別表4 一般検査用試薬・消耗備品 一般 試薬・備品名 規格 ......2019/06/01 · 別表4 血液凝固検査用試薬・消耗備品 部門 【 血液 ・凝固】
止血・凝固・線溶 -...
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止血・凝固・線溶 止血・血栓形成機序は、血小板の活性化および組織因子の発現を引き金に、主に血小板膜 表面上でおこる凝固因子の濃縮と、次々に進行する凝固因子の活性化（蛋白分解反応）によ り説明される。同時に、凝固阻止・線溶機構の活性化をも促し、過度の血流障害や血管閉塞 を防ぐ。これらの複雑な調節機構は、血小板・凝固（調節）因子・血管内皮細胞それぞれの、 時間的かつ空間的な位置関係をイメージすることで理解しやすくなる。 本講義では、簡単な模式図を使って、血小板の止血機構および凝固・線溶調節機構の基本 を概説する。またこれら構成因子の破綻によっておこる、代表的な出血・血栓性疾患について も説明する。 講義資料
Transcript of 止血・凝固・線溶 -...
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1
2
1
2 c-AMPCa
3
4
5
6
7
1
2
1
1
2
1 Osler
2 Ehlers-Danlos
1 Henoch-Schnlein
2
3
4
5
3
1
2 Bernald-Soulier
3 May-Hegglin
4 von Willebrand
5 Gray platelet syndrome
-1-
P3
P4
P6
P6
P6
P7
P8
P8
P9
P10
P11
P12
P12
P12
P13
P14
P15
P15
P15
P15
P15
P15
P15
P15
P15
P15
P16
P16
P16
P16
P16
P16
P16
P16
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4von WillebrandvWD
5Hemophilia
6ITP: Idiopathic Thrombocytopenic Purpura
/ Primary Immune Thrombocytopenia
7DIC: Disseminated Intravascular Coagulation
2
1
2
1 AT
2 C
3 S
4 FV LeidenAPC
5
3TMA: Thrombotic Microangiopathy
1 TTP: Thrombotic Thrombocytopenic Purpura
2 HUS: Hemolytic Uremic Syndrome
3 TMA
4APS: Antiphospholipid Syndrome
5HIT: Heparin-induced Thrombocytopenia
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P17
P18
P19
P20
P21
P22
P23
P23
P23
P23
P23
P23
P24
P24
P24
P24
P25
P26
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()
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1.
1. von Willebrand(vWF) GPIb/IX/Vetc.
(ADPP2Y1)
2. 4PF42PDGF etc.ADP etc. TXA2
3. Ca2+GPIIb/IIIa vWFADPP2Y12
, P11
1 PGI2GPIIb/IIIavWF
2
-4-
Ca!
vWF!!
!Ca!!Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI21!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
PF4PDGF etc.
-
ADP, P78
1. 35
2. 33.
ADP GPIb/IXvWF
4. Rumpel-Leede52
3 EDTA2(Ca) GPIIb/IIIa EDTA
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Ca!
vWF!!
!Ca!!Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI2!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
PF4PDGF etc.
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c-AMPCa
1.
COX-140-300mg/dayPGI2TXA2
PGI2
, TXA2
, PGI2
TXA3TXA2
2. c-AMPCa ADP
ADPP2Y12TTP, P24
PDEPDE3PDE5
5-HT2
7-10
GP IIb/IIIa!
ADP etc.
PF4PDGF etc.
ADPPGI2
AC!PLA2
TXA2
&
COX-1!
Ca++!
c-AMP!
5-HT2
PIP2
IP3
5AMP
PDE!
EPA&
2.
-
3.
VII ()XI12
101/10
-7-
XI XIa
XII XIIa HMWK
Ca2+
a Ca2+
a IIICa2+IV
a
II
a
Ca2+PF3 /vWF a
Ca2+ a
XI
XIa
Ca2+
Ca2+
XIII XIIIa I
prothrombinase
tenase
&
+
PT&TTHPT
APTT
etc.
-
III1Ca2+IVCa2+3PF3IXXXIII, XI, VIII, VII, V
PT: prothrombin time1113, INR 0.91.1 +Ca2+ PT-INR = PT/ PTISI2
1 1LPS
TNF, IL-12 1.5-5Vit,K
PTTTHPTPTPTHPTTTPIVKA-II3HPT
3 Vit.K
XIIIXIXVIII
Ca2+tenaseXXIIHMWKAPTT, P10
APTT: activated partial thromboplastin time2740 +XIIXIHMWK, etc.Ca2+
APTTAPTT%
372
XIII4
,
SF12
-ATTAT, P9
4 XIIIAPTTPT
vWFT1/21.5-5T1/220-24T1/21-2T1/22.8-4.4K
-8-
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XI XIa
XII XIIa HMWK
Ca2+
a Ca2+
a Ca2+
a
a
Ca2+ /vWF a
Ca2+ a
XI
XIa
Ca2+
Ca2+
XIII XIIIa
prothrombinase
tenase
&
4.
2, P10
-
Lys
5.
/FDP DEDDD1 FDP21 D2 FDP
DFDPDFDPD
C-2-APPIC, P11
t-PAtissue-plasminogen activator
-10-
Lys
XI! XIa!
XII! XIIa!HMWK!
Ca2+!
a!Ca2+!
!a!Ca2+&
! a! !
! a!
Ca2+! /vWF!a&
Ca2+& !a&
XI!XIa!
Ca2+&
Ca2+&
XIII! XIIIa!
prothrombinase&
tenase&
t-PA!
Plasminogen!
Plasmin!
Plasminogen!
/ FDP/&D-
&
-
6.
TAFIthrombin activatable fibrinolysis inhibitor2Polyphosphate2C
PAI-1plasminogen activator inhibitor-112
t-PA8, P201-ATantitrypsinC2-APantiplasmin1XIII2
-2-APPIC
LpaLpaapoaPAI-1
1 PAI-12-APXIII
2
-11-
Lys Lys
XI! XIa!
XII! XIIa!HMWK!
Ca2+!
a!Ca2+!
!a!Ca2+&
! a! !
! a!
Ca2+! /vWF!a&
Ca2+& !a&
XI!
XIa!
Ca2+&
Ca2+&
XIII! XIIIa!
prothrombinase&
tenase&
t-PA!
Plasminogen!
Plasmin!
Plasminogen!
/ FDP/&D-
&
2-AP!XIII! PAI-1&
Protein C&
1-AT&
Lp(a)!
TAFI&
/
/Polyphosphate
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7.
1. Vit.KXVIIIXCS Vit.K ATP,
, Xa/APTT , , Xa/
APTT Xa Xa, , , , ,
ATIIIATIII
F1+2()PT-INRTATFDPD APTTXa
tenase
4NOACnovel oral anticoagulant NOAC514
C2. t-PA, ,
-12-
Lys
XI! XIa!
XII! XIIa!HMWK!
Ca2+!
a!Ca2+!
!a!Ca2+&
! a! !
! a!
Ca2+! /vWF!a&
Ca2+& !a&
XI!
XIa!
Ca2+&
Ca2+&
XIII! XIIIa!
prothrombinase&
tenase&
t-PA!
Plasminogen!
&
AT&
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1
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1. a) Ehlers-Danlosb) Henoch-Schnlein2. 1) a) FanconiMay-HegglinWiskott-Aldrichb) i) ii)ITPiii) TMADICiv) 2) a) Bernald-SoulierGray plateletb) i)ii)iii) 3. a) von WillebrandXIIIb) DICK4. a) PAI-12-APb) DICt-PA
1.
XIII
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2.
1. Osler : AD
(endoglin etc.)
2. Ehlers-Danlos
1. Henoch-Schnlein2-11
Quincke
Henoch-Schnlein
PTAPTTXIIIIgA
IgA
XIII
2.
Henoch-Schnlein
3. Zn
4.
5. C
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3.
1. GPIIb/IIIaADP
2. Bernard-SoulierGPIbGPADPvWF
3. May-HegglinADIIAMYH94. von WillebrandADGPIbvWFvWF5. Gray platelet syndrome-storage pool1
1. NSAIDs2. GPIbvWF
3. 4.
Ca!
vWF!!
!Ca!!Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI2!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
Ca!
XIII!1.
2. Bernard-Soulier
5. /-storage pool4. von Willebrand
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von WillebrandvWF12p12270kDa500kDa20000kDavWF37157%O25%
vWDvWF
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4. von WillebrandvWD
Ca!
vWF!!
!Ca!!Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI2!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
von Willebrand
VIIIC vWFAg vWFRCof RIPA 1 AD
2A AD 2B GPIb AD 2M AD 2N VIII AD or AR 3 AD or AR
von WillebrandvWDvWF
12APTT
DDAVP/vWFDDAVPvWF2BvWD3vWD
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5. Hemophilia)
AXq28BXq27
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Ca!
vWF!!
!Ca!!
Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI2!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
H. pyloriCagA etc.
PAIgG
?&
5%5/l>8/l
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7. DICDisseminated Intravascular Coagulation
(1)overt DIC(DIC)non-overt DIC(DIC)non-overt DIC1
1. DIC()(LPS)(TNF, IL-1)PAI-1
TATPICFDP/DATTM2. DICAPL
PAI-12-APAPLIITATPICFDP>D3. DIC
DIC ()1. 2. FDP 3. Fibrinogen 4. PT
()1. SF 2. TAT 3. PIC 4. AT 5. TM (non-overt DIC)11.
2. () 3. >Xa, APTT (+)21. (+) 2. Na, Na
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2
-21-
-
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1.
3Virchows triad
1. 2. 3. a) ATCSFV Leidenb) DICTMAAPCHITPV, ETPNHLpaTMA
+ +
1. 502.
3. 4. Vit.K6-8C
TTP APS HIT
+ - - + - - APTT
ADAMTS13 2GPI
PF4/HIT
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2.
XI! XIa!
XII! XIIa!HMWK!
Ca2+!
a!Ca2+!
!a!Ca2+&
! a! !
! a!
Ca2+! /vWF!a&
Ca2+& !a&
XI!XIa!
Ca2+&
Ca2+&
XIII! XIIIa!
prothrombinase&
tenase&
t-PA!
Plasminogen!
Plasmin!
&
AT /
/ Protein S!
Protein C!
DVTdeep vein thrombosisPEpulmonary embolism
/
1. ATADATtypeItypeII
2. CADCtypeItypeII DIC3. SADStypeItypeII
4. FV LeidenAPCAD3%V APC
5.
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1. () 2. 3. APTTPTDIC
1. (TTPThrombotic Thrombocytopenic Purpura)Moschcowitz5ADAMTS139q34vWFvWF(UL-VWFM)Upshaw-Schulman90%(ADAMTS13)ADAMTS13UL-VWFM
TTP()(>5/l)
2. HUSHemolytic Uremic SyndromeGasser3ADAMTS13(O-157)Vero
(VT)UL-VWFMHUS(atypical HUS: aHUS)aHUS(C5)
3. TMASLEQuininemitomycine CHELLP
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3. TMAThrombotic Microangiopathy
Ca!
vWF!
!!Ca!!
Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! PGI2!!
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
ADP etc.
Ca!
VT!
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4. APSAntiphospholipid Syndrome
APS1SLE20-40%
APSlupus anticoaglant: LAAPTT
2-GPI 2-GPICL/2-GPI1. 2-GPI 2. 2-GPICL/2-GPI 3. 2.4. 2. 3
Budd-Chiari
(*1)
*22/lsecondary ITP
PSL
*1 CL/2-GPI*2 Vit.K
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&
XI XIa
XII XIIa HMWK
Ca2+
a Ca2+
a Ca2+
a
a
Ca2+ /vWF a
Ca2+
a
XI
XIa
Ca2+
Ca2+
XIII XIIIa
prothrombinase
tenase
/
2-GPI /
LA
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5. HITHeparin-induced Thrombocytopenia
HITAPSDIC5-10%
4PF4PF4/IgGHITHITHITBHITHIT-IgG4
HIT50-85anamnestic responseantigen assayfunctional assay
51410024HIT
56/lFDPDTAT
C
a
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Ca!
vWF!!
!Ca!!
Ca!!
GP Ib/IX/V!
GP IIb/IIIa!
GP IIb/IIIa!
TXA2!
Plt!
collagen etc.! !
Thrombin!
XIII!
Fib!Fib!Fib!Fib!
S&
Ca!
PF4 HIT
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285 ver. 3.7
