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When blood vessel ruptures….
• When you get a cut and your blood vessel ruptures, blood
platelets collect at the site of the wound. They create a
temporary plug to stop the bleeding. In order to produce a
strong blood clot, a series of 12 plasma proteins, or
coagulation “factors” act together to make a substance called
fibrin, which seals the wound.
• A bleeding disorder known as hemophilia could cause your
body to create certain coagulation factor incorrectly, or not at
all. Some medications, liver disease, or vitamin K deficiency
may cause abnormal clot formation.
• Symptoms of a bleeding disorder include:
• easy bruising
• bleeding that won’t stop, even after applying
pressure to the wound
• heavy menstrual periods
• blood in the urine
• swollen or painful joints
• nosebleeds
• Hemostasis or haemostasis :
is a complex process which causes the
bleeding process to stop. It refers to the
process of keeping blood within a damaged
blood vessel.
Hemostasis is maintained in the body via
three mechanisms:
• Vascular spasm - Damaged blood vessels constrict.
• Platelet plug formation - Platelets adhere to
damaged endothelium to form platelet plug (primary
hemostasis) and then degranulate.
• Blood coagulation - Clots form upon the conversion
of fibrinogen to fibrin, and its addition to the platelet
plug (secondary hemostasis).
THE CLOTTING MECHANISM
INTRINSIC EXTRINSC
PROTHROMBIN THROMBIN
FIBRINOGE
N
FIBRIN(II) (III)
(I)
V
X
Tisue ThromboplastinCollagen
VII
XII
XI
IX
VIII
FIBRINOLYTIC PHASE
• ANTICLOTTING MECHANISMS ARE ACTIVATED TO
ALLOW CLOT DISINTEGRATION AND REPAIR OF THE
DAMAGED VESSEL.
HEMOSTASIS
• DEPENDENT UPON:
 Vessel Wall Integrity
 Adequate Numbers of Platelets
 Proper Functioning Platelets
 Adequate Levels of Clotting Factors
 Proper Function of Fibrinolytic Pathway
So What Causes Bleeding Disorders?
VESSEL DEFECTS
PLATELET DISORDERS
FACTOR DEFICIENCIES
VESSEL DEFECTS
VITAMIN C DEFICIENCY
BACTERIAL & VIRAL INFECTIONS
ACQUIRED
PLATELET DISORDERS
THROMBOCYTOPENIA (INADEQUATE NUMBER OF PLATELETS)
Causes
DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES
THROMBOCYTOPATHY )ADEQUATE
NUMBER BUT ABNORMAL FUNCTION .(
causes
UREMIA
INHERITED DISORDERS
MYELOPROLIFERATIVE DISORDERS
DRUG INDUCED(ASPIRIN,)
FACTOR DEFICIENCIES
• Inherited:MOPHILIA A
1. HEMOPHILIA B
2. V W DISEASE
• Acquired:
1. Anticoagulant therapy
2. Liver diseases
3. DIC
LABORATORY EVALUATION
• PLATELET COUNT
• BLEEDING TIME (BT)
• PROTHROMBIN TIME (PT)
• PARTIAL THROMBOPLASTIN TIME (PTT)
• THROMBIN TIME (TT)
PLATELET COUNT (CBC)
NORMAL 100,000 - 400,000 CELLS/MM3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Sever Thrombocytopenia
PROTHROMBIN TIMEPROTHROMBIN TIME
Measures Effectiveness of the ExtrinsicMeasures Effectiveness of the Extrinsic
PathwayPathway
NORMAL VALUENORMAL VALUE
10-15 SECS10-15 SECS
11-16 sec depends……..11-16 sec depends……..
PT
• The prothrombin time: is therefore the time required for the plasma
to clot after an excess of thromboplastin and an optimal
concentration of calcium have been added.
• Measures the function of the Extrinsic Pathway.
• Sensitive to Factors I, II, V, VII, X.
• The PT evaluates patients suspected of having an inherited or
acquired deficiency in these pathways.
Principles
• When preformed tissue
thromboplastin and calcium chloride
are added to citrated plasma, the
plasma clots. The time taken for the
clot to appear is called Prothrombin
time (PT).
Procedure
• Requirements.
• Patient‘s platelet-poor plasma
• Normal, control‘ plasma‗
• Thromboplastin Reagents
• Glass Tubes Automatic Micropipettes of 100
μl
• A Water Bath set at 37°C Stop watches
• A Table Lamp
Performance
• Set the table lamp behind the water bath in such a way that the tubes can
be seen against it but the eyes of the scientist are protected from direct
light.
• Place four plain glass tubes in the water bath to warm at 37°C.
• Deliver 100 μl of test plasma in a test tube and wait for 2 minute.
• Deliver 200 μl of commercial tissue thrombo plastin and
• start the stopwatch simultaneously.
• Mix the contents and leave. After 6-8 seconds, examine the tube against
shielded light for clot formation, by tilting.
• Keep on doing so every 1-2 seconds by briefly taking the tube out of the
water.
• Stop the stopwatch when a visible clot is formed in the test tube and
note the time.
• Repeat the procedure once again on the test plasma. Take the mean of
the two recorded times. Repeat the test on the control plasma as done
for the patient‘s plasma
Precautions:
• The blood should be collected through a clean
venipuncture & without much stasis.
• The proportion of anticoagulant and blood should be
precise and appropriate.
• The samples should not be allowed to stand at room
temperature for too long.
• If a delay is expected, these should be transported on
crushed ice.
• The platelet-poor plasma should be separated as soon as
possible.
• The blood should be collected and processed using
disposable plastic syringes, tubes and pipettes.
• The test should always be performed in clean glass tubes.
• The results are also reported as a ratio between the
patient‘s Prothrombin Time & that of the test plasma
or as INR.
• Interpretations:
• Prothrombin Time is prolonged in deficiency of
Factors II, V, VII and X as well as in the presence of
Heparin. This can occur in the following conditions:
Oral anticoagulant therapy (Vitamin K antagonists)
Obstructive jaundice Liver disease Haemorrhagic
disease of the newborn Malabsorption Vitamin K
deficiency Hereditary deficiency of concerned
PT RESULT PTT RESULT
EXAMPLES OF CONDITIONS THAT MAY BE
PRESENT
Prolonged Normal Liver disease, decreased vitamin K,
decreased or defective factor
VII, chronic low-
grade disseminated intravascular
coagulation (DIC), anticoagulation
drug (warfarin) therapy
Normal Prolonged Decreased or defective factor VIII,
IX, XI, or XII, von Willebrand
disease (severe type), presence
of lupus anticoagulant,
autoantibody against a specific
factor (e.g., factor VIII)
Prolonged Prolonged Decreased or defective factor I, II, V
or X, severe liver
disease, acute DIC, warfarin
overdose
Normal Normal or slightly prolonged May indicate normal hemostasis;
however, PT and PTT can be
normal in conditions such as mild
deficiencies in coagulation
factor(s) and mild form of von
Willebrand disease. Further testing
may be required to diagnose these
conditions.
nterpretation of PT and PTT in Patients with a Bleeding or Clotting Syndrome
THE CLOTTING MECHANISM
INTRINSIC EXTRINSC
PROTHROMBIN THROMBIN
FIBRINOGE
N
FIBRIN(II) (III)
(I)
V
X
Tisue ThromboplastinCollagen
VII
XII
XI
IX
VIII
When is it ordered?
• Used to monitor oral anticoagulant therapy (Warfarin /
Coumadin).
• When a patient who is not taking anti-coagulant drugs
has signs or symptoms of a bleeding disorder.
• When a patient is to undergo an invasive medical
procedure, such as surgery, to ensure normal clotting
ability.
An elevated prothrombin time may indicate the
presence of:
 Vitamin K deficiency
(Vitamin K is needed to make prothrombin and other clotting factors)
 DIC
 liver disease
 a deficiency in one or more of the following factors:
 I, II, V, VII, X.
 Anticoagulant (warfarin)
INR
• A PT test may also be called an INR test.
• INR (international normalized ratio) stands for a way of
standardizing the results of prothrombin time tests, no
matter the testing method.
• So your doctor can understand results in the same way
even when they come from different labs and different
test methods.
• Using the INR system, treatment with (anticoagulant
therapy) will be the same. In some labs, only the INR is
reported and the PT is not reported
INR
• An INR of 1.0 means that the patient PT is normal.
• An INR greater than 1.0 means the clotting time is
elevated.
• INR of greater than 5 or 5.5 = unacceptable high risk of
bleeding,whereas if the INR=0.5 then there is a high
chance of having a clot.
• Normal range for a healthy person is 0.9–1.3, and for
people on warfarin therapy, 2.0–3.0, although the target
INR may be higher in particular situations, such as for
those with a mechanical heart valve.
PARTIAL THROMBOPLASTIN TIME
Measures Effectiveness of the Intrinsic
Pathway
NORMAL VALUENORMAL VALUE
25-40 SECS25-40 SECS

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prothrombin time

  • 1.
  • 2. When blood vessel ruptures…. • When you get a cut and your blood vessel ruptures, blood platelets collect at the site of the wound. They create a temporary plug to stop the bleeding. In order to produce a strong blood clot, a series of 12 plasma proteins, or coagulation “factors” act together to make a substance called fibrin, which seals the wound. • A bleeding disorder known as hemophilia could cause your body to create certain coagulation factor incorrectly, or not at all. Some medications, liver disease, or vitamin K deficiency may cause abnormal clot formation.
  • 3. • Symptoms of a bleeding disorder include: • easy bruising • bleeding that won’t stop, even after applying pressure to the wound • heavy menstrual periods • blood in the urine • swollen or painful joints • nosebleeds
  • 4. • Hemostasis or haemostasis : is a complex process which causes the bleeding process to stop. It refers to the process of keeping blood within a damaged blood vessel.
  • 5. Hemostasis is maintained in the body via three mechanisms: • Vascular spasm - Damaged blood vessels constrict. • Platelet plug formation - Platelets adhere to damaged endothelium to form platelet plug (primary hemostasis) and then degranulate. • Blood coagulation - Clots form upon the conversion of fibrinogen to fibrin, and its addition to the platelet plug (secondary hemostasis).
  • 6. THE CLOTTING MECHANISM INTRINSIC EXTRINSC PROTHROMBIN THROMBIN FIBRINOGE N FIBRIN(II) (III) (I) V X Tisue ThromboplastinCollagen VII XII XI IX VIII
  • 7. FIBRINOLYTIC PHASE • ANTICLOTTING MECHANISMS ARE ACTIVATED TO ALLOW CLOT DISINTEGRATION AND REPAIR OF THE DAMAGED VESSEL.
  • 8. HEMOSTASIS • DEPENDENT UPON:  Vessel Wall Integrity  Adequate Numbers of Platelets  Proper Functioning Platelets  Adequate Levels of Clotting Factors  Proper Function of Fibrinolytic Pathway
  • 9. So What Causes Bleeding Disorders? VESSEL DEFECTS PLATELET DISORDERS FACTOR DEFICIENCIES
  • 10. VESSEL DEFECTS VITAMIN C DEFICIENCY BACTERIAL & VIRAL INFECTIONS ACQUIRED
  • 11. PLATELET DISORDERS THROMBOCYTOPENIA (INADEQUATE NUMBER OF PLATELETS) Causes DRUG INDUCED BONE MARROW FAILURE HYPERSPLENISM OTHER CAUSES
  • 12. THROMBOCYTOPATHY )ADEQUATE NUMBER BUT ABNORMAL FUNCTION .( causes UREMIA INHERITED DISORDERS MYELOPROLIFERATIVE DISORDERS DRUG INDUCED(ASPIRIN,)
  • 13. FACTOR DEFICIENCIES • Inherited:MOPHILIA A 1. HEMOPHILIA B 2. V W DISEASE • Acquired: 1. Anticoagulant therapy 2. Liver diseases 3. DIC
  • 14. LABORATORY EVALUATION • PLATELET COUNT • BLEEDING TIME (BT) • PROTHROMBIN TIME (PT) • PARTIAL THROMBOPLASTIN TIME (PTT) • THROMBIN TIME (TT)
  • 15. PLATELET COUNT (CBC) NORMAL 100,000 - 400,000 CELLS/MM3 < 100,000 Thrombocytopenia 50,000 - 100,000 Mild Thrombocytopenia < 50,000 Sever Thrombocytopenia
  • 16. PROTHROMBIN TIMEPROTHROMBIN TIME Measures Effectiveness of the ExtrinsicMeasures Effectiveness of the Extrinsic PathwayPathway NORMAL VALUENORMAL VALUE 10-15 SECS10-15 SECS 11-16 sec depends……..11-16 sec depends……..
  • 17. PT • The prothrombin time: is therefore the time required for the plasma to clot after an excess of thromboplastin and an optimal concentration of calcium have been added. • Measures the function of the Extrinsic Pathway. • Sensitive to Factors I, II, V, VII, X. • The PT evaluates patients suspected of having an inherited or acquired deficiency in these pathways.
  • 18. Principles • When preformed tissue thromboplastin and calcium chloride are added to citrated plasma, the plasma clots. The time taken for the clot to appear is called Prothrombin time (PT).
  • 19. Procedure • Requirements. • Patient‘s platelet-poor plasma • Normal, control‘ plasma‗ • Thromboplastin Reagents • Glass Tubes Automatic Micropipettes of 100 μl • A Water Bath set at 37°C Stop watches • A Table Lamp
  • 20. Performance • Set the table lamp behind the water bath in such a way that the tubes can be seen against it but the eyes of the scientist are protected from direct light. • Place four plain glass tubes in the water bath to warm at 37°C. • Deliver 100 μl of test plasma in a test tube and wait for 2 minute. • Deliver 200 μl of commercial tissue thrombo plastin and • start the stopwatch simultaneously. • Mix the contents and leave. After 6-8 seconds, examine the tube against shielded light for clot formation, by tilting. • Keep on doing so every 1-2 seconds by briefly taking the tube out of the water. • Stop the stopwatch when a visible clot is formed in the test tube and note the time. • Repeat the procedure once again on the test plasma. Take the mean of the two recorded times. Repeat the test on the control plasma as done for the patient‘s plasma
  • 21. Precautions: • The blood should be collected through a clean venipuncture & without much stasis. • The proportion of anticoagulant and blood should be precise and appropriate. • The samples should not be allowed to stand at room temperature for too long. • If a delay is expected, these should be transported on crushed ice. • The platelet-poor plasma should be separated as soon as possible. • The blood should be collected and processed using disposable plastic syringes, tubes and pipettes. • The test should always be performed in clean glass tubes.
  • 22. • The results are also reported as a ratio between the patient‘s Prothrombin Time & that of the test plasma or as INR. • Interpretations: • Prothrombin Time is prolonged in deficiency of Factors II, V, VII and X as well as in the presence of Heparin. This can occur in the following conditions: Oral anticoagulant therapy (Vitamin K antagonists) Obstructive jaundice Liver disease Haemorrhagic disease of the newborn Malabsorption Vitamin K deficiency Hereditary deficiency of concerned
  • 23. PT RESULT PTT RESULT EXAMPLES OF CONDITIONS THAT MAY BE PRESENT Prolonged Normal Liver disease, decreased vitamin K, decreased or defective factor VII, chronic low- grade disseminated intravascular coagulation (DIC), anticoagulation drug (warfarin) therapy Normal Prolonged Decreased or defective factor VIII, IX, XI, or XII, von Willebrand disease (severe type), presence of lupus anticoagulant, autoantibody against a specific factor (e.g., factor VIII) Prolonged Prolonged Decreased or defective factor I, II, V or X, severe liver disease, acute DIC, warfarin overdose Normal Normal or slightly prolonged May indicate normal hemostasis; however, PT and PTT can be normal in conditions such as mild deficiencies in coagulation factor(s) and mild form of von Willebrand disease. Further testing may be required to diagnose these conditions. nterpretation of PT and PTT in Patients with a Bleeding or Clotting Syndrome
  • 24. THE CLOTTING MECHANISM INTRINSIC EXTRINSC PROTHROMBIN THROMBIN FIBRINOGE N FIBRIN(II) (III) (I) V X Tisue ThromboplastinCollagen VII XII XI IX VIII
  • 25. When is it ordered? • Used to monitor oral anticoagulant therapy (Warfarin / Coumadin). • When a patient who is not taking anti-coagulant drugs has signs or symptoms of a bleeding disorder. • When a patient is to undergo an invasive medical procedure, such as surgery, to ensure normal clotting ability.
  • 26. An elevated prothrombin time may indicate the presence of:  Vitamin K deficiency (Vitamin K is needed to make prothrombin and other clotting factors)  DIC  liver disease  a deficiency in one or more of the following factors:  I, II, V, VII, X.  Anticoagulant (warfarin)
  • 27. INR • A PT test may also be called an INR test. • INR (international normalized ratio) stands for a way of standardizing the results of prothrombin time tests, no matter the testing method. • So your doctor can understand results in the same way even when they come from different labs and different test methods. • Using the INR system, treatment with (anticoagulant therapy) will be the same. In some labs, only the INR is reported and the PT is not reported
  • 28. INR • An INR of 1.0 means that the patient PT is normal. • An INR greater than 1.0 means the clotting time is elevated. • INR of greater than 5 or 5.5 = unacceptable high risk of bleeding,whereas if the INR=0.5 then there is a high chance of having a clot. • Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve.
  • 29. PARTIAL THROMBOPLASTIN TIME Measures Effectiveness of the Intrinsic Pathway NORMAL VALUENORMAL VALUE 25-40 SECS25-40 SECS