Transcript 幻灯片 1 - Shandong University

Coagulation Tests
Institute of Diagnostics
Zhong Ning
Email: [email protected]
Copyright 2004, Medicine School of Shandong University
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Summary
• Hemostasis Process
• Coagulation Process
• PT，APTT，PLT and Fibrinogen
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1. Hemostasis
BV Injury
Tissue
Factor
Neural
Blood Vessel
Platelet
Coagulation
Constriction
Activation
Primary hemostatic plug
Activation
Reduced
Plt-Fusion
Blood flow
Thromibn,
Fibrin
Stable Hemostatic Plug
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FLASH链接
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2. Coagulation Process
• Twelve factors are involved in the
coagulation process. Pic 1
• Most of factors are manufactured by liver.
• Vitamin K correlated factor: II, VII, IX, X .
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Factor I
Fibrinogen
Factor VIII
Antihemophilic
globulin
Factor II
Prothrombin
Factor IX
Partial
thromboplastin
component
Factor III
Thromboplastin Factor X
Stuart-Prower
factor
Factor IV
Calcium
Factor XI
Plasma
thromboplastin
antecedent
Factor V
Labile or
proaccelerin
Factor XII
Hageman factor
Factor VII
Stable factor or
proconvertin
Factor XIII
Fibrin-stabilizing
factor
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• The coagulation process can be initiated in
Two ways. Pic 2
• The coagulation occurs in Four stages.
 Stage I : release of platelet factors
 Stage II: generation of thromboplastin
 Stage III: conversion of prothrombin to
thrombin
 Stage IV: formation of fibrinogen to
fibrinogen
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Intrinsic 12,11,9,8
(aPTT-)
Extrinsic-7
(PT)
Common Path (TT)
FX  FXa
Prothrombin Thrombin
Fibrinogen  Fibrin
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Coagulation Pathways
Intrinsic Pathway
Extrinsic Pathway
IX
Tissue Factor + VII
X
Contact
XI
TF Pathway
TF-VII a
PL
XIIa HK a
Common Pathway
Prothrombin
XIa
IXa
PL (Tenase)
VIIIa
Xa
(Prothrombinase)
Protein C, Protein
S, Antithrombin III
PL
XIII
Va
Thrombin
Fibrinogen
Fibrin
(weak)
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XIIIa
Fibrin
(strong)
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Classification:
•
Disorders of Blood vessels
•
Disorders of Platelets
•
Disorders of Coagulation
•
Other disorders
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1.Capillary Fragility (Tourniquet Test;
Rumpel-Leede Capillary-Fragility Test)
• Purpose of test:
• Assesses fragility of capillary walls.
• Evaluates bleeding tendencies.
• Identifies thrombocytopenia*.
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Description of test
• Operator applies a blood-pressure cuff to the upper
arm and inflates it to a point midway between
diastolic and systolic pressure. For example, if your
blood pressure is 120/80, the cuff is inflated to 100
mmHg.
• Pressure is maintained for 5 minutes then released.
• The number of petechiae are counted, and their size
is recorded. Petechiae are small red spots of blood
under the skin caused by leakage of blood cells
through an abnormally fragile capillary.
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TEST RESULTS
• Test values:
• The size and number of petechiae are observed.
Normal values:
• A few petechiae may normally be present before
the test. Less than 10 on the forearm after the test is
considered normal.
• Scale for reporting number of petechiae: 0 to 10 =
1+ 10 to 20 = 2+ 20 to 50 = 3+ 50 or more = 4+
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What HIGH or INCREASED may indicate:
•
•
•
•
•
•
•
•
•
•
•
•
•
Conditions unrelated to bleeding defects, such as scarlet fever*,
measles, influenza*, chronic kidney disease, hypertension* and
diabetes* can increase capillary fragility.
DIC*.
Dysproteinemia*.
Fibrinogen*.
Polycythemia vera*.
Prothrombin*.
Purpura senilis*.
Scurvy*.
Severe factor-VII deficiency*.
Thrombasthenia*.
Thrombocytopenia*.
Vitamin-K deficiency.
Von Willebrand's disease*.
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2.Bleeding Time
• This is a test that measures the speed at
which small blood vessels close off to stop
bleeding (the condition of the blood vessels)
and platelet function
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Perform the Test
• A blood pressure cuff is
placed on the upper arm
and inflated. Two incisions
are made on the lower arm.
These are about 10 mm
(less than 1/2 inch) long
and 1 mm deep (just deep
enough to cause minimal
bleeding).
• The blood pressure cuff is
immediately deflated.
Blotting paper is touched to
the cuts every 30 seconds
until the bleeding stops.
The length of time it takes
for the cuts to stop bleeding
is recorded.
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Normal Values
• The bleeding stops within 1 to 9 minutes
(what is considered normal varies from lab
to lab, depending on how the test is
measured).
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abnormal results mean
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•
•
•
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A vascular (blood vessel) defect
A platelet function defect
Thrombocytopenia (low platelets)
Primary thrombocythemia
Von Willebrand's disease
Drugs that may increase bleeding times
include dextran, indomethacin, and
salicylates (including aspirin).
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3. Prothrombin Time
• PT measure the factors in Extrinsic way
such as VII, X, II.
• II, VII , IX, X, are manufactured by liver
and required Vitamin K.
• PT alse used to measure the effectiveness of
the coumarin type of anticoagulation drugs,
such as warfarin.
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【Measurement】
• Reference values : 12~15 seconds, over the
control 3 seconds make sense.
• Percentages : 60~140% . ( It means the
prothrombin activity)
• PT ratio : the ratio of the PT to control.
• International Normalized Ratio (INR)
• INR : PT ratio convert to INR according ISI
(International Sensitivity Index) .
• Recommendations value: INR 2.0~3.0
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Clincal Significance of PT
Increased PT :
• liver diease or damage such as cirrhosis of
liver.
• Unable to absorb Vitamin K from
gastrointestinal tract.
• True deficiency of Vitamin K.
• DIC
Decreased PT
• No diagnostical significance
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4. Partial Thromboplastin Time
• PTT demonstrate the lack of factors, except
factor VII.
• PTT test the function of Instrinsic clotting
system.
• PTT is useful to screen for general plasma
deficiencies.
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• The purpose of PTT is to monitor heparin
therapy.
• If the PTT is abnormal, further test are
needed to pinpoint exactly which factors is
defective or deficient
• Reference value: 22~34 seconds
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Clinical Significance in PTT
Increase PTT
• Lack of factor VIII------Hemophilia A
• Lack of factor IX------ Hemophilia B
• Taking heparin: PTT is kept about 1.5~2.5
times the control value.
• DIC
Decrease PTT
• No diagnostical significance
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3. Activated Clotting Time
• The ACT is used to monitor intrinic
system .
• The reference value is different from PTT.
• There is the same clinical significance
between ACT and PTT.
• ACT can measured at the bedside.
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5. Platelet Count
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• Platelets are manufactured in bone marrow
by megakarocyte.
• Platelets are only fragments of ctyoplasma.
• They are removed by spleen when they are
old or damage.
Reference value
150,000~350,000/㎜3
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Clinical Significance of Platelet
Count
Increase Platelet Count (Trombocytosis)
• Malignant tumor
• Polycythemia vera
• Splenecytomy
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Low Platelet Count (Thrombocytopenia)
• ITP ( idiopathic thrombocytopenic purpura)
• Acute mass loss of blood
• AIDS
• Hemolytic Disorders
• Hypersplenism ( overactive spleen )
• Administration of Heparin
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6.Disseminated Intravascular
Coagulation (DIC)
• DIC is characterized by
– the systemic activation of the coagulation
system followed by activation of fibrinolytic
system
– high thrombin and plasmin generation
• DIC is not a disease itself, but is a
manifestation of a serious underlying
disorder.
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Causes of DIC
• Infection
- bacterial sepsis, viral
infections
• Neoplasm
- AML, adenocarcinoma
• Obstetrical disorders - retained dead fetus,
abruption, etc
• Trauma/surgery
• Others
- brain injury, crush, burns, etc.
- acute hemolytic transfusion
reaction, etc.
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Hemostatic Balance
PAI-1
Antiplasmin
Tissue factor*
Prot. S
Prot. C
TFPI
Fibrinolytic System
Clotting Factors
Procoagulant
ATIII
Anticoagulant
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DIC
• An acquired syndrome
characterized by
systemic
intravascular
coagulation
• Coagulation is always
the initial event
SYSTEMIC
ACTIVATION OF
COAGULATION
Intravascular
deposition of
fibrin
Depletion of
platelets and
coagulation
factors
Thrombosis of
small and
midsize vessels
Bleeding
Organ failure
DEATH
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Pathophysiology of DIC
• Activation of Blood Coagulation
– Tissue factor/factor VIIa mediated thrombin
generation via the extrinsic pathway
• complex activates factor IX and X
– TF
• endothelial cells
• monocytes
• Extravascular:
– lung
– kidney
– epithelial cells
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Pathophysiology of DIC
PATHOPHYSIOLOGIC
EVENTS
LABORATORY
MANIFESTATIONS
CLINICAL
MANIFESTATIONS
underlying disorder
depletion of clotting factors
prolonged PT, PTT
tissue factor release
thromboctyopenia (consumption)
activation of intrinsic
pathway of coagulation
(systemic thrombin
generation)
hemorrhage
depletion of physiologic anticoagulants
decreased fibrinogen
generalized intravascular
fibrin deposition
microangiopathic hemolytic anemia
thrombosis/infarction
activation of
fibrinolytic system
(systemic plasmin
generation)
increased FDP and D-dimer
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Laboratory Tests Used in DIC
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•
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D-dimer*
Antithrombin III*
F. 1+2*
Fibrinopeptide A*
Platelet factor 4*
Fibrin Degradation
Prod
• Platelet count
• Protamine test
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•
•
•
•
•
•
Thrombin time
Fibrinogen
Prothrombin time
Activated PTT
Protamine test
Reptilase time
Coagulation factor
levels
*Most reliable test
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Occult Blood Test
• Occult Blood (OB) means Hidden blood
that can’t easily been found the presence of
blood.
• Sometimes it is called Guaiac Test
• Gastroccult is specifically designed to test
for occult blood.
• This test always is used to test the feces
(stool).
• Healthy person is negative
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Clinical Significance of OB
Positive:
UGB : upper gastrointestinal bleeding
Such as:
• Bleeding esophageal varices
• Colon polyp or colon cancer
• Esophagitis
• Gastritis
• GI (gastrointestinal) trauma
• GI tumor
• Hemorrhoids
• Fissures
• Inflammatory bowel disease
• Peptic ulcer
• Complications of recent GI surgery
• Angiodysplasia of the colon
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False-Positive
• Red meat
• High-fiber diet
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