B L E E D I N G D I S O R D E R

น ง น ช ส ร ะ ช ย น น ท

ภ า ค ว ช า ก ม า ร เ ว ช ศ า ส ต ร

O U T L I N E S

Basic knowledge

Symptoms and signs

Investigation Treatment

B A S I C H E M O S T A S I S

H E M O S TA S I S

TF-FVIIa

Thrombin

Fibrin

FVIII

FXIFV

FIXa

Platelet

vWF

GPIb/IX/VGPIIb/IIIa

Platelet

Platelet

Fibrin

Vascular Platelet Coagulation protein

2-AntiplasminPAI-1

Plasminogen Activators

Plasminogen Activation Plasmin

Degradation

Fibrin

Degradationproducts

Fibrin strands network

-

-

H E M O S TA S I S : F I B R I N O LY S I S

D-dimer

B L E E D I N G

S Y M P T O M S

Asymptomatic

Hypermenorrhea

Petechiae

Epistaxis

Ecchymosis and joint bleeding

Severe bleeding

CNS

GI

Bleeding after

surgical

procedure

Primary HemostasisSecondary Hemostasis

HEMOSTASIS LEVELS OF CLOTTING FACTORS

DeficiencyLocation gene

(Chro.)Clinical features

Hemostaticlevel

Half life

Afibrinogenemia 4 Severe 0.5 g/L 2-4 d

Prothrombin 11 Severe 20-30 3-4 d

Factor V 1 Severe 15-20 36 h

Factor V and VIII 18 Moderate NA

Factor VII 13 Severe 15-20 4-6 h

Factor VIII X Severe 30-40 8-12 h

Factor IX X Severe 25-30 12-24 h

Factor X 13 Severe 15-20 40-60 h

Factor XI 4 Moderate/mild 15-30 40-70 h

Factor XII 5 No bleeding NA NA

Factor XIII 6, 1 Severe Not known 11-14 d

BLEEDING AND PLATELET COUNT

• Usually occur when platelet count <100,000/cumm

• Surgical bleeding platelet <50,000/cumm

• Spontaneous bleeding platelet <20,000/cumm

Slichter SJ Trans Med Review 2004;18:153-167

All bleed

Excluded skin and epistaxis

Gross bleeding

H I S T O R Y O F S U S P E C T E D B L E E D I N G D I S O R D E R

• Prolonged

• Excessive

• Inappropriate

• Unusual site

• Family history

ISTH-BAT Adults and Pediatrics

Q U E S T I O N 1

• Which of the following is the symptoms of platelet

disorder?

A. Muscle bleeding

B. Hemarthrosis

C. Large ecchymosis

D. Epistaxis

D I S O R D E R O F P L A T E L E T

Quantity Quality

• Platelet count <150,000/ cumm.

• Immune thrombocytopenic purpura <100,000/cumm

Thrombocytopenia Platelet Dysfunction

Platelet

vWF

GPIIb/IIIa

Platelet

C O A G U L AT I O N

TF-FVIIa

Thrombin

Fibrin

FVIII

FXIFV

FIXa

Hemophilia A, B: Factor VIII, IX

Liver disease: Multiple factors

DIC: Multiple factors

Drug: warfarin, heparin

L A B O R A T O R Y T E S T I N H E M O S TA S I S

M E A S U R E M E N TMeasurement Laboratory Tube

Procoagulant APTT, PT/INR, TT

Platelet CBC + blood smear

Platelet function PFA-100, platelet aggregation test(Bleeding time)

Fibrinolysis Euglobulin lysis time

Global hemostasis ThromboelastometryThrombin generation

S P E C I M E N C O L L E C T I O N

Good technique

• Proper vein

• Tourniquet time < 1 min

• Needle size 20-22 G

• Double syringe technique

(discard 1-2 ml)

Proper time- Test within 2 h in room

temperature or within 4 h in ice water (2-4oC)

Good sample

- Concentration and amount of

sodium citrate 3.2% trisodiumcitrate ratio 9:1 or 4.5 ml. in 0.5 ml of sodium citrate (Hct 25-55%)

- Volume of anticoagulant =

0.5x (100-Hct) or

55

(100-Hct) V

(595- Hct)

ปรมาณเลอดทจะใสลงไปในหลอดเลอดทม anticoagulant อย 0.5 มล = (60x4.5) / (100-Hct)

Extrinsic pathway

(monitored by PT)

(tissue factor; thromboplastin)

VIIa VII(III)

Ca++

X

Xa

VaCa++

Phospholipid

Plus

Prothrombin(II)

Thrombin(IIa)

Fibrinogen (I) Fibrin (Ia)

Common pathway(monitored by aPTT,PT, TT)

COAGULATION CASCADEIntrinsic pathway

(monitored by aPTT)

XII Hageman factor(collagen)

XIIa

XI XIa

IX IXa

X

Ca++

VIIIa(IIa) Ca++

PhospholipidPlus

FXIII

Prothrombinase complex: Xa, Va, PL, ca 2+

Tenase complex: IXa, VIIIa, PL, Ca 2+

HK+PK→Kallikrein

TT

C OA G U LO G R A M

Coagulogram Activator Sensitivity

Activated partial thromboplastin time

Phospholipid <30-40%

Prothrombin time Tissue thromboplastin <30-40%

Thrombin time Thrombin Fibrinogen <100 or >400 mg/dL

I N D I C A T I O N O F C O A G U L O G R A M

• Screening hemostasis

before major surgery

•Monitoring anticoagulant:

heparin, warfarin

• Screening of bleeding

disorder

Test Heparin Warfarin

Thrombin time I N

Prothrombin time I I

Partial thromboplastin

time

I Nb

D = decreased; I = increased; N = no change aDecreased in 25% of cases; bIncreased with high drug dosage

I N T E R P R E T A T I O N & I N V E S T I G A T I O N

Prolonged APTT or PT

Mixing APTT, PT with normal plasma 1:1

Uncorrected

Lupus anticoagulant

Corrected

Incubate 2 h at 37c

Uncorrected

Inhibitor to clotting factor

Corrected

Factor deficiency

R/O lipidemic, icteric, hemolyzed

P L A T E L E T F U N C T I O N A N A L Y S I S

• Normal Col/Epi 154±33, Col/ADP 98±17 sec

• Sensitive for diagnosis of vWD and platelet

function defect when compared to bleeding

time

• Monitoring of ASA (prolonged Epi)

• Limitation: prolonged CT in thrombocytopenia

and anemia, shorten CT in high vWF, fibrinogen

and RBCMembranecoated with

agonists(Col, ADP EPI )

Citrated Whole Blood

Aperture

Agonist Concentration Pathway

ADP 5-10 umoL ADP receptor and cyclooxygenase or G-protein pathway

Epinephrine 2-10 umoL Epinephrine receptor and cyclooxygenase or G-protein

pathway

Collagen 5-10 ug/mL Membrane receptor and cyclooxygenase or G-protein

pathway

Thrombin 0.3 U/mL Protease activated factor (PAR) 1 and PAR 4

Ristocetin 1.0 mg/mL GPIb/IX integrin and aggregation with vWF

Arachinodic acid 1 mM Cyclooxygenase pathway

P L A T E L E T A G G R E G A T I O N T E S T

C O M P L E T E B L O O D C O U N T A N D B L O O D S M E A R

• Immature platelet fraction (IPF)

-Young platelet has high RNA content

-Marker of bone marrow function

-Not affected by fragmented RBC or large platelet size

• Normal <10%

G LO B A L H E M O S TA S I S T E S T S

-Thromboelastometry

P H A S E S O F C O A G U L A T I O N

T H R O M B O E L A S T O M E T R Y

Extem: tissue thromboplastin

Intem: ellagic acid

Fibtem: tissue thromboplastin and cytochalasin D

Heptem: heparinase (inhibit heparin)

Aptem: aprotinin (inhibit plasminogen)

Clotting factor and anticoagulation

protein

Platelet and fibrinogen

Platelet, and fibrinogen

Platelet and fibrinogen

Fibrinolysis, factor XIII

T H R O M B O E L A S T O G R A P H Y

Normal Hyperfibrinolysis

Fibrinogen deficiency Platelet dysfunction

L A B O R A T O R Y

I N V E S T I G A T I O N

Screening

CBC, blood smear,

PT, APTT,

Bleeding time/PFA-100

Coagulogram

PT, APTT abnormal

APTT: FVIII, FIX, FXI

PT:FVII

PT and APTT: liver disease DIC

BT/PFA-100+APTT

BT/PFA-100, APTT normal or prolonged vWD

BT/PFA-100

BT/PFA-100 prolonged: Platelet disorder

Normal screening test : FXIII, fibrinolysis

FXII kallikrein

FXI FXIa

FVIIIa

PL, Ca2+

FlX FlXa

Intrinsic pathway

Tissue factor

PL, Ca2+

FVIIa FVII

Extrinsic pathway

FX

Prothrombin Thrombin

Common pathway

FXa

FVIIIa

PL, Ca2+

Fibrinogen Fibrin

APTT PT

TT

Q U E S T I O N 2

• Which of the following screening test is abnormal in hemophilia?

A. APTT

B. PT

C. TT

D. APTT and PT

E. APTT, PT and TT

C O M M O N P L A T E L E T D I S E A S E S

•Thrombocytopenia• Congenital

• Acquired

• Dysfunction

E T I O L O G Y O F T H R O M B O C Y T O P E N I A

• Destructive

thrombocytopenia• Immune

• Immune thrombocytopenia

• Neonatal thrombocytopenia

• Drug

• Non-immune (platelet activation

and consumption

• Surgery or trauma

• Thrombotic microangiopathy

• Congenital heart disease

• Kasabach-Merritt syndrome

• IAHS

• Hypersplenism

Impaired production

Hereditary disorders

Small sized platelet

Normal sized platelet

Large sized platelet

Acquired disorders

Infection: CMV, EBV, HIV, parvovirus

Nutritional deficiency

Bone marrow failure, MDS or

infiltration

Drugs and radiation

Neonatal hypoxia and placental

insufficiency

D R U G S I N D U C E D T H R O M B O C Y T O P E N I A

• Usually occur about 1 week after initiation and recover 1-2 days after

stopping medication

• Mechanisms

• Decrease production

• Chemotherapy

• Thiazide diuretic

• Accelerated platelet destruction

• Drug dependent antibody

• Heparin, quinine, penicillin, sulfonamide, NSAIDs, anticonvulsant, anti-

rheumatic, antidiabetic diuretic, GPIIb/IIIa inhibitor, rifampicin and ranitidine

A C Q U I R E D T H R O M B O C Y T O P E N I A

DHF ITP KMS DICLeukemiaIAHS

I M M U N E T H R O M B O C Y T O P E N I A

• History of acute mucocutaneous bleeding

• Normal physical examination

Cooper N. BJH 2014;165:756-767.

Immune mediated acquired thrombocytopenia platelet <100,000/uL

Complete blood count

with blood smear

-Anemia from blood loss

-Some large platelet, no abnormal cell

E T I O L O G I E S O F P L A T E L E T D Y S F U N C T I O N

Inherited

Acquired Drug, herbalsLiver and kidney diseaseMyelodysplastic syndromeParaproteinemiaMyeloproliferative diseaseAPDE

Hermansky Pudlak, Chidiak Higashi

Gray platelet syndrome

Scott syndrome

Bernard SoulierGlanzmann

thrombastenia

Storage pool disease

A N T I P L A T E L E T

Drug Platelet effect Approximate duration of increased bleeding risk*

Aspirin Irreversible 5 days

Ibuprofen Reversible 24 hours

Naproxen Reversible Up to 4 days**

Thienopyridines (Clopidogrel) Irreversible 7 days

Dipyridamole Reversible Minimal to no risk

with procedures

Long-acting

dipyridamole / aspirin

Reversible / irreversible 5 days

Cilostazol Reversible Minimal to no risk

with procedures

*Individual patient risks and circumstance should be considered.

**Based on minimal data; no time points between 2 hours and 4 days.

A C Q U I R E D P L A T E L E T D Y S F U N C T I O N

W I T H E O S I N O P H I L I A

• Common age group 3-7 years

• Laboratory

• eosinophilia (>500)

• 86%, pale stained and large

platelet

Parasite of allergen

Immune complex

Y

Platelet dysfunction

Platelet release

Propose pathogenesis

M I N I M A L P L A T E L E T A N D C O N D I T I O N

• No risk of bleeding 10,000/uL

• Sepsis, infants, DIC 20,000/uL

• Minimal Procedure 50,000/uL

• Internal, mucosal bleeding 50,000/uL

• CNS, life threatening bleeding 75,000-100,000/uL

Pisciotto PT, Transfusion 1995;53:498-502

C O M M O N C O A G U L A T I O N D I S O R D E R

• Congenital

• Most common vWD and Hemophilia

• Acquired

• Liver disease, DIC

H E M O P H I L L I A

Severe <1%

Mild-Moderate ≥1-40%

APTT Prolonged

B L O O D C O M P O N E N T A N D F A C T O R C O N C E N T R A T E

F O R T R E A T M E N T O F H E M O P H I L I A

สวนประกอบของเลอด ขนาดทใช เพม

FFP, FDP 10 มล./กก. ปจจยการแขงตวของเลอด 10-15% ยกเวนแฟคเตอร IX 7-10%

Cryoprecipitate 0.2 ยนต/กก.* แฟคเตอร VIII 15-20%, fibrinogen 80-100 มก./ดล. von Willebrand factor, factor XIII

Cryo-removed plasma 10 ยนต/กก. เพมทกแฟคเตอร 10-15% ยกเวนแฟคเตอร IX 7-10% และไมเพมแฟคเตอร V, VIII fibrinogen

Factor VIII concentrate

1 ยนต/กก. เพม factor VIII:C 2%

Lyophilized cryoprecipitate 1 ยนต/กก. เพม factor VIII:C 2%

Factor IX concentrate หรอ PCC

1 ยนต/กก. เพม factor IX:C 1%

*cryoprecipitate 1 ยนต ม FVIII:C 40-60 ยนต ถาเปน cryoprecipitate ทม FVIII:C 80-100 ยนต/ถง การให 0.1 ยนต/กก. จะเพม FVIII:C ได 15-20%

R E C O M M E N D E D P L A S M A F A C T O R L E V E L A N D D U R A T I O N

ชนดของอาการเลอดออก ระดบปจจยการแขงตวของเลอด (%)

จดเรมตน ระดบต าสดทยอมรบได1. เลอดออกทกลามเนอ การเยบแผลหตถการทางทนตกรรม 20-30 -

2. เลอดออกในกลามเนอขนาดใหญ (ยกเวน iliopsoas) เลอดออกในขอ ปสสาวะเปนเลอด แผลฉดลก

40-60 20-30

(นาน 3-7 วน)

3. ผาตดขนาดเลกถงปานกลาง เชน ผาตดไสตงอกเสบ เลอดออกในสมอง, ทางเดนอาหาร, ล าคอ, อวยวะส าคญ และ iliopsoas)

80-100 40-50

(1-2 สปดาห หรอจนแผลหายยกเวน iliopsoas ใหจนกวา hematoma หายไปและ เลอดออกในสมองให

เพอปองกนอยางนอย 3-6 เดอน)

4. ผาตดขนาดใหญ เชน ผาตดขอหรอผาตดสมอง 80-100 40-50

(นาน 1-2 สปดาห หรอจนแผลหาย ยกเวนเลอดออกในสมองใหเพอปองกนอยางนอย 3-6 เดอน)

T R E A T M E N T O F H E M O P H I L I A

ผปวยนอก หรอ หอสงเกตอาการ 150,000บาท ไมเกน 2 ครง ตอ เดอนผปวยในภาวะฉกเฉน 300,000 บาท ตอ ครง

“Early treatment to primary prophylaxis”

ลงทะเบยนในสถานพยาบาลทจดทะเบยนดแลผปวย

V O N W I L L E B R A N D D I S E A S E

Platelet

vWF

GPIb/IX/V

GPIIb/IIIaPlatelet

Von Willebrand factor functions

-Platelet adhesion to endothelium and

Attachment between platelet

-Carrier protein of factor VIII

Classification and mode of inheritance

-Type 1 Quantitative defect: AD

-Type 2 Qualitative defect: AD except 2N

-Type 3 Severe deficiency: AR

L A B O R ATO R Y D I AG N O S I S

Specific Test (consult hematologist)

• vWF:Ag vWF multimer

• Ristocetin cofactor activity Genetic study

• Collagen binding assay Platelet aggregation

induced by ristocetin

Screening test

• Normal plt count and smear except type 2B

• Normal or prolonged bleeding time, PFA-100

• Normal or prolonged APTT

Diagnosis

• Type 1: VWD <30% (if no bleeding symptom) 30-50% (if bleeding symptoms)

• Type 2: VWF:Rco/VWF:Ag <0.6

• Type 3: VWF: Ag <10%

Nochols WL et al Haemophilia ;14:171-232.

T R E A T M E N T O F V O N W I L L E B R A N D D I S E A S E

• DDAVP 0.3 mcg/kg/dose in 0.9% NSS 15 mL intravenous in

15-30 mins in VWD type 1, type 2A

• Tranxenamic acid 10 mg/kg/dose IV, 15-20 mg/kg/dose oral

q 4-6 h

• Factor VIII conc. (vWF/FVIII): Alphanate, Immunate

Mannuccio PM Engl J Med 2004;351:683-94.

S U P P O R T I V E T R E A T M E N T

• Antifibrinolytic agent

• Tranexamic acid

• 10 mg/kg/dose intravenously

• 15-20 mg/kg/dose orally

• 5% solution mouth rinse

• Desmopressin• DDAVP 0.3 mcg/kg

D I S S E M I N A T E D I N T R A V A S C U L A R C O A G U L A T I O N

Acquired syndrome,

characterized by the systemic

intravascular activation arising

from different causes, can cause

damage to the microvasculature

result in organ dysfunction

P A T H O G E N E S I S O F D I S S E M I N A T E D I N T R A V A S C U L A R C O A G U L A T I O N

Mononuclearcell

Endothelium

Activated plt

Inflammatory cell

TF

ThrombinFibrin

Cytokines

Inhibit fibrinolysis

Impaired anticoagulant function

Neutrophil

Intravascular

clot

C O N D I T I O N S A S S O C I A T E D W I T H D I S S E M I N A T E D I N T R A V A S C U L A R C O A G U L A T I O N

Sepsis and severe infection

Trauma

Organ destruction e.g. pancreatitis

Malignancy

Solid tumors

Leukemia

Obstetric

Amniotic fluid embolism

Placental abruption

Pre-eclampsia

Vascular abnormalities

Large hemangioma

Vascular aneurysm

Severe liver failure

Toxic and immunological insults

Recreational drugs

ABO transfusion incompatibility

Transplant rejection

D I A G N O S I S I S T H S C O R I N G S Y S T E M

Laboratory Score

Platelet count>100<100<50

012

Level of fibrin markersNo increaseIncreased but <5x upper limit of normalIncreased but ≥5x upper limit of normal

023

Prolonged prothrombin time<3 sec≥3 sec but <6 sec≥6 sec

012

Fibrinogen >1.0 g/L≤1.0 g/L

01

Score ≥ 5 Overt DIC

Levi M Blood 2018;131:845-854

O U T C O M E O F D I C A N D S C O R I N G S Y S T E M ( J M H L W )

Wada H et al Thromb. Hemost. 1995;74:848-52

I complete remissionII partial remissionIII unchangedIV exacerbationV dead

Leukemia Non-leukemia

H E M O S T A S I S I N L I V E R D I S E A S E

M O D E L O F H E M O S T A S I S I N L I V E R D I S E A S E

• Impaired synthetic of coagulation

factors and anticoagulant

• Hyperfibrinolysis vs

hypofibrinolysis

• Decrease vitamin K absorption

• Platelet dysfunction vs

hyperactivity

L A B O R A T O R Y T E S T I N G

Loss of Reserve Laboratory testProcoagulant INR, APTT, fibrinogen

Natural anticoagulant PC, PS, AT

Fibrinolysis D-dimer

Platelet Platelet count

Global coagulation assay Thromboelastometry, thrombin generation

Endothelial vWF

Magnusson M et al. Arch Dis Child 2016;101:854–859

W A R F A R I N A N D

B L E E D I N G M A N A G E M E N T

กรณ อาการเลอดออก การรกษา

ม ไมมINR < 5 ✓ หยดยา 1 วน

ตดตามคา INR เมอไดคาทตองการ ปรบยาลดลง

INR > 5 - <10 ✓ หยดยา 1-2 วน ตดตามคา INR เมอไดคาทตองการ ปรบยาลดลง

INR > 10 ✓ หยดยา warfarin ใหวตามน เค 2-5 มก.ทางปาก INR จะลดลงภายใน 24-48 ชวโมง เมอคาอยในระดบทตองการ ปรบยาลดลง

INR เทาไรกตาม

✓ วตามน เค 1-10 มก. ทางหลอดเลอดพจารณาให FFP หรอ prothrombin complex concentrate ขนกบความรนแรงของอาการเลอดออก*

Common

anticoagulant

related bleeding

T R E A T M E N T O F

H E P A R I N R E L A T E D

B L E E D I N G

ระยะเวลาตงแตไดรบยา heparin ครง

สดทาย (นาท)

ขนาดยา protamine ตอ 100 ยนต ของ

heparin

(มก.)

<30 1

30-60 0.5-0.75

60-120 0.375-0.5

>120 0.25-0.375

M A S S I V E B L O O D L O S S

• Hemorrhage is a leading cause of

preventable traumatic death for patients

of all ages, accounting for 20%-40% of

all early trauma-related mortality

Nosanov L. The American Journal of Surgery 2013; 206:655-660.

M A S S I V E T R A N S F U S I O N

• Replacement blood components >1 blood volume in 24 hr

• Replacement of 50% BV in 3 h

- Premature infant: 90-100 ml/kg

- Term infant-3 months: 80-90 ml/kg

- Children older than 3 months: 70 ml/kg

- Very obese children: 65 ml/kg

- Adult: 60 ml/kg

• Adults >10 U of PRBCs in 24 hr

C A U S E O F M A S S I V E B L E E D I N G

Trauma

Surgery

Uncontrolled bleeding

Uncontrolled bleeding

Massive Blood loss

CoagulopathyPlatelet disorderAnticoagulant, antiplatelet

H O W T O E VA L U AT E ?Classification of hemorrhage

Parameter I II III IV

Blood loss (ml) <750 750-1500 1500-2000 >2000

Blood loss (%) <15% 15-30% 30-40% >40%

Pulse rate (beats/min) <100 >100 >120 >140

Blood pressure Normal Decreased Decreased Decreased

Respiratory rate

(breaths/min)14-20 20-30 30-40 >35

Urine output (ml/hr) >30 20-30 5-15 Negligible

CNS symptoms Normal Anxious Confused Lethargic

Modified from Committee on Trauma . CNS = central nervous system

Gross JB et al Anesthesiology 1983

Trigger volume 40 ml/kg (older children)

C O A G U L O P A T H Y A N D B L O O D

C O M P O N E N T T R A N S F U S I O N

Coagulopathy

Acidosis

BleedingSevere trauma Tissuehypoxia

Hypothermia

Colloid and Crystalloid infusion

Massive RBCtransfusion

Dilution of coagulation factors

and platelet

↓37oC

•Hypotension

•Platelet dysfunction

•Enzyme defect

Hypothemia

CoagulopathyAcidosis

Lethal

trauma triad

COMPLICATION

M A N A G E M E N T O F M A S S I V E B L E E D I N G

• Stop bleeding

• Identified site of bleeding

• Surgical or interventional management

• Restoration of coagulation

Crystalloids

Colloids

RBC

FFP/PCC

Fibrinogen

Platelet

0 0.5 1.0 1.5 2.0

Blood volume replacement

2.5

Hct = 21-24%

Fig = 1.0 g litre-1

Plt < 50x109 litre-1

PT, aPTT >1.5 x normal

FLUID & BLOOD COMPONENT

I N V E S T I G AT I O N

• Complete blood count

• Coagulogram (APTT, PT and TT)

• Fibrinogen, euglobulin clot lysis time

• Thromboelastometry

• Liver function and renal function test

• Urine examination

• Arterial blood gas

• Serum lactate, electrolyte Ca, ionized Ca and

albumin

T H R O M B O E L A S T O M E T R Y A N D G U I D A N C E O F T R A N S F U S I O N

• A systematic review or 9 randomized clinical trials, mostly

cardiac surgery in 776 adults

• Benefit: reduced bleeding, reduction of patients receiving

transfusion as a combined FFP and platelet

• No difference in mortality event rate

Wikkelsoe AJ et al Acta Anaesthesiol Scand 2011;55:1174-1189

R E P L A C E M E N T T H E R A P Y

Coagulation Therapy Dose

Hct <24% RBC10 ml/kg (10%)

1 U adult (3%)

APTT, PT >1.5x FFP

20 ml/kg then 10

ml/kg

q 6-12 hr

Fibrinogen <150 mg/dL

CPP0.2-0.4 u/kg q 12-

24 hr

Platelet <50,000/mcL

Platelet

0.4 u/kg increase

40,000-

80,000/mcL or LPPC 8 U

A D D I T I O N A L T R E A T M E N T

Condition Management

Hemophilia A Factor VIII conc 50 U/Kg

Hemophilia B Factor IX conc 50 U/Kg

Factor VII deficiency Factor VII 15-30 mcg/Kg/dose

Hyperfibrinolysis Tranexamic acid 10 mg/kg/dose

Warfarin induced bleeding

4-PCC 25-50 U/Kg/dose

Immune thrombocytopenia

IVIg 0.8-1 g/Kg, Methylprednisolone 30 mg/Kg/day

R E P L A C E M E N T T H E R A P Y: A D U LT

• Ratio of PRC: FFP: Platelet (and/or) 1:1:1 is now

recommendation especially in adult

Zehtabchi S. Academic Emergency Medicine 2009; 16:371-378.

S Y S T E M A T I C R E V I E W R E P L A C E M E N T T H E R A P Y : C H I L D R E N

• Important message

• Early use of thromboelastometry

• Ratio of transfusion (FFP:Plt:RBC) 1:1:1 or 1:1:2 did not

change the outcomes but increase FFP and plt transfusion in

lower ratio

• Ratio 1:1:1 is required when replacement is > 40 mL/Kg

• Tranexamic acid in severe trauma could reduce transfusion

requirement

Maw G Pediatr Emergency Care 2018;34:594-8

R E C O M B I N A N T A C T I V A T E D F V I I• Fail conventional therapy

• rFVIIa should be used when

• Fibrinogen concentration >100 mg/dL

• Platelet count >50,000/mcL

• PH >7.2

• Dose of rFVIIa

• 200 follow by 100 mcg/kg within 1-3 hr

• 40-150 mcg/kg can stop bleeding in

75% of patients

FVIIa +TF

FXa

Thrombin

Persistent massive

bleeding

rFVIIa 100 mcg/kg (dose แรก)

เลอดหยดไหล ภาวะเลอดออกลดลงเปนอยางมาก

Dose ตอๆ ไป เวนชวง 1-4 ชม.(ปกตใชประมาณ 1-4 doses)

rFVIIIa 100 mcg/kg (dose ท 2) เวนชวง 30 นาท จาก dose แรก.

พยายามแกไข• Hct >24%• Plt >50,000-10,000/uL.• Fibrinogen 100 mg/dL.• T 37oC• pH >7.2

ภาวะเลอดออกลดลงบาง

rFVIIa PROTOCOL

C O N C E P T O F M A S S I V E T R A N S F U S I O N G U I D E L I N E

Massive blood loss

Crystalloid loading

PRC gr O low titer

PRC: FFP (common ratio 1:1)

PRC: FFP: platelet (common ration1:1:1)

PRC: FFP: platelet: CPP

Lab. test

S U M M A R Y

• Hemostasis consists of

• Vascular, platelet, coagulation

protein

• Symptoms of suspected bleeding

disorder

• Prolonged bleeding after injury

• Excessive bleeding

• Multisystem

Common hemostasis defect

• Platelet

• Thrombocytopenia

• Dysfunction

• Coagulation

• Congenital

• Acquired

Platelet 0.2 U/Kg

20,000-40,000/uL

rFVIIa

100 mcg/kg

FIX 1 U/kg increase 1%

FVIII 1 U/kg increase 2%

FFP 10 cc/Kg

10%

CPP 0.2 U/Kg

Fib 80-100 mg/dL

THANK YOU