Platelet and coagulation disorder
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Platelet and coagulation disorder

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Platelet and coagulation disorder Platelet and coagulation disorder Presentation Transcript

  • RAFEAH RUSLI 03-200904-00277RAFIDAH ABRAHAM 03-200904-00324RANDY B. GUBUD 03-200904-00264SANDRA LOUIS 03-200904-00274SARTIKA AMRAN 03-200904-00180VERA DIANE 03-200904-00244Presenting…PLATELET & COAGULATIONDISORDERS
  • 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 View slide
  • Platelet formation: View slide
  • 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 plateletsActivated 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 Thrombospondin For platelet aggregation GP Ia/IIa Receptor for Collage GP Ib/IX/V Receptor for insoluble VW For 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 diseaseCondition PT APTT Bleeding timeHemophilia A Normal Increased NormalHemophilia B Normal Increased normalVon Willebrand disease Normal Increased increased Symptoms of von Willebrand disease:  Abnormal menstrual bleeding  Bleeding of the gums  Bruising  Nosebleeds  Skin rash
  • 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 GLANZMANNAND 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 GLANZMANNAND 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 syndromes 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 DEFICIENCYSYNDROME 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 THROMBOCYTOPENICPURPURA (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 doesnt 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 isnt 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 THROMBOCYTOPENICPURPURA (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 THROMBOCYTOPENICPURPURA (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
  • Giant Platelet Giant PlateletThrombocytosis Thrombocytopenia