hemostasis and blood coagulation prepared by hamad alassaf [email protected] 2015 1
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Hemostasis and
Blood Coagulation
Prepared byHamad ALAssaf
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Hemostasis, Coagulation
1. Vascular Spasm
2. Platelet plug
3. Formation of clot
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Platelets
- Formed in bone marrow, 140-440,000 /µl
- Sequestered in spleen (30%)
- 2-4 m in diameter, life span 8-12 days, no nucleus
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Platelets
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Clot Formation
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Surface Contact
XII-----XIIa
XI-----XIa
IX-----IXa
X-----------Xa------------X
Intrinsic
Prothrombin Thrombin
Fibrinogen Fibrin
Extrinsic
TissueDamageTF-VIIa
Common
XIII
XIIIaStableFibrin
TF (Tissue factor)
TF
VII
Formation of a Clot
VIIIaVIII
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Extrinsic Pathway
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Intrinsic Pathway
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• Plasminogen = circulating globulin
- Plasmin = proteolytic enzyme, similar to trypsin
- digest fibrin threads, fibrinogen, and other clotting factors
- Significance: removal of tiny little clots
• Plasminogen activators:- Tissue Plasminogen Activator (TPA), urokinase, streptokinase
• Plasminogen inhibitors:- plasminogen activator inhibitor (PAI-1) inhibits TPA
- Alpha2-antiplasmin blocks binding plasminogen to fibrin
Fibrinolytic System
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I. Vitamin C deficiency: lack of stable collagen (elderly, alcoholics)collagen synthesis when dysfunctional, cause the most severe symptoms of scurvy
. (Prevent healing of rupture capillaries).
II. Hepatic failure: almost all clotting factors are made in the liver
III. Vitamin K deficiency:
- required for II (prothrombin), VII, IX, and X
- fat malabsorption due to lack of bile secretion
IV. Hemophilia:
- Factor VIII (hemophilia A 1/10,000),
- Factor IX (hemophilia B 1/100,000)
- chromosome X
Coagulation Defects
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V. Thrombocytopenia:
- bleeding small capillaries and blood vessels (mucosal, skin)
- low number of platelets
- Purpura- autoimmune (common)
VI. Disseminated Intravascular Clotting:
- abnormal bleeding and clot formation
- critically ill patients
- coagulation and clot lysis in uncontrolled manner
- due to massive tissue damage
- depletion of clotting factors
Coagulation Defects
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Used for Thromboembolic conditions such as :- Venous thrombosis, pulmonary embolism
- artificial heart valves, by-pass surgery
- long-term bed immobilization
HEPARIN ( iv or subcutaneous): immediate anticoagulation It produces its major anticoagulant effect by inactivating thrombin and activated factor
X (factor Xa) through an antithrombin (AT)-dependent mechanism. Prolong PTT
COUMARINS (e.g. warfarin given orally ):
compete Vitamin K 2 - 4 days to act reverse coagulation. Prolong PT
Anti Coagulation
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Platelet count:- 150-300,000/ µl
- thrombocytopenia - aplastic anemia, autoimmune, platelet function
myeloproliferative, uremia, drugs (aspirin, antibiotics), von Willebrand Disease
Bleeding Time:- time for skin wound to stop bleeding
- normal value < 6 minutes
- done to assess platelets function.
Clotting Time: - the time required for blood to form a clot
- Normal value of clotting time is 2 to 6 minutes.
- used to diagnose hemophilia
Thrombin Time: - to evaluate the level and function of fibrinogen.
- Normal values are 12 to 14 seconds.
Blood Coagulation Tests
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Tests of Clotting Pathway
X
VII
XII
XI
IX
VIII PTAbout 12 seconds
aPTTAbout 25 – 39 seconds
Activated PartialThromboplastin Time
Prothrombin Time
Intrinsic Extrinsic
V
ThrombinProthrombin (II)
The PTT is used to evaluate the coagulation factors XII, XI, IX, VIII, X, V, II (prothrombin) and I (fibrinogen).
PT test evaluates the coagulation factors VII, X, V, II, and I (fibrinogen).
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PT result PTT result Common condition present
Prolonged Normal Liver disease, decreased vitamin K, decreased or defective factor VII.
Normal Prolonged
Hemophilia A or B (decreased or defective factor VIII or IX) or factor XI deficiency, von Willebrand disease, factor XII deficiency, or lupus anticoagulant present.
Prolonged ProlongedDecreased or defective factor I (fibrinogen), II (prothrombin), V or X, severe liver disease, disseminated intravascular coagulation (DIC).
Normal Normal indicate normal hemostasis.
Prothrombin Time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway.
Partial Thromboplastin Time (PTT) is a performance indicator of the efficacy of both the "intrinsic" and the common coagulation pathways.