HEMA TEST 3
001
1. role of endothelial cells
AT - prostacyclin, NO, TFPI, tPA, uPA
PT - VWF, PAI, TAFI
2. platelet structure
peripheral = glycocalyx
sol gel = utubule coil, open canalicular, dense tubular
inner organelle
BM produce plat 7-10d
TPO in liver, kidney, BM
lifespan 8-12d
3. primary hemostasis
adhesion
activation
aggregation
4. VWF cleave by ADAM
bind site: collagen, plat, heparin, FVIII
synthesis site: endothelial & megaK
plat adhesion, protect FVIII
002
1. coagulation cascade/secondary hemostasis
extrinsic/initiation TF+VIIa
intrinsic/amplification XII=XI=IX
common/propagation X to Xa
PT to T = thrombin burst
fibrinogen to fibrin
2. natural inhibitor
C&S = VIIIa, Va, PAI inhibitor
TFPI = extrinsic
AT = thrombin, intrinsic & common inhibitor
3. fibrinolysis
plasminogen to plasmin by tPA, uPA
((PAI inhibit tPA, uPA
((a2 antiplasmin & macroglobulin inhibit plasmin
fibrin clot to FDP
((fibrin inhibit by TAFI
clear by RES
((thrombin + thrombomodulin inhibit fibrinolysis
003
Qty: FBC, PBF, BMAT
Qty: BT, PFA, PAT, FCM, EM
women higher platelet 20%
Menstruation low platelet
Strenuous exercise, smoker high platelet
PFT in vivo, add antagonist: AA, collagen, ADP, epinephrine
9 whole blood:1 AC
centrifuge within 4h (4°C) to get PPP
PT 11-14s
Extrinsic
Liver ds, AC, VK, DIC
APTT 26-36s
Liver ds, AC, massive transfusion, DIC
Intrinsic
TT 15-19s
Fibrinolytic ds, FDP, heparin contamination
Fibrinogen 1.5-4 g/l
Clauss method
High: age, female, pregnant, post menopause, acute, malignancy
Low: Liver ds, AC, massive transfusion, DIC, inherited ds
FDP <10ug/ml
AVTE, acute myocardial infarction, pneumonia, DIC, thrombolytic therapy
Mixing study = patient sample + normal plasma
APTT & PT remain prolong = inhibitor present - lupus anticoagulant
If corrected = factor deficiency
If corrected when immediate mix but prolong after 2h incubation = FVIII inhibitor (time dependent)
INR for warfarin titre
Warfarin = IV medication = fast acting = INR
Heparin = oral = slow acting
004 acquired more common
1. bleeding history
pinpoint petechiae
purpura >3mm
ecchymoses >1cm
grade 3 & 4 need transfusion - hemodynamic compromise
2. hereditary vascular defect
hereditary hemorrhagic telangiectasia = AD vascular dysplasia
recurrent epistaxis 鼻血
Ehlers Danlos = collagen abN
hyperextend joint
3. acquired vascular defect
simple easy bruising
senile purpura = CT atrophy hand
VC def = collagen defect
steroid purpura = cushing
Henoch Schonlein purpura = IgA vasculitis + URTI
infective purpura
4. thrombocytopenia
increased consumption
reduced production = BM failure
increased destruction
artefactual = plat clump = non pathogenic
5. immune thrombocytopenia
primary 无因
secondary 有因
new dx within 3 mth
persistent 3-12 mth
chronic >12 mth
severe need tx
B cell: coated Ab present to splenic macrophage engulf
T cell: platelet apoptosis
increased autoreactive T & cytotoxic T
reduced regulatory T activity
TPO high/normal
children acute, vaccine/infection
15-50y female bleeding severity
giant platelet = low platelet
BM with megaK
6. inherited platelet ds
megaK + protoplatelet & granule
membrane glycoprotein
7. acquired plat dysfx
cause: drug, hema ds, systemic + plat dysfx
tx desmopressin
tranexamic acid
005 inherited bleeding ds
single/dual factor def
1. HA = F8 Xq + VWF
isolated prolong APTT
corrected mixing APTT
intron 22 inversion
single ntd change
HB = F9 Xq
normal PT
single ntd change
management, tx, complication - HIV & develop inhibitor
2. VWD
low VWF, FVIII
12p
type 1 AD, qty def VWF low
type 2 qlty def VWF (fx loss)
type 3 AR, no VWF, qty def VWF = Hemophilia
tx desmopressin
tranexamic acid + hormonal
VWF concentrate
3. rare ds
mct bleed
FXIII AR
FII
FVII AR
FX umbilical
FXI AR high fibrinolysis
aFib
hypoFib
dysFib AD
tx tranexamic acid
PCC
006 acquired ds
1. acquired coagulopathy due to systemic ds
thrombocytopenia & plat dysfx = impaired coagulation = activate plasminogen + proteolytic enzyme = high fibrinolysis
VK fat soluble
VKD FII, VII, IX, X
a. HDN:
inefficient placenta transfer, liver immature, breast milk
ct, GI, intracranial bleed
abN PT & APTT
low VKD
tx prophylaxis
VKDB in adult:
liver ds, biliary obstruction, pancreatic/small bowel ds, long antibiotic use
mild prolong PT
tx IV VK, PCC
b. abnormal coagulation @ liver ds
high fibrinolysis, VWF, hypersplenism + portal hypertension, thromboplastin
c. disseminated IV coagulation DIC
not localized, mainly small vessel
endothelial damage = organ damage
clot everywhere
fibrinolysis
microthrombi formation
MAHA + skin lesion = gangrene
acute
subacute
d. other
critical illness:
ICU
high fibrinogen
prolong APTT no tx
massive transfusion syndrome
e. thrombotic microangiopathies TMA
MAHA
thrombocytopenia
ischemia
neuro, cardio, GI symptoms, jaundice, renal, non specific feature
hemolysis = low haptoglobin, high LDH
thrombotic thrombocytopenic purpura TTP:
ADAM <10%
microvascular thrombosis
MAHA, ischemia, multiorgan failure
congenital acute
acquired immune - autoAb aid ADAM
tx FFP, caplacizumab, remove inhibitor
hemolytic uremic syndrome HUS:
E coli toxic
children diarrhea
MAHA
thrombocytopenia
renal
develop microthrombi
complement mediated HUS:
no E coli toxic
mutation
cause by infection/pregnancy
tx anti C5 monoclonal Ab
f. COVID
endothelial injury, hypercoagulability, inflammation
DVT, PE
2. acquired isolated factor deficiencies
a. HA
F8
no gene mutation
elderly w chronic ds, malignancy, post partum
new onset - mct bleed, hematoma
isolated prolong APTT
autoAb aid F8
b. VWS
3. drug induced coagulopathy
a. HIT (heparin)
heparin treat clot
HIT Ab aid F4 & heparin
low plat
venous & arterial thrombosis
tx stop heparin, change anticoagulant, IV Ig
b. VITT (vaccine) 4-42d
COVID
Ab aid F4 & heparin
low plat
arterial/venous thrombosis @ cerebral & splanchnic vessel
high d-dimer
neutrophil activation
007
1. Virchow triad
stasis = 行动不便/不爱动的人 = valves dysfx, muscle inactive
hypercoagulability 因severe anemia，polycythemia cancer，nephrotic syndrome，sepsis from bacterial endotoxin，药物&lifestyle
vascular injury = direct injury 受伤（手术等；indirect injury 化疗糖尿病败血症sepsis
2. antiphospholipid APS
autoimmune ds
pregnancy/recurrent thrombosis, aPL = LAC, anti B2 GP1
clot @ placenta = miscarriage
prolong APTT
not corrected mixing APTT
assay: dRVTT, APTT w low PL, cardiolipin & B2 GP1
types: primary idiopathic, secondary, catastrophic multiorgan thrombosis
3. VTE @ calf
migrate to pulmonary = PE
red emboli = RBC + fibrin
provoked 有因 & unprovoked 无因
long term VTE:
post thrombotic syndrome
chronic TE hypertension
4. PE
5. arterial thrombosis
heart & brain = stroke
white emboli = plat
tx DOAC, antiplat drug
6. thrombophilia test for
recurrent miscarriage
splanchnic vein/cortical vein sinus thrombosis
thrombosis @ unusual site
unprovoked VTE + <45y
family h/o
7. list unusual site of thrombosis
CVST
retina
upper limb
SVC
IVC
abdominal
renal
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