Heme key points Flashcards
Complete
1
Q
Tx for aplastic anemia, and what percent of patients will get disease control with this treatment?
A
Cyclosporine and antithymocyte globulin; 70%
2
Q
Allogenic HSCT is potentially curative for aplastic anemia. Which patients can you consider it in?
A
Younger than 50 w/ compatible donors
3
Q
Efficacy of hematopoietic GFs in aplastic anemia?
A
Ineffective
4
Q
Dx of pure red cell aplasia?
A
Bone marrow exam- also helps r/o secondary causes
5
Q
Tx of idiopathic pure red cell aplasia (2 general options)
A
Prednisone monotherapy
Prednisone + either cyclosporine or cyclophosphamide
6
Q
How long does it take to see improvement once you start treating idiopathic red cell aplasia with immunosuppression?
A
1-3 months
7
Q
Dx and Tx of drug-induced neutropenia?
A
Dx: history, timing, and exclusion of other causes
Tx: removal of the offending med
8
Q
Dx and prognostication of MDS?
A
BM Bx and aspiration w/ cytogenetic studies
9
Q
What subset of MDS can get away with no Tx at all or infrequent transfusions?
A
Those with low-risk MDS
10
Q
2 options for Dx of CML?
A
Detect the (9;22) translocation in peripheral blood with either:
- RT-PCR
- FISH
11
Q
What class of drug is used as initial and subsequent therapy for CML?
A
TKIs targeting BCR-ABL
12
Q
What CV ADE is common to all TKIs, and how should you monitor for it?
A
Prolongation of the QT interval; periodic EKG monitoring
13
Q
4 components of evaluation of erythrocytosis?
A
- Pulse ox
- Peripheral smear
- Measurement of serum epo
- Eval for JAK2 mutation
14
Q
2 components of initial therapy for most patients with P. vera?
A
Low-dose ASA + phlebotomy
15
Q
Which two subgroups of patients with P. vera can treated with hydroxyurea + phlebotomy?
A
- Those older than 60
2. Higher risk of thromboembolism
16
Q
Tx of essential thrombocythemia in patients with low risk of thromboembolic Cpx?
A
Obs
17
Q
Tx of essential thrombocythemia in patients with high risk of thromboembolic Cpx?
A
Platelet-lowering therapy
18
Q
Tx for primary myelofibrosis is primarily palliative except in younger patients, who can get what treatment?
A
Allo HSCT
19
Q
What drug has a dramatic lytic effect on peripheral and tissue Eos in hypereosinophilic syndrome but is problematic for long-term use?
A
Steroids
20
Q
Tx of steroid-refractory primary hypereosinophilic syndrome w/ activating mutations of PDGF receptors alpha or beta?
A
Imatinib- leads to durable and dramatic responses
21
Q
What is the defining clinical clue to APL?
A
DIC
22
Q
Defining mutation of APL?
A
t(15;17)
23
Q
What drug leads to prompt resolution of the DIC a/w APL?
A
ATRA
24
Q
What’s an alternate to chemo used to consolidate remission in otherwise healthy patients with high-risk ALL?
A
Allo HSCT
25
What drug can be added in treatment of Ph chr + ALL?
Dasatinib
26
3 indications for G-CSF?
1. Stimulate nphil production in autoimmune neutropenia
2. HSC mobilization
3. Hasten nphil recovery s/p cytotoxic chemo
27
3 main indications for epo?
1. Anemia of CKD is iron, B12, and folate levels are okay
2. Hasten recovery in non-curative chemo-assoc anemia
3. Reduction of transfusion requirements in MDS
28
3 clinical scenarios where allo HSCT is most helpful?
1. Aplastic anemia
2. High-risk MDS
3. Acute leukemias
29
Basic pathophys of acute GVHD?
Graft T cells recognize pt's normal guy, skin, and liver sinusoids as foreign
30
Tx of acute GVHD?
High-dose steroids
31
2 main indications for serum and urine protein electrophoresis for plasma cell dyscrasias?
Suspected:
1. Symptomatic PCD requiring intervention
2. ASx PCD at high risk of progression to a clinically symptomatic condition
32
What test can detect monoclonal free light chains before they're detectable by uPEP?
Serum free light chain assay
33
What's the most sensitive test for detecting monoclonal free light chain gammopathies?
Serum free light chain assay
34
A combo of what 3 tests will detect almost all plasma cell dyscrasias?
1. sPEP
2. Serum immunofixation
3. Serum free light chain assay
35
Definition of MGUS? (3 components)
1. M protein level less than 3 g/dL (or less than 500 mg/24 hr of urinary monoclonal free light chains)
2. Clonal plasma cells comprising less than 10% of the bone marrow cellularity
3. Absence of plasma cell dyscrasia-related signs or symptoms
36
Definition of smoldering multiple myeloma? (3 components?
1. No evidence of myeloma-related signs or symptoms requiring therapy
Plus either:
-Serum M protein level of 3 g/dL or greater (or more than 500 mg/24 hr of urinary monoclonal free light chains)
-Clonal plasma cells comprising 10% or more of the bone marrow cellularity
37
Define symptomatic multiple myeloma. (3 components)
1. Presence of serum M protein
2. Bone marrow plasma clonal cells of 10% or greater
3. End-organ damage (CRAB)
38
Management of smoldering multiple myeoma? Give freq of checkups and 4 labs to be done at each.
q3-6 mo. Get CBC, creatinine, serum Ca, repeat M protein
39
Tx of choice for smoldering multiple myeloma at low risk of progression?
Expectant Mx w/ monitoring q3-6 mo
40
What treatment for eligible multiple myeloma patients is a/w improved PFS and sometimes OS?
Auto HSCT w/ high-dose mephalan after initial induction therapy
41
3 components of Dx of AL amyloidosis?
1. Presence of amyloid deposits in the tissue Bx sample (from abd fat pad, marrow, or organ Bx)
2. Proof that amyloid deposits are monoclonal free light chains
3. Confirmation to clonal plasma cell disorder
42
Efficacy of auto HSCT in AL amlyoidosis
In select patients, it's shown
- high hematologic response rates
- improved organ fxn
- durable PFS and OS
43
What percent of patients with Waldenstroms have Sx of hyperviscosity?
31%
44
Symptomatic hyperviscosity is a medical emergency, requiring what Tx?
Plasmapheresis
45
7 Sx of hyperviscosity (as seen in Waldenstroms, etc)
1. HA
2. Blurred vision
3. Hearing loss
4. Tinnitus
5. Dizziness
6. AMS
7. Nasal and oropharyngeal bleeding
46
What are 3 hyperviscosity-related findings you may see on fundoscopic exam of a Waldenstroms patient?
1. Dilated retinal veins
2. Papilledema
3. Flame hemorrhages
47
MC disease a/w mixed cryoglobulinemia?
Hep C
48
Management of type 1 cryoglobulinemia with hyperviscosity?
Plasmapheresis + treatment of the underlying disorder
49
Tx of mixed cryoglobulinemia?
Treatment of the underlying disease. Add immunosuppressive therapy for pts w/ more severe manifestations of vasculitis
50
How can you use retic count to Ddx btwn rbc underproduction vs destruction in determining cause of anemia?
Retic count is low in underproduction and high in destruction
51
Hematopathologic hallmark of iron deficiency anemia?
Microcytic hypochromic anemia
52
In iron-deficiency anemia, what's the sequence of anemia, morphologic changes in the cells, and changes in the iron studies.
Changes in iron studies -> anemia -> morphologic cell changes
53
Describe transferrin sat and serum ferritin level in iron deficiency anemia
Transferrin sat: less than 15%
| Ferritin level: less than or equal to 12 ng/mL
54
What iron replacement is the cheapest option and also just as effective as any of the more expensive PO options?
Ferrous sulfate
55
Inflammatory anemia: describe MCV, serum iron level, and TIBC
Normocytic
Low serum iron
Low TIBC
56
Management of inflammatory anemia?
Treat the underlying disease
57
In CKD, underproduction anemia affects what percent of those with a GFR less than 25 to 30?
90%
58
Underproduction anemia in CKD is usually _____chromic and _____cytic with what sort of retic count?
Normochromic, normocytic with low retic
59
Use of epo levels in Dx of anemia of CKD?
Not helpful
60
How can you use MMA and homocysteine levels to Ddx btwn B12 and folate deficiency?
B12 deficiency: both are high
| Folate deficiency: MMA normal, homocysteine high
61
Initial therapy in most patients w/ B12 deficiency?
High-dose PO B12 supplementation of 1000-2000 micrograms/d. This is usually as effective as parenteral admin in most pts, even in those w/ intrinsic factor deficiency.
62
Tx of folate deficiency?
PO folate, 1-5 mg/d until complete hematologic recovery
63
Can you use PO folate to treat folate deficiency in malabsorption conditions?
Yup
64
What should you check for B12 deficiency before treating folate deficiency?
Large doses of folic acid can lead to improved hematopoiesis but won't fix the CNS/PNS injuries a/w B12 deficiency
65
Patients with chronic hemolytic anemia require what supplement?
Folic acid
66
4 vaccines that pts w/ chronic hemolytic anemia must get?
Pneumococcal, HIB, flu, meningococcal
67
Peripheral smear findings in acute hemolysis 2/2 G6PD deficiency (2)?
Bite cells, Heinz bodies
68
Describe the following findings in the thalassemias:
1. MCV
2. Special cells on smear
3. Erythrocyte count
4. Iron studies
1. Microcytic
2. Target cells
3. Elevated or normal
4. Normal
69
Electrophoresis findings in beta-thal?
Slightly increased A2 and fetal Hb
70
Electrophoresis findings in alpha-thal?
Normal, unless they have 3 deletions- then some HbH
71
3 common disease-altering strategies in congenital hemolytic anemias?
HSCT
Prophylactic transfusions
Hydroxyurea therapy
72
Describe 5 benefits of hydroxyurea therapy in sickle cell disease?
1. Decrease vaso-occlusive epidoes
2. Decrease acute chest syndrome
3. Decrease trasfusion requirements
4. Decrease hospitalization
5. Prolong OS
73
Sickle cell patients shouldn't get TFNs unless they're in one of these 2 situations?
Symptomatic anemia
| Signs of end-organ damage
74
3 physical findings in warm AIHA?
Pallor, jaundice, splenomegaly
75
6 lab findings in warm AIHA?
```
Increased retics
Elevated bili
Decreased/absent haptoglobin
Increased LDH
Positive antiglobulin (Coombs)
Spherocytes
```
76
Mainstay treatment for warm AIHA?
Steroids
77
Mainstay treatment for cold agglutinin disease?
Cold avoidance
78
3 causes of macroangiopathic hemolytic anemia
Heart valve disorders (esp mechanical heart valves)
Intracardiac tumors
Rupture of chordae tendineae
79
What causes march hemoglobinuria?
Repetitive trauma to the soles of feet or palms of hands, like with marching or running
80
4 infectious causes of hemolytic anemia
Plasmodium species
Babesia microti
C. perfringens
Bartonella bacilliformis
81
What's the most sensitive and cost-effective initial screening test for hemochromatosis?
Elevated transferrin sat
82
What 3 groups of patients should be screened for hereditary hemochromatosis?
Active liver disease
First degree relatives of pts w/ classic HFE-related hemochromatosis
Abnormal iron studies
83
What's the best way to prevent morbidity/mortality in hemochromatosis patients?
Prompt and aggressive phlebotomy treatments before end-organ complications occur
84
How do you treat patients with secondary iron overload w/ ongoing anemia?
Iron chelation
85
Describe clinical diagnosis of TTP
Presence of thrombocytopenia and microangiopathic hemolytic anemia in the absence of other causes of these findings, and may include neuro Sx, abdominal pain, renal disease, and fever.
86
How can you treat atypical HUS?
Infusions of eculizumab
87
Why shouldn't you use antiplatelet antibody testing recommended for immune-mediated thrombocytopenia?
It has such low sensitivity and specificity. In fact, no diagnostic test can ID immune-mediated thrombocytopenia.
88
When may pts w/ ITP require therapy (2)?
Platelet count
89
Diagnosis of HIT requires what two tests?
Serologic testing w/ ELISA
| Functional testing w/ serotonin-release assay
90
What should you expect in a pt w/ clinical bleeding but a normal platelet count, PT, and aPTT?
Qualitative platelet defect
91
Bleeding into muscles or joints in characteristic of what type of disorder?
Humoral clotting factors
92
Mucosal bleeding is characteristic of what type of disorder?
Primary hemostasis
93
4 features correlated with a higher likelihood of an underlying bleeding disorder in women being evaluated for menorrhagia
1. Nighttime "flooding"
2. Passing clots larger than a quarter
3. Duration longer than 8 days
4. Development of iron deficiency
94
Describe the aPTT, PT, and aPTT mixing study in hemophilia A and B
Long aPTT, normal PT, and aPTT mixing study will fully correct
95
What test is diagnostic of hemophilia A or B?
Measurement of baseline factor activity (8 for A, 9 for B)
96
Describe general Tx of hemophilia
Factor concentrates, given prophylactically or in response to bleeding
97
5 tests (and their results) in diagnosing vWD
1. vWf antigen and activity levels of 30% or less
2. Factor VIII levels normal or low
3. Platelet function analyzer-100: prolonged
4. PT normal
5. aPTT: normal or slightly prolonged
98
2 drugs you can use to treat menstrual or other minor bleeding or for surgical Ppx in vWd?
Estrogen-containing OCPs
| Desmopressin
99
Describe the following labs in coagulopathy of liver disease:
1. PT
2. aPTT
3. Fibrinogen levels
4. Fibrinogen function
5. Factor VIII levels
1. PT: long
2. aPTT: long
3. Fibrinogen levels: low
4. Fibrinogen function: possibly dysfunctional
5. Factor VIII levels: supranormal
100
Why can fibrinogen possibly be dysfunctional in coagulopathy of liver disease?
Abnormal glycosylation
101
Patients with coagulopathy of liver disease may be deficient in what vitamin, further exacerbating their coag probs?
Vitamin K- so replete if you suspect a deficiency
102
How do you treat significant bleeding in coagulopathy of liver disease (3)?
Cryoprecipitate, FFP, and platelets
103
Two components of treatment of acquired factor VIII inhibitor?
Treat bleeding episodes w/ recombinant activated factor VIII. Immunosuppression to eradicate the inhibitor.
104
Core focus of management of DIC?
Treatment of the underlying cause
105
You have a patient w/ a history of alloimmunization who now has repeat alloantibody screening that's negative. Can they get RBCs containing antigens to which they're alloimmunized? Why or why not?
Nope! Anamnestic responses can occur, resulting in delayed hemolytic transfusion reactions
106
Transfusion threshold for hemodynamically stable, hospitalized medical and post-surgical pts?
Less than 7-8
107
If you have to give Rh(D)-positive platelets to an Rh(D)-negative woman of childbearing potential, what should you do to decrease the risk of alloimmunization?
Coadminister anti-D immune globin
108
Definition of platelet transfusion refractoriness?
Increase in platelet count less than 10,000 when measured within 1 hr after transfusion
109
2 general causes of platelet transfusion refractoriness?
Alloimmunization vs non-immune factors
110
Name some non-immune factors that can cause platelet transfusion refractoriness (4)
Sepsis
Hypersplenism
DIC
Meds (including ampho B)
111
In pts w/ heme malignancies undergoing chemo or HSCT, what's your platelet transfusion threshold?
Less than 10,000
112
Efficacy of FFP in treatment of mild coagulopathies (INR 1.85 or less)?
Ineffective
113
What 4 factors does inactivated 4-factor prothrombin complex concentrate contain?
II, VII, IX, and X
114
Combo of what 2 things is used in treatment of major warfarin-associated bleeding?
Vitamin K + inactivated 4-factor prothrombin complex concentrate
115
8 s/s of acute hemolytic transfusion reaction?
```
Fever
Chills
Dyspnea
Red urine
Flank pain
Kidney injury
DIC
HypoTN/shock
```
116
3 components of therapy for acute hemolytic TFN reaction?
1. TFN discontinuation
2. IV hydration
3. Appropriate CV support
117
When do delayed hemolytic TFN reactions present, and what are the 3 main Sx?
2-10 days after TFN, p/w fever, jaundice, and worsening anemia
118
Are delayed hemolytic TFN reactions primarily intravascular or extravascular?
Extravascular
119
6 s/s a/w TFN-associated circulatory overload?
Dyspnea, hypoxia, tachycardia, HA, HTN, and findings of volume overload
120
When does TRALI occur and how does it present?
W/in 6 hr of TFN of rbcs, platelets or FFP. P/w acute lung injury that escalates quickly and includes dyspnea, hypoxia, fever, chills, and hypoTN.
121
2 primary interventions for all non-hemolytic transfusion reactions?
TFN discontinuation + supportive care
122
What type of transfusion reaction are patients with IgA deficiency at particularly high risk for?
Anaphylactic TFN rxn
123
3 components of Tx of transfusion anaphylactic rxn?
1. DC TFN
2. Exclude other transfusion rxns
3. Appropriate anaphylaxis Mx
124
2 components of Mx of allergic rxn during TFN?
1. DC TFN to r/o a more severe allergic rxn
| 2. Antihistamines
125
When does TFN-associated GVHD present?
Several days to one month after TFN
126
7 s/s of transfusion-associated GVHD?
1. Diffuse maculopapular rash
2. Jaundice
3. Abdominal pain
4. n/v
5. Diarrhea
6. Severe pancytopenia
7. Abnormal LFTs
127
Basis of Mx of a suspected TFN-associated bacterial infection?
Abx therapy w/ gram +/- coverage
128
3 advantages of erythrocyte exchange over rbc TFN in sickle cell disease?
1. Doesn't increase blood viscosity
2. Avoids iron overload
3. More effectively decreases the concentration of HbS
129
2 reasons EBM recommends against routine thrombophilia testing?
ID of inherited abnormalities doesn't:
- alter duration of recommended anticoagulation
- reliably predict the risk of recurrence
130
MC inherited thrombophilia?
Factor V Leiden
131
Testing for factor V leiden: screening and confirmatory tests?
Screen w/ activated protein C resistance assay
| Confirm w/ PCR testing for the factor V leiden
132
How does heterozygous prothrombin G20210A mutation change risk of initial VTE and recurrence of VTE?
Increases risk of initial VTE 3x, but no increased risk of recurrence
133
Do you routinely screen for cancer in all pts w/ unprovoked VTE?
Nope
134
How long should patients with anti-phospholipid antibody syndrome and Hx of unprovoked VTE undergo anticoagulation?
Indefinitely- there's a high rate of recurrent VTE
135
What 3 groups of contraceptive present the greatest risk of VTE?
4th gen estrogen-progesterone contraceptives, and contraceptive rings and patches
136
How do progestin-releasing IUDs change risk of VTE?
They don't
137
Name 3 strong RFs for arterial and venous thrombosis
Polycythemia vera, essential thrombocythemia, and myelofibrosis
138
VTE Ppx should be considered for every hospitalized patients based on risk assessment for what two things?
VTE and bleeding
139
A low probability Wells score plus what else rules out VTE?
Negative D dimer
140
General Tx of proximal DVT?
Anticoagulant therapy
141
2 components of Tx of PE w/ hypoTN?
Thrombolytic therapy + anticoagulation
142
Duration of anticoagulation for provoked VTE?
3 months
143
What is the only clear indication for an IVC filter?
Acute pelvic or proximal leg DVT who can't be anticoagulated bc of active bleeding or a very high risk of bleeding
144
Treatment of non-extensive superficial venous thrombophlebitis?
Symptomatic therapy w/ analgesics, anti-inflammatories, and warm or cold compresses
145
What percent of upper extremity DVTs are primary vs secondary?
20% primary, 80% secondary
146
80% of upper extremity DVTs are 2/2 one of which two causes?
Central venous catheters or cancer
147
MC RF for Budd-Chiari?
A myeloproliferative neoplasm (ex- polycythemia vera, ET, and primary myelofibrosis)
148
Duration of anticoagulation for acute portal or mesenteric vein thrombosis?
At least 3 mo
149
What are the two diagnostic tests of choice for cerebral and sinus vein thrombosis?
CT venography and MR venography
150
Duration of anticoagulation for cerebral and sinus vein thrombosis a/w a transient RF?
3-6 mo
151
Duration of anticoagulation for unexplained cerebral and sinus vein thrombosis in which no higher risk thrombophilia has been detected?
6-12 mo
152
Duration of anticoagulation for cerebral and sinus vein thrombosis a/w a higher risk thrombophilia?
Long term
153
Duration of anticoagulation for recurrent cerebral and sinus vein thrombosis?
Long term
154
What dosing strategy will allow you to achieve therapeutic aPTTs most quickly when selecting an unfractionated heparin dose?
Weight-based heparin dosing normograms
155
What agent reverses warfarin anticoagulation?
Protamine
156
What feature of LMWH allows weight-based dosing w/o lab monitoring?
Predictable pharmacokinetics
157
Which patients should only get LMWH with extreme caution or not at all?
Severe renal disease (CrCl less than 30)
158
Why can fondaparinux be dosed once daily? And why can is be given w/o lab monitoring?
It has a half-life of approx 17 hr.
| It doesn't bind significantly to plasma proteins
159
Describe admin of fondaparinux in patients with poor kidney function
Use w/ caution in CrCl of 30-50
| CI w/ CrCl less than 30
160
What else can you give a patient who is taking daily warfarin but has fluctuating INRs?
100-150 microg/d of vitamin K
161
Describe efficacy of 4 factor prothrombin complex concentrate vs 3 factor prothrombin complex concentrate in restoration of individual clotting factor activity.
4 factor can do it in close to 100% of pts. 3 factor must be supplemented w/ FFP or low dose of recombinant activated VIIa.
162
6 features common to apixaban, dabigatran, edoxaban, and riveroxaban?
1. Rapid onset of action
2. No need for routine monitoring
3. No dietary restrictions
4. Short half-lives
5. CI or dose adjustment needed in moderate to severe CKD
6. Lack of reversal agents
163
Pregnant women with Hb values below what should prompt a search for anemia other than gestational? Give value for 1st tri and different value for 2nd/3rd tri
Less than 11 in first tri, less than 10 in second and third tri
164
How does prophylactic transfusion (exchange or normal) affect number of pain crises and pregnancy-related M/M in pregnant sickle cell pts?
Reduces number of pain crises but doesn't affect M/M
165
What two lab abnormalities are a clue to something other than gestational thrombocytopenia?
Platelets less than 50k or schistocytes
166
In pregnant pts w/ ITP, you don't need to treat it unless platelets drop below what? How does this change in the final month?
Less than 30k
| Platelet count of 50k or greater is desired in the final month in case of CS
167
What's the most effective therapy for HELLP, preE, and acute fatty liver of pregnancy?
Emergent delivery of the fetus
168
Pregnancy is a/w how much of an increased risk of thromboembolism? When is the greatest risk of VTE?
5x increased risk. First 6 wk post-partum
169
Tx of choice for VTE in pregnancy?
Weight-based LMWH
170
Duration of anticoagulation therapy for VTE during pregnancy?
At least 6 wk postpartum for a therapy duration of at least 3 mo
