Hematology Flashcards
crizanlizumab MOA, route of admin, goal of treatment
p-selectin binding reduces adhesion of sickles to endothelium
IV therapy
reduce pain crises
deficiency in which enzyme causes methemoglobinemia and why cyanosis
cytochrome b5 reductase, reduced ability to turn methemoglobin to normal oxyhemoglobin, holds on to o2 and doesn’t release it to the tissues
which hemoglobinopathy is associated with methemoglobinemia and why is this important to know
HbM or H, cannot reduce with methylene blue
gene, function and inheritance for pyruvate kinase (PK) deficiency
PKLR gene, ATP production for RBC, AR inheritance
treatment for PK deficiency
Mitapivat, PK enzyme activator raises RBC count and reduces transfusions
Hemolytic anemia with Leg cramps, pain with exercise, motor regression, cerebellar tumors, mutation and inheritance
Phosphoglycerate kinase deficiency, PGK-1, xlinked
labs and smear for G6PD
blister cells, heinz bodies, acute hemolysis
shock and acute hemoglobin drop in sickle cell disease
acute splenic sequestration crisis
goal of hbF on hydrea
hgf >20
MOA voxeletor, admin route and goal of treatment
Increases affinity of hgb for oxygen and stabilizes cell to prevent sickling, oral drug, goal to increase hgb levels
moa L-glutamine
anti-oxidant
blood smear with mild sickling, crystals with RBC with distorted shapes, target cells, microspherocytes, elevated MCHC
SC disease
brilliant cresyl blue stain with golf ball inclusion
HgH disease (severe alpha thal)
Hb Constant Spring, the severity of anemia
non-deletional alpha thalessemia due to abn elongation/instability of the alpha chain, more sever than other alpha that variants
alpha thal trait ( ), ( ); symptoms
(–,a), (–,a)
mild microcytic anemia
alpha thal carrier ( ), ( ); symptoms
(–, a), (a,a)
Slightly low MCV and MCH
beta thal minor or trait ( ), ( )
b/b+ or b0/b
Only one gene has a mutation
Microcytic anemia, HgA2>3.5
beta thal intermedia ( ), ( ); symptoms
Beta intermedia is b+/b+ or b0/b+
Microcytic anemia, variable levels, occasional transfusion
beta thal major ( ), ( ); symptoms
Transfusion dependent
Severe anemia, microcytosis, high output heart failure, bone abnormalities, HSM, renal enlargement, iron overload
MOA of luspatercept
inhibits TGFbeta which increases differentiation and proliferation of erythroid precursors
Hb Lepore
two normal alpha chains and two delta fusion chains due to gene cross over. Functional hgb that moves like HgS on electrophoresis.
Hets are like beta that minor, homozygotes with more severe beta that major phenotype
South asian ovalocytosis mutation and inheritance, smear
misfolding of band 3, AD, oval shaped RBC with hemolytic anemia
abetalipoproteinemia symptoms and smear
cannot absorb fat; steatorrhea, retinitis pigmentosa, neurologic deficits, FTT; vitamin E deficiency causes acanthocytes
sideroblastic anemia, congenital; mutation and treatment
ALAS2 deficiency, poor heme synthesis with iron deposition in mitochondria, treat with high doses of vitamin B6
smear with massive basophilic stippling and hemolytic anemia
hereditary pyrimidine-5-nucleosidease deficiency
Osler-webber-rendu findings and mutation
telangiectasias, epistaxis, AVMs, mutas in SMAD4, ACVRL1, ENG
reduced inhibitor development in hemophilia if this type of factor is used
plasma derrived with vwf rather than recomb,
when to test for VWF levels in woman
first 5 days of the menstrual cycle due to least estrogen effect
Heydes sydrome
acquired type IIA VWF from aortic stenosis shearing, AVM bleeding
emicizumab MOA and use
bridges IXa and X to restore function to VIII; only for prophylactic (with or without inhibitor) not for active bleeding
factor XIII deficiency lab pattern and role of this factor and treatment
elevation of both PT and PTT, stabilizes fibrin at the end of the cascade, treat with fibrogammin, cryo or ffp
young woman with thrombosis in common iliac vein and why
may-thurner syndrome, compression by R common iliac artery
axillary subclavian thrombosis in repetitive injury/activity
paget-schrooetter syndrome, thoracic outlet compression
OCPs and clots why
decreases antithrombin III, protein S, increases factor levels and platelet activity
patient with thrombosis with marfanoid appearance, seizures, myopia, iridonesis, subluxation of the lens, developmental delay and short stature; treatment
homocysteinuria, treat with B6
pancytopenia, macrocytosis, normal B12 but high homocysteine and MMA levels, name the disorder
transcobalmin II deficiency; cannot move B12 to cells
juvenille hemochromatosis age of onset, gene and inheritance
age <30, AR, HJV gene, severe clinical presentation
ferroportin mutation unique features in lab and biopsy, gene and inheritance
FPN-1 mutation, AD
cannot shuttle iron to cells which results in high ferritin but normal to reduced transferritin saturation and mild anemia
Liver biopsy with iron in kupffer cells rather than hepatocytes
TFR2 hemochromatosis, mechanism, severity, inheritance, age of onset
increased intestinal absorption, AR TFR2 mutation, young <30, less severe than HJV
cause of porphyria; treat porphyria and MOA
Cause is enzyme error in heme synthesis results in accumulation of toxic heme byproducts
hemin= suppresses ALAS synthesis to reduce ALA and PBG production
givosiran= siRNA against 5-aminovulinic acid synthase 1 to decrease ALA and PBG production accumulation
treatment for erythropoietic protoporphyria (EPP)
afamelanotide= alpha melanocyte stimulating hormone protects against oxidant damage to reduce skin rash and pain with sun exposure
disease with chronic blistering photosensitivity and associated causes, treatment
porphyria cutanea tarda due to familial UROD mutation, hepatitis C, hepatic iron overload in deficiency of uroporphyrinogen decarboxylase
-treat underlying disease, phlebotomy, hydroxychloroquine
what is hereditary aceruloplasminemia and what is diagnostic lab
ceruloplasmin defect which causes poor iron transportation
high ferritin but normal transferrin sat and has neurologic deficits
low serum copper, low serum iron, anemia
need iron chelation therapy
iron refractory iron deficiency anemia, labs, cause and treatment
impaired oral iron absorption and utilization due to mutations in TMPRSS6 genes
normal ferritin, low saturation, microcytic anemia
IV iron partial responses
atransferrinemia labs, cause, mutation, treatment
AR absence of transferrin, microcytic anemia with elevated ferritin but low transferrin levels, treated with FFP to replace the transferrin protein to allow iron to reach RBCs
iron chelation 3 drugs IV verus oral, which one in renal disease but can cause what concerning side effect
deferoxamine is IV, deferiprone and deferasirox are oral, deferiprone is used in renal disease but can cause agranulocytosis
inheritance and mutations that cause hereditary eliptocytosis
alpha-spectin, beta-spectin, band-3, protein 4.1, glycophorin C, autosomal dominant
inheritance and mutations that cause hereditary spherocytosis, helpful lab finding, diagnostic test
spectrin, ankyrin, band 3
elevated MCHC >36
osmotic fragility test, eosin-5-maleimide test
extreme microcytosis MCV 30-50 with severe neonatal jaundice
hereditary pyropoikilocytosis, most severe form of HE
smear and coombs in warm AIHA, treatment
spherocytes, IgG+ C3+/- or both
steroids +/- rituximab
smear and coombs in cold AIHA, what are underlying causes, treatment
agglutination, C3+ (IgG neg)- cleared in liver after bound by IgM
lymphoma, lymphoproliferative disorder, autoimmune disorders, infections
warm RBCs
if severe: treat with plasmapheresis or sutimlimab (C1s), IVIG
sutimlimab MOA and treats what disease
cold AIHA/cold agglutinin, C1s target to reduce compliment activation
paroxsysmal cold hemoglobinuria, age, symptoms, test, coombs, treatment
children, viral infection followed by cold causes back pain, weakness, nausea, fever, dark urine; C3+ (IgG neg), positive donath-landsteiner test
treat with cytoxan, rituxan or steroids
mechanism of anemia in lead poisoning, smear
reduced heme synthesis due to pyrimidine-5-nucleosidase deficiency which causes chronic hemolysis, basophilic stippling and accumulation of nucleotides in RBCs
recurrent fever, inflammation of skin, recurrent osteomyelitis, sweet syndrome, anemia; gene
majeed syndrome, congenital dyserythropoetic anemia, LPIN2 gene
transient erythroblastopenia of childhood; labs, treatment
pure red cell aplasia in children often after viral infection, 1-2 months duration then complete recovery; anemia with normal MCV, low reticulocytes, no evidence of leukemia
Diamond blackfan anemia presentation, age, other findings, treatment, gene, risk for what
red cell only failure age <1
craniofacial abnormalities, thumbs abnormal, organ development defects, RSP19 gene
Cancer risk with AML, MDS, colon cancer, genital cancers, sarcoma
Mcleod neuroacanthocytosis syndrome; inheritance and genetic issue, smear findings , symptoms
X-linked absence of Kell blood group antigens, acanthocytosis and hemolysis, weakness, movement disorders, dilated cardiomyopathy, psych symptoms
hereditary stomatocytosis, lab findings, inheritance, mutation, testing
do not do what for treatment
hemolytic anemia, elevated MCHC, AD inheritance of PIEZO1 mutation, osmotic fragility test, ektacytometry, genetic testing
no splenectomy due to increase thrombosis and pulm HTN
MOA of dabigatran (pradaxa)
reversal agent
IV versions names
anti-thrombin oral med
idarucizumab
argatroban, bivalrudin
xarelto moa, reversal, check which lab
direct x inhibitor
reverse with andexanet alpha
check creatinine clearance (CI in <30)
which is the linker for platelet to vwf
which disorder is this mutated
what is the platelet aggregation testing like
what is the status of the platelets in this disorder
Gp1b
bernard-soulier
no activation with risocetin
giant platelets and thrombocytopenia
what is the linker between platelets for aggregation
what disorder is this mutated
what is the platelet aggregation testing like
what is the status of the platelets in this disorder
GpIIb/IIIa
glanzmanns
no activation with ADP, epi, collagen, normal ristocetin
normal platelt size and count
what factor deficiency causes no bleeding risk
factor XII (12)
MOA of heparin
binds and inactivates X, IX, XII, VII, and II, kallikrein and plasmin
elevated PT and PTT with increased TT and reptilase time
dysfibrinogenemia
factor V deficiency, treatment goals, other causes
milder than hemophilia A or B
PT and PTT both elevated
pre-op goal of >20% level for factor V
acquired in autoimmune diseases, cancer, antibiotics or MPNs
difference between HELLP and ALFP, cause of ALPF
liver dysfunction is worse with ALFP and with more symptoms
AST/ALT/bili rapid rise, nausea, vomiting, ascites, hypoglycemia, coagulopathy
less HTN
deficiency of fetal enzyme LCHAD accumulates long chain fatty acids that are toxic to maternal liver
moa of clopidogrel
moa of aspirin
ADP inhibitor which decreases platelet aggregation
TXA2 inhibitor (thromboxane) which decreases platelet aggregation
storage pool disorder platelet agg testing results
robust primary ADP but less secondary ADP wave. reduced responses but some to collagen, epi, ristocetin.
differentiate type 2B vwd from platelet type vwd
LD-RIPA:
- 2B is vwf stickiness, therefore donor and native platelets will have LD-RIPA activity with patient plasma
- platelet type is platelet stickiness. therefore donor plasma and native plasma will have activity with patient platelets. Donor plasma will also have increased activity with patient platelets.
occulocutaneous albinism, pulmonary fibrosis, granulomatous colitis; name of syndrome and cause
hermansky pudlak and due to dense granule defect
congenital TTP due to absence of ADAMSTS13 name of syndrome, treatment
upshaw-schulman
treat with plasma infusions (not plasmaphersis since they have no inhibitor to remove)
quebec platelet disorder, defect, inheritance, clinical finding
delayed onset bleeding due to deficiency in fibrinolysis, increase urokinase plasminogen activator in alpha granules which degrades them and leads to decreased factor V, vwf and fibrinogen
MOA fostamatinib and use
inhibits spleen tyrosine kinase, used in refratory ITP
grey platelet syndrome cause and effects, lab finding, mutation
large platelets, thrombocytopenia, mild bleeding, absence of alpha granules, grey platelets on smear, NBEAL2, myelofibrosis due to granules released in marrow
Jacobsen syndrome, paris-trousseau TCP; mutation, findings
thrombocytopenia with large granules, stunted growth, facial dysmorphism; ETS1 and FLI1 mutations cause fusion of alpha granules
may-hegglin anomaly findings, risks, cause
thrombocytopenia with large platelets, neutrophil inclusions; due to dense granule deficiency, MYH9 mutations (RUNX1 is one),
sensorinural hearing loss, cataracts, renal failure due to glomerulonephritis
GATA1
X-linked thrombocytopenia with large platelets, mild hemolytic anemia and splenomegaly
Mediterranean macrothrombocytopenia findings and mutation
thrombocytopenia with large platelets, stomatocytes, GP1BA or B genes
post-transfusion purpura
cause
test you can do
treatment
severe autoimmune platelet destruction 5-10 days after transfusion of red cells
absence of HPA-1a on recipient platelets with prior sensitization (pregnancy or transfusion) causes antibody development which destroys donor platelets
test for HPA antibodies
treat with IVIG, steroids, plasmapheresis
passive alloimmune thrombocytopenia cause (and contrast to Post Transfusion Purpura)
TCP that develops hours after transfusion of plasma from a donor with pre-made anti-HPA-1 antibodies (versus PTP which is 5-10 days)
check for HPA antibodies in the transfused product. They are often a female multiparous donor.
neonatal alloimmune TCP versus neonatal autoimmune TCP
mom makes antibodies against paternal antigens in baby platelets and causes neonatal TCP, mom has normal platelet count and no h/o ITP. transfuse maternal platelets.
versus mom has ITP and this is transferred to the child, treat with IVIG if severe
Thrombocytopenia with absent radius findings and mutation
thrombocytopenia improves with age, heart issues, tetrology of fallot, kidney issues, short forearms, PBM8A mutation
quinine moa in thrombocytopenia
immune-mediated destruction due to quinine binding to GP IIb/IIIa and resulting in macrophage clearance by spleen
scott syndrome cause and testing
defective platelet phospholipid structural matrix
test platelet factor 3 via prolonged russel viper venom time or annexin V binding assay
VEXAS syndrome what does it stand for and what does it cause
think vacuoles
bone marrow failure syndrome with (V)acuoles on BMB, E1 enzyme, X linked, Autoinflammatory Somatic Syndrome
chondritis, vasculitis, alveolitis, PMR like syndrome, thromboembolism, bone marrow failure
what is is cryo
fibrinogen, factor VIII,, XIII, vwf
transfusion reactions compare and contrast:
FNHTR, AHRT, DHRT, TRALI, TACO, Allergy, sepsis
FNHTR vs sepsis- just fever verus fever and septic symptoms
FNHTR vs AHTR- just fever versus fever and flank pain, vomiting, SOB, hematuria (hemolysis labs and urine with free hemoglobin)
AHRT vs DHRT- with in 24 hours with fever, flank pain, vom, sob, hematuria verus days to weeks later mild hemolysis, jaundice
TRALI vs TACO- trali within 6 hrs of transfusion, negative pro-BNP versus fluid overload
passenger lymphocyte syndrome what is it and what does it cause
donor lymphocytes produce antibodies against recipient red cells which causes complement mediated hemolysis when there is ABO mismatch transplantation
self limited over days to months
hemolytic anemia of the newborn what is it and what does it cause, which mismatches are at risk
mom makes antibodies against the baby RBC antigens
O mom makes antibodies against A or B baby
Rh negative mom makes antibodies against Rh+ baby
leukoreduced versus irradiated blood (for whom)
leukoreduction prevents FNHTR
irradiation prevents transfusion-associated GVHD in transplanted patients, and those with severe leukopenias
drugs that cause neutrophillia
lithium, steroids, epinephrine, ATRA or G-csf
drugs that cause neutropenia
clozapine, beta-lactam abx, anti-thryroid meds, ticlopidine (antiplatelet drug), phenytoin, rheum meds (hydroxychloroquine, methotrexate, sulfasalazine), rituximab
delayed separation of umbilical cord without pus
Leukocyte adhesion deficiency
kostmann syndrome, mutation and presentation
severe chonic neutropenia, ELANE gene, HAX1 or WAS
severe neutropenia <200 at birth, oral and skin infections
marrow with arrest of WBC at promyelocyte stage
MDS/AMl risk, transplant
cyclic neutropenia mutation and presentation
3 week cycle of neutropenia that lasts for a week (<200), recurrent fevers/inflammation, lymphadenopathy, pharyngitis, gingivitis, stomatitis
treated with g-csf
no aml risk
alloimmune neonatal neutropenia cause and presentation
mom makes antibodies against babys neutrophils, resolves 8 weeks after birth, poor separation of umbilical cord and infections
HNA-1a is target, late myeloid arrest on marrow
LGL leukemia T-cell flow, work up and presentation, treatment, associated disorder
CD3+ CD57+, TCR +
chronic neutropenia, splenomegaly
associated with RA
observe and treat if symptomatic with methotrexate
Chronic NL lymphocytosis versus NK leukemia
indolent versus aggressive with B symptoms, HSM, GI and CNS involved, multiple cytopenias, organ failure, coagulopathy
Flow for chronic: CD56+ CD16+ verus acute CD8 is also positive
treat with observation/immunosuppression verus referral, clinical trial, transplant
occuloctaneous albinism, infections, neutropenia; mutation and cause, marrow, risk
chediak-higashi
AR mutation in CHS1/LYST which results in abnormal lysosome trafficking (melanocytes)
marrow with lysosome vesicles in neutrophils
HLH risk in childhood
chronic granulomatous disease, mutation causes what problem and what infections are most problematic, how to diagnose
NADPH oxidase defect prevents phagocyte respiratory burst
Dihyrodamine 123 (DHR) or NADPH oxidase activity (nitroblue-tetrazolium)
catalase positive bacteria staph aureus, serratia, ecoli, kleb, nocardia, burkholderia, aspergillus
PNH presentation, work up, gene, treat
hemolytic anemia, thrombosis, cytopenias, aplastic anemia
flow with granulocytes with decreased CD55/59, unchecked complement medicated destruction
PIG-A gene codes for GPI for CD55 (C3 convertase inhibitor), CD59 (MAC blocker)
treat if hemolytic with eculizumab, ravulizumab, pegcetacoplan
Bone marrow failure with short stature, skin hyperpigmentation (cafe au lait spots) and microcephaly, developmental delay, kidney problems, abnormal thumbs, deafness, renal abn, congenital hip dislocation
fanconi anemia
fanconi anemia mutations and cause; cancer risk
FANC genes, inability to repair DNA damage
AML/MDS, SCC of head and neck, gyn
Rare mutation FANCD1/BRCA2 childhood leukemia, medulloblastoma, wilms tumor
reticulated skin pigmentation, nail dystrophy, leukoplakia, pulmonary fibrosis, cirrhosis; name mutation and cancer risk; treatment
dyskeratosis congenita
TERT mutations, telomeres are short
AML and SCC risk, GI malig
androgens to increase Hgb
schwachman-diamond syndrome; mutation and inheritance, associated symptoms, risk, conditioning regimen
bone marrow failure syndrome with pancreatic insufficiency, malabsorption, short stature, bone abnormalities
AR SBDS mutation
AML/MDS
HCT with RIC (increased cardiac risk with cyclophosphamide)
bloom syndrome what and associated symptoms, mutation, risk
BLM mutation in DNA helicase causes genomic instability
immunodeficiency
short stature, sensitivity to sun, butterfly rash, early COPD, high pitched voice, large nose, prominent ears, cancer risk
causes of aplastic anemia
radiation, benzene, viruses, autoimmune disease, thymoma, pregnancy, idiopathic, genetic causes
treat aplastic anemia
horse (over rabbit) ATG, cyclosporine, eltrombopag or HCT if <40
causes of secondary pure red cell aplasia
drugs, thymoma, hypoplastic MDS, LGL leukemia, parvo virus infection
Job syndrome/HIES, mutation, symptoms/findings
recurrent infections with two row of teeth, elevated IgE, eosinophilia, hyperextendible joints, fractures, eczema
STAT3 mutation
barth syndrome, mutation, symptoms
Barth= heart
X-linked taz gene
Immunodeficiency, neutropenia that can be cyclic
dilated cardiomyopathy, skeletal myopathy, short stature, chubby cheeks
WHIM mutation, cause and symptoms, treatment
CXCL4 mutation AD, can’t mobilize immune cells out of marrow
warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (leukopenia in serum not marrow)
plerixafor mobilizes cells, IVIG
familial platelet disorder mutation and risk
RUNX1, AD, mild to moderate TCP and dysfunction
familial MDS/AML syndrome
secondary cause of myelofibrosis, marrow findings and treatment
autoimmune myelofibrosis with mild fibrosis, lymphoid aggregate and no dysplasia, no MPN mutation
steroid responsive
monoMAC syndrome mutation associated symptoms and risk
AD GATA2 causes dendritic cell monocyte B and NK lymphocyte deficiency
erythema nodosum and pulmonary alveolar proteinosis
risk for mycobacterial infections and also viral, fungal, bacterial and viral cancers, MDS/AML, melanoma, HPV and leiomyosarcoma EBV+
MOA of empalumab and use
Interferon gamma blocking antibody used in relapsed/refractory HLH
gaucher disease mutation, symptoms, marrow findings
AR GBA gene causes accumulation of glucocerebroside which causes disease
pancytopenia, hypogammaglobulinemia, impaired neutrophil chemotaxis
skeletal deformity, AVN, short stature, pulmonary HTN
marrow with wrinkled tissue paper appearance of macrophages and histiocytes with a single nucleus
congenital dyserythropoietic anemia symptoms
isolated anemia, jaundice, splenomegaly, iron overload, skeletal abn especially in distal limbs, syndactyly, absence of phalanges, hypoplastic ribs
familial Mediterranean fever symptoms and mutation, treatment
AD mutation of MEFV gene which encodes for pyrin and causes dysregulation of the inflammatory system, particularly neutrophils
fever, pleuritis, synovitis that wax and wane, infertility and SBO
Amyloid A buildup
treat with colchicine or IL-1 inhibitors
Ferric carboxymaltose risk
hypophosphatemia
ASXL1 gene is involved in
epigenetic regulation
