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Hemostasis and

Blood Coagulation

Prepared byHamad ALAssaf

Alassaf_h@yahoo.com2015

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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

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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.