Platelet disorders

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  • 2. CHEMOTHERAPHY, RADIATION, DRUG ACTIONS
    Radii- bone in the arm
  • Oncogenic conditions- metastatic cancer, lymphoma, leukemia, myeloma, myelofibrosis, granulomatous dse
  • THROMBOCYTOPENIA DUE TO INCREASE PLATELET DESTRUCTION MAY CAUSED BY IMMUNOLOGIC THROMBOCYTOPENIA
  • Platelet disorders

    1. 1. QUANTITATIVE AND QUALITATIVE DISORDERS
    2. 2.  MOST COMMON CAUSE OF ABNORMAL BLEEDING AND GENERALLY ATTTRIBUTED TO THE FF. CAUSES: 1. Decrease platelet production 2. Decreased platelet survival time due to increase destruction and/or consumption 3. Increased platelet sequestration by the spleen, & 4. Dilution of the platelet count by multiple blood transfusions.
    3. 3. 1. CONGENITAL HYPOPLASIA OF THE MEGAKARYOCYTES IN THE BM a) FANCONI SYNDROME- d/t pancytopenia b) TAR SYNDROME- thrombocytopenia w/ absent radii c) NEWBORNS AS A RESULT OF INTRAUTERINE EXPOSURE TO DRUGS (THIAZIDES) AND VIRAL INFECTIONS (RUBELLA) 2. ACQUIRED HYPOPLASIA OF MEGAKARYOCYTES  DUE TO THERAPEUTIC AGENT ACTIONS  THIAZIDE DIURETICS, ESTROGEN HORMONE AND ALCOHOL SELECTIVELY DECREASES MEGAKAYOCYTE PRODUCTION
    4. 4. 3. INFILTRATION OF THE BM BY MALIGNANT CELLS  Thrombocytopenia associated to such oncogenic conditions is due to marrow replacement or toxin inhibitors of thrombopoiesis produced by the abnormal cells. 4. INEFFECTIVE THROMBOPOIESIS  Characterize by normal to increased marrow megakaryocytes in association with decreased circulating platelets.  Due to defective platelet formation, abnormal marrow release of platelets, or destruction of platelets in the BM.  Found in Px w/: a) Megaloblastic Anemia b) DiGuglielmo’s Syndrome c) Paroxyxmal nocturnal hgburia d) Myelodysplastic syndromes and leukemia
    5. 5.  HEREDITARY CONDITIONS ASSTD W/ INFFECTIVE PLATELET PRODUCTION a) Autosomal dominant thrombocytopenia b) May-Hegglin anomaly c) Wiscott-Aldrich syndrome 5. DISORDERS OF THE CONTROL OF THROMBOPOEISIS  Not common; Result from an impairment in the mechanism that control platelet production.  Cyclic Thrombocytopenia is a condition in which thrombocytopenia and normal platelet counts alternate at regular intervals
    6. 6.  INCREASE PLATELET DESTRUCTION: IMMUNOLOGIC THROMBOCYTOPENIA 1. IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)  THROMBOCYTOPENIA OCCURS IN THE ABSENCE OF ANY DISEASE ASSOCIATED WITH DECREASE PLATELET OR TOXIN EXPOSURE. a) Acute ITP – 2-6 years old; after recovery from viral infection; self limiting i. STAINED BLOOD SMEAR presents: young, large platelet w/ abnormal shapes ii. Dec. Platelet survival time- due to destruction by immune complexes or foreign Ag adsorbed by platelets as a result of an infection iii. Spontaneous remission
    7. 7. b) Chronic ITP- adult; mostly 20-40 years women ii. Circulating platelet are young w/ short lifespan and IgG are elevated. iii. Thrombocytopenia is due to clearing of the Ab coated platelets by slpeen and liver. iv. Tx is costicosteroid therapy or splenectomy v. Rare remission c) Recurrent ITP- found in Px that does not experience permanent remission ff the CITP Tx. ii. Characterized by alternating intercals of thrombocytopenia and normal platelet count. iii. Tx Immunosuppressive drugs and plasmapheresis d) Neonatal ITP- transplacental passage of antiplatelet Ab and occurs most freq when mother is thrombocytopenic at the time of delivery
    8. 8. 2. DRUG INDUCED IMMUNOLOGIC THROMBOCYTOPENIA a) Antibiotics, hypnotics, analgesics, heavy metals, diuretics, chloroquine, digitoxin, heparin and tolbutamide b) Both the drug and Ab must be present in the system at the same time for platelets destruction. c) Thrombocytopenia will occur after 12 hour of drug intake but the time can be still delayed d) Megakaryocyte in the BM is normal e) Removal of the fending drug is usually curative to normalize platelet
    9. 9. 3. IMMUNOLOGIC THROMBOCYTOPENIA  Condition that is indistinguishable to chronic ITP 4. POST TRANSFUSION PURPURA  Occurs 7-10 days after blood transfusion containing platelets.  Result from sensitization of individuals negative for the platelet Ag PIA1 . This Ag is found 97% in normal population.  Primary immunization occurs during pregnancy. 5. ISOIMMUNE NEONATAL THROMBOCYTOPENIA  Analogous to HDN  Non-immunologic since thrombocytopenia is due to increase platelet consumption  Occurs as a result of maternal antiplatelet Ab produces in response to fetal Ag inherited from the father.  Usually affects the first child and platelet Ag PIA1 has most often been asstd.
    10. 10. 6. Inc. platelet consumption; non-immunologic thrombocytopenia  Thrombotic thrombocytopenic purpura (TTP)- unknown exact cause; serious dse a) Hemolytic anemia- trauma to RBC b) Changing neurologic Sx c) Fever & d) Renal abnormalities e) DIC-When progress *caused by thrombi in the capillaries and arterioles through out the body. Peripheral blood smear: poikilocytosis and normoblasts *most commonly found in women (40 yrs. Mean age) 7. Hemolytic uremic syndrome  Resembles TTP  Primary in children  Intravascular clotting is confined to kidney  Tx- dialysis, plasma transdusion or exchange & antihypersensitive therapy
    11. 11. 7. NONIMMUNOLOGIC THROMBOCYTOPENIA  Thrombocytopenia may be present in a number of rickettsial, bacterial, viral or malarial infections- due to Increase consumption of platelets and less commonly as a result of decrease production.  Thrombocytopenia related to cardiopulmonary bypass can result from DIC, dilution, sequestration, platelet destruction in the oxygenerator and increase fibrinolysis.
    12. 12.  An abnormal distribution of platelets may also cause thrombocytopenia.  Normally the spleen pools approximately one-third of the total spleen (splenomegaly).  An increased percentage of the platelets will be found in the spleen, thereby producing thrombocytopenia.  Increased splenic pooling is differentiated from destruction of platelets
    13. 13. thrombocytopenia
    14. 14. Multiple transfusions
    15. 15. Splenic pool Transfusion
    16. 16.  A platelet count increased above normal will be found as a result f a variety of circumstances.  Reactive thrombocytosis
    17. 17. Generally responds when the lying disorder is treated. Following splenectomy, the platelet count will generally rise during the first postoperative week, peak at about 2 to 3 weeks, and return to normal over a period of several months.
    18. 18. Thrombocytosis following major surgery usually occurs during the first postoperative week, with the platelet count generally decreasing to normal levels within about 2 weeks. Within about a day or so following acute blood loss, a reactive thrombocytosis may occur as a result of increased bone marrow stimulation.
    19. 19.  Marked increase in the platelet count  Associated with thrombotic and /or hemorrhagic complications.  Common in myeloproliferative disorder that includes:  Essential thrombocytosis  Chronic Myelogenous Leukemia  Polycythemia Vera  Myeloid Mataplasia
    20. 20. Thrombocythemia Middle age patients (both male and female) bleeding or thrombosis with bleeding episodes predominating (Gastrointestinal hemorrhage) Bleedin g in arterial and venous circulati on Splenome galy is a frequent finding
    21. 21.  Hereditary Qualitative Platelet Disorder  Acquired Qualitative Platelet Disorder Functional Platelet Disorder Platelet Adhesion Platelet Aggregation Platelet Secretion or Release Reaction
    22. 22.  Bernard-Soulier Syndrome  Inherited as an autosomal recessive trait  Bruising and moderate to severe bleeding ** CHARACTERISTICS **  Giant Platelets (20 um in diameter)  Coarse granulation and vacuoles  Mild thrombocytopenia
    23. 23. PLATELET Lack glycoprotein 1b (GP1b) Lack glycoprotein V AND IV Function as Receptor in vonWillebrand factor Unable to adhere normally to vascular endothelium Do not bind coagulation factor XI normally
    24. 24. CHARACTERISTICS o MEGAKARYOCYTE (in BM) = Normal to slightly increased o PLATELET - Bleeding time is PROLONGED but clot refraction is NORMAL - Platelet aggregation is NORMAL with ADP, epinephrine and collagen, but ABNORMAL ristocetin and thrombin - DECREASED platelet retention in glass beads column
    25. 25. vonWillebrand’s Disease - ABSENT or ABNORMAL form of vonWillebrand factor = impaired platelet adhesion - NORMAL in Aggregation studies with ADP, collagen and epinephrine - ABNORMAL ristocetin-induced aggregation
    26. 26.  An aggregation disorder is when platelets do not bind with fibrinogen and other proteins in order to stick to other platelets. As a result the platelets cannot form a plug to stop the bleeding from a damaged blood vessel.  A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder.  platelet aggregation studies show a defective primary response in the presence of collagen, epinphrine, ADP, and thrombin but normal response with ristocen
    27. 27. Diagnose:  platelet retention is markedly increased  platelet count is generally normal but may  occasionally be slightly decreased.  clot retraction is decreased to absent  bleeding time is prolonged Blood tests show: that bleeding time is much longer than normal that the platelets do not clump together at all (platelet aggregation is absent). Wright stain blood smear: it appear as morphologically normal and show aggregating agents.
    28. 28. Also called Glanzmann’s thrombosthenia -is major inherited bleeding disorder characterized by the failure of platelets to aggregate when stimulated with adenosine diphosphate (ADP) or other physiologic agonists. It is inherited or passed down from a child's parent(s). This disorder causes moderate to severe bleeding symptoms:  Bleeding from the mouth  Bleeding with dental procedures  Nose bleeds  Bruising or small purplish red dots under the skin  Bleeding for a long time after an injury or surgery  Girls or women may have heavy periods  Infant boys may have bleeding after circumcision
    29. 29. A secretion disorder is when the damaged blood vessel takes more time for the bleeding to stop due to missing chemicals that signals the platelets to stick together. As a result, it takes a lot longer for the bleeding from a damaged blood vessel to stop. This is the most common platelet disorder.
    30. 30. Two groups: 1.Storage pool disorder  defective platelet release reaction due to a lack of dense bodies and/or granules.  mild to moderate bleeding tendency, and easy bruising  Abnormalities of the dense bodies or a granules
    31. 31. 2. Aspirin-like defects  platelets have normal granules but defective release  deficiency of the enzyme cyclo-oxygenase or thbormalrombozane synthetase  have a prolonged bleeding time and abnormal aggregation with ADP, epinephrine, and collagen.
    32. 32. Three platelet function disorders involve platelet secretion: 1. Alpha Granule Deficiency, called Gray Platelet Syndrome, there is a lack of important proteins within the alpha granule inside the platelet. This problem slows down normal platelet adhesion, aggregation and repair of the blood vessel 2. Dense Granule Deficiency, called Delta Storage Pool Deficiency, there is a lack of storage granules for certain substances needed for normal platelet activation. Their absence slows down platelet activation and blood vessel constriction. 3. Abnormalities of the granule secretory mechanism occur when the normal granules fail to release their contents when platelets are activated.
    33. 33. - Very large platelets & abnormalities in platelets adhesion & aggregation *Ehlers-Danlos Syndorme  Hereditary Afibrinogenemia - prolonged bleeding time - abnormal platelet aggregation with ADP *glycoprotein storage disease type 1 (G-6-PD deficiency) - bleeding time is also prolonged - platelet defects may be secondary to the metabolic defect
    34. 34. - Acquired disorders of platelet function are associated with a number of conditions & with the ingestion of certain drugs. • - metabolites that are toxic to the platelets accumulate in the plasma. - Platelet release reaction, aggregation, retention are all abnormal & bleeding time is prolonged. - Platelet dysfunction & abnormal platelet-vessel wall interaction - Dialysis is of temporary therapeutic value; the administration of cryoprecipitates will aid in controlling major bleeding episodes.
    35. 35. Platelet dysfunction & bleeding disorders will be present in the various Multiple myeloma & Waldenstrom’s macroglobinemia -abnormalities of the platelet aggregation & reduced platelet retention are thought to be due to: - coating of the platelet membrane - vessel walls with the abnormal proteins
    36. 36.  Megakaryocyte in the BM may be small & somewhat abnormal  Resultant platelets abnormal - defective platelet aggregation - defective release mechanism
    37. 37.  (polycytothemia vera, chronic myelogeneous leukemia, myeloid metaplasia, & essential thrombocythemia) -Display fuctional abnormalities in addtion to thrombocytosis -Common complications: -bleeding and/or thrombosis  Myeloid metaplasia -bleeding time is prolonged -defective platelet adhesion, aggregation, & storage pool deficiencies  Abnormal platelet aggregation- polycythemia vera  Thrombocythemia- platelets appear in large & morphologically abnormal  Prolonged bleeding time & defective aggregation- chronic myelogenous leukemia
    38. 38. Inc. amounts of - Present in DIC, fibrinogenolysis, & liver disease - Inhibit ADP induced platelet aggregation Fragments D & E -absorb onto the platelet surface, interfere with platelet function & will inhibit thrombin induced platelet aggregation
    39. 39.  Iodiophatic thormbocytopenia purpura  Autoimmune disorders -systemetic lupus erythromatosis - Antibodies have been shown to cause platelet lysis, platelet aggregation & serotonin release
    40. 40.  Inhibit platelet function  Aspirin  - inhibit release reaction & secondary wave of the aggregation  - Direct result of aspirin’s ability to inactive the enzyme cyclo-oxygenase  - Effect of aspirin : lasts for the life of the platelet  - Presence of aspirin: defective platelet aggregation with ADP, epinephrine & collagen  - Other drugs that induce qualitative platelet abnormalities:  -antihistamines, antidepressants & antibiotics, heparin dextran & other plasma expanders, ethanol & certain local anesthetics

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