Blood Coagulation Process

What sample is needed for Blood Coagulation studies?

1. If the plasma is needed, take 5 ml of venous blood and add sodium citrate as the anticoagulant.
2. Perform the assay immediately or as soon as possible.
3. For factors II, V, VII, and X,  place the citrated plasma on ice immediately, and the sample is stable for 2 hours.
   1. Freeze if it is delayed >2 hours.

What are the Indications for Blood Coagulation studies?

1. To measure the coagulation factor concentration in the blood.
2. To find the inherited or acquired bleeding disorders.
3. If there is a history of bruises or excessive bleeding.
4. If there is prolonged PT or PTT.
5. Acquired conditions like Vit. K deficiency or liver disease.
6. It may be advisable to monitor the treatment of a patient with factor deficiency.

How will you define the blood coagulation process?

1. Blood coagulation is a process that involves a series of biochemical reactions, transforming blood coagulation factors into an insoluble gel through the conversion of soluble fibrinogen into fibrin.
2. The body’s first reaction to bleeding is to constrict the blood vessels.
   1. This will be effective in small blood vessel injuries but not in large blood vessels.

How will you divide blood coagulation factors based on physical characteristics?

1. Contact proteins:
   1. Hageman factor (XII).
   2. Plasma thromboplastin component (XI).
   3. Prekallikeri (PK).
   4. High-molecular-weight kininogen (HMWK).
2. Prothrombin protein:
   1. Prothrombin (II).
   2. Stable factor (VII).
   3. Christmas factor (IX).
   4. Stuart-Power factor (X).
3. Fibrinogen group:
   1. Fibrinogen (I).
   2. Labile factor (V).
   3. Antihemophilic factor (VIII).
   4. Fibrin stabilizing factor (XIII).

How will you describe the Blood coagulation process?

1. The blood coagulation process involves:
   1. A series of biochemical reactions.
   2. It transforms circulating substances into an insoluble gel.
   3. This gel is formed by the conversion of fibrinogen to fibrin.
   4. This whole process needs blood coagulation factors, phospholipids, and calcium.
2. The blood coagulation process consists of:
   1. Extrinsic pathway.
   2. Intrinsic pathway.
3. In blood vessel injuries, the clotting factors are activated to plug the injured site.

What are the phases of the blood coagulation process?

The first stage, the primary phase:

1. It is initiated by platelet aggregation.
2. Platelets adhere to collagen and undergo shape changes.
3. Platelets degranulate and release:
   1. Ionized Ca⁺⁺.
   2. Magnesium.
   3. Serotonin.
   4. Epinephrine.
   5. Phosphate.
   6. ADP and ATP.
   7. Alpha granules release fibrinogen, platelet-derived growth factor, plasminogen activator inhibitor, albumin, β-thromboglobulin, fibrinonectin, and factor V (absorbed from plasma).
   8. The release of these chemicals leads to secondary aggregation, which is irreversible.
4. Ultimately, platelets change shape and adhere to each other.

The second stage, the secondary phase:

1. It is the activation of clotting factors.

The third stage, in Phase Three:

1. Factor X is activated by proteases (VIIa, IXa, and XIIIa).
2. Va can activate IX and X directly.
3. The above reaction is responsible for thrombus formation.
4. The adherent and aggregated platelets release factor V and expose factor 3, accelerating the coagulation process.
5. It will stabilize the platelet plug with a fibrin clot.

 What are the blood coagulation pathways?

The intrinsic pathway:

1. It is initiated by foreign substances like collagen, subendothelium, or phospholipids, which will activate factor XII, involving contact factors and factor XI.
2. Where factor XII and other proteins form a complex on the injured endothelium.
3. XII   XIIa    XI to  XIa and form a complex of VIII + XI + X.
4. Activated Xa is formed.
5. Then, the common pathway starts.

The extrinsic pathway:

1. It is a complex formation between the Tissue factor (factor III or thromboplastin) and factor VII.
2. Activated factor VIIa forms, which stimulate factor X.
3. Alternatively, factor VIIa activates factors IX and X.

Common pathway:

1. The common pathway begins with the activation of factor X through either extrinsic or intrinsic pathways, or both.
2. (Xa)  converts  Prothrombin to Thrombin (active form)  in the presence of factor V, calcium, and phospholipids on the surface of platelets.
3. Thrombin converts Fibrinogen to Fibrin, which polymerizes into a stable clot.
4. Thrombin also activates factor VIII to stimulate platelet aggregation and fibrin polymerization.
5. Prothrombin is a Vit K-dependent factor.

6. Plasmin degenerates the fibrin polymer into fragments that are taken up by the phagocytic cells.
7. Fibrinogen is considered an acute-phase protein and is increased in many diseases.

What are the normal values of clotting factors?

• Reference values are different from various sources.

What are the causes of deficiency of blood coagulation factors?

1. Inherited genetic defects.
2. Acquired.
3. Drug therapy.

What are the causes of acquired factor deficiency?

1. Snake venom.
2. Liver diseases.
3. Uremia.
4. Vit. K deficiency.
5. Anticoagulant ingestion of warfarin.
6. Massive blood transfusion.
7. Some of the cancers.
8. Disseminated intravascular coagulopathy.
9. There is a balance between the factors leading to clotting and the factors causing dissolution.

What is the relationship of blood coagulation factors with other diseases?

1. Factor XII deficiency was observed as an increased risk of Myocardial infarction and venous thrombosis.
2. Fibrinogen is also considered a coronary risk factor that leads to stroke.
3. Determine the exact factor deficiency for the replacement therapy.

Fibrinogen:

What are the causes of Fibrinogen level increase?

1. Acute inflammatory reactions.
2. Trauma.
3. Coronary heart disease.
4. Cigarette smoking.

What are the causes of decreased fibrinogen levels?

1. Liver diseases like hepatitis and cirrhosis.
2. DIC (disseminated intravascular coagulopathy).
3. Fibrinolysis.

Prothrombin:

What are the causes of decreased Prothrombin levels?

1. Vit. K deficiency.
2. Liver disease.
3. Oral anticoagulants.
4. Circulating inhibitors or lupus-like anticoagulants.
5. Decreased synthesis.

Factor V deficiency:

What are the causes of Factor V deficiency?

1. Liver diseases.
2. Factor V inhibitor.
3. Myeloproliferative disorders.
4. DIC and fibrinolysis.
5. Mild decrease in the newborn.

Factor VII deficiency:

What are the causes of Factor VII deficiency?

1. Liver diseases.
2. Kwashiorkor.
3. Normal newborn.
4. Treatment with coumarin-like drugs.

Factor VIII:

What are the causes of increased Factor VIII?

1. Late normal pregnancy.
2. Thromboembolic conditions.
3. Liver diseases.
4. Postoperative patients.
5. Normal newborn.
6. Rebound phenomenon after sudden stoppage of coumarin-like drugs.

What are the causes of Factor VIII deficiency?

1. Due to the presence of factor VIII inhibitors.
2. DIC.
3. Von Willebrand disease.
4. Myeloproliferative disorders.

Factor IX:

What are the causes of Factor IX deficiency?

1. Liver diseases and cirrhosis.
2. Nephrotic syndrome.
3. Anticoagulant antibody formation.
4. Normal newborn.
5. Drugs like Dicoumarol.
6. DIC.
7. Vit K Deficiency.

Factor X:

What are the causes of Factor X deficiency?

1. Vit K deficiency.
2. Liver Diseases.
3. Oral anticoagulants.
4. DIC.
5. Amyloidosis.
6. Normal newborn.

Factor XI:

What are the causes of Factor XI deficiency?

1. Liver diseases.
2. Intestinal malabsorption leads to Vit K deficiency.
3. DIC.
4. Newborn.

Factor XII:

What are the causes of Factor XII deficiency?

1. Nephrotic syndrome.
2. Liver diseases.
3. Chronic myelocytic leukemia.
4. Normal newborn.

Factor XIII:

What are the causes of Factor XIII deficiency?

1. Postoperative patients.
2. Liver diseases.
3. In a persistently increased fibrinogen level.
4. Acute myeloid leukemia.
5. DIC.
6. Circulating anticoagulants.

What are the causes of coagulation factor deficiency?

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