manifestation: HYPERVISCOSITY
MYD88 mutation, slightly more common in older men
May develop peripheral neuropathy, visual disturbance
Kappa light chain excretion.
Rouleau formation and + Coombs test
144
Treatment of Waldenstroms Macroglobulinemia
Plasmapheresis
| Bortezomib, bendamustine, Rituximab
145
POEMS syndrome
Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes
Hepatomegaly, LAD
Circulating pro-inflammatory cytokines
146
Treatment of POEMS syndrome
Radiotherapy
147
Gamma Heavy Chain Disease (Franklin's Dz)
LAD, fever, anemia, HSM, weakness, palatal edema
Association with autoimmune diseases
Diagnosis based on anomalous serum M component
Thrombocytopenia, eosinophilia, non-dx bone marrow
Therapy when symptomatic = chemo, rituximab
148
Alpha Heavy Chain Disease (Seligmann's Dz)
Most common of heavy chain diseases
CHRONIC DIARRHEA, wieght loss, malabsorption
LAD of mesenteric and paraaortic nodes
Antibiotics or chemotherapy if unresponsive
149
Mu Heavy Chain Disease
Very rare, occurs with CLL
Vacuoles in malignant lymphocytes and excretion of kappa light chains in the urine
Treat as you would treat CLL
150
Plasma cell dyscrasias
Clonal proliferation of IG-secreting plasma cells
151
Hallmark feature of plasma cell dyscrasias
Isolated peak in the gamma region on serum protein electrophoresis representing a SINGLE complete immunoglobulin molecule (M-protein)
152
Likely diagnosis with A:G ratio <1
Plasma cell disorder (MGUS, myeloma, etc)
153
Multiple Myeloma features
Triad: marrow plasmacytosis >10%, lytic bone lesions, serum or urine M component
Hypercalcemia, hypogammaglobulinemia
154
Treatment of multiple myeloma
Thalidomide (-imib) + Dexamethasone
| Biphosphonates to control hypercalcemia
155
Treatment of Waldenstrom's Macroglobulinemia
Pentastatin, 2CDA
