Heme - Coagulation Intro

Front 1

Components necessary for hemostasis

Back 1

Vessel wall/vascular endothelium
Platelets
Plasma coagulation proteins
Physiologic protease inhibitors
Endogenous anticoagulants
Fibrinolytic system

Front 2

Excess coagulation caused by disorders in ... (3)

Back 2

Blood vessels
Coagulation and fibrinolytic factors
Blood flow

Front 3

Excess bleeding caused by disorders in ... (3)

Back 3

Platelets
Blood vessels
Coagulation factors.

Front 4

5 phases of hemostasis

Back 4

Primary hemostasis (platelet plug)
Secondary hemostasis (coagulation phase - formation of a fibrin clot)
Fibrin formation/stabilization
Termination of coagulation reactions
Fibrinolysis

Front 5

Primary hemostasis

Back 5

Vasoconstriction (reduce flow to injured area and allows procoag factors to localize)
and formation of platelet plug (requires von Willebrand factor, platelets, fibrinogen)

Front 6

von Willebrand Factor Synthesis

Back 6

Synth in endothelial cells and megakaryocytes.
Post-trans multimerization. Multimers stored in Weibel-Palade bodies in endothelium and alpha granules in platelets.

Cleaved into smaller multimers by ADAMTS13

Front 7

vWF function

Back 7

Tether platelets to subendothelium in vascular injury. (binds collagen on one side and platelets on the other via gp1b)
Support coagulation by chaperoning factor VIII (prolonging its half life and localizing it to the site of injury)

Defiency --> bleeding disorder.

Front 8

Platelets

Back 8

Anucleate cells - products of BM megakaryocytes.
Contain granules
Lifespan - one week - 10 days
Contains pro and anticoagulant proteins.

Front 9

Normal platelet numbers

Back 9

150000-400000 per microliter.

Front 10

Platelet activation

Back 10

Pseudopods spread over subendothelium. (increased surface area)

Degranulation of alpha and dense granules

Thromboxane A2 synthesis

Front 11

Alpha granules

Back 11

In platelets,
PROTEINS
Contains fibrinogen, vWF, factor V, other proteins

Front 12

Dense granules

Back 12

In platelets,
SMALL MOLECULES
Contains ADP, ATP, serotonin, calcium.

Front 13

Thromboxane A2 function

Back 13

More vasoconstriction, platelet aggregation, platelet activation (feedback - because platelet activation is what synthesizes thromboxane A2.)

Front 14

Platelet aggregation

Back 14

Other platelets are recruited by activation products release.

GpIIb/IIIa on the platelet binds fibrinogen. On the other side of that fibrinogen is another gpiia/iiib.

Front 15

Phosphatidyl serine and phophatidyl ethanolamine

Back 15

Allow coagulation factors to bind on platelet surface (referred to as platelet factor 3 (PF3) activity.

Front 16

Defect in PF3 ability

Back 16

Scott syndrome

Front 17

Glanzmann thrombasthenia

Back 17

Deficiency in GPIIb/IIIA receptor.

Front 18

General function of secondary hemostasis

Back 18

Form sturdy fibrin clot by...

Fibrin forming a mesh around platelets
Stabilizing the platelet plug while the BV heals
Enzyme cascade is activated to convery soluble fibrinogen to fibrin.

Front 19

Location of secondary hemostasis

Back 19

Phospholipid surface (e.g. platelet membrane)

Front 20

Which factors don't exist?

Back 20

Factors IV or VI.

Front 21

Coagulation factors - location of synthesis

Back 21

In liver

exceptions -
Factor VIII (liver AND vascular endothelium)
Factor V - also in alpha granules in platelets.
vWF - megakaryocytes and endothelial cells

Front 22

Vit K dependent coagulation factors

Back 22

II, VII, IX, X. Also prot C and S

Front 23

Endogenous anticoagulant factors

Back 23

Proteins S, C, Z

Front 24

Tissue factor

Back 24

Expressed on cell surface by monocytes in response to vascular injury mainly, and also by damaged endothelial cells

Function - Complexes with factor VII to turn it into VIIa.

Then these two directly catalyze X to Xa (direct) and also catalyze IX to IXa, which then catalyzes X to Xa in the presence of factor VIII and Ca++.

Physiologic initiator of coagulation along with factor VIIa.

Front 25

Factor IX requirements to cleave X to Xa

Back 25

Calcium and factor VIIIa (in her ppt she just says "factor VIII").
These two are needed to bind to the platelet membrane.

And remember, VIII is in the area via vWF

Front 26

Xa function

Back 26

Converts prothrombin (II) to thrombin (IIa) in the presence of Va.

V is stored IN platelets (alpha granules) and released at site of injury during platelet activation.

Front 27

Prothrombinase complex

Back 27

Va anchors Xa and prothrombin (II) in close proximity on platelet phospholipid.

Front 28

Thrombin - factor #

Back 28

IIa

Front 29

Thrombin - function

Back 29

Catalyzes a small amount of fibrin monomer (Ia) from fibrinogen (I).

Feedback - activates XI to XIa (it is what converts IX to IXa - this is the thrombin burst [how most thrombin is made]). Also activates V and VIII.

Activating XIII - to stabilize fibrin (turn it into cross-linked fibrin)

Protects established clot (thrombus) from fibrinolysis.

Inhibits coagulation when the time comes.

Front 30

Fibrinogen - synthesis locatin

Back 30

Platelets secrete it.

Front 31

Three sources of thrombin

Back 31

Primary generation, amplification, propagation.

Front 32

Hemophiliacs - Often what is their malfunction?

Back 32

Can't perform thrombin burst (amplification).

Front 33

Mechanism of Fibrinogen to Cross-linked fibrin

Back 33

Thrombin cleaves FPA and FPB off of fibrinogen. XIIIa allows fibrin monomers to cross-link with each other.

Front 34

Controlling coagulation

Back 34

Hemodilution - Activated coag factors diluted by systemic circ.

Hepatic clearance - Activ coag factors cleared by the liver

Endogenous anticoagulants
Activated protein C/S
Antithrombin (AKA antithrombin III)
Tissue factor pathway inhibitor (TFPI)
Protein Z

Fibrinolysis via plasmin.

Front 35

Severe liver disease

Back 35

May blood or clot too much because liver makes coagulation factors, but then also clears them away.

Front 36

Antithrombin system

Back 36

Inhibits Xa and thrombin - made in liver and endothelial cells - Heparin increases this activity

***(2-10 Hanna Heparin)

Front 37

Tissue factor pathway inhibitor

Back 37

Produced by endothelial cells

Inhibits Xa

Inhibits factor VIIa/TF with the help of Xa.

Front 38

Activated protein C/S system

Back 38

S is the cofactor. Inhibits factor VIIIa and Va

Thrombin actually acting as an anticoagulant here because when thrombin bind thrombomodulin on the endothelial cell surface, thrombin changes shape (can't activate coag factors anymore) and protein C becomes activated.

Front 39

Fibrinolysis

Back 39

Plasminogen synthesized by liver and circulates. Binds to fibrin,

cleaved to plasmin by plasminogen activators. (urokinase plasminogen activator or tissue plasminogen activator - UPA/TPA)

Plasmin cleaves fibrin to release fibrin degradation products (D-dimers)

Front 40

Plasminogen activator inhibitor 1

Back 40

Stored in platelets. Major inhibitor of tissue plasminogen activator (TPA).

Front 41

Alpha-2-antiplasmin

Back 41

Inhibitor of plasmin.

Front 42

Bleeding disorders (overbleeding) due to deficiencies in...

Back 42

Alpha-2-antiplasmin or Plasminogen activator inhibitor-1

Front 43

ADP receptor

Back 43

When bound, activates platelets.