Describing platelets and their function in coagulatory hemostasis and vascular-thrombocytic hemostasis.

1. VISITH DANTANARAYANA
GROUP 201

2.  ALSO KNOWN AS PLATELETS.
 FRAGMENTS OF CYTOPLASM DERIVED FROM
MEGAKARYOCYTES.
 NO NUCLEUS
 2 – 3 µm IN MAXIMUM DIAMETER
 BICONVEX DISCOID SHAPED OR LENS SHAPED.

4. 150,000 TO 400,000 PER CUBIC
MILLIMETER.
 LOW PLATELET CONCENTRATION:
THROMBOCYTOPAENIA
 ABNORMALLY HIGH PLATELET
CONCENTRATION: THROMBOCYTOSIS
Men as a group have slightly higher
mean values than women.

6.  FORMATION OF PLATELET PLUGS IN
HEMOSTASIS.
◦ ACTIVATION
◦ ADHESION
◦ AGGREGATION
◦ COHESION OR PLUG FORMATION

7.  SUPPORTING COAGULATORY
MECHANISMS
 PHAGOCYTOSIS
 STORAGE AND TRANSPORT OF
SUBSTANCES

8. THE PROCESS WHICH CAUSES BLEEDING TO
STOP, MEANING TO KEEP BLOOD WITHIN A
DAMAGED BLOOD VESSEL.

9.  HEMOSTASIS AS A WHOLE HAS THREE MAJOR
STEPS:
 VASOCONSTRICTION
 VASCULAR-THROMBOCYTIC HEMOSTASIS
 COAGULATORY HEMOSTASIS

10. SEEN AS A VASCULAR SPASM.
 THE PAIN RECEPTORS OF THE
SMOOTH MUSCLES OF THE DAMAGED
VESSEL WALL INITIATES THE SPASM.
 SEROTONIN AND THROMBOXANE
RELEASED BY THE ENDOTHELIUM OF
DAMAGED VESSEL WALL ALSO ASSIST
IN THE PROCESS.

12. WHEN AN ANEURYSM RUPTURE OCCURS IT COULD
RELEASE TOXINS THAT COULD INITIATE VASCULAR
SPASMS IN NEARBY ARTERIES OR VEINS.

15.  WHEN UNDAMAGED, ENDOTHELIAL CELLS ARE
ATTACHED TO THE SUBENDOTHELIAL
COLLAGEN BY VON WILLEBRAND
FACTOR (VWF) WHICH THESE CELLS PRODUCE.
VWF IS ALSO STORED IN ENDOTHELIAL CELLS
AND SECRETED CONSTITUTIVELY INTO THE
BLOOD. PLATELETS STORE VWF IN THEIR
GRANULES.
 VON WILLEBRAND FACTOR IS A TERTIARY
GLYCOPROTEIN.

16.  WHEN THE ENDOTHELIAL LAYER IS
DISRUPTED, COLLAGEN AND VWF ANCHOR
PLATELETS TO THE SUBENDOTHELIUM.
PLATELET GP1B-IX-V RECEPTOR BINDS WITH
VWF; AND GPVI RECEPTOR BINDS WITH
COLLAGEN.

19.  PAF is produced by a variety of cells, but
especially those involved in host defense,
such
as PLATELETS, ENDOTHELIAL CELLS, NEUTROP
HILS, MONOCYTES, AND MACROPHAGES.
 Platelet activation begins seconds after
adhesion occurs. It is triggered
when collagen from the subendothelium,
and/or tissue factor from the media and
adventitia

20.  Tissue factor also binds to factor VII in the blood,
which initiates the extrinsic coagulation cascade
to increase thrombin production. Thrombin is a
potent platelet activator, which also promotes
secondary fibrin-reinforcement of the platelet
plug. Platelet activation in turn degranulates and
releases factor V and fibrinogen, potentiating the
coagulation cascade. So in reality the process of
platelet plugging and coagulation are occurring
simultaneously rather than sequentially, with
each inducing the other to form the final clot.

21.  GP IIB/IIIA ACTIVATION
 GRANULE SECRETION
 MORPHOLOGY CHANGE
 COAGULATION FACILITATION

22.  Platelets secrete thromboxane A2, which acts
on the platelet's own thromboxane
receptors on the platelet surface (hence the
so-called "out-in" mechanism), and those of
other platelets. These receptors trigger
intraplatelet signaling, which
converts GPIIb/IIIa receptors to their active
form to initiate aggregation.

23.  Platelets contain dense granules, lambda granules
and alpha granules.
 GRANULE CHARACTERISTICS:
 α granules (alpha granules) – containing P-
selectin, platelet factor 4, transforming growth factor-
β1, platelet-derived growth factor, fibronectin, B-
thromboglobulin, vWF, fibrinogen, and coagulation
factors V and XIII).
 δ granules (delta or dense granules) –
containing ADP or ATP, calcium, and serotonin).
 γ granules (gamma granules) – similar to lysosomes and
contain several hydrolytic enzymes.
 λ granules (lambda granules) – contents involved in clot
resorption during later stages of vessel repair.

25.  Aggregation begins minutes after activation,
and occurs as a result of turning on
the GPIIb/IIIa receptor, which allows these
receptors to bind with vWF or fibrinogen.

30.  THE CLOTTING FACTORS ARE THE GROUP OF
CHEMICALS THAT ARE CONSTANT CIRCULATION
IN THE BLOOD OR PRESENT IN TISSUES OF THE
BLOOD VESSELS.
 THESE COMPOUNDS ARE RESPONSIBLE FOR THE
FORMATION OF A BLOOD CLOT.
 CLOTTING FACTORS ARE USUALLY INACTIVE BUT
ONCE THERE IS TISSUE INJURY TO THE WALL OF
THE BLOOD VESSEL, THE FIRST FACTOR IS
ACTIVATED.
 THIS HAS A CYCLICAL EFFECT WITH EACH
FACTOR ACTIVATING THE NEXT.

31.  FACTOR I
Name : FIBRINOGEN
Source : Liver
Pathway : Both extrinsic and intrinsic
Activator : THROMBIN
Actions : When fibrinogen is converted into
fibrin by thrombin, it forms long strands that
compose the mesh network for clot formation.

32.  FACTOR II
Name : PROTHROMBIN
Source : Liver
Pathway : Both extrinsic and intrinsic
Activator : PROTHROMBIN ACTIVATOR
Actions : Prothrombin is converted into
thrombin which then activated fibrinogen into
fibrin.

33.  FACTOR III
Name : THROMBOPLASTIN / TISSUE FACTOR
Source : Platelets (intrinsic) and damaged
endothelium (cells) lining the blood vessel
(extrinsic).
Pathway : Both extrinsic and intrinsic
Activator : INJURY TO BLOOD VESSEL
Action : Activates factor VII (VIIa).

34.  FACTOR IV
Name : CALCIUM
Source : Bone and absorption from food in
gastrointestinal tract
Pathway : Both extrinsic and intrinsic
Action : Works with many clotting factors for
activation of the other clotting factors. These
are called calcium-dependent steps.

35.  FACTOR V
Name : PROACCERIN / LABILE FACTOR / AC-
GLOBULIN (AC-G)
Source : Liver and platelets
Pathway : Both extrinsic and intrinsic
Activator : THROMBIN
Action : Works with Factor X to activate
prothrombin (prothrombin activator).

36.  FACTOR VII
Name : PROCONVERTIN / SERUM
PROTHROMBIN CONVERSION ACCELERATOR
(SPCA) / STABLE FACTOR
Source : Liver
Pathway : Extrinsic
Activator : FACTOR III (TISSUE FACTOR)
Actions : Activates Factor X which works with
other factors to convert prothrombin into
thrombin.

37.  FACTOR VIII
Name : ANTI-HEMOPLYTIC FACTOR /
ANTIHEMOPHILIC FACTOR (AHF) OR GLOBULIN
(AHG) / ANTIHEMOPHILIC FACTOR A
Source : Endothelium lining blood vessel and
platelets (plug)
Pathway : Intrinsic
Activator : THROMBIN
Actions : Works with Factor IX and calcium to
activate Factor X.
DEFICIENCY : HEMOPHILIA A

38.  FACTOR IX
Name : CHRISTMAS FACTOR / PLASMA
THROMBOPLASTIN COMPONENT (PTC) /
ANTIHEMOPHILIC FACTOR B
Source : Liver
Pathway : Intrinsic
Activator : FACTOR XI AND CALCIUM
Actions : Works with Factor VIII and calcium to
activate Factor X.
DEFICIENCY : HEMOPHILIA B

39.  FACTOR X
Name : STUART PROWER FACTOR / STUART
FACTOR
Source : Liver
Pathway : Extrinsic and intrinsic
Activator : FACTOR VII (EXTRINSIC) / FACTOR IX
+ FACTOR VIII + CALCIUM (INTRINSIC)
Actions : Works with platelet phospholipids to
convert prothrombin into thrombin. This
reaction is made faster by activated Factor V.

40.  FACTOR XI
Name : PLASMA THROMBOPLASTIN
ANTECEDENT (PTA) / ANTIHEMOPHILIC FACTOR
C
Source : Liver
Pathway : Intrinsic
Activator : FACTOR XII + PREKALLIKREIN AND
KININOGEN
Actions : Works with calcium to activate Factor
IX.
Deficiency : Hemophilia C

41.  FACTOR XII
Name : HAGEMAN FACTOR
Source : Liver
Pathway : Intrinsic
Activator : CONTACT WITH COLLAGEN IN THE
TORN WALL OF BLOOD VESSELS
Actions : Works with prekallikrein and
kininogen to activate Factor XI. Also activates
plasmin which degrades clots.

42.  FACTOR XIII
Name : FIBRIN STABILIZING FACTOR
Source : Liver
Activator : THROMBIN AND CALCIUM
Actions : Stabilizes the fibrin mesh network of
a blood clot by helping fibrin strands to link to
each other. Therefore it also helps to prevent
fibrin breakdown (fibrinolysis).

43.  PREKALLIKREIN
Source : Liver
Pathway : Intrinsic
Actions : Works with kininogen and Factor XII
to activate Factor XI.
 KININOGEN
Source : Liver
Pathway : Intrinsic
Actions : Works with prekallikrein and Factor
XII to activate Factor XI.

44.  COAGULATION CAN PHYSICALLY TRAP
INVADING MICROBES IN BLOOD CLOTS.

45.  Also, some products of the coagulation
system can contribute to the INNATE IMMUNE
SYSTEM by their ability to increase vascular
permeability and act as CHEMOTACTIC
AGENTS FOR PHAGOCYTIC CELLS.

46.  In addition, some of the products of the
coagulation system are directly antimicrobial.
For example, beta-lysine, an amino acid
produced by platelets during coagulation, can
cause lysis of many Gram-positive bacteria by
acting as a cationic detergent.

47.  Five mechanisms keep platelet activation and the
coagulation cascade in check. They prevent the
UNNECESSARY THROMBOSIS.
 PROTEIN C
 ANTITHROMBIN
 TISSUE FACTOR PATHWAY INHIBITOR
 PLASMIN
 PROSTACYCLIN

49.  HEMOPHILIAS - The three main forms
are hemophilia A (factor VIII
deficiency), hemophilia B (factor IX deficiency
or "Christmas disease") and hemophilia
C (factor XI deficiency, mild bleeding
tendency).
 VON WILLEBRAND DISEASE - Defect in VON
WILLEBRAND FACTOR (VWF), which mediates
the binding of GLYCOPROTEIN IB (GPIB) to
collagen.

50.  BERNARD-SOULIER SYNDROME is a defect or
deficiency in GPIb. GPIb, the receptor for vWF,
can be defective and lead to lack of primary
clot formation (primary hemostasis) and
increased bleeding tendency. This is an
autosomal recessive inherited disorder.

51.  THROMBASTHENIA OF GLANZMANN AND
NAEGELI (GLANZMANN THROMBASTHENIA) is
extremely rare. It is characterized by a defect
in GPIIb/IIIa fibrinogen receptor complex.
When GPIIb/IIIa receptor is dysfunctional,
fibrinogen cannot cross-link platelets, which
inhibits primary hemostasis. This is an
autosomal recessive inherited disorder.

52.  THROMBOSIS is the pathological development of
blood clots. These clots may break free and
become mobile, forming an EMBOLUS or grow to
such a size that occludes the vessel in which it
developed.
 An EMBOLISM is said to occur when
the thrombus (blood clot) becomes a mobile
embolus and migrates to another part of the
body, interfering with blood circulation and
hence impairing organ function downstream of
the occlusion.
THIS LEADS TO ISCHEMIA AND THEN NECROSIS OF
THE TISSUE.

53.  Mutations in FACTOR XII have been
associated with an asymptomatic
prolongation in the clotting time and possibly
a tendency toward THROMBOPHLEBITIS. Other
mutations have been linked with a rare form
of HEREDITARY ANGIOEDEMA (TYPE III).

55.  PROCOAGULANTS
The use of adsorbent chemicals, such
as zeolites, and other hemostatic agents are
also used for sealing severe injuries quickly
(such as in traumatic bleeding secondary to
gunshot wounds). Thrombin and fibrin glue are
used surgically to treat bleeding and to
THROMBOSE ANEURYSMS.
DESMOPRESSIN IS USED TO IMPROVE PLATELET
FUNCTION BY ACTIVATING ARGININE
VASOPRESSIN RECEPTOR 1A.

56.  COAGULATION FACTOR CONCENTRATES ARE
USED TO TREAT HEMOPHILIA, TO REVERSE THE
EFFECTS OF ANTICOAGULANTS, AND TO TREAT
BLEEDING IN PATIENTS WITH IMPAIRED
COAGULATION FACTOR SYNTHESIS OR
INCREASED CONSUMPTION. PROTHROMBIN
COMPLEX
CONCENTRATE, CRYOPRECIPITATE AND FRESH
FROZEN PLASMA ARE COMMONLY USED
COAGULATION FACTOR
PRODUCTS. RECOMBINANT ACTIVATED HUMAN
FACTOR VII IS INCREASINGLY POPULAR IN THE
TREATMENT OF MAJOR BLEEDING.

57.  TRANEXAMIC ACID AND AMINOCAPROIC
ACID INHIBIT FIBRINOLYSIS, AND LEAD TO
A DE FACTO REDUCED BLEEDING RATE.
BEFORE ITS WITHDRAWAL, APROTININ WAS
USED IN SOME FORMS OF MAJOR SURGERY TO
DECREASE BLEEDING RISK AND NEED FOR
BLOOD PRODUCTS.

58.  ANTICOAGULANTS (ANTITHROMBICS,
FIBRINOLYTIC, AND THROMBOLYTICS) ARE A
CLASS OF DRUGS THAT WORK TO PREVENT
THE COAGULATION (CLOTTING) OF BLOOD.

59.  These oral anticoagulants are derived
from COUMARIN, which is found in many plants.
A prominent member of this class
is WARFARIN (COUMADIN). It takes at least 48 to
72 hours for the anticoagulant effect to develop.
 These anticoagulants are used to treat patients
with deep-vein thrombosis (DVT), pulmonary
embolism (PE) and to prevent emboli in patients
with atrial fibrillation (AF), and
mechanical prosthetic heart valves.

60.  Heparin is a biological substance, usually
made from pig intestines. It works by
activating ANTITHROMBIN III, which blocks
thrombin from clotting blood.
 LOW MOLECULAR WEIGHT HEPARIN, a more
highly processed product, is useful as it does
not require monitoring of
the APTT coagulation parameter (it has more
predictable plasma levels) and has fewer side
effects.

61.  FONDAPARINUX is a synthetic sugar
composed of the five sugars
(pentasaccharide) in heparin that bind to
ANTITHROMBIN. It is a smaller molecule than
low molecular weight heparin.

62.  Drugs such
AS RIVAROXABAN, APIXABAN AND EDOXABAN
WORK BY INHIBITING FACTOR Xa DIRECTLY
(UNLIKE THE HEPARINS AND FONDAPARINUX,
WHICH WORK VIA ANTITHROMBIN
ACTIVATION).

64.  A class of medication that act
as anticoagulants (delaying blood clotting) by
directly inhibiting
THE ENZYME THROMBIN (FACTOR II).
 THERE ARE 3 TYPES:
UNIVALENT
BIVALENT
ALLOSTERIC INHIBITORS

65.  BATROXOBIN - A TOXIN FROM SNAKE VENOM
 HEMENTIN – ANTICOAGULANT PROTEASE
FOUND IN THE SALIVA OF THE GIANT
AMAZON LEECH.