การแปลผล Coagulation study

วนัเสาร์ที่ ๒๔ พฤศจิกายน พ.ศ.๒๕๕๕ฤยิง่ยง ชินธรรมมิตร์

ศิริราช

F12aTFTF

in vitroCoagulation

HMWKPK

F11a FF77aa

TFTF Coagulation

Intrinsic Extrinsic pathwayExtrinsic pathway

F9aFF77aa

APTT

pathwayExtrinsic pathwayExtrinsic pathway

F10aF8aF5a

APTT PPTT

F2a

F5aCommon pathwayCommon pathway

Fibrin monomer / polymerThrombin timeThrombin time

Fibrin monomer / polymer

TFTFin vivo

CoagulationF12a

HMWKPK

F11a FF77aa

TFTF Coagulation: Cell-based

F9aFF77aa

Activatedplatelets

F10aF8aF5a

TFTF--bearbearinging cellcell

F2a

F5aInitiationAmplificatiionFF22aa

Fibrin monomer / polymer

AmplificatiionPropagation

FF22aa

Fibrin monomer / polymer

F13a

cross-linked fibrin

Clinical Approach to BleedingClinical Approach to Bleeding

• Local vs. Systemic bleeding vs. Mixed• Primary vs Secondary hemostatic defectPrimary vs. Secondary hemostatic defect

vs. MixedC it l A i d Mi d• Congenital vs. Acquired vs. Mixed

eg Myoma uteri injured arteryeg, Myoma uteri, injured artery, tumor bleed, Peptic ulcer,

telangiectasia angiodysplasiatelangiectasia, angiodysplasia

Systemic BleedingPrimary Secondary (PLT, Bl.vv.) (Coag. F)

C it l Gl th H hili d f fCongenital Glanzmann throm-basthenia, Bernard-S li d CNT di

Hemophilia, def. of FXI,V,VII,X,I,V+VIII,

Soulier synd, CNT dis etc.

vWDvWD

Acquired AA,AL,ITP,TTP,APDE,ui ti l t l t

warfarin,heparin, vit.K remia,antiplatelet def, FVIII inhibitor

acq.vWD, DIC, cirrhosis, MMacq.vWD, DIC, cirrhosis, MM

Prolonged PT normal APTTProlonged PT, normal APTTCongenitalCongenital• F7 defF12a

F11aTFTF

in vitroCoagulation

HMWKPK F7 assay

Acquired• Liver dis

F11a

F9a

F10a

F7aF7a

F8aAPTT PPTT

Intrinsicpathway

Extrinsic pathwayExtrinsic pathway

• Warfarin• Vit K def

F10a

F2a

F8aF5a

Thrombin timeThrombin time

Common pathwayCommon pathwayClinical DxTry Rx + F/U

• Vit. K defFibrin monomer / polymerThrombin timeThrombin time

• DIC – clinical, d-dimer,fib ifibrinogen

• Def. of fibrinogen F7 inhibitor mixing test• F7 inhibitor – mixing test

Normal PT prolonged APTTNormal PT, prolonged APTT

Congenital• Def of F8 9 11 12;

F12a

F11aTF

in vitroCoagulation

HMWKPK Factor assay

• Def of F8,9,11,12; vWD

F11a

F9a

F10a

F7a

F8aAPTT PT

Intrinsicpathway

Extrinsic pathway

A i dF10a

F2a

F8aF5a

Thrombin time

Common pathwayAcquired• Heparin Hx

Fibrin monomer / polymerThrombin time

• Inhibitor of F8,9,11,12• Lupus anticoagulantLupus anticoagulant

Clinical, specific test

Prolonged APTT, Normal PT

Bl di N bl di

R/O heparin

Bleeding No bleeding

Mixing test Mixing test

Correctable? Correctable?Correctable? Correctable?

Yes No Yes NoYes• Def of F8 9 11

No• F8 inhibitor

Inhibitor of

Yes• F12 def

Def of

No• lupus anti-coagulantF8,9,11

• vWD• Inhibitor of F9,11

• Def ofHMWK,PK

coagulant

Mixing Study : Patient Plasma + Normal Pooled Plasma (NPP) 1:1Normal Pooled Plasma (NPP) 1:1

Patient APTT (Control APTT)

APTT postmix APTT incubated(C t l APTT i b t d)

Pt (Control APTT)

Pt Pt(Control APTT incubated)

Factor+NPP

+ NPP37….%

NPP

F t

NPP

Factorimmediate

37oc1-2 hr

NPPAll

Factor….%

Factor….%

AllFactor100%

Mixing Study : Hemophilia AHemophilia A Plasma + Normal Pooled Plasma (NPP) 1:1Normal Pooled Plasma (NPP) 1:1

APTT 50 sec (control 26 sec)

APTT 28 sec APTT 32 sec( t l 30 )

Pt, (control 26 sec)

Pt, Pt,(control 30 sec)

HphA HphA+

HphA+37F8 =

1%NPP

+ NPPimmediate

37oc1 hr

NPP F8 ~50%

F8 ~4 %

F8 = 100%

50% 45%

100%

Mixing Study : LA+ve Plasma + Normal Pooled Plasma (NPP) 1:1Normal Pooled Plasma (NPP) 1:1

APTT 44 sec (control 26 sec)

APTT 40 sec APTT 45 sec( t l 30 )

Pt, (control 26 sec)

Pt, Pt,(control 30 sec)

LA+ LA++

LA++37NPP+ NPPimmediate

37oc1 hr

NPP

Mixing Study : Acq.FVIII inhibitorAcq.FVIII inhibitor Plasma + Normal Pooled Plasma (NPP) 1:1Normal Pooled Plasma (NPP) 1:1

APTT 50 sec (control 26 sec)

APTT 40 sec APTT 52 sec( t l 30 )

Pt, (control 26 sec)

Pt, Pt,(control 30 sec)

F8inh F8inh+

F8inh+37F8 =

1%NPP

+ NPPimmediate

37oc1 hr

NPP

F8 = 100%100%

Mixing Test (1 : 1)aPTT (sec) after incubation time of :incubation time of :

Incubation Mixture 15 min 30 min 1 hr 2 hr

Normal plasma alone 32 32 36 40

Normal plasma plus - FVIII def plasma 37 37 41 45 FVIII def. plasma (no inhibitor)

plasma + inh 1 BU

37 37 41 45

- plasma + inh. 1 BU- plasma + inh. 5 BU

3743

3847

4555

5364

- plasma + inh. 20 BU 54 61 77 92

Prolonged PT prolonged APTTProlonged PT, prolonged APTTCongenital Factor assayg• Def of F10,5,2,1,5+8AcquiredAcquired• DIC• Liver dis• Liver dis• Warfarin

Vit K d f• Vit. K def• Heparin high dose• Snake venom• Inhibitor of F10,5,2,1• Paraproteinemia• Amyloidosis (F10 def)

Prolonged both aPTT and PT

Thrombin Time or Fibrinogen

normal prolonged

F.II, V, X Heparin contaminationF.II, V, XDeficiencyHereditary: single factor def.

HereditaryHypo-, A-, Dys-fibrinogenemia

Acquired: combined factor def.Liver impairment, vitamin K def.,

AcquiredDIC

warfarin, DIC, amyloidosisInhibitor

Massive transfusionCirrhosis (advance)

Specific factor inhibitor Snake venom

Case Study 1Case Study 1

M 77 yr, large palpable ecchymoses• PT 82 5 sec (9 9 – 12 7); INR = 8 64PT 82.5 sec (9.9 12.7); INR 8.64• aPTT 84.7 sec (22.4 – 31.6)• Platelet adequate• Never bleed• Never bleed

Most likely Dx?

Case Study 2Case Study 2

F 55 yr • Nephrotic syndrome • Mixing APTT (1:1) 27 secp y• Plan kidney Bx

PT 10 (9 12) Most likely Dx? FFP?• PT 10 sec (9-12)• APTT 42 sec (22-30)

Most likely Dx? FFP?

( )• Never bleed

Dx?• Dx?

Case Study 3Case Study 3M 66 yM 66 y• CVT consult Med

( )• Postop (D3) AVR • Bleeding via ICD• Off heparin iv 12 hr• PRC FFP cryoPRC, FFP, cryo.• PT 22 sec (9-12)

APTT 180• APTT >180 sec• Most likely Dx? Mx?

Case Study 4Case Study 4

M 62 y• Multiple myelomap y• Fracture humerus

PT 14 (9 12)• PT 14 sec (9-12)• APTT 35 sec (22-30)( )• Never bleed

Management?• Management?

Case Study 5Case Study 5F 26 yr • PT 37.8 sec (control 13.5)F 26 yr• SLE 1 yr

PT 37.8 sec (control 13.5)• Mixing PT (1:1) 14.7• APTT 72.5 sec (control 28.4)

• spont. ecchymosis, hemothorax

( )• Mixing APTT (1:1) 32.7• TT 17.9 sec (control 17.6)• LA +ve

Most likely Dx?Most proper Ix?Most proper Ix?

Case Study 6Case Study 6D WD? M ?M 27 y

• EcchymosisDx vWD? Mx?

Specimen kept at 4ocy• No other symptom• CBC normal

p p

• CBC normal• PT & PTT normalLab outside hospital• vWF Rco 35% (50-150)• FVIII = 38%

Good Blood Sample?• Correct anticoagulation?...3.2% citrate• Tube properly filled? Adeq bl vol• Tube properly filled?... Adeq. bl. vol.,

correct sequence of tubes filling• Collected through venous line?...heparin !!• Hct >55%? excess citrate !!• Hct >55%?...excess citrate !!• Sample clotted? Hemolyzed?• Plasma – platelet-poor?... LA false -ve• Time from blood draw to analysis? F8• Time from blood draw to analysis?...F8,

vWF activity, protein S; APTT ratio in heparin monitoringheparin monitoring

Case Study 7Case Study 7

F 30 y• Preg G3P2

Most likely Dx?g

• Vaginal delivery• ทําหมัน แผลมีเลือดซึมไม• ทาหมน แผลมเลอดซมไม

หยุดPlatelet adequate• Platelet adequate

• PT 10 sec (9-12)• APTT 46 sec (22-30)• Never bleed (Surgery, e e b eed (Su ge y,

dental extraction)

Case Study 8Case Study 8M 75 y Most likely Dx? Ix?M 75 y• HT, DLP, CAD

E l h i

Most likely Dx? Ix?

• Easy large ecchymosis• Check before dental

procedure• Platelet 81,000• PT 14.3 (10-13)• APTT 29.3 (22.0-32.4)( )• Normal LFT • no risk of vit. K defno risk of vit. K def

Case Study 9Case Study 9F 23 y OPD case M t lik l D ?F 23 y, OPD case• Preg, G1P0

C/S

Most likely Dx?Mx?

• Plan C/S• CBC – normal Mixing APTT (1:1)

= 27 sec (22-30)• PT 10 sec (9-12)• APTT 120 sec

= 27 sec (22-30)

APTT 120 sec• Never bleed on dental

procedureprocedure• No family Hx of bleed