Hematology Flashcards
Plasma versus serum
Only plasma has clotting factors
Ankyrin
Anchors RBC microfilaments to plasma membrane. One of proteins that car be mutated in hereditary spherocytosis.
Band neutrophils
Immature, notfully segmented
Seen in bm and active infection whenthere is mass neutrophil release
Hypersegmented neutrophils
Abnormal maturati due to B 12 and folate deficiencies
Basophilicspecific granules contain…
Histamine and heparin
Basophilia in which cancer
. CM L
Bernard soulier syndrome
Platelet disorder
Loss of gpib ie adhesion to vessel walls
Bleeding
Glanzmann thrombasthenin /
Platelet disorder
Loss ofGP2b/3a receptors ie platelet aggregation
Bleeding
Myeloid toerythroid range in bm
2-4 m: 1 e
Blast cells are replaced with… At a rate of about… % per decade in bm
Adipose
10%
First differentiated stage myeloid
Promyelocyte
First stage of specificgranulation myeloid
Myclocyte
Para-aortic lymph nodes
Kidneys, ovaries, uterus, testes
Cervical lymph nodes
Head and neck
Hisar lymphnodes
Lungs
Mediastinaltymphnodes
Trachea andesophogus
Axillazy lymph nodes
/ Upper limbbreast and skin aboveembilicus
Celiac lymph nodes
Liver stomachspleen pancreas upper duodenum
Sm lymph nods
Lover duodenum, jejunum, ileum, colon thrusplenic-feare
I’m lymph nodes
Colon from splenic plexure upper rectum
Internal iliaclymphnores
Lower rectum, bladder, vagina, cervix,prostate
Superficial inguind lymph nodes
Anal canal, skin below umbilicus, scrotum, vulva
Popliteal lymphnodes
Dorsolateral foot and posterior calf
Stave cells
Physicallyform filter in red pulp to remove damaged or aged RB Cs
Pentose phosphate pathway
Detour fromglycolysic
To make nadph
Membrane antioxidant
2,3- bpg
Glycolysis detour
Enhances O2 release
G6pd
Glucose 6 phosphate dehydrogenase
Involved in reduction of nadp+ to nadph
Mutation —> RBC damage
Porphyria
Family ofdisorders related to interruptedheme metabolism
Sideroblastic anemia
Defect in heme synthesis at Ala synthase first step
Due to B6deficiency
Possible sfx ofisoniazid For TB
Bilirubin
Ultimateproduct of heme breakdown
Unconjgated travels thru body via albumin
Conjugated by liver to be water soluble
Converted tourobili nogen by gut bacteria
Re absorbed or excreted in bile, urine
Gilbert syndrome
Decreased activity of UDP glucuronyltransferase ie bilirubinconjugation leading to jaundice on physical stress illness orexertion
Hepcidin
’ Iron transportmolecule
Mutation leads to uncheckedexport from enterocytes and macrophages ie iron overload inblood
Hereditary hemochromocjosis
Ferritin
BindsFerricironinside of enterocyes and macrophages
Catalyst neutralizer and storage reservoir
Ferroportin
Transports iron across enterocyte or macrophage membrane into blood
Transferrin
Binds ferric iron for transport in blood
Deferoxamine
Iron Che later
Fanconi anemia
Hereditary aplasticanemia
Short stature, cafe an laïi spots,radial and thumb defects
Hydroxyurea
’ Sickle cell t x
Increases fetalhemogeobin
Infective stagemalaria
Sporozite
Feeding stage malaria
Trophozite
Lives in RBCand feeds on hemoglobin
Shizont
Replication phase of malaria in liver cells
Chloroquine
Malaria drug
Preventsconversion of toxic hemoglobin . breakdown product fpix into neutral hemozoin by malarial heme polymerase
Thus fpix kills malaria
Relapsing malarias
Vivax and ovale
Dormant phase inliver
Need autimalarialthat enters liver
Most common malaria
Falciparum
Also must dangerous
But no dormant phase
Fever intervalsmalarias
Falciparum 24h
Vivax and ovals 48h
Malariae 72h
Ring insideesythrocyte
Malarial trophozite
Basopbilia
Usually cml
Reactive lymphocytosis with Downey 2 cells
Usually mono
Steroids Leukocytosis
Fairly common and benign response tosteroids if mature cells but ro infection important
Left shiftblood smear
More immatureveutrophits
Steps ofdot formation
Vessel constrict
Platelet plu g
Fibrin seal - thrombin fibrin fibrinogen
Intrinsic pathway
11
9
8
Common 10 (5 cofactor) 2 1
Extrinsic pathway
7 t tissue factor tf
Common 10/5 = 2 > 1
Anticoagsnatural
Turn off:
Antithrombin
C + S
Dissolve:
Plasmin
Inhibitors ofplatelet adhesion
No
Endothelial atpase
Prostacyclin pgi2
Sterrically; intactendothelial cells
Plate let chemoattracte.
VWF
Also tethers
Vw f bindingpartner
GPIb
Tethers and activates
Gpiii a /Iib
Binds fibrinogen
Thromboxane az
Arachadonicaciddevivatire
Activates otherplatelets
Induces vasoconstriction
Fibrinogen and thrombin
Fibrinogen bridgesplatelets andthrombin stabilizes via conversion of fibrin ogen to fibrin
Tissue factor
Released fromdamaged tissue, and vitiatescoagulationcascade
Intrinsic and extrinsic
T f initiates extrinsic shut off quickly intrinsic finishes
E=7
I=11-9_8
Factor 7 deficiency
Asymptomatic
Heparin
Potentates antithrombin to inhibit all serine proteases i.e. New or continuedclotting
Does not dissolve c lots
Plasmin
Breaks down clots
Potentate by t PA
D dimers
Clot bits
More specifically degradation products of cross-linked je. Clotted fibrin
Very sensitive but lowspecificityeven forpathogenic events in general, so used toro if negative but needs addition al to ri
Ristocetin
Assay
If no aggreg action problem w/ VwF GPIb interaction
Von willebranddisense or Bernard soulierrespectively
Platelet threshold severe bleeding
30000
Thrombopoetin
Constituitivelysccreteel by lifer
Warfarin
Vitamins K antagonist
2 7 9-10
Intrinsic and extrinsic so pt and ptt,
7 most sensitive so effects monitoredw/ pt/inr
Antiphospholipid coa g assays
Clinicallyensymptomatic or cause thrombosis
Bind reagent in test so false positivefor bleeding
Thrombocytopenia vs factor bleeding sites
T= skin and mucous membrane s petechia
Includesnosebeeds, heavy periods,gum bleeding
Fr excessivebleeding hours after trauma
If severe manybleed into joints. and deep issue
Hemophilia A
Factor 8
X linked
Hemophilia B
Factor 9 x linked
Less common
Vwf tests
Ptt ie intrinsic decreased as vWF normally prevents degradation offactor 8
Ristocetin platelet aggregationabnormal
Thromboticthrombocytopenic purpor a
Opposite of vwf disease.
Impaired breakdown of vwf
Thrombosis with eventual platelet consumption and bleeding
vWD genetics
Autosomal dominant most common with homozygous more severe
Can be recessive depending on subtype
Coags in hemophilia
Normal because extrinsic arm is normal
PTT prolonged
Dic causes
Things that dump prrcoagulants into blood or things that damage entihelium
Most commonly malignancy obstetric complications sepsis and trauma
Others include snake bites and lupus.
Adamts 13
Cleaves large VWF
Defective in ttp
Hemolyticuremic syndrome
Thromboticmieroangiopathy similar to Ttp but caused by toxins
Most common e-coli 0157 h7
Second Shig.a toxin
Thrombocytopenia - microangiopathis hemolytic anemia -acute renal failure
coags in TTP/HUS and DIC
elevated PT and PTT in DIC
NORMAL in TTP/HUS since clots are primarily platelet only without much consumption of coagulation factors
TTP clinical
neuro abnormalities
microangiopathic hemolytic anemia
thrombocytopenia purpura
fever
abnormal renal fx
typically adults
HUS clinical
bloody diarrhea usually
vomiting –> dehydration and hyponatremia
acute renal failure d/t direct effects of toxin on kidney
decreased urine output
uremia
thrombocytopenia
purpura, petechia, oozing blood
no fever or neuro findings usually except secondary to decompensation
usually kids <5 w/ recent diarrheal infection
Bernard soulier sx
GPIb defect - no binding to vWF
autosomal recessive
severe bleeding
giant platelets
can cooccur w/ heavy chain non-muscle myosin 9 defects (glomerulonephritis, sensorineural deafness, cataracts) or filamin A defects (hemorrhage, coagulopathy, macrothrombocytopenia)
bernard soulier tx
recombinant 7a
eltrombopag - thrombopoeitin agonist
platelet transfusions
glanzmann thrombasthenia sx
GPIIb/IIIa - fibrinogen can’t bind platelets together
autosomal recessive
severe
normal platelet morphology but no clumping
may cooccur w/ leukocyte adhesion deficiency
Glanzmann thrombasthemia tx
7a
HSCT
platelet or blood transfusion
common presentation:
- infant w/ severe infection
- delayed detachment of umbilical cord
- easy bruising/bleeding
- Fix
gray platelet syx
reduction or absence of alpha granule - minimal to no platelet plug formation
giant, pale platelets
inheritance depends on genes
uremia coags
decreased platelet aggregation
decreased granule secretion i.e fx
factor 5 leiden
most common thrombotic disorder
constitutively active F5
hereditary - because it cannot bind and be cleaved by protein C
APLS
most common acquired thrombotic disorder
heparin resistant thrombotic disorder
antithrombin deficiency
heparin potentiates antithrombin so does nothing if it’s deficient
high doses might still work
very uncommon
budd chiari syx
obstruction of hepatic vein
abd pain - hepatomegaly
as an uncommon site for clotting raises suspicion of a thrombotic disorder
AT deficiency test
heparin cofactor assay first
AT antigen levels next
rarely genetic testing
reasons to test for thrombotic disorders
at least one unprovoked DVT/other clot
Recurrent clotting episodes
Unusual locations
warfarin induced skin necrosis
can occur in anyone but Protein C+S deficiency confers highest risk
should prompt evaluation for C+S deficiency
happens b/c warfarin decreases synthesis of most clotting factors including anti-coags C+S. C+S decrease fastest meaning there is a transient hypercoag period. If C+S are already deficient this is extreme.
tx: d/c warfarin
avoid by bridging w/ heparin (doesn’t work as well in C+S deficient but does help in normal)
purpura fulminans
acute rapid widespread coagulability including hemorrhagic necrosis and skin infarction
usually d/t C+S deficiency
-xaban
direct factor “Xa” inhibitors
oral
api-, riva-, edo-
direct thrombin inhibitors e.g.
dabigatran PO
argatroban
bivalirudin
lepirudin
reversal warfarin
immediate: fresh frozen plasma (FFP)
then vitamin K
reversal heparin
protamine sulfate
clopidegrel
antiplatelet
used when aspirin c/I or as second agent in dual therapy
P2Y12/ADP receptor blocker
abciximab
anti platelet
anti-GPIIb/IIIa receptor
dipyridamole
antipltelet
phosphodiesterase inhibitor
vasodilator
indic`ated in prior stroke
-eplase
thrombolytics
e.g. alteplase aka tPA
tenecteplase now first choice d/t long t/12 and most specificity
all activate plasmin
thrombolytic antidote
aminocaproic acid
transexamic acid
reserve for life threatening d/t sfx
if less severe just d/c-ing should be sufficient
