Normal blood Coagulation and role of phospholipids

Why the term, APL is so relevant? Why phospo-lipids are so important in throbotic process in placental bed or any other thrombosis? Rile of Phospo lipids?? Ans; Well, let us start from the beginning enabling thereby  to understand the basics of coagulation and relevance of lipids in APL syndrome  which is a nightmare for Obstetricins,:-Blood coagulation is a process that changes circulating substances within the blood into an insoluble gel.  Normally, the gel plugs any  leaks in blood vessels and stops the loss of blood. The process s called coagulation and the biological agents(organic & inorganic)  requires many factors  which are designated since early 1020s as  coagulation factors, calcium and phospholipids.

• The coagulation factors (proteins) are manufactured by the liver.
• Ionized calcium ( Ca++ ) is available in the blood and from intracellular sources.
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• What about phospholipids?? Ans: Phospholipids are prominent components of cellular and platelet membranes. They provide a surface upon which the chemical reactions of coagulation can take place.

Coagulation can be initiated by either of two distinct pathways.

• The Intrinsic pathway can be initiated by events that take place within the lumen of blood vessels. The Intrinsic pathway requires only elements (clotting factors, Ca++, platelet surface etc.) found within, or intrinsic to the vascular system.
• The Extrinsic pathway is the other route to coagulation. It requires Tissue Factor (tissue thromboplastin), a substance which is "extrinsic to", or not normally circulating in the vessel. Tissue Factor is released when the vessel wall is ruptured.

Regardless of whether the Extrinsic or Intrinsic pathway starts coagulation, completion of the process follows a common pathway. The common pathway involves the activation of factors: X, V, II, XIII and I. Both pathways are required for normal hemostasis and there are positive feedback loops between the two pathways that amplify reactions to produce enough fibrin to form a lifesaving plug. Deficiencies or abnormalities in any one factor can slow the overall process, increasing the risk of hemorrhage.

The coagulation factors are numbered in the order of their discovery. There are 13 numerals but only 12 factors. Factor VI was subsequently found to be part of another factor. The following are coagulation factors and their common names:

• Factor I - fibrinogen
• Factor II - prothrombin
• Factor III - tissue thromboplastin (tissue factor)
• Factor IV - ionized calcium ( Ca++ )
• Factor V - labile factor or proaccelerin
• Factor VI - unassigned
• Factor VII - stable factor or proconvertin
• Factor VIII - antihemophilic factor
• Factor IX - plasma thromboplastin component, Christmas factor
• Factor X - Stuart-Prower factor
• Factor XI - plasma thromboplastin antecedent
• Factor XII - Hageman factor
• Factor XIII - fibrin-stabilizing factor

Liver is the store house or reservoir of coagulation factor( Fatty liver of insulin resistance, Cirrhosis, HELLP, PIH , Acute Fatty necrosis, Jaundice, OCP) all can compromise hepatic synthesis of coagulatory factors.

Vit K dependent factors are  from Liver:-The liver must be able to use Vitamin K to produce Factors II, VII, IX, and X. Dietary vitamin K is widely available from plant and animal sources. It is also produced by normal intestinal flora. A deficiency is rare but may occur:

• in newborns because they must first develop normal flora to produce Vitamin K, or
• when the flora is disturbed by broad-spectrum antibiotics.

At birth and throughout childhood, Factor VIII levels are the same as adult values. Many other factor levels are below adult levels at birth, some as low as 10% of adult levels. Theses levels increase toward the adult levels by age 6 months, although they may remain mildly below adult normal range throughout childhood. Despite lower levels, newborns and children do not normally experience bleeding. This confers some level of antithrombolic protection in youth. During pregnancy Factor XI can decrease, but fibrinogen and factor VIII increase.

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Of the factors below, which is not produced in the liver?

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 Factor IV
 Factor V
 Factor X
 Factor VIII

The most important inherited conditions contributing to development of clotting events in children include deficiencies of natural anticoagulants such as proteins C and S, and antithrombin. When considered individually, other inherited clotting disorders, such as the factor V Leiden mutation (also called activated protein C [APC] resistance) or the prothrombin 20210 mutation are less important risk factors in children.

Causes of Blood Clots

The formation of blood clots in the veins is related to three abnormalities commonly known as “Virchow’s triad”. The processes of Virchow’s triad include the following:

·      Damage to blood vessels

·      Excessive clotting ability (hypercoagulability)

·      Pooling of blood (stasis)

Maintaining normal blood flow involves careful coordination of the three main clotting processes— procoagulant (promotes clotting), anticoagulant (prevents clotting), and fibrinolytic (clot breakdown) systems. Over the past 30 years, our understanding of the mechanisms that lead to clotting and clotting disorders and their treatment has significantly improved.

Procoagulant clotting proteins are essential in the starting and progression of normal clot formation. The naturally occurring anticoagulant proteins are needed to regulate clotting once it has started. This clotting process keeps the clot at the area of injury by controlling the procoagulant system. Once a stable clot has formed and bleeding has been controlled, the fibrinolytic system removes the clot and restores the normal structure of the blood vessels.

In clotting diseases, the causes of clotting may be related to increased levels of procoagulants, decreased levels of natural anticoagulants, or defects in the fibrinolytic system. In addition, abnormalities in the blood vessels contribute to development of clots.

Inherited Causes of Blood Clots

Inherited causes of blood clots are related to a genetic (inherited) tendency for clot formation that generally occur at a young age (for example, occurring before 40 or 45 years), with or without an apparent cause, and with a tendency to recur.

Table 1 provides a list of inherited causes of blood clots. For more detailed information on these conditions, click on the individual condition or visit the section on Inherited Causes of Blood Clots.

Table 1. Inherited Causes of Blood Clots
Increased Levels of Procoagulants	Decreased Levels of Anticoagulants	Abnormal Fibrinolysis	Other Inherited Causes
Factor V Leiden mutation or activated protein C resistance*	Antithrombin	Plasminogen Deficiency	Paroxysmal Nocturnal Hemoglobinemia
Prothrombin 20210 mutation	Protein C	Decreased Levels of Tissue Plasminogen Activator (t-PA)