CH. 35 + Module 2

Hemostasis

Hemostasis

• Cessation of bleeding

• It occurs within the intravascular compartment lined with endothelium.

Primary Hemostasis

Refers to the role of blood vessels and platelets in the initial response to a vascular injury or to the commonplace desquamation of dying or damaged endothelial cells

Secondary Hemostasis

It describes the activation of a series of coagulation proteins in the plasma, mostly serine proteases, to form a fibrin clot

Physiologic Hemostatic System

A tightly regulated balance between formation and dissolution of hemostatic plugs modulated by a series of enzymes and scaffolding proteins.

• Platelets, Granulocytes & Monocytes

• Coagulation Protein System (Clot Forming)

• Fibrinolysis Protein System (Clot Lysing)

• Anticoagulation Protein System (Regulating)

Factors involved in Normal Hemostasis and Thrombosis:

Coagulation System (Clot Forming)

It serves to form thrombin that initiates the proteolysis of fibrinogen, —> leading to fibrin clot formation

Fibrinolytic System (Clot Lysing)

It functions to lyse the clot formed by thrombin.

Anticoagulation System (Regulating)

It regulates all enzymes of the coagulation and fibrinolytic systems, so that no inappropriate excess of clotting or bleeding occurs

Vasoconstriction

It is a short-lived reflex reaction of the smooth muscle in the vessel wall produced by the sympathetic branches of the autonomic nervous system.

The platelets adhere to the subendothelial collagen fibers, spread pseudopods along the surface, and aggregates.

This happens if vascular injury exposes the endothelial surface and underlying collagen

Epinephrine and Serotonin

These hormones promote vasoconstriction

ADP

This increases the adhesiveness of platelets

Platelet cohesion

IIb/IIIa receptors mediate the recruitment of local platelets by forming fibrinogen bridges between platelets—a process called?

Glycoprotein IIb / IIIa

This receptor is specific for platelets and is the most abundant platelet membrane protein with approximately 50,000 receptors per platelet

Platelet aggregation

This is the gold standard test to determine platelet function

• Collagen

• Proteolytic enzymes (thrombin)

• Biological amines

Agents capable of producing platelet aggregation in vitro:

Aggregation

It results from bridges formed by fibrinogen in the presence of calcium produce a sticky surface on platelets

Fibrinogen

It provides basis for platelet consolidation & stabilization

Irreversible platelet plug

Fibrinogen process involves the precipitation of polymerized fibrin around each platelet, and the result is a fibrin clot that produces an?

• Electronic Particle Counter

• Examination of stained blood film

Used for Quantitative Determination of Platelet:

• PBS

• Platelet Count

• Template Bleeding Time

• Petechiometer

Used for Qualitative Assessment of Platelet:

Qualitative

Type of laboratory assessment done if the platelet count is normal

Bleeding Time w/ or w/o Aspirin

• In vivo measurement of platelet adhesion and aggregation on locally injured vascular subendothelium.

• Provides an estimate of the integrity of the platelet plug and thereby measures the interaction between the capillaries and platelets

Clot Retraction

It reflects the number and quality of platelets, fibrinogen concentration, fibrinolytic activity, and packed red cell volume

directly

The degree of clot retraction is __________ proportional to the number of platelets.

inversely

The degree of clot retraction is _____________ proportional to the hematocrit and the level of the blood coagulation factor fibrinogen

• ADP

• Collagen

• Epinephrine

• Snake venom

• Thrombin

• Ristocetin

Agents that can be used to aggregate platelets:

Platelet-rich plasma is treated with a known aggregating agent. If aggregated, cloudiness or turbidity can be measured using a spectrophotometer.

Principle of Platelet Aggregation test

• Purpura associated with direct endothelial cell damage.

• Purpura associated with an inherited disease of the connective tissue.

• Purpura associated with decreased mechanical strength of the microcirculation.

• Purpura associated with mechanical disruption of small venules.

• Purpura associated with microthrombi (small clots).

• Purpura associated with vascular malignancy.

Types of Vascular Disorders

Wiskott-Aldrich syndrome

It demonstrates the smallest platelets seen

May-Hegglin anomaly

It is characterized by the presence of large platelets and the presence of Döhle-like bodies in the granulocytic leukocytes

Alport syndrome

Disorder that exhibits giant platelets and thrombocytopenia

Bernard-Soulier syndrome

• Demonstrates the largest platelets.

• In this disorder, it has been demonstrated that the giant platelets are probably an artifact of the slide

Giant Platelet syndrome

Bernard-Soulier syndrome is also known as?

Reactive Thrombocytosis

This is also called secondary thrombocytosis

Weibel-Palade bodies

Endothelial cells (EC) secrete von Willebrand factor (VWF) from storage sites called?

Von Willebrand factor (VWF)

It is a large multimeric glycoprotein that acts as the necessary bridge that binds platelets to exposed subendothelial collagen in arterioles and arteries where blood flows rapidly

Platelets

• These are produced from the cytoplasm of bone marrow megakaryocytes.

• They serve as the body’s first line of defense against blood loss.

Adhesion

It is the property by which platelets bind nonplatelet surfaces such as subendothelial collagen

Aspirin

It is a drug commonly used for its antiplatelet effect, and functions via the arachidonic acid pathway to decrease platelet activity

Endothelial cell

CH. 35 REVIEW QUESTIONS:

What intimal cell synthesizes and stores von Willebrand factor (VWF)?

Tissue factor

CH. 35 REVIEW QUESTIONS:

What subendothelial structural protein triggers coagulation through activation of factor VII?

Fibrinogen

CH. 35 REVIEW QUESTIONS:

What coagulation plasma protein should be assayed when platelets fail to aggregate properly?

Carboxylates the factors to allow calcium binding

CH. 35 REVIEW QUESTIONS:

What is the primary role of vitamin K for the prothrombin group factors?

Thrombin proteolysis of fibrinogen

CH. 35 REVIEW QUESTIONS:

What is the source of prothrombin fragment F1.2?

Factor IXa, factor X

CH. 35 REVIEW QUESTIONS:

What serine protease forms a complex with factor VIIIa, and what is the substrate of this complex?

TPA

CH. 35 REVIEW QUESTIONS:

What protein secreted by endothelial cells activates fibrinolysis?

APC and protein S

CH. 35 REVIEW QUESTIONS:

What two regulatory proteins form a complex that digests activated factors V and VIII?

Mediate platelet adhesion and serve as a carrier molecule for factor VIII

CH. 35 REVIEW QUESTIONS:

What are the primary roles of VWF?

The liver

CH. 35 REVIEW QUESTIONS:

Most coagulation factors are synthesized in:

Lead to the formation of a stable fibrin clot

CH. 35 REVIEW QUESTIONS:

The events involved in secondary hemostasis:

Factor XIII

CH. 35 REVIEW QUESTIONS:

Which of the following coagulation factors is activated by thrombin and mediates the stabilization of the fibrin clot?

AT, TFPI

CH. 35 REVIEW QUESTIONS:

Which of the following endogenous plasma inhibitors is (are) important for the control of excessive thrombin generation?