HEMATOLOGY: CHAPTER 35 - RODAKS 6TH EDITION

Hemostasis

is a complex physiologic process that keeps circulating blood in a fluid state and then, when an injury occurs, produces a clot to stop the bleeding, confines the clot to the site of injury, and finally dissolves the clot as the wound heals

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

- rapid, short-lived

Secondary hemostasis

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

- delayed, long-term

Endothelial cells

form a smooth, unbroken surface that eases the fluid passage of blood

Prostacyclin

a platelet inhibitor and a vasodilator that is synthesized through the eicosanoid pathway and prevents unnecessary or undesirable platelet activation in intact vessel

Nitric oxide

induces smooth muscle relaxation and subsequent vasodilation, inhibits platelet activation, and promotes angiogenesis and healthy arterioles

Tissue Factor Pathway Inhibitor (TFPI)

This controls the activation of tissue factor pathway also called the extrinsic coagulation pathway

Weibel-Palade bodies

ECs secrete von Willebrand factor (VWF) from storage sites called ___________________________ when activated by vasoactive agents such as thrombin

von Willebrand factor (vWF)

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

ADAMTS13

also secreted from ECs, serves an important function as it cleaves large VWF multimers into shorter chains that support normal platelet adhesion.

P-selectin

an adhesion molecule that promotes platelet and leukocyte binding

PAI-1

a TPA control protein that inhibits plasmin generation and fibrinolysis

Platelets

serve as the body's first line of defense against blood loss

Adhesion

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

GP Ib/IX/V

VWF binds platelets through their __________________ membrane receptor

Aggregation

is the property by which platelets bind to one another

GP IIb/IIIa

Fibrinogen binds to _________________ receptors on adjacent platelets and joins them together in the presence of ionized calcium (Ca2+)

Secretion

Property where platelets discharge the contents of their granules

Fibrinogen

What is the name of Factor I?

Prothrombin

What is the name of Factor II?

Tissue Factor

What is the name of Factor III?

Ionic Calcium

What is the name of Factor IV?

Proaccelerin

What is the name of Factor V?

Christmas Factor

What is the name of Factor IX?

Stuart-Prower Factor

What is the name of Factor X?

Hageman Factor

What is the name of Factor XII?

Fletcher Factor

What is the name of Prekallikrein?

Fitzgerald factor

What is the name of High-Molecular-Weight Kininogen (HMWK)

Fibrinogen

is the substrate for the enzymatic action of thrombin and is the primary enzyme of the coagulation system

Cascade

Pathway wherein if one factor is activated, it also activates the next factor in the sequence

serine proteases

The coagulation factors thrombin (factor IIa), factors VIIa, IXa, Xa, XIa, XIIa, and pre-K are enzymes called _______________________

inactive zymogens

Serine proteases are synthesized as ______________________ consisting of a single peptide chain

Fibrinogen

is the ultimate substrate of the coagulation pathway

Ionized calcium

is required for the coagulation complexes that assemble on platelet or cell membrane phospholipids.

Prothrombin (factor II), factors VII, IX, and X and the regulatory proteins protein C, protein S, and protein Z

These are dependent on vitamin K during synthesis to produce a functional structure ; named Prothrombin group

Vitamin K

is a quinone found in green leafy vegetable and is produced by the intestinal organisms Bacteroides fragilis and Escherichia coli

Extrinsic tenase

is composed of factor VIIa and tissue factor, and it activates factors IX and X, which are components of the next two complexes, intrinsic tenase and prothrombinase, respectively

Intrinsic tenase

is composed of factor IXa and its cofactor VIIIa; it also activates factor X but much more efficiently than the TF:VIIa complex.

Prothrombinase

is composed of factor Xa and its cofactor Va; this converts prothrombin to thrombin in a multistep hydrolytic process that releases thrombin and a peptide fragment called prothrombin fragment 1.2

Thrombomodulin

a transmembrane protein constitutively expressed by vascular ECs, is a thrombin cofactor in the protein C pathway.

Von Willebrand Factor

is a large multimeric glycoprotein that participates in platelet adhesion and transports the procoagulant factor VIII.

Factor XII, HMWK, Fletcher

These are also known the "contact factors"

Thrombin

is the main enzyme of the coagulation pathway with multiple key activities.

fibrinopeptides (FP) A and B from the a and b chains of the fibrinogen molecule

The primary function of thrombin is to cleave _____________________________________________

Liver

Where is fibrinogen synthesized or produced?

Tissue Factor Pathway Inhibitor

is a Kunitz-type serine protease inhibitor and is the principal regulator of the TF pathway

EC protein C receptor (ECPR)

is a transmembrane protein that binds protein C adjacent to the thrombomodulin-thrombin complex

Protein S

the cofactor that binds and stabilizes APC, is synthesized in the liver and circulates in the plasma in 2 forms

Free Plasma

Only this type of plasma of protein S can serve as the APC cofactor

Antithrombin

was the first of the coagulation regulatory proteins to be identified and the first to be assayed routinely in the clinical hemostasis laboratory

Heparin

What does Antithrombin requires in order to have an effective anticoagulant activity?

True

True or False.

Antithrombin activity is amplified 2000-fold by binding to heparin.

ZPI

in the presence of its cofactor protein Z, is a potent inhibitor of factor Xa

Protein Z

- is a vitamin K-dependent plasma glycoprotein that is synthesized in the liver

- increases the ability of ZPI to inhibit factor Xa 2000-fold

Protein C inhibitor

is a nonspecific, heparin-binding serpin that inhibits a variety of proteases, including APC, thrombin, factor Xa, factor XIa, and urokinase

Fibrinolysis

the final stage of hemostatic activation and is the systematic, accelerating hydrolysis of fibrin by plasmin

Plasminogen

- is a 92,000 Dalton plasma zymogen produced by the liver

- it is a single-chain protein possessing 5 glycosylated loops and is responsible for digesting fibrin/fibrinogen

kringles

Plasminogen is a single-chain protein possessing 5 glycosylated loop termed as _________________

Plasmin

is a serine protease that systematically digests fibrin polymer by the hydrolysis of arginine-related and lysine-related peptide bonds

tissue plasminogen activator (tPA)

Serine protease secreted by activated endothelium, activates plasminogen

Urokinase plasminogen activator (uPA)

Serine protease secreted by kidney cells, activates plasminogen

Plasminogen activator inhibitor-1 (PAI-1)

Serpin secreted by endothelium, inhibits tissue plasminogen activator

a2-Antiplasmin

A serpin that inhibits free plasmin

Thrombin activatable fibrinolysis inhibitor (TAFI)

Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites blocking TPA and plasminogen binding

a2-AP

is synthesized in the liver and is the primary inhibitor of free plasmin.

Thrombin-thrombomodulin complex

TAFI is a plasma procarboxypeptidase synthesized in the liver that becomes activated by __________________________________

D-dimer

The D-D fragment is also called ______________

Clotting Time

Measures the period required for blood to clot or solidify after it has been extracted from the body

Lee and White Method

A macromethod in which there is a need to extract 3 mL of venous blood and to gently tilt tube 3 every 30 seconds until blood solidifies

Stypven Time

Has the Russell's Viper Venom and is used for determination of common pathway deficiencies

Daboia russelii

What type of snake is used under stypven time?

Thrombin time

used to measure the availability of functional fibrinogen

Bovine & Lyophilisate

What are the reagents used in thrombin time?

Reptilase

Cleaves the fibrinogen peptide to form fibrin monomers

Duckert's Test

Used for FXII deficiency

5M urea solution, thrombin, 0.025 CaCI2

Reagents used in Duckert's Test