Module 2: OVERVIEW OF HEMOSTASIS FUNCTIONS OF THE VASCULAR

SYSTEM AND VASCULAR DISORDERS

- We will be talking here about blood vessels in relation to the maintenance hemostasis
and also coagulation factors.
- Generally, when we talk about hemostasis this involves the interplay or the interaction of
blood vessel, the platelets and the coagulation factors.
OVERVIEW OF HEMOSTASIS

• Hemostasis came from the Greek words, heme (meaning blood) and stasis (meaning
halt).
• It is defined as the mechanism which involves the interaction of vasoconstriction,
platelet adhesion and aggregation, and coagulation enzyme activation. (concepts)
Note:
▪ This is the mechanism where bleeding is stop whenever injury happens.
▪ Important concepts that compose homeostasis:
➢ Platelets, blood vessels, coagulation factors (coagulation proteins) with
its activators and inhibitors, and fibrinolysis.
▪ We should consider hemostasis as a system; it will not attain its balance or it will not
be normal unless certain part of the system is defective or something happens
▪ Problems in homeostasis may lead to bleeding or thrombosis (excessive
clotting).
▪ Fibrinolysis leads to wound healing and repair.
HEMOSTASIS
• Bleeding is stopped, or the excessive blood loss upon injury is prevented through the
formation of hemostatic plug, blood clot, or thrombus.
NOTE:
▪ The main goal of this system is the formation of hemostatic plug, blood clot or the
thrombus
▪ The mechanism of hemostasis is to balance these two conditions; bleeding and
clotting condition or the excessive clotting which means thrombosis
▪ The maintenance of this condition so that one and the other will not happen so this
involve the interaction between platelets, blood vessels, coagulation factors or
proteins (other term) and the mechanism of fibrinolysis
▪ Fibrinolysis is also involved in the hemostatic system because this will be the last
part where it would to wound healing and repair. Every wound will heal (awtsu).
STOP THE BLEEDING!
 CELLULAR ELEMENTS AND PLASMA COMPONENT OF HEMOSTASIS

A. Cellular Elements
• Vascular intima – blood vessel
• Extravascular tissue factor (TF)- bearing cells
• Platelets

B. Plasma Components
• Coagulation
• Fibrinolytic proteins
• Inhibitors
NOTE:
• Generally, most of the activators of the coagulation/ hemostatic system are called
coagulation enzymes.

PROCESS AND RELATED FUNCTIONS OF THE HEMOSTATIC MECHANISM

1. Maintain blood in a fluid state while it remains circulating within the vascular system
2. Contact among damaged blood vessel, blood platelet, and coagulation proteins to arrest
bleeding at the site of injury or blood loss by formation of a hemostatic plug
3. Development of a blood clot around the injury to limit this process to the vicinity of the
damage
4. Fibrinolytic removal of excess hemostatic material to ensure the eventual removal of
the plug and reestablish vascular integrity when healing is complete.
NOTE:
▪ The anticoagulant concept here comes into place, so in order that there will be no
clotting and the blood flow will circulate smoothly within the vascular system, it is
important to maintain hemostasis
➢ It is also important that the hemostatic system should have an
anticoagulant property.
▪ Heparan sulfate or heparin– natural anticoagulant.
▪ The site of the injury can be localized because of the formation of blood clot or
hemostatic plug
▪ The clot should not stay long on the site of injury because eventually the injured area will
be healed only if the hemostatic system of the certain individual is normal and also it is
important that the fibrinolytic system is normal or in balance within the hemostatic
system
▪ Fibrinolysis – removal of the excess hemostatic plug/ material that was localized on the
injured area but they make sure that the wound is healed or repaired so that there is no
bleeding and the vascular integrity is reestablished
5 BASIC SEQUENCE OF THE HEMOSTATIC PROCESS

Step Phase Description

Step 1 Vasoconstriction Serotonin and thromboxane A2 promote
vasoconstriction at the site of injury
Step 2 Platelet Adhesion Platelets adhere to exposed endothelial connective
 tissue

Step 3 Platelet aggregation Interaction and adhesion of platelets to one another

to form initial platelet plug
Step 4 Fibrin-platelet plug Coagulation factors interact on platelet surface to
formation produce fibrin; fibrinplatelet plug then forms at the
site of vessel injury
Step 5 Fibrin stabilization Fibrin clot is stabilized by factor XIII
NOTE:

• Steps 1-3 are generally involved in primary hemostasis.

• Steps 4-5 involved in secondary hemostasis.
• Two substances that lead to the vasoconstriction of the blood vessel will be Serotonin
and thromboxane A2
• Platelet adhesion - when endothelial tissue is exposed (when we say expose maybe
there is certain damage on that part), it will facilitate or trigger platelet adhesion.

• Aggregation - interaction and adhesion of platelets to one another forming initial platelet
clot
• Adhesion - the adherence of platelets to exposed site or injury.
• Platelet aggregation –There are two important plugs or clot that can be formed in the
hemostatic system:
a. Platelet plug/clump/clot
b. Fibrin clot or fibrin-platelet plug
• Step 4: The roles of coagulating proteins here are involved. The second type of clot will be
the fibrin clot (fibrin- platelet plug). It is composed of fibrin and platelets.
• Step 5: It is not enough to only form a fibrin-platelet plug, it should be stabilized. If not
stabilized, there is a tendency of blood leakage resulting in bleeding. Factor XIII or
coagulation factor XIII is called fibrin stabilizing factor. (In order that this fibrin clot will be
formed)
STAGES OF HEMOSTASIS

1. Primary Hemostasis
• Refers to 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.
• Platelets are activated and as a result they adhere to the site of injury and to each other,
plugging the injury.
• Steps 1, 2, and 3 of the hemostatic process are involved in primary hemostasis.
2. Secondary Hemostasis
• Describes the activation of a series of coagulation proteins in the plasma to
form a fibrin clot.
• This insoluble fibrin forms a mesh that is incorporated into and around the platelet
plug formed from the primary hemostasis.
• This mesh serves to strengthen and stabilize the blood clot.
 • Steps 4 and 5 of the hemostatic process are involved in secondary hemostasis.

NOTE:
• The final event of hemostasis is fibrinolysis, the gradual digestion and removal of the
fibrin clot as healing occurs.
• These two systems interact simultaneously in early- and late-hemostatic events.
• Pathological thrombosis, or pathological bleeding can occur whenever hemostasis is
dysregulated.
DIFFERENCES BETWEEN PRIMARY AND SECONDARY HEMOSTASIS

Primary Hemostasis Secondary

Hemostasis
Activation/ • Activated by desquamation and • Activated by large injuries
initiation process small injuries to blood vessels to blood vessels and
• Procoagulant substances exposed surrounding tissues
or released by damaged or • The activator, tissue
activated endothelial cells factor, is exposed on cell
membranes
Components Involves vascular intima (blood Involves platelets and
involved vessels) and platelets coagulation system/factors

Product/clot formed Platelet clumps, primary Stable fibrin clot

hemostatic plug, platelet plug
Response Rapid, short-lived response Delayed, long-term response

NOTE:

• Activation and initiation process: (What triggersthe activation of primary and

secondary hemostasis)
• Primary hemostasis:
- Ex. desquamation of the uterine lining during menstrual period
- Procoagulant: favors clot formation or it will favor coagulation
- Response is rapid, short lived because it is activated by small injuries
• Secondary Hemostasis
- Stable fibrin clot (product formed) - stable because of the action of factor 13
- Response is delayed, long term because it is activated by
large injuries
aside from primary and secondary hemostasis also the fibrinolytic system is involved
So, the end product of secondary hemostasis is stabilized fibrin clot, this clot should
not stay long. This should be removed immediately. The process of fibrinolysis will
be the mechanism where there is gradual dissolution and removal of the clot as
healing occurs.
Whenever the hemostatic system is dysregulated or it is not maintained either
 pathological bleeding or pathological thrombosis will occur.

COMPONENTS OF PRIMARY HEMOSTASIS

1. Blood Vessels: arteries, veins, and microcapillary system (arterioles, capillaries,
and venules)
2. Extravascular Components: endothelial cells and connective tissues
3. Platelets

BLOOD VESSELS

• Consist of arteries, veins, and microcapillary system

(arterioles, capillaries, and venules)
• Structured into three layers:
1. Inner layer (vascular intima)
- provides the interface between circulating blood and the body tissues;
monolayer of metabolically active endothelial cells (ECS)

2. Middle layer (vascular media)

- supporting the endothelial cells; internal elastic lamina composed of elastin and
collagen

3. Outer layer (vascular adventitia)

- subendothelial connective tissue
a. Collagen and fibroblasts in veins
b. Collagen, fibroblasts, and smooth muscle cells in arteries

• Initiate hemostasis
- Vasoconstriction
- Minimizes flow of blood into the wound area and brings the hemostatic components
of the blood closer to the vessel walls

NOTE:
• Vascular intima - general term used in the blood vessel
• Endothelial cells is also known as endothelial lining or endothelium
• The artery in Subendothelial connective tissue is composed of smooth muscle
cells and it is absent in the vein structure
• Innermost layer - the layer that is easily comes in contact with the blood cells within the
blood vessel
• Internal elastic lamina - outside the endothelial lining
VASCULAR INTIMA
1. Endothelium (innermost vascular lining) – has
important role in hemostasis
2. Internal elastic lamina (supporting structure
of the endothelial cells)
• Elastin
• Collagen
3. Subendothelial connective tissue
• Collagen
• Fibroblasts in veins
• Smooth muscle cell – only in the artery (not
present in the structure of the vein)

NOTE:
• Endothelial lining – the layer or part where it easily come with contact with the blood
cells within the blood vessel
• Internal elastic lamina – outside of the endothelial lining (the green layer) •
Subendothelial connective tissue – this will be the outer layer

ENDOTHELIAL VASOCONSTRICTOR-VASODILATOR BALANCE

Constrictor Dilator
Endothelin-I Prostacyclin

Angiotensin-II Nitric oxide

Constrictor Dilator
Vasoconstrictor Other EDRF-like substances

Prostaglandins
NOTE:
• The endothelial vasoconstrictor-vasodilator substances are present in the pro-coagulant or
anticoagulant properties in the endothelial lining

ENDOTHELIAL FUNCTIONS
• Angiogenesis
• Coagulation
• Inflammation
• Immune responses
• Synthesis of stromal components
• Vascular tone regulation
• Special metabolic functions
NOTE:
• Angiogenesis - growth of the blood vessels
• Coagulation - certain coagulation factors are also present on the endothelial cells
• Synthesis of stromal components especially for wound healing and repair
• Vascular tone and regulation - Present of certain substances such as vasodilator
and vasoconstrictor

A. ANTICOAGULANT SPECIFIC PROPERTIES OF INTACT VASCULAR ENDOTHELIUM

Endothelial Cell Structure/ Anticoagulant Property

Substance
Vascular endothelium is Present a smooth,
composed of rhomboid cells contiguous surface
ECs secrete prostacyclin The eicosanoid platelet
inhibitor
ECs secrete nitric oxide A vascular “relaxing” factor

ECs secrete the An anticoagulant that

glycosaminoglycan heparan regulates thrombin
sulfate generation
ECs secrete TFPI A regulator of the extrinsic
pathway of coagulation
ECs express the protein C An integral component of the
receptor EPCR protein C control system
ECs express cell membrane A protein C coagulation
thrombomodulin control system activator
ECS secrete TPA Activates fibrinolysis
NOTE:
• Anticoagulant we do not expect here for the formation of clot
• Generally, there are three properties involved in the maintenance of hemostasis
a. Pro-coagulant properties
b. Anti-coagulant Properties
c. Fibrinolytic Properties
• Generally, without injury the blood vessel has its anticoagulant property.
(Anticoagulant properties of intact vascular endothelium, meaning without injury)
- This is how the body maintains that the blood does not
clot

• Vascular endothelium
- Rhomboid cells: in parallel with each other, continuous, (tupad-tupad). So, there will
be no parts of the blood vessels that will be exposed. So, if there is no exposure, there
will be no trigger of coagulation. The rhomboid shape is very important to maintain
the anticoagulation property.
- If not smooth, some of the platelets might be trapped on
the rough surface, and release of certain substances from the platelets will occur and
will trigger clotting and forming of coagulation.

• ECs secrete prostacyclin

- It is a platelet inhibitor so it will no activate platelets so there is no coagulation.

• ECs secrete nitric oxide

- Blood vessels are relaxed, no constriction so if there is no constriction there is no
clotting, blood flow is smooth.

• ECs secrete the glycosaminoglycan heparan sulfate

- Heparan sulfate: natural anticoagulant / in vivo form of heparin (commercial name);
antithrombin. The substance is called heparin sulfate.
• ECs secrete TFPI
- TFPI (Tissue Factor Pathway Inhibitor)
- The tissue factor that is exposed during injury will trigger secondary hemostasis. So,
meaning if the tissue factor will be inhibited there is no clotting and coagulation. That’s
why it involves in anticoagulant properties.

• ECs express the protein C receptor EPCR

- EPCR (Endothelial Protein CReceptor)
- Protein C is one of the regulatory mechanisms of coagulation, meaning it is an inhibitor
of coagulation.
- Important here is you would know why these substances or structures possess
 anticoagulant properties.

• ECs express cell membrane thrombomodulin

- Thrombomodulin would activate protein C to control coagulation (involved in the Protein C
regulatory mechanism)
ECs secretes TPA (Tissue plasminogen activator) – activate fibirnolysis
- Fibrinolysis will counteract your coagulation; clot cannot be formed kay na lyse na sya

Figure 1.4: Anticoagulant properties of intact vascular endothelium

NOTE:
• The Endothelial Cell Protein C Receptor (ECPCR) binds protein C.

• Thrombomodulin (TM) catalyzes the activation of the Protein C pathway.

• Protein C pathway downregulates coagulation by digesting activated factors V and VIII,
thereby inhibiting thrombin formation.
• Tissue Plasminogen Activator (TPA) activates fibrinolysis, so if the fibrin clot undergoes
lysis, no clotting anticoagulant will be expected.
- The presence of (TFPI) does not allow the exposed
tissue factor to coagulate.
• Nitric Oxide is a relaxing factor of the blood vessel.
• If platelets are inhibited and are not activated, clotting will not occur. Thus, nitric oxide,
CD 39 marker, and prostacyclin have anticoagulant properties. (this three are anti-
platelet)
- Heparan sulfate, TM, EPCR, and TFPI also have anticoagulant properties.
• t-PA and u-PA (urokinase-plasminogen activator) have profibrinolytic properties that
inhibit coagulation.
• The formation of the endothelial cells is continuous, meaning they are in close
contact/parallel with each other. Therefore, if there is no exposure on the certain parts of the
blood vessels, especially collagen and tissue factors, coagulation will not be initiated or
activated
• Protein S is also regulatory mechanism same with Protein C

B. PROCOAGULANT PROPERTIES OF DAMAGED VASCULAR INTIMA

Structure/Substance Procoagulant Property

Smooth muscle cells in Induce vasoconstriction

arterioles and arteries
Exposed subendothelial Binds VWF; binds to and
collagen activates platelets
Damaged or activated ECs Important for platelet binding
secrete WWF to collagen at site of injury:
platelet adhesion as a first
line of defense against
bleeding
Damaged or activated ECs Promote platelet and
secrete adhesion molecules: leukocyte binding and
Pselectin, ICAMS, PECAMS activation at site of injury
Exposed smooth muscle Tissue factor exposed on cell
cells and fibroblasts membranes
ECs in inflammation Tissue factor is induced by
inflammation

NOTE:
• Procoagulant properties appear whenever damage is present.
• Vasoconstriction is important as a procoagulant property.
- When the blood vessels constrict, it will slow down the blood flow and localize the blood
cells (RBCs and platelets) needed for clot formation.
• When a certain part of the blood vessel is exposed, it will trigger coagulation.
• If the collagen is exposed due to injury, it will bind to VWF (Von Willebrand factor)
 Von Willebrand Factor (VWF).
- It will also bind and activate platelets. In result, the primary homeostasis will be activated, and
platelet clot will be formed. That’s why this is Pro-anticoagulant property.
- The binding of the VWF on the collagen also triggers platelet adhesion on the endothelial lining
and for the formation of the platelet clot.
- VWF is secreted from the activated or damaged endothelial cells.
- Platelets adhere on the exposed collagen through the VWF. (Platelet’s adhesion)
- VWF is the bridge or connector between the platelets and exposed collagen

• “What happens if platelets adhere to exposed collagen?”

- Clotting or activation of the platelet will follow eventually aggregation and eventually
formation of platelet clot
- How can you stop that bleeding on the certain area or at the certain part of the collagen if the
platelets would not adhere. The platelets should stay wherein the injured site.
- So the platelets, need to adhere on the exposed collagen

• Damaged or activated ECs secrete adhesion molecules; P-selectin, ICAMs,

PECAMs
- ICAMs: Intracellular Adhesion Molecules
- PECAMs: Platelets Endothelial Cell Adhesion Molecules
If there is injury, the body has the mechanism to protect the injury from infection or
inflammation especially if there is damage or open wound or injury on a certain layer of
the blood vessel. The role of leukocyte is to prevent further severity of infection or
inflammation. (Importance of leukocyte)
• Exposed smooth muscle cells and fibroblasts
- Smooth muscle cells and fibroblasts are the outermost layer of intima. These contain tissue
factor. Tissue factor will be exposed on cell membrane and take note tissue factor is factor 3 in
coagulation cascade. When the tissue factor is exposed, this might be activated resulting to
clotting or coagulation that’s why it’s procoagulant property

• ECs in inflammation
• Tissue factor is induced by inflammation
- If there is inflammation, tissue factor might be activated. It will activate specific type of
pathway. Tissue factor will proceed with the extrinsic pathway of coagulation. When tissue
factor is induced by inflammation this will result to the activation of coagulation pathway
resulting to the formation of fibrin clot

• Specific substances/structures that has a procoagulant property

- Result is formation of either platelet clot or fibrin clot
- Main triggering factor: there should be a damage on the vascular intima.
- If no damage, vascular intima is still intact and substances will not proceed to perform
their roles
 Figure 1.5: Representation of Procoagulant properties of damaged vascular intima

NOTE: Refer to figure 1.5

• If there will be release of VWF, platelets will adhere to the site of injury and platelet clot will form
and further the fibrin clot will also be formed that’s why procoagulant.
• Exposed tissue factor also, if this will be exposed, extrinsic pathway of coagulation will occur.
- Tissue factor is Tissue factor 3 and next that will activate is factor 7, so 3 & 7 extrinsic
pathway will occur.

C. FIBRINOLYTIC PROPERTIES OF VASCULAR INTIMA

1. TPA: tissue plasminogen activator
2. PAI: plasminogen activator inhibitor
3. TAFI: thrombin-activatable fibrinolysis inhibitor

NOTE:
• The importance of plasminogen activator, this will result to the formation of plasmin. Plasmin is
the enzyme that cleaves/lyse the fibrin clot. That’s why it’s called fibrinolysis because it will lyse
the clot. Tissue plasminogen activator will activate plasminogen forming plasmin and plasmin will
lyse the fibrin clot during fibrinolysis.
• PAI inhibits TPA in order to balance with fibrinolysis because continuous fibrinolysis will cause for
the fibrinogen to dissolve which is an important coagulation factor.
• PAI and TAFI are inhibitor of fibrinolysis
• TPA is activator of fibrinolysis
 NOTE: Refer to Diagram
• Smooth EC Lining – smooth flow of platelets and blood cells.
• PGI2 (Prostacyclin) – antiplatelet/anticoagulant.
• Nitrous Oxide – a relaxant that allows the blood vessels to relax. No vasoconstriction.
Anticoagulant.
• Heparan Sulfate – natural anticoagulant.
• TFPI – inhibits tissue factor. No intrinsic coagulation and no clotting.
• Thrombomodulin – one of the activators of Protein C that regulates coagulation that prevent
anticoagulant.
• Protein C receptor same with your regulatory mechanism.
• TPA (activator) – activates plasminogen to plasmin resulting to fibrinolysis.
Procoagulant property:
• Vasoconstriction – every time blood vessels constrict, there is concentration in the blood cells
resulting to the activation of platelets that can localize the clot on the site of injury.
• VWF – facilitates the adhesion of the platelets to the collagen.
• ADAMTS13 – a receptor for the VWF.
• P-Selectin – an adhesion molecule for the platelets.
• There will be binding of the collagen, VWF, and platelets every time collagen is exposed.
• TF Exposed – Factor 3 will activate Factor 7 resulting to an intrinsic coagulation pathway that will
then result to clot.
• PAI and TAFI – inhibitor of fibrinolysis. If the fibrin did not lyse, the clot is still there. That’s why it is
procoagulant property.
 NOTE: Refer to diagram^
• A – Anticoagulant
• If anticoagulant property favors more than pro-coagulant property, the thrombin will
decrease resulting to no clot formation because there will be nobody to convert
fibrinogen to fibrin and eventually fibrin clot.
• Thrombin is the enzyme that converts fibrinogen to form fibrin and eventually fibrin clot.
• B – Procoagulant
• If there is increase interplay of increase role of procoagulant, thrombin will increase in order to
convert fibrinogen to fibrin in order to form the clot.

Please take note the important concepts on the part 1:

Components that comprised the hemostasis

➢ Cellular components
➢ Plasma
components Stages of
hemostasis
➢ Primary
➢ Secondary
➢ Fibrinolytic system

HEMOSTASIS CONCEPT IS BALANCE TO BALANCE ALL, TO ACTIVATE AND INHIBIT OR VICE VERSA.
MODULE 2 PART 2

Vascular Disorders

*Mucosal Surfaces

 Diagnosis:
1. LABORATORY TEST
2. MEDICAL HISTORY
3. RULING OUT SOURCES

Notes:

 Patients with vascular disorders will have manifestations on its mucosal surfaces. But for the
other components of the hemostatic system (platelets and coagulation factors), the extent of
severity is more severe for platelet and coagulation disorders than the disorders in the vascular
system.
 Easy bruising and spontaneous bleeding are the most common manifestations for patients
suffering from vascular disorders.
 Diagnosis for vascular disorders generally it will be based on medical history and ruling out of
the sources
 The hemostatic system is composed of platelets, blood vessels, and coagulation factors. The
certain cause of bruising and bleeding must be first ruled out if it is from the platelet disorder,
coagulation disorder, or vascular disorder since bruising and bleeding is also present for
coagulation and platelets disorder
 Laboratory tests can only supplement or aid in the diagnosis of a certain vascular disorder but it
can’t specify or confirm. The medical history is also important in order for the physician to
specify and diagnose the condition
 Easy bruising is also present in platelet and coagulation disorder, generally when we say
bleeding this because of Laboratory tests
 The endothelial cell will compose the vascular lining which is part of the vascular intima that is
why bleeding occurs.

CAUSES OF BLEEDING
1. Platelet abnormality
2. Defect in platelet-endothelial cell interactions
3. Plasma protein defect
TERMS MEANING
PETECHIAE  - Small red or purple spot caused by
bleeding into the skin
 < 3 mm

PURPURA  Recurrent bruising in multiple locations

 3mm -1cm

ECCHYMOSIS  Bruising
 > 1 cm

HEMOPTYSIS - Coughing out of blood

HEMATOMA  A solid swelling of clotted blood within the
tissues

HEMATURIA  Presence of blood in urine

EPISTAXIS - Recurrent, uncontrolled nose bleed
- Longer than 10 minutes

HEMARTHROSIS - Bleeding in joint spaces

- Common feature of hemophilia patients

HEMATEMESIS  Vomiting of blood

MELENA  Presence of blood in stool
MENORRHAGIA - Excessive menstrual flow

DISORDERS CAUSED BY VASCULAR DEFECTS

A. HEREDITARY VASCULAR DISORDERS

1. Hereditary hemorrhagic telangiectasia (Rendu-
Osler-Weber syndrome)
• Autosomal dominant
• Defect: thin-walled blood vessels with discontinuous
endothelium
- Inadequate smooth muscle & inadequate/missing
elastin
- Blood vessels are fragile & prone to rupture
• Manifestations:
 - Face, lips, tongue, under the tongue, conjunctiva, nasal mucosa, fingers,
toes, trunk
- Often in organs (bleeding), epistaxis or nose bleeding
- Blanching lesions - (hallmark) when you apply pressure on the lesion it
will disappear and when you remove the pressure on the lesion it will again
re appear
- From puberty throughout lifetime (worsen with age)- drug nga gna
induced/ supplement is collagen or kulang synthesis of vascular
layers which is collagen

LABORATORY FINDINGS
 Normal bleeding time & tourniquet test
 Other related telangiectasia:
 Associated with liver disease & pregnancy
a. Cherry-red hemangiomas (common in elder men and women)
b. Ataxia-telangiectasia (Louis-Bar syndrome)
c. Chronic actinic telangiectasia

Telangiectasia

 Dilated superficial blood vessels that create small, focal red lesions (blanching lesion) (dilation of blood
vessel = web like structures)

Figure 1.6: Telangiectasia

NOTE:

• Telangiectasia- It will manifest in the face, under the tongue, the trunk, and the lips. It is also present
in the mucosal surfaces
 2. Hemangioma-thrombocytopenia syndrome (Kasabach-
Merritt syndrome) or congenital hemangioma
Manifestations:
- Vascular tumor: giant cavernous hemangioma

- Thrombocytopenia and bleeding diathesis

- Fibrin clot formation, platelet consumption, and red cell destruction secondary to vascular
obstruction at the site of the tumor

 associated with acute or chronic DIC( Disseminated intravascular coagulopathy) , sequestration

of platelets & MAHA

- Hemangiomas are visceral or subcutaneous, rarely both (tumor in blood vessels)

- External hemangiomas become engorged with blood and resemble hematomas

- Congenital = bata (Present at birth) (Thrombocytopenia=low platelets)

- Mortality rate is 30%

NOTE:

• There will be a double problem because the patient will have a tumor in the blood vessel and decrease
platelets that will lead to bleeding diathesis.

• Bleeding diathesis - simply termed as bleeding condition.

• There will be a fibrin clot formation because the body will respond to the part of the blood vessel
which will have the formation of a tumor. So the inflammation part will activate the coagulation

• Why is there platelet consumption?

- Since the coagulation is activated and the platelets are used up it will result to thrombocytopenia

• Why is there red cell destruction?

- Since there is a presence of tumor it will obstruct the blood flow that will make smaller/thin pathways
for the red blood cells to pass through and that will lead to lysis of RBCs. It is related to
Microangiopathic haemolytic anemia

• Sequestration with platelets because the platelets are used up.

• DIC - Disseminated Intravascular Coagulation or Coagulopathy.

- There is a presence of DIC because of the continuous formation of fibrin clot that will result in
excessive coagulation or clot formation.

Figure 1.7: External hemangioma

Visceral – deep organs of the body there is a presence of vascular tumor

• In the photo it represents the subcutaneous hemangioma

3. Ehlers-Danlos syndrome and other genetic disorders

Autosomal dominant, recessive, X-linked trait

• Defect:
-Defective collagen production, structure & crosslinking

- Inadequate connective tissue - Some with platelet abnormalities

• Laboratory findings:
- Positive tourniquet test

- Prolonged bleeding time

NOTE:

• Generally, the defective part or layer is the collagen which results to inadequate connective tissue
• Lab findings - since platelet abnormalities are involved so it is evident that it will be positive for
laboratory tests to check for primary hemostasis.

• Manifestations: fragile tissues - easy to form bruising and hematoma

• Since mainly collagen is the problem so easy bruising until arterial puncture.
• Manifestations:
- Hyperextensible skin

-Hypermobility & laxity of joints

- Fragile tissues

- Bleeding & subcutaneous hematoma

-Easy bruising to arterial rupture

HEREDITARY STRUCTURAL MALFORMATIONS (miscellaneous)

4. Pseudoxanthoma elasticum
• Fragmentation & mineralization of elastic fibers

• Autosomal recessive disorders

5. Osteogenesis imperfecta
• Autosomal dominant disorders
Pseudoxanthoma Osteogenesis
• Defective collagen formation
elsticum imperfecta
• Osteogenesis - problem in bone structure (bone deformity/bone abnormality)

6. Marfan syndrome
• Autosomal dominant disorders

• Decreased strength and elasticity of blood vessels

 B. ACQUIRED VASCULAR DISORDERS
1. Allergic/Anaphylactoid Purpura
 Nonthrombocytopenic purpuras with allergic, manifestation skin
rash, edema, malaise, headache, fever
 Caused by foods, drugs, cold, insect bites, vaccinations

Henoch-Schonlein Purpura
- Appropriately applied when the condition is an acute IgA mediated disorder
Mechanism:
Allergic reaction that is mediated by
- polyarthralgia, nephritis, abdominal pain, purpuric skin lesions
IgA that forms purpuric lesion
(brownish red)
-Affecting children 3 to 7 years old,

-twice greater risk for males than females IgA mediated allergic reaction results to vasculitis -
inflammation of blood vessels
- targets/damaging blood vessel wall resulting to
Defect: vasculitis vasculitis and purpuric lesion
Involving the skin, joints, kidneys, gastrointestinal tract, and the lungs (less common)

- Autoimmune vascular injury,

- Autoimmunity to vessel wall components

– Skin lesion (palpable purpura) on feet, elbows, knees, buttocks, chest - urticarial, pinkish, and red
to hemorrhagic - brownish red eruption, petechiae

- Laboratory findings:
a. Normal platelet count, tourniquet test, bleeding time, coagulation

b. Increased WBC & ESR,

C. anemia in severe types

NOTE:
• Nonthrombocytopenic – no decrease in the number of platelets (normal platelet
concentration)

• It is termed allergic or anaphylactoid because it is related to allergic manifestation

• It is just a reaction to certain factors

• Arthralgia – weakening of the joints

• Nephritis – inflammation of nephrons

• There is a difficulty in the diagnosis of this condition since rash is manifested as delayed

SKIN LESION ( Palpable)

•urticarial, pinkish, red to hemorrhagic

• When it bleeds it will have a brownish red eruption

• Lesions here could be seen on the feet, elbows, knees, buttocks, and chest

• IgA is involved so it will result in autoimmune vascular injury.

- IgA will attack your specific cell on the blood vessel.

• Autoimmunity to vessel wall components resulting to vasculitis

Lab findings:
• WBC – since the condition is inflammation (vasculitis) there is an increase level of WBC

• ESR – indication of nonspecific inflammation. ESR level is increased due to inflammation and is related
to anemia if severe. Take note, it is hemorrhagic and it could develop to anemia due to excessive blood

Figure 1.9: Henoch-Schonlein Purpura

NOTE: Refer to Figure 1.9

• Lesions are urticarial pinkish and eventually become hemorrhagic.

• Notice that blood ooze out from the lesions

• There are also brownish red erruptions

• Problem: if a child is affected, they cannot tolerate since makatol (urticarial). Kaluton niya and
eventually ga bleed ang lesion.

• Although it is allergy type it could lead to anaphylactoid type.

• Anaphylaxis – tight airway lining and hard breathing

2. Drug-induced vascular purpura

• Drug-induced vasculitis occurs in the presence of functionally adequate platelets

• Aspirin, warfarin, barbiturates, antibiotics, sulfonamides, diuretics, digoxin, methyldopa, iodides,

belladonna, atropine, quinine, procaine penicillin, phenacetin, chloral hydrate

• Few petechiae to massive petechial eruptions

• Defect:
- Development of Antibody to vessel walls

- Development of immune complexes

- Changes in vessel wall permeability

NOTE:

• Related to ingestion of certain drugs

• Same with Allergic Anaphylactoid Purpura or HenochSchonlein Purpura, it will develop into vasculitis
since the target here are the blood vessel wall

• Since there is already vasculitis in the blood vessel, it will change the vessel wall permeability. It cannot
maintain the permeability between the interstitial fluid and intravascular or intracellular fluids especially
the vessel wall so there will be escape or leakage of fluids or possibly entry of fluids

• In Henoch-Schonlein Purpura, lesions are purpuric lesions.

• In drug induced vascular purpura, lesions are small or few petechiae until there are petechial
eruptions

3. Paraproteinemia

• Increase concentration of plasma paraprotein

• Resulting to abnormalities in platelet aggregation, secretion, and procoagulant activity

• Affects 1/3 of patients with IgA myeloma and Waldenström macroglobulinemia 5% of patients with
IgG myeloma (usually IgG3) Paraproteins: gamma globulins (IgA,
IgG, Macroglobulin which is IgM)
• Defects: - they coat platelets ang coagulation
factor
- Coating of platelet membrane with paraprotein (dysfunction of platelets)
a. Inhibited platelet adhesion and activation receptor functions

b. Inhibits assembly of clotting factors on the platelet surface

- Inhibit fibrin polymerization

NOTE:
• The effect is not just to the primary hemostasis but also to the secondary hemostasis since
procoagulant activity is affected

• Culprit here is the paraprotein. At normal concentrations, presence in plasma is okay but, the problem
here is increased concentration

• Problem is in myeloma condition or in macroglobulinemia, meaning the problem is the excess

immunoglobulin in the form of IgA or IgG specifically IgG3

• Immunoglobulins could be considered under the paraproteins that circulate in the plasma

• Defects:
- Remember that the platelets have receptors especially needed for their function. Since paraprotein will
coat this receptor, the platelets will be dysfunctional

- Since the receptor of platelet will not function, no coagulation factor will continue in secondary
hemostasis or coagulation pathway will not continue in secondary hemostasis because of the inhibition
of the assembly of clotting factors on the platelet surface

4. Amyloidosis
• Amyloid (amyloid fibrous protein - coat/deposit in blood vessel wall and surrounding tissue)

- Fibrous protein consisting of rigid, linear, nonbranching, aggregated fibrils approximately 7.5 to 10 nm
wide and of indefinite length

- Various proteins serve as subunits of the fibril - amyloid proteins consists of monoclonal light chains
(λ more frequently than κ) ( includes lambda and kappa light chains)

• Defect: deposition of abnormal quantities of amyloid tissue in vascular wall & surrounding tissue
• Purpura, hemorrhage, thrombosis

• Laboratory findings: Abnormal platelets function and decreased platelets

5. Senile purpura or Cachetic purpura
• old age, More common in elderly men than women and severity increase with age

• Defect:

- Lack of collagen support for small blood vessels

- Loss of subcutaneous fat & elastic fibers (causes saggy skin)

• "Age spots” or brown spots

- Brown stain

- 1 to 10 mm flat dark blotches

- Do not blanch with pressure & resolve slowly

- Extensor surface of forearms and backs of hands, occasionally on face and neck

• Laboratory findings: increased capillary fragility

Figure 1.10: Senile Purpura

6. Scurvy (Vitamin C deficiency)

• Insufficient dietary intake of Vitamin C (vitamin c is needed for collagen synthesis)

• Decrease collagen synthesis

• Weakening capillary walls

- resulting to Purpuric lesions

7. Corticosteroid purpura and Cushing's disease
• Excess endogenous glucocorticosteroids in Cushing's syndrome and therapeutic glucocorticoids

• Excessive breakdown of collagen

 Thin fragile skin

 vessel wall fragility
 bruising

8. Cutaneous bleeding & bruising

• Women with emotional problems

• Women experience this more often due to changes in hormone/hormonal levels (during or after
menstruation)

Purpuras of Unknown Origin

• Purpura simplex (easy bruisability)

• Psychogenic purpura
(both gadula overtime)

C. INFECTION-RELATED BLEEDING DISORDERS

a. Bacterial - Meningococcemia and septicemia, typhoid, scarlet fever, diphtheria, tuberculosis,
endocarditis, leptospirosis, etc.

b. Viral - Smallpox, influenza, measles

c. Rickettsial - Rocky Mountain spotted fever, typhus

d. Protozoal - Malaria, toxoplasma

NOTE: Meningococcemia is caused by Neisseria meningitidis.

1. Purpura fulminans (bacterial infection that leads to bleeding disorder)

• Hemorrhagic condition usually associated with sepsis or previous infection
• Cutaneous manifestation of DIC
NOTE: Either excessive bleeding or excessive thrombosis will happen if a patient has DIC.

2. Waterhouse-Friederichsen Syndrome
• Adrenal gland failure due to bleeding into the adrenal glands caused by severe bacterial
infection
• caused by Neisseria meningitides

Types of vascular disorders:

• Vascular disorders are the congenital (hereditary) disorders usually involving structural
malformation in the layers of the blood vessels and formation of lesions either petechial or
purpuric.
• Acquired type with varying causes
• Unknown causes. If the purpuric condition cannot be explained or confirmed, it is termed as
purpura simplex.
• Infection related bleeding disorder that depends on the causative agent