HPHS221W1

PLATELETS

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 GENERAL CHARACTERISTICS
• VERY SMALL, 2-4 MICRONS IN DIAMETER
• APPROXIMATELY 250-500000 PER CUBIC MILLIMETRE
• LIFE SPAN 7-10D, N.COUNT – 150-400X109/L
• 36 HOURS IN SPLEEN - 1/3 OF PLT IN SPLEEN
• ESSENTIAL FOR CLOTTING OF DAMAGED VASCULATURE
• THROMBOPOIETIN-REGULATES PLATELETS PRODUCTION
• IMPORTANT IN FORMING CLOTS IN DAMAGED VESSELS
• PLATELETS ARE CYTOPLASMIC FRAGMENTS DERIVED FROM MEGAKARYOCYTES ALSO
CALLED THROMBOCYTES
• AS CELL FRAGMENTS THERE ARE NO ORGANELLES, BUT THEY DO HAVE GRANULES AND
ARE IMPORTANT IN BLOOD CLOTTING.
• THE GRANULES CONTAIN SECRETORY PRODUCTS
• ADP
• SEROTONIN
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• EPINEPHRINE
 PLATELETS

•Function in: process of blood clotting &

protection of vascular channels from
internal damage.
•Can adhere to each other and collagen
of connective tissue.
•HOWEVER, DON’T adhere to WBC or
RBC.
•Good plug, but don’t adhere to blood 3

cells themselves!
ORIGIN OF PLATELETS

MEGAKARYOCYTE
IN BONE MARROW
PLATELET BUD

PLATELET

RBC
FORMATION OF PLATELETS

• HEMOCYTOBLAST MYELOID
STEM CELLS
MEGAKARYOBLASTPROMEGA
KARYOTES MEGAKARYOTES
(LARGE MULTILOBED
NUCLEUS) PLATELETS
(ANUCLEATED PARTS OF
MEGAKARYOCYTES CYTOPLASM
)

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 HEMOSTASIS
• STOPPAGE OF BLOOD FLOW AFTER DAMAGE
• HEMOSTATIC MECHANISM EFFECTIVE IN DEALING WITH INJURIES IN
SMALL VEINS- ARTERIOLES, CAPILLARIES, AND VENULES.
• VENOUS BLEEDING LEADS TO LESS RAPID BLOOD LOSS BECAUSE
VEINS HAS LOW BLOOD PRESSURE.
• HEMATOMA- IS THE ACCUMULATION OF BLOOD IN THE TISSUE AS A
RESULT OF BLEEDING FROM OTHER VESSEL TYPE.

• GENERAL CHARACTERISTICS
• VASCULAR SPASM (VASOCONTRICTION AT INJURED SITE)
• PLATELET PLUG FORMATION (PLUGGING THE HOLE)
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• COAGULATION (BLOOD CLOTTING-COMPLEX MECHANISM)
HEMOSTASIS:
BV Injury

Tissue
Neural Factor

Blood Vessel Platelet Coagulation

Constriction Activation Activation
Primary hemostatic plug

Reduced
Plt-Fusion Thromibn,
Blood flow
Fibrin

Stable Hemostatic Plug

PROCESS- PRIMARY HEMOSTASIS
• IN A NORMAL INDIVIDUAL, COAGULATION IS INITIATED WITHIN 20
SECONDS AFTER AN INJURY OCCURS TO THE BLOOD VESSEL
DAMAGING THE ENDOTHELIAL CELLS.
• PLATELETS IMMEDIATELY FORM A HAEMOSTATIC PLUG AT THE SITE OF
INJURY. THIS IS CALLED PRIMARY HAEMOSTASIS.
 VASCULAR SPASM
• VASCULAR SPASM RESULTS FROM DAMAGE TO
THE BLOOD VESSELS. THE DAMAGED TISSUE
SECRETES FACTORS THAT CAUSES
CONTRACTION.
• VESSELS CONSTRICT TO MINIMIZE BLOOD
LOSS (THIS IS PROTECTIVE TO MAINTAIN BP).
• ENDOTHELIAL LAYER BECOMES STICKY TO AID
IN THE CLOTTING PROCESS
• FIRST RESPONSE TO VASCULAR INJURY-
VASOCONTRICTION IS STIMULATED
• COMPRESSION OF VESSEL BY ESCAPING
BLOOD.
• INJURY “CHEMICAL” RELEASED BY INJURED
CELLS 9

• REFLEXES FROM ADJACENT PAIN RECEPTORS.

 FORMATION OF PLATELET PLUG
• THE PLATELET PLUG FORM AROUND SITE OF VESSEL DAMAGE
AND IS STARTED BY THE STICKY ENDOTHELIUM AT DAMAGED
SITE.
• THE PLUG RESULTS IN A DECREASE BLOOD LOSS (MAINTAIN BP)
• THE PLUG FORMATION IS NECESSARY FOR PRODUCTION OF A
BLOOD CLOT
• PLATELETS PRODUCE THROMBOXANE A2-GRANULE RELEASE.
• SEROTONIN RELEASE ENHANCES VASCULAR SPASM
• ADP-ATTRACTS AND STIMULATES PLATELETS AT SITE.
• PROSTACYLIN-INHIBITS AGGREGATION AT OTHER SITES 10
 SEQUENCE OF EVENTS LEADING TO
FORMATION OF A PLATELET PLUG AND
VASOCONSTRICTION

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FORMATION OF A PLATELET PLUG

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Fig. 12-73
 SECONDARY HAEMOSTASIS

• SECONDARY HAEMOSTASIS THEN FOLLOWS—PLASMA

COMPONENTS CALLED COAGULATION FACTORS
RESPOND (IN A COMPLEX CASCADE) TO FORM FIBRIN
STRANDS WHICH STRENGTHEN THE PLATELET PLUG.
• CONTRARY TO POPULAR BELIEF, COAGULATION FROM A
CUT ON THE SKIN IS NOT INITIATED BY AIR OR DRYING
OUT, BUT BY PLATELETS ADHERING TO AND ACTIVATED BY
COLLAGEN IN THE BLOOD VESSEL ENDOTHELIUM.
• THE ACTIVATED PLATELETS THEN RELEASE THE CONTENTS
OF THEIR GRANULES, THESE CONTAIN A VARIETY OF
SUBSTANCES THAT STIMULATE FURTHER PLATELET
ACTIVATION AND ENHANCE THE HAEMOSTATIC PROCESS.
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 COAGULATION CASCADE
• THE COAGULATION CASCADE OF SECONDARY HEMOSTASIS HAS
TWO PATHWAYS, THE CONTACT ACTIVATION PATHWAY
(FORMERLY KNOWN AS THE INTRINSIC PATHWAY)
• AND THE TISSUE FACTOR PATHWAY (FORMERLY KNOWN AS THE
EXTRINSIC PATHWAY) THAT LEAD TO FIBRIN FORMATION.
• IT WAS PREVIOUSLY THOUGHT THAT THE COAGULATION
CASCADE CONSISTED OF TWO PATHWAYS OF EQUAL
IMPORTANCE JOINED TO A COMMON PATHWAY.
• IT IS NOW KNOWN THAT THE PRIMARY PATHWAY FOR THE
INITIATION OF BLOOD COAGULATION IS THE TISSUE FACTOR
PATHWAY. THE PATHWAYS ARE A SERIES OF REACTIONS, IN
WHICH A ZYMOGEN (INACTIVE ENZYME PRECURSOR) OF A
SERINE PROTEASE AND ITS GLYCOPROTEIN CO-FACTOR ARE
ACTIVATED TO BECOME ACTIVE COMPONENTS THAT THEN
CATALYZE THE NEXT REACTION IN THE CASCADE
 BLOOD COAGULATION: CLOT
FORMATION
• IS THE TRANSFORMATION OF BLOOD INTO A SOLID GEL TERMED A
CLOT OR THROMBUS
• CONSIST MAINLY OF A PROTEIN POLYMER KNOWN AS FIBRIN
• CLOTTING OCCURS AROUND THE ORIGINAL PLATELET PLUG AND IS
THE DOMINANT HEMOSTATIC DEFENCE
• FUNCTIONS- IS TO SUPPORT AND REINFORCE THE PLATELET PLUG
AND SOLIDIFY BLOOD THAT REMAINS IN THE WOUND CHANEL

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 Prothrombin

Xa
Va

Thrombin

Fibrinogen Fibrin
BLOOD COAGULATION: CLOT
FORMATION
• PLATELET CELLS ACTIVATED BY
DAMAGE - PF3 AND/OR
TISSUE FACTOR PRODUCED BY
PLATELET CELLS FACTOR X
ACTIVATED PROTHROMBIN
ACTIVATOR (ENZYME)
PRODUCED PROTHROMBIN
CONVERSION THROMBIN
(ANOTHER ENZYME) THROMBIN
STIMULATES: FIBRINOGEN---
FIBRIN MESH
1. ANTICOAGULANT- CHEMICAL
THAT INHIBITS CLOTTING
2. PROCOAGULANT- CHEMICAL
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THAT PROMOTES CLOTTING

 CLOTTING CASCADE
• INTRINSIC PATHWAY- WITHIN
THE DAMAGED VESSEL.
• MORE PROCOAGULANTS
NEEDED (I-XIII) TOWARD
PF3 AND FACTOR X
• ALLOWS MORE SCRUTINY
BEFORE CLOTTING
OCCURS
• EXTRINSIC PATHWAY-IN
OUTER TISSUE AROUND
VESSEL
• TISSUE THROMBOPLASTIN
(TISSUE FACTOR)- SKIPS
INTRINSIC STEPS STRAIGHT
TO PF3 AND FACTOR X
• ALLOWS RAPID RESPONSE
TO BLEEDING OUT OF 19

VESSEL
 AFTER ACTIVATION OF FACTOR X

• FACTOR X, PF3 (THROMBOPLASTIN), FACTOR V, CA++ PROTHROMBIN

ACTIVATOR PROTHROMBIN CONVERTEDTHROMBIN (ACTIVE ENZYME).
• THROMBIN STIMULATES: FIBRINOGEN FIBRIN (MESHWORK)
• CA++ AND THROMBIN  FACTOR XIII (FIBRIN STABILIZER)

• NOTE: PLASMA CALCIUM IS REQUIRED AT VARIOUS STEPS.

• CALCIUM CONCENTRATION IN THE PLASMA CAN NEVER GET LOW
ENOUGH TO CAUSE CLOTTING DEFECT

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 CLOTTING FACTOR

• CLOTTING FACTORS ARE PRODUCED BY THE LIVER AND

SECRETED INTO BLOOD IN INACTIVE FORMS WHICH
ARE ACTIVATED DURING THE CLOTTING CASCADE
• PLASMA WITHOUT CLOTTING FACTORS IS CALLED
SERUM.
• HEMOPHILIA IS A GENETIC DISORDER, CHARACTERIZED
BY DEFICIENCIES IN CLOTTING FACTORS, USUALLY
FACTOR XIII
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 CLOT RETRACTION

• ACTOMYOSIN-CAUSES CONTRACTION OF PLATELETS

• BLOOD SERUM-PLASMA WITHOUT CLOTTING FACTORS.
• PLATELET-DERIVED GROWTH FACTOR (PDGF)-STIMULATES FIBROBLAST
MIGRATION AND ENDOTHELIAL GROWTH

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 DISSOLVING BLOOD CLOTS

• HEALING OCCURS OVER 2-10

DAYS.
• TISSUE PLASMINOGEN
ACTIVATOR (TPA)- CAUSES THE
ACTIVATION OF PLASMINOGEN
• PLASMINOGEN PLASMIN
• PLASMIN DEGRADES PROTEINS
WITHIN THE CLOT
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Dissolve clot
 FACTORS LIMITING GROWTH AND
FORMATION OF CLOTS
• LIMITING NORMAL CLOT GROWTH
• BLOOD MOVES TOO FAST TO
ALLOW PROCOAGULANTS
• FACTORS INTERFERE WITH
NORMAL CLOTTING
1. PROTHROMBIN III-DEACTIVATES
THROMBIN
2. PROTEIN C-INHIBITS CLOTTING
FACTORS
3. HEPARIN- INHIBITS THROMBIN;
PREVENTS ADHERENCE OF PLATELETS TO
INJURED SITES

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 Role of Coagulation Factors in Clot
Formation Disorders
• Hemophilia
– Genetic disorder caused by deficiency of gene
for specific coagulation factor

• Von Willebrand’s disease

– Reduced levels of vWf
– Decreases platelet plug formation

• Vitamin K deficiencies
– Decreased synthesis of clotting factors

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 Aspirin as an Anticoagulant
• Low doses—anticoagulant
– Inhibits formation of thromboxane A2

• High doses
– Inhibits formation of prostacyclin

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 Clot Controllers
• To prevent the clot from becoming unnecessarily large (don’t want
to completely clog arteries), there is swift removal of clotting
factors and inhibition of active clotting factors.

• Also most of the thrombin is bound to the fibrin threads. This

prevents systemic clotting. Unbound thrombin is inactivated by
Antithrombin III and protein C.

• Heparin is an anticoagulant contained in mast cells and basophils

as well as being found on the surface of endothelial cells. This
inhibits thrombin by enhancing Antithrombin III and clotting by
inhibiting the intrinsic pathway.

• Heparin is also given in synthetic versions to prevent clots in high

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risk patients.
 Endothelial Cells

• Normally endothelial cells are smooth and

intact and prevent platelets from adhering.

• They also secrete NO and prostacyclin, which

prevent platelet aggregation.

• Inappropriate clotting causes serious problems

including stroke, heart attacks, tissue ischemia
and death.
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 Causes and treatments
• Anything that roughens up the endothelium can cause inappropriate
clotting. Things like inflammation and altherosclerosis, diabetes and
hypertension (diabetes and hypertension both result in endothelial
cells’ dysfunction and death).

• Slow-moving blood (too high hematocrit), bed-ridden patients, long

flight with no movement of the lower limbs, all allow clotting factors
to accumulate.

• Aspirin, heparin and warfarin are all used clinically to prevent clots.
Aspirin is an antiprostaglandin that inhibits the formation of TxA2.
Heparin is injected clinically. Warfarin (originally a rat poison) is
taken orally and is called coumadin. This is a mainstay for people
with atrial fibrillation. 29
 Clotting Disorders

• Thromboembolytic disorders, which result from

inappropriate clot formation.

• Bleeding disorders, which are caused by the

prevention of normal clotting functions.

• Disseminated intravascular coagulation

disorders, which involve widespread clotting
and severe bleeding.
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 Thromboembolytic Conditions
• A thrombus is a clot that forms and persists in an unbroken
blood vessel.

• It can block the vessel if it is large enough. This leads to

ischemia and tissue death downstream from the clot. This is a
cause of fatal heart attacks.

• Embolus or emboli is a clot that is free-floating in the blood

stream. This is a problem since it can wedge in a vessel
(referred to as an embolism).

• Pulmonary embolisms impair the body’s ability to get

enough oxygen, while cerebral embolisms cause strokes. 31
 Bleeding Disorders
• Thrombocytopenia is characterized by a lack of
platelets, which causes spontaneous bleeding in small
blood vessels.

• Even normal movement causes internal hemorrhaging

(petechiae) in the skin.

• Anything that affects bone marrow can cause this. For

example chemotherapy, irradiation etc. The only
treatment is platelet transfusions.

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 Bleeding Disorders

• Impaired liver function causes a lack of

procoagulants. This can be treated with vitamin
K shots (newborns) if that is deficient.

• Severe cases like total impairment of liver

function associated with cirrhosis and hepatitis
can require transfusions.

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ROLE OF THE LIVER

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Fig. 12-77
 Hemophilia
• These are a genetic X-linked disorders seen primarily in men.
• Hemophilia A or classical hemophilia is a lack of factor VIII
(~77% of cases).
• Hemophilia B is a lack of factor IX.
• Hemophilia C can be seen in both sexes and is mild. It is a lack of
factor XI. It is mild because IX (which is activated by XI) can also be
activated by VII.
• Symptoms occur early in life and can be disabling. Bleeds can impair
joint function. It is treated by transfusions of plasma and injections of
purified clotting factors. This is expensive to treat and inconvenient to
the patient. Surgery, simple dental procedures etc., can be life-35
threatening.
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