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PLATELET & COAGULATION DISORDERS
RAFEAH RUSLI 03-200904-00277RAFIDAH ABRAHAM 03-200904-00324RANDY B. GUBUD 03-200904-00264SANDRA LOUIS 03-200904-00274SARTIKA AMRAN 03-200904-00180VERA DIANE 03-200904-00244
Presenting…
Objective:
Describe platelet List the types of platelet &
coagulation disorder Describe briefly about the disorders Laboratory diagnosis
Platelet Platelets are produced in blood cell formation
(thrombopoiesis) in bone marrow megakaryoblast > pro-megakaryocyte > immature
megakaryocyte > megakaryocyte > Platelet Platelets or thrombocytes are small irregularly shaped non-nucleated 2–3 µm in diameter. lifespan of circulating platelets is 5 to 9 days. platelet production is regulated by thrombopoietin
(hormone which produced by the liver and kidneys) Old platelets are destroyed by phagocytosis in the
spleen and by Kupffer cells in the liver
Platelet formation:
Platelet cont… The platelet structure has 3 zones:
Peripheral Structural Organelle
Structural zone Consists of the cytoskeleton The cytoskeleton forms the support for the maintenance of the
platelet’s discoid shape Regulate contractile system that allows, upon activation, shape
change, pseudopod extension, internal contraction, and release of granular constituents.
Resting platelets
Activated platelets
Platelet
Platelet cont…
Organelle zone consists of the granules and cellular components These organelles serve in the metabolic processes of the platelet and
store enzymes. dense granules contain non-metabolic adenosine triphosphate (ATP)
and adenosine diphosphate (ADP), serotonin, and calcium alpha granules contain adhesive proteins such as fibrinogen,
fibronectin, von Willebrand factor (VWF), thrombospondin, and vitronectin.
alpha granules also contain growth-promoting substances such as platelet-derived growth factor (PDGF), platelet factor 4, and transforming growth factor.
Coagulation factors including factor V, high molecular weight kininogen, factor XI, and plasminogen activator inhibitor-1 are also present in the alpha granule.
Platelet cont…
Membrane / peripheral zone Consist of typical phospholipid bilayer membrane Embedded in this structure are different kind of glycoprotein.
Glcoprotein Function
GP IIb/IIIa Receptor for fibrinogen, VWF, fibronectin, vitronectin and ThrombospondinFor platelet aggregation
GP Ia/IIa Receptor for Collage
GP Ib/IX/V Receptor for insoluble VWFor platelet adhesion
GP VI Receptor for Collagen
General function of platelet The function of platelets is the maintenance of hemostasis. Platelets helps in blood clotting. Wound repair Platelets secrete platelet-derived growth factor (PDGF). Granule secretion. Adhesion and aggregation. Pro-coagulation. Cytokine signalling. Phagocytosis. Transport of enzyme and proteins critical to clotting. Formation of a platelet plug to slow blood loss. Contraction of a clot after it has formed, which then reduces
the size of the vessel break.
platelet ultrastructure…..
Alpha granules Dense bodies
VwF ADP
Fibronectin ATP
Thrombospondin Serotin
Types of disorder:
Divided into: Coagulation disorder Platelets disorder
Coagulation disorder include: Henophilia Von Willebrand disease
Platelet disorder include: Deficiency Of Vitamin K. Bernard - Soulier Syndrome. Thrombasthenia Of Glanzmann And Naegeli (Glanzmann
Thrombasthenia) Gray Platelet Syndrome. Dense Granule Deficiency Syndrome. Thrombotic Thrombocytopenic Purpura (TTP). Idiopathic Thrombocytopenic Purpura (ITP).
Hemophilia Definition: disease associated with prolonged bleeding
due to the deficiency in clotting factor. Hemophilia is a X-linked disease Types of Hemophilia:
Hemophilia A Factor 8 deficiency, x linked disease
Hemophilia B Factor 9 deficiency, x-linked disease
Hemophilia C Factor 11 deficiency, autosomal genetic disorder
Symptoms of hemophilia: Bruising Bleeds easily Bleeding into a joint Bleeding into the muscles Bleeding from injury or bleeding in the brain Other sources of bleeding (eg. Stool & urine)
Von Willebrand disease
The most common hereditary coagulation abnormality Can also be acquired as a result of other medical conditions Due to the deficiency of von Willebrand factor (vWF) Von Willebrand factor - mediates binding of glycoprotein Ib
to collagen This binding mediate activation of platelets and formation of
primary hemostasis Defect in this factor, resulting glycoprotein IB does not bind
to collagen. Thus unable to activate platelets, primary hemostasis does
not occur
Lab findings: comparison between Hemophilia A, Hemophilia B & von Willebrand disease
Symptoms of von Willebrand disease: Abnormal menstrual bleeding Bleeding of the gums Bruising Nosebleeds Skin rash
Condition PT APTT Bleeding time
Hemophilia A Normal Increased Normal
Hemophilia B Normal Increased normal
Von Willebrand disease
Normal Increased increased
Bernard-Soulier syndrome
Also known as hemorrhagiparous thrombocytic dystrophy It is due to deficiency of glycoprotein Ib (GPIb), the receptor
for von willebrand factor Lacks of GPIb cause vWF unable to bind to the glycoprotein finally lead to decrease in primary clot formation / primary
hemostasis Characterized by
Characterized by abnormally large platelets / giant platelets Characterized by prolonged bleeding time, thrombocytopenia, increased
megakaryocytes, and decreased platelet survival
Some of the symptoms: Purpura. Epistaxis. Menorrhagia. Gingival and gastrointestinal bleeding.
Deficiency of Vitamin K Role of Vitamin K in blood coagulation:
Important in maturation of clotting factor. modification of certain proteins required for blood coagulation
If the clotting factor does not mature, it is useless in the hemostasis process.
Factor which causes the deficiency of vitamin K Disturbed intestinal uptake. By therapeutic or accidental intake of vitamin k-antagonists or
very rarely. By nutritional vitamin k deficiency
Some of the possible symptoms of vitamin K deficiency: Risk of massive uncontrolled bleeding Hematomas
THROMBASTHENIA OF GLANZMANN AND NAEGELI extremely rare coagulopathy can be inherited in an autosomal recessive manner or
acquired as an autoimmune disorder due to deficiency in glycoprotein IIb/IIIa (GpIIb/IIIa) glycoprotein IIb/IIIa (GpIIb/IIIa) is receptor for
fibrinogen. When glycoprotein IIb/IIIa (GpIIb/IIIa) receptor is
dysfunction, fibrinogen cannot bind to the platelets. As a result, no fibrinogen bridging of platelets to other
platelets occur In other words, primary hemostasis inhibited and
prevent platelets aggregation Bleeding time is significantly prolonged
THROMBASTHENIA OF GLANZMANN AND NAEGELI
Symptoms includes:
Increased mucosal bleeding.
Epistaxis.
Menorrhagia.
Increased bleeding post-operatively.
The bleeding tendency is variable but may be severe.
Platelet numbers and morphology are normal.
Platelet aggregation is normal with ristocetin, but impaired with
other agonists such as ADP, thrombin, collagen or epinephrine.
GRAY PLATELET SYNDROME
Gray platelet syndrome (GPS) is a rare inherited bleeding disorder.
The abnormal alpha-granules appear grey on blood films stained by the May-Grünwald-Giesma stain - hence, the syndrome's name.
It caused by the inability of platelets to store alpha-granule proteins.
The platelets' haemostatic proteins are not released at the site of vascular injury.
Thus slows aggregation and vessel repair And contribute to the bleeding tendency. Symptoms may include:
platelets that have a gray appearance severe thrombocytopenia myelofibrosis splenomegaly
DENSE GRANULE DEFICIENCY SYNDROME
it is a bleeding disorder caused by a deficiency in dense granules in the platelets
Dense granules release chemicals in the clotting process and help platelets stick together to form clots.
Lacks of dense granules in platelets means lacks of storage sites for substances for clotting.
Therefore no chemicals which facilitates in the clotting process will be released.
Finally leads to slow platelet activation, and prolonged bleding.
THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) A blood disorder that causes blood clots to form in small blood
vessels around the body, and leads to a low platelet count. The two main types of TTP are inherited and acquired. In inherited TTP, the ADAMTS13 gene is faulty and doesn't
prompt the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed.
Acquired TTP is the more common type of the disorder. The ADAMTS13 gene isn't faulty. Instead, the body makes antibodies (proteins) that block the activity of the ADAMTS13 enzyme.
A lack of activity in the ADAMTS13 enzyme causes TTP. The ADAMTS13 gene controls the enzyme, which is involved
in blood clotting. The enzyme breaks up a large protein called von Willebrand
factor that clumps together with platelets to form blood clots.
IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) Also known as immune thrombocytopenic purpura, is
classified as an autoimmune disease. The term “idiopathic” indicates that the disease is of an
unknown cause or origin: in other words, modern medicine has not yet figured out what it is.
And the word “purpura” comes from a description of the bruise-colored skin of someone afflicted with the disease: the purple color caused by blood that leaked under the skin.
IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) Idiopathic thrombocytopenic purpura is a bleeding disorder
in which the immune system destroys platelets Persons with the disease have too few platelets in the blood The two types of ITP are acute (temporary or short-term)
and chronic (long-lasting). Acute ITP generally lasts less than 6 months. It mainly occurs in children
—both boys and girls—and is the most common type of ITP. Acute ITP often occurs after a viral infection.
Chronic ITP lasts 6 months or longer and mostly affects adults. However, some teenagers and children do get this type of ITP. Chronic ITP affects women two to three times more often than men.
Symptoms: Abnormally heavy menstruation. Bleeding into the skin causes a characteristic skin rash that looks like
pinpoint red spots. (petechial rash) Easy bruising. Nosebleed or bleeding in the mouth.
Lab diagnosis
Status of platelet & coagulation process can be screened by using the following simple lab test: Bleeding Time Clotting time Activated partial thromboplastin time (APTT) Prothrombin time (PT) Full Blood Count Peripheral Blood Film May-Grünwald-Giesma stain
Bleeding time
Function: Basic screening test of platelet function
Procedure: Place a blood pressure cuff on the arm and inflare it to 40mm Hg Clean the area of the fore arm below the anticubital fossa with 70%
alcohol. There should be no superficial veins in the area selected Make 2 skin punctures in rapid succession, each 3mm deep, by using
disposable lancets Start the stop-watch as soon as bleeding starts. Wipe off the blood at 15
seconds interval by touching lightly with a blotting paper Record the time taken for the blood to stop flowing in the both
punctures and determine the mean time. Remove the blood pressure cuff and cover the puncture site with plaster
Result: Normal range : 2-6 minutes Borderline : 6-10 minutes (Test should be
repeated)
Bleeding time:
Clotting time: Function:
To measure he time required for a sample of blood to coagulate in vitro under standard conditions
Procedure: Make a clean venipuncture with minimum trauma to the connective
tissue Start stop-watch as soon as the blood enters the glass syringe. Draw 4ml of blood and deliver 1ml each into 4 glass tubes previously
warmed to 37ºC Place the tube immediately at 37ºC water bath At the end of each minutes, gently tilt one tube to see if the blood is clotted. Continue tilting the tube one after the other at one minute interval till one of them can
be tilted at 90º without the blood flowing out. Note the time Continue with the remaining tubes and take the average of the clotting time in all the 4
tubes
Reference values: Normal values : 5-10 minutes Prolonged clotting time is a marked deficiency in one of the coagulation factors of
intrinsic pathway.
Replaced by APTT
Activated partial thromboplastin time
Function: Evaluate intrinsic pathway Measure all coagulating factor except factor VII and XIII Monitor heparin therapy
Procedure: Pre-warmed APTT reagent at 37ºC for at least 10 minutes. Collect blood specimen in blue top tube Centrifuge and separate the plasma from blood Add 100µl of APTT reagent into a test tube, then add 100µl of plasma into the test
tube and incubate for 2-3 minutes Then add 100µl calcium chloride reagent to the plasma Start stop-watch until clot formed Record the time at which clot form
Reference value: Normal range : 35-45 seconds
Prothrombin time Function:
Used to evaluate the extrinsic pathway (factor 1,2,5,7, and 10) Also used to monitor warfarin therapy
Procedure: Collect blood in blue top tube. Centrifuge blood and separate plasma from blood Make sure to pre-warmed PT reagent 37ºC for at least 10 minutes
before use. Place 100µl plasma into test tube. Pre-warm plasma for 2-3 minutes at 37ºC Then add 200µl of PT reagent to the tube, simultaneously start the stop-watch and
record the time required for clot formation.
Reference value: Normal range : 11-14 seconds
Coagulation pathway:
Other lab test: Full blood count:
Normal range : 150,000 – 400,000 /ul Those with coagulation / platelet disorder :
thrombocytopenia
PBF: Giant platelet may present thrombocytopenia
Special staining: MGG stain for Gray platelet syndrome
Thrombocytosis
Giant Platelet Giant Platelet
Thrombocytopenia
End of PresentationThank You!!
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