Benign Hematology Flashcards
1
Q
Time frame of delayed hemolytic transfusion reaction (DHTR)?
A
5-10 days
2
Q
What happens to reticulocytes in a DHTR? Is COOMBS positive or negative?
A
decreased, positive
3
Q
3 features of acute hyperhemolysis
A
- destruction of recipient and donor RBC
- low retics
- negative COOMBS
4
Q
Treatment for pure red cell aplasia from parvovirus?
A
supportive. may require IVIg. typically resolves in few days to weeks
5
Q
Parvovirus binds to _ antigen on RBC to cause RBC lysis.
A
P antigen
6
Q
RBC antigens features?
1. Kell
2. Duffy
3. Kidd
4. Rh
A
- determine ABO type and is MC target for autoimmune and alloimmune lysis
- Malarial Plasmodium receptor target
- on membrane of RBC and kidney; urea transporter
- serves as ammonium transporter
7
Q
MC cause of OM in sickle cell pts?
A
salmonella. (staph aureus in general pop)
8
Q
Why is meperidine CI in SCD?
A
causes seizures
9
Q
Asplenia vaccine recommendations?
A
- Neisseria meningitidis
- Strep pneumoniae
- Haemophilus infuenza
- seasonal flu and hep B
10
Q
Preferred iron formulation in pregnancy?
A
Iron sucrose (venofer) and sodium ferric gluconate (ferrlecit)
11
Q
What is methemoglobin (Hb M)?
A
Methemoglobin is a form of hemoglobin that has been oxidized, changing its heme iron configuration from the ferrous (Fe2+) to the ferric (Fe3+) state. Unlike normal hemoglobin, methemoglobin does not bind oxygen and as a result cannot deliver oxygen to the tissues.
12
Q
Normal arterial pO2 and cyanosis?
A
methemoglobinemia with Hb M >10%. when > 40% seizures, coma, death. treat with methylene blue and supplemental O2
13
Q
Gel type in electrophoresis that can distinguish between HbA2 vs HbC; HbS vs HbD; HbF vs HbA
A
Citric agar
14
Q
FDA approved pill for hemolytic anemia from pyruvate kinase def?
A
Mitapivat (pyrukynd)
15
Q
Phosphoglycerate kinase deficiency inheritance and gene affected?
A
X-linked recessive; PGK1 gene
16
Q
Spleen regresses after blood transfusion?
A
splenic sequestration crisis
17
Q
Voxelotor?
A
increases affinity of hb for oxygen, preventing polymerization and sickling of RBCs in SCD
18
Q
Crizanlizumab
A
Ab against P-selectin to prevent sickle cell crisis frequency
19
Q
SC disease specific presentation?
A
proliferative retinopathy; milder crisis
20
Q
Betibeglogene autotemcel (beti-cel)?
A
gene therapy for transfusion dependent b-thal transduced by lentiviral vector via HCST, 89% pts achieve transfusion independence
21
Q
Abnormal folding of which protein leads to Southeast Asia ovalocytosis (RBC appear as stomatocytic elliptocytosis)?
A
Band 3
22
Q
MC coombs pattern for warm AIHA? cold agglutinin disease?
A
warm IgG+, C3+
cold ag disease IgG-, C3+
23
Q
RBC antigen inplicated in cold agglutinin disease?
A
i Ag
24
Q
Tx for cold agglutinin disease with severe life-threatening hemolysis?
A
plasmapheresis or IVIG (both have transient effect)
25
Tx of primary cold agglutinin disease with anemia and/or symptoms?
BR (bendamustine rituximab)
26
Tx Cold Agglutinin Disease with anemia requiring transfusion and/or severe symptoms?
Sutimlimab (monoclonal Ab against C1)
27
coombs pattern for paroxysmal cold hemoglobinuria (PCH)? Tx of acute episode?
IgG-, C3+
supportive, avoid cold. can offer steroids if dont respond in 1-2 weeks. rarely offer cyclophosphamide, rituxan, and azathioprine if persistent hemolysis
28
Mutations in hereditary spherocytosis?
SPT (spectrin), ANK (ankyrin), and SLC (band 3)
29
Definitive test for diagnosis of hereditary spherocytosis? Tx?
Eosin-5-maleimide (EMA); folic acid, pRBC and splenectomy
30
Inheritance pattern for Hereditary Eliptocytosis
AD
31
McLeod neuroacanthocytosis syndrome?
lack of kell Antigen. X-linked
32
auto rec disorder that interferes with absorption of fat-soluble vitamins (A, D, E, K)?
abetalipoproteinemia (acanthocytes)
33
neonatal jaundice; chronic non-immune, non-spherocytic, hemolytic anemia; iron overload
pyruvate kinase def
34
lead poinsoning leads to deficiency in?
pyrimidine-5-nucleotidase
35
metformin can lead to decrease absorption of Vit _?
B12 -> megaloblastic changes in BM, pancytopenia
36
GCSF can lead to ARDS via what mechanism?
sequestration of granulocytes in the pulmonary circulation
37
Tx for acquired methemoglobinemia with G6PD def?
ascorbic acid (Vit C)
38
MC cause of pure red cell aplasia in children?
TEC (transient erythroblastopenia of childhood) -- healthy child suddenly develops anemia with low retics
39
Oral iron with fewer GI side effects?
Ferric maltol (non-salt formulation)
40
RBC with fish-mouth central pallor?
stomatocyte
41
Does cyanosis occur in carboxyhemoglobin or hemoglobin variant with high oxygen affinity?
NO
42
Osler-Weber Rendu syndrome (aka hereditary hemorrhagic telangiectasia HHT) has 4 main characteristics?
1. recurrent nosebleeds
2. multiple mucocutaneous telangiectasia
3. visceral involvement
4. first degree relative with HHT
43
Define mild, moderate and severe hemophilia A?
Mild: 5-50%
Mod: 1-5%, bleed after injury/surgery
Severe: <1% Factor VIII, spontaneous bleeding
44
Factor dosing in hemophilia A/B?
Factor 8: 1U/kg raises by 2%
Factor 9: 1U/kg raises by 1%
Goal during severe-life threatening bleed is 100% (Give 50U/kg of F8 or 100U/kg of F9).
Goal during joint bleed is 50% (Give 25U of F8 or 50U of F9)
Maintenance goal. Keep factor level >50%
45
Hemophilia A factor goal prior to surgery?
Goal for surgery is 80-100%, do not let drop below 50%.
46
Hemophilia A factor goal prior to surgery?
Goal for surgery is 60-80%
47
Ppx F8 dosing for hemophilia A?
20-30 U/kg three times per WEEK
goal > 1%
48
Benefits of emicizumab for Hemophilia A? MOA?
-SubQ
-weekly dosing
-no structural relationship to F8 therefore no inhibitor development
MOA: IgG4 Ab to F9a and F10, bridging these two factors and restoring the function of the mission activated FVIII.
*Cannot use in active bleeding
49
Tx for severe bleeding when high-titer factor VIII inhibitor (>5 bethesda units) is present?
activated PCC (prothrombin complex concentrate aka FEIBA) or recombinant human factor 7a, or recombinant porcine factor 8.
50
Most common coagulation factor deficiency in amyloid light-chain amyloidosis?
acquired factor X deficiency
51
Goal of VWF and F8 level at time of delivery and 3-5 days postpartum?
>50
52
how do you differentiate between primary fibrinolysis and DIC?
DIC has elevated D-dimer
53
Tx for hereditary factor X deficiency?
Coagadex (factor X plasma derived concentrate)
54
Triad of aortic stenosis, intestinal angiodysplasia, and TYPE IIA vWD? Tx?
Heyde's Syndrome. Valve replacement will resolve the anemia and vWD
55
What does FEIBA (factor eight inhibitor bypassing activity) contain?
prothrombin, factor 7, 9, 10
56
What does Kcentra (prothrombin complex concentrate PCC) contain?
Factor 2, 7, 9, 10 and protein C and S
57
Indication for rebinyn?
on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis with hemophilia B
58
Ideal prophylactic treatment for hemophilia A that has least chance of developing inhibitor?
emicizumab > plasma-derived factor VIII containing vWF > everything else
59
Humate P dose prior to tooth extraction?
20-40U single infusion, goal>50%
59
Substance in synthetic cannabinoids that causes severe bleeding? MOA?
brodifacoum, potent vit K antagonist. give high doses of vit K for months considering half-life is 20 days
59
Humate P dose prior to surgery
40-60U load followed by :
minor surgery: 20-40U every 12-48hours x1-5 d
major surgery: 20-40U every 8-24 hours x7-14 days
Goal > 50%
59
preferred treatment for type 1C, 2, and 3 VWD?
Humate-P (intermediate-purity factor VIII prep that contains vWF)
60
Humate P dose for spont or traumatic bleed?
25U daily for 2-4d for goal>50%
61
best rapid treatment for uremic platelet bleed?A
DDAVP
62
ABs to GP IIb/IIIa, prolonged PFA closure times, and absent platelet aggregation with ADP, collagen, adrenaline, and sodium arachidonate?
Acquired Glanzmann's thrombasthenia (this is an autoimmune disorder -- CONGENITAL Glanzmann's is a qualitative or quantitative defect of the platelet membrane GP IIb/IIIa, the adhesive receptors, fibrinoogen and vWF)
63
PT/PTT in factor 13 def?
normal
64
Tx goal for bleed associated with Factor 13 def?
>5%. can give FFP, Cryo or recombinant F13 or plasma-derived F13
65
Goal of Factor 5 level for treatment or ppx?
>20%
66
Tx warfarin skin necrosis?
d/c warfarin
give vit K, heparin gtt, and PCC/FFP
GIVE ALL THREE!
67
Characteristics of WVD Type 1?
Most common (75%)
Concordant reduction in VWF activity and Ag
All multimers present in decreased amounts
Ratio Act:Ag >0.7
68
Characteristics of WVD Type 1C?
concordant reduction in VWF activity and Ag due to rapid clearance from circulation
Tx impacted due to shorter half-life of VWF
69
Characteristics of WVD Type 2A?
Loss of PLT binding to VWF
reduction of HMW multimers
Act:Ag < 0.7
70
Characteristics of WVD Type 2B?
INCREASED PLT binding to VWF leading to accelerated clearance causing thrombocytopenia and decreased VWF
Act:Ag < 0.7
Autosomal dominant
Enhanced responsiveness to ristocetin
Do not give DDAVP as it will worsen thrombocytopenia. give VWF concentrate instead
71
Characteristics of platelet-type pseudo-VWD?
enhanced PLT binding by VWF with accelerated platelet clearance and thrombocytopenia, similar to type 2B, but the mutation lies in the platelet GP1b receptor rather than the VWF protein
Enhanced responsiveness to ristocetin
Treatment is PLT transfusion
72
Characteristics of WVD Type 2M?
reduced binding of PLT to GP1b (similar to type 2A) or collagen
distribution of multimers is NORMAL
Act:Ag <0.7 (different than type I)
73
Characteristics of WVD Type 2N?
reduced binding of VWF to factor VIII, leading to low F8
low F8 activity to VWF:Ag ratio
NORMAL VWF Activity (RCo) to VWF:Ag ratio (>0.7) unlike type 2A, 2B and 2M
similar presentation to Hemophilia A (F8 association) with joint and soft tissue bleeding
74
Characteristics of WVD Type 3?
absent levels of VWF. very low F8
severe bleeding
RARE
75
Compare and contraste VWD Type 2B with Platelet-type pseudo VWD?
both have Enhanced responsiveness to ristocetin
type 2B: LD-RIPA is enhanced with patient-derived PLASMA. treat with VWF concentrate
Platelet-type VWD: LD-RIPA enhanced with patient-derived PLATELETS. treat with PLT transfusion
76
PNH treatment that targets C5
Eculizumab
Ravulizumab
77
PNH treatment that targets C3
Pegcetacoplan
78
Which are the low risk thrombophilias that do not require AC during pregnancy if no personal or family hx of VTE?
Prot c or s def
Heterozygote for either F2 or F5L mutation
79
High risk thrombophilias in preg? Treatment?
ATIII def
Homozygote F2 or F5L
Compound heterozygote F2/F5L
Prot C def in combination with another hereditary defect
post-partum AC x6 wks if no family hx or personal hx of VTE
ppx AC during and after preg if personal OR family hx of VTE
80
What histopathological finding is needed to diagnose catastrophic APS?
small vessel occlusion in at least one organ
81
FDA approved indication for betrixaban? MOA?
ppx for hospitalized patients at risk for VTE
direct Factor Xa inhibitor
82
Defect in Glanzmann's disease? Aggregation study results?
integrin alpha IIb beta 3 (formerly GPIIb/IIIa)
robust aggregation to ristocetin (due to intact GP Ib/IX receptor) and nothing else
83
Aggregation studies in Bernard-Soulier disease?
aggregation to everything except ristocetin due to missing GP Iba/GP1bbeta/IX/V platelet receptor which binds vWF
84
Aggregation studies for storage pool disorders?
primary ADP - robust aggregation
secondary ADP - less aggregation
collagen - less aggregation
ristocetin - less aggregation
prolonged bleeding time
Deficiency in dense or alpha granules
85
PFA-100 results in prolonged collagen-epinephrine response but normal collagen-ADP response
aspirin exposure
86
PFA-100 results in prolonged collagen-epinephrine response AND prolonged collagen-ADP response
rule out anemia and thrombocytopenia first. then likely vWD
87
Oculocutaneous albinism, pulm fibrosis, colitis, and lack of second wave on ADP aggregometry?
Hermansky-Pudlak syndrome (lack of dense granules)
ATP:ADP ratio > 2 is also suggestive of a dense granular disorder
88
Platelet aggregation:
1. Aspirin?
2. P2Y12?
1. lack of arachodonic acid response
2. decrease response to collagen, epinephrine, and arachodonic acid; also lack of 2nd wave of ADP
89
Marker of alpha granules of platelets?
P-selectin (CD62p)
90
marker for dense granules of platelets?
CD63
91
Pneumonic to remember VWD Type 2 subtypes?
Type 2:
-A has Abnormal multimers
-B Binds platelets
-M has Multimers
-N has No 8 (decrease binding to factor 8)
92
VWF level goal for neuraxial anesthesia?
50-150%
use vwF concentrate
93
Differentiate between Platelet-type VWD vs Type 2B?
Gold standard is mutational analysis
Platelet-type has a mutation in GP1b
Type2B has mutation in A1 domain of VWF gene
Both have enhanced ristocetin induced platelet agglutination and both are autosomal dominant
94
HIT evaluation:
Do you need Serotonin Release Assay if:
1. high probability of HIT by 4T score and PF4 OD>1.5?
2. int probability of HIT by 4T score and PF4 OD>2?
3. PF4 OD between 0.6-1.5?
4. PF4 OD <0.6
1. No; HIT already confirmed
2. No; HIT already confirmed
3. yes
4. No; HIT already excluded
95
median PLT count in HIT?
60k
96
how do you monitor
1. argatroban
2. heparin
3. LMWH (if needed)
4. dabigatron
5. other DOACs
1. PTT; or ECT (ecarin clotting time)
2. PTT; or anti-Xa
3. anti-Xa
4. TT or ECT
5. anti-Xa
97
4 things to do for acute warfarin skin necrosis?
1. stop warfarin
2. start heparin
3. give vit K
4. give source of protein C (protein c concentrate or FFP)
98
Syndrome for hereditary TTP?
Upshaw-Schulman syndrome
Auto recessive
99
Increased expression of urokinase plasminogen activator?
Quebec Platelet disorder
100
treatment for Glanzmann thrombasthenia if refractory to platelets?
recombinant factor VIIa (NovoSeven)
101
What is spontaneous HIT and what are the most common scenarios?
HIT without prior exposure to heparin product
Seen following ortho surgery, following viral/bacterial infection, or associated with monoclonal gammopathy
102
Fostamatinib is a TKI against which kinase?
SYK (spleen tyrosine kin)
can be used in refractory ITP
103
Name the condition:
thrombocytopenia, myelofibrosis, elevated B12, reduction in alpha-granules?
Gray Platelet syndrome
Auto rec
mutation in NBEAL2 gene
Treat with platelet transfusion, DDAVP and splenectomy
104
How do you differentiate between a storage pool defect vs secretion defect in platelets?
Both will have similar aggregation studies hallmarked by an absence of secondary aggregation to ADP BUT storage pool defect will have ABNORMAL ELECTRON MICROSCOPY
105
Difference between platelet aggregometry of aspirin vs P2Y12 inh (clopidogrel)?
Aspirin will have ABSENT arachidonic acid signal
106
iron that requires test dose
InFeD (iron dextran)
107
Diagnosis for hereditary hemochromatosis?
If ferritin >200 (men) or >150 (women) AND if transferrin saturation >45%, then send MUTATION analysis for C282Y and H63D
C282Y/C282Y: confirmed Hereditary Hemochromatosis
C282Y/H63D: 60% have intermediate iron overload
C282Y/WT: no iron overload
H63D/H63D: no iron overload
108
Indications for iron chelation in patients with thalassemia who receive chronic transfusions
1. ferritin > 1000
2. MRI liver with iron concentration >3mg Fe/g dry weight
3. >10u pRBC per year
109
When do clinical symptoms begin for
1. hereditary hemochromatosis
2. juveniile hemochromatosis
1. later in life >40yo; Gene affected=HFE
2. <30yo. Gene affected=HJV/HAMP
110
1. Goal ferritin in patients with hemochromatosis treated with PHLEBOTOMY?
2. goal ferritin when treated with iron chelation?
1. weekly or bi-weekly phlebotomy for ferritin goal <100. hold if HCT <36%
2. <1000. hold if ferritin <500.
111
Who is more at risk of developing cardiomyopathy, endocrinopathies (DM), from chronic transfusion -- SCD or beta-thal patients?
beta-thal
112
treatment of a pregnant pt with hemochromatosis to prevent liver complications in the newborn?
IVIg
113
tx of erythropoietic protoporphyria (EPP)?
avoid sun
afamelanotide (can improve sunlight tolerance)
114
only hereditary hemochromatosis disorder that is autosomal dominant and has high hepcidin?
Ferroportin Disease (FPN1 mut)
115
Tx for asymptomatic hereditary hemochromatosis without organ damage but ferritin >500?
phlebotomy with goal ferritin of 50-100 -- however be cautious with offering to pts with anemia or heart failure --> offer iron chelator to these pts instead
116
Three iron chelators you should know:
Deferoxamine
Deferiprone
Deferasirox
1. Which iron chelator is PO?
2. which is SubQ or IV
3. which causes agranulocytosis
1. Deferiprone
Deferasirox
2. Deferoxamine
3. Deferiprone
117
Which is the rarest porphyria that is classified as ACUTE (neuro sx) and the only ACUTE porphyria to be inherited in an autosomal recessive manner?
d-ALA dehydratase porphyria
118
Acute hepatic porphyria treatment when abdominal pain refractory to hemin?
Givosiran
119
Whats in cryo?
fibrinogen
F8
F13
vWF
Fibronectin
120
How do you prepare maternal blood for transfusion in fetus?
wash RBCs (same as for patients with IgA deficiency or prior severe allergic reactions)
121
How do you confirm TRALI?
test the donor for anti-HLA. if confirmed, then that person should not be allowed to donate blood ever again.
122
DHTR occurs 1-28 days after transfusion. Pathophysiology?
pt previously sensitized to a donor RBC antigen and has a low level AB to it. Ag is typically minor (non-ABO) and most commonly Kidd or Rh. COOMBS POSITIVE and hemolysis labs positive.
123
what is post-transfusion purpura?
Delayed transfusion reaction to platelets, similar pathophysiology to DHTR but instead to HPA-1a antigen on platelet. Treat with IVIg or steroids, or in severe cases with PLEX.
124
PLEX is 1L treatment for:
TTP
SCD stroke or ACS
Guillain BS
Myasthenia gravis
Chronic inflammatory demyelinating polyneuropathy
125
oculocutaneous albinism, photosensitivity, bacterial infections and albinism. BMB shows giant inclusion bodies in the leukocyte precursor cells (i.e. large lysosome vesicles in PMNs)
Chediak Higashi syndrome (AR -- mut in CHS1/LYST gene)
126
Tests to diagnose Chronic Granulomatous Disease?
Nitroblue-tetrazolium (NBT) is negative (does not turn blue) in pts with CGD
BEST TEST IS: dihydrorhodamine 123 (DHR) - this is a neutrophil function test
127
Treatment for chronic granulomatous disease (CGD)?
bacterial and fungal ppx lifelong
IFN gamma to prevent infections
128
Tx and MOA for PNH?
Eculizumab or Ravulizumab
both are monoclonal AB against C5
If this fails, do allo transplant
129
Characteristics of PNH?
Dx via flow looking for decreased CD55 and CD59. Mut in PIG-A gene that encodes GPI anchor leading to absence of CD55/59 on cell surface which normally inhibit complement, thus cells are susceptible to complement mediated hemolysis (negative coombs)
DVT is weird locations (PVT, MVT etc)
130
cafe au lait spots, developmental delays, kidney problems, short stature, abnormal thumbs, and bone marrow aplasia?
Fanconi anemia. They have increased risk of solid cancers. Diagnosis with testing for chromosome breakage in lymphocytes.
allo transplant only cure
131
medications that cause agranulocytosis?
clozapine
phenytoin (anti seizure meds)
antithyroid meds
antimalarials (quinine, hydroxychloroquine)
NSAIDS
MTX
PCN
ticlopidine
132
Define aplastic anemia
pancytopenia with hypocellular marrow and without abnormal infiltrate or marrow fibrosis
Severe disease defined as ANC <500 and PLT< 20, OR ANC<200 alone, then should go straight to HLA-matched sibling donor if <40yo. Can use horse ATG+cyclosporine +/- promacta as bridge.
133
What are primary bone marrow conditions that cause pancytopenia with a cellular marrow?
leukemias
MF
metastatic tumors
134
two rows of teeth?
hyperimmunoglobulin E, recurrent infection syndrome (HIES)
elevated serum IgE, eosinophilia, mut in STAT3
135
-Auto Dom
-RPS19 gene defect
-Onset of macrocytic anemia <1yo
-elevated erythrocyte adenosine deaminase
-low retics
-paucity of erythroid precursors on BM
-increase risk of MDS/AML, colon cancer, genital cancer, sarcomas
-congenital abnormalities of head, neck, genitals, thumbs, heart
Diamond Blackfan (BABY-fan) anemia
TREAT WITH STEROIDS (prednisone) -- if this fails than allo transplant
136
Common mutation found in Erdheim-Chester Disease and Langerhan Cell Histiocytosis? Tx?
BRAF v600E, Vemurafenib
MAP kinase mut or no mutation --> give cobemetinib
137
HbE and Hb C have mutations on which globin chain?
beta
138
HbE
beta globin chain mut
Asians
phenotype similar to beta-thal
139
HbCC
mild hemolysis
splenomegaly
crystals inside RBC
elevated MCHC
140
What is the difference between HbH and HbH Disease?
HbH Disease is a severe alpha thalassemia (a-/--) that has few alpha globin chains and thus HbH (bb/bb) and Hb Barts (gg/gg) is produced. Electrophoresis of HbH Disease shows HbA, HbH and Hb Barts
141
Hydrops Fetalis?
No alpha globin genes (--/--), thus no HbA. incompatible with life. Die in utero or within hours of birth. Only make Hb Barts (gg/gg)
142
Hb Constant Spring
alpha thal. heterozygotes are asymptomatic.
results in elongated alpha chain
143
Basophilic stippling?
think pyrimidine 5-nucleoside deficiency
144
Hb Lepore?
Hb Lepore variant is two normal alpha globin chains (HbA) and two delta-beta globin fusion chains that occur due to crossover at the delta and beta gene loci.
Does not sickle. On Hb Electrophoresis it migrates to the same position as HbS
Homozygotes have severe anemia. Heterozygotes are similar to beta-thal carries
HbA/Lepore:
HbA 85%
Hb Lepore 10%
Hb A2 <3%
Hb F = 5%
normal hemoglobin (MCV 70-80)
Hb Lepore/Lepore:
HbA 0%
Hb Lepore 100%
Hb A2 <1%
Hb F = 5-30%
Anemia with hb 4-9, MCV 50-65
145
MC cause of HUS?
STEC (shiga toxin producing E coli 0157:H7) - GI symptoms like bloody diarrhea/abd pain
Another cause is complement-mediated activation (use eculizumab or ultomiris) -- no GI symptoms
146
MYH9 related disorders?
hereditary macro-thrombocytopenia
Children/young adults
AD inheritance
cataracts, hearing loss, CDK
147
bilobed neutrophil with cytopenias?
Pelger Huet anomaly
MDS
148
Do you do PLEX in transplant associated TMA?
No.
Occurs 150 d after transplant. treat by changing immunosuppression, control BP, treat infections or GVHD. Consider rituximan, eculizumab.
149
Tx HUS?
supportive
May need hemodialysis
Dont give ABx
If severe neuro sx, can give eculizumab
do not give PLEX
150
tx for congenital TTP?
FFP
no role for PLEX, steroids, or any other immune/inhibitor-directed therapy
151
tx for the fetus that has neonatal ITP from the mother?
if PLT<20k, give IVIg and consider PLT transfusion
152
telomere disorder characterized by dystrophic nails, lacey pigmentation, oral leukoplakia, EARLY GREY HAIR, dental caries, and PULM FIBROSIS?
Dyskeratosis congenita (mut in telomerase/telomeres genes like TERC and TERT)
give androgens (Danazol)
153
Tx refractory HLH?
emapalumab (ab against IFN-Y)
154
Most useful diagnostic test in HLH?
elevated sIL-2R (sCD25) and CXCL9. If these are negative, unlikely HLH
HLH is confirmed by detecting a mutation in one of the associated genes on NGS testing (PRF1, UNC13D, STX11, STXBP2, Rab27A, SH2D1A, BIRC4, LYST, ITK, SLC7A7, XMEN, HPS)
also helpful is reduced NK cell activity on flow which showed reduced/absent NK cell perforin and CD107alpha
elevated CXCL9 and CXCL10 also correlate with lymphoma-associated HLH
155
WHIM syndrome?
warts (HPV)
hypogammaglobulinemia
immunodeficiency
myelokathexis - apoptosis of PMN in BM, thus peripheral neutropenia is seen
mutation in chemokine rec CXCR4, preventing release of PMNs and lymphocytes into bloodstream
Tx: plerixafor inhibits CXCR4 binding, thus mobilizing stem cells
156
TPO receptor is encoded on which gene, which is the gene mutated in Congenital Amegakaryocytic Thrombocytopenia?
MPL
HCT only curative therapy
PLT transfusions work
TPO does not work
157
Clonal Hematopoiesis of Indeterminate Potential (CHIP)?
a pathogenic mutation without an underlying condition (i.e no evidence of AML or MDS)
MC mutations are DNMT3A, ASCL++XL1, and TET2
158
preferred oral iron in pts with underlying GI disorders?
Ferric maltol
