This document discusses hemostasis, bleeding disorders, and platelet disorders. It begins by explaining normal hemostasis and the mechanisms involved in maintaining a fluid blood state and forming clots at sites of injury. It then defines bleeding disorders as problems with blood clotting that result in abnormal bleeding. Common causes discussed include defects in blood vessels or blood itself, clotting factor deficiencies, platelet abnormalities, and liver disease. Finally, it examines several specific platelet disorders like thrombocytopenia, immune thrombocytopenic purpura, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and those resulting from bone marrow infiltration or disseminated intravascular coagulation.

1. HEMOSTASIS, BLEEDING AND CLOTTING DISORDERPresented by :Nik Khairiyah Bt Raja MohammedMohamad Nizar B. Muhamad YatimNuradibah Bt ShahrulNuramalina Bt Ahmad Ehsan

2. In the absence of blood vessel damage :platelets are repelled from each other and from endothelium of blood vessel.endothelial cell secretes prostacyclin and nitric oxide (NO) -act as vasodilator & inhibit platelet aggregation.plasma membrane of endothelial cell contain enzyme (CD39) - breakdown ADP to AMP + Pi.

3. Normal HemostasisDef : consequence of tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels while introducing the rapid formation of a localized hemostatic plug at the site of vascular injury.- from Robbins Basic Pathology 8th editionMechanism vasocontriction

4. formation of platelet plug

5. coagulation cascade

6. fibrinolysisNormal hemostasis

7. Coagulation cascade

8. Normal hemostasis

9. Bleeding DisorderDef : Bleeding disorders is a general term for a wide range of medical problems that lead to poor blood clotting and continuous bleeding.characterized clinically by abnormal bleeding, which can either be spontaneous or become evident after some inciting event.can result from : defects in the blood vessel

10. abnormalities in the blood itself

11. blood clotting factor

12. plateletSource from : National Haemophilia Association

13. Source from : Nelson Essential of Pediatrics 5th edition

14. Diagnostic approach1) Identify clinical featuresa) age of onset - neonate - toddler - adolescentb) family history - family tree - genderc) bleeding history - previous surgical / dental procedure - presence of systemic disorder - drug history - unusual pattern or inconsistent historyd) pattern of bleeding - mucous membrane bleeding & skin haemorrhage - bleeding into muscles or into joints - scarring and delayed haemorrhageSource from : Tom Lissauer, Graham Clayden Illustrated Textbook of Paediatric 3rd edition

15. 2) Screening testTestMechanism TestedNormal ValueDisorderBleeding time (BT)Hemostasis, capillary & platelet function3-7 min beyond neonateThrombocytopenia, von Willebrand diseasePlatelet countPlatelet number150 000 – 450 000 / mm^3ThrombocytopeniaProthrombin time (PT)Extrinsic & common pathway< 12 sec beyond neonate; 12-18 sec in term neonateDefect in Vit K-dependent factor, liver disease, DICActivated partial thromboplastin time (APTT)Intrinsic & common pathway25-40 sec beyond neonate; 70 sec in term neonateHemophilia, von Willebrand disease, DICSource from : Nelson Essential of Pediatrics 5th edition

16. in neonate (term infant), the level of all clotting factors except factor VIII & fibrinogen are LOWER, much lower in preterm infants.therefore, the results have to be compared with normal values in infants of a SIMILAR GESTATIONAL & POSTNATAL AGE.sometimes necessary to exclude an Inherited Coagulation Factor Deficiency by testing the coagulation of both parents.

17. Thank you….

18. PLATELET DISORDER, what is it?MUHAMMAD NIZAR BIN MOHAMMAD YATIM

19. WHAT IS PLATELET ? Oblong disk shapeSize- 2-4 µm on the long axisVolume- 5-12 fLProduced in bone marrow by megakaryocte cellPlatelet count in blood- 150,000-350,000 µLLife span- ????Function- ??

20. Classification of platelet disordersQuantitative disorderAbnormal distribution

21. Dilution effect

22. Decreased production (leukemia and some anemia)

23. Increased destructionQualitative disordersInherited disorders (rare)

24. Acquired disorders (medication, chronic renal failure, cardiopulmonary bypass)Glanzmann’sthrombasthenia Bernard-Soulier syndromePRIMARYITPTTPTAR syndromeWiskott-Aldrich syndromeNeonatal isoimmuneSECONDARYMalignancyAplastic anemiaDIVCSepsisDrug-inducedHemolytic-uremic syndromeHypersplenismAutoimmune(SLE)HIV

25. THROMBOCYTOPENIADefined as reduced in the platelet count< 150, 000µL that characterized by spontaneous bleeding, a prolonged bleeding time, and a normal PT and PTT.The risk of bleeding depends on the level of the platelet count:Mild thrombocytopenia (platelet <150 000 cells/µL)

26. Moderate thrombocytopenia (platelet 20 000 - 50 000 cells/µL)

27. Severe thrombocytopenia (platelet <20 000 cells/µL)Sign and symptombruising, petechiae, purpura and mucosal bleeding (epistaxis @ gum bleeding)

28. major haemorrhage like severe GI bleeding, intracranial bleeding or haematuria is less common

29. normal platelet count may present in platelet dysfunctionCongenital (Fanconianaemia, Wiskot-Aldrich SyndromeDecreased production of plateletsAcquired (aplastic anaemia, marrow infiltration, drug induced )Increased platelets destructionImmunologic destruction (ITP, SLE , Alloimmune neonatal thrombocytopenia)AetiologyNonimmunologicdestruction (HUS, TTP,DIC, CHD)SequestrationHypersplenismDilutionalMassive blood transfusion

30. 1.IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)DEFINITION

31. Isolated thrombocytopenia with otherwise normal blood count in a patient with no clinically apparent associated conditions that can cause thrombocytopenia (such as HIV infection, SLE, lymphoproliferative disorders, alloimmune thrombocytopenia, and congenital or hereditary thrombocytopenia).

32. Caused by immune- mediated destrcuction of circulating platelet d/t anti-platelet autiantibodies

33. There are two clinical subtypes of ITP:

34. Acute ITP.

35. Chronic ITP (starts after the disease has been present for > 6 months).Feature of Acute and Chronic ITP

36. PATHOGENESISInappropriate immune recovery follows an acute viral infection in children.Autoantibodies (IgG or IgM) directed against platelet membrane antigens (especially glycoprotein complex IIb/IIIa). Phagocytosis of antibody-coated platelets by the reticuloendothelial system.Increased destruction of platelets – Thrombocytopenia.

37. CLINICAL MANIFESTATIONSOnset is usually sudden for acute ITP and in chronic ITP, it is insidious onset.Petechiae or purpuraFeet, legs, arms, and buttocks.Mucosal bleeding.Palatal petechiae, epistaxis, hematuria, menorrhagia, GI bleeding.Rarely, intracranial hemorrhage may occur in long standing severe thrombocytopenia.

39. DIAGNOSISHistory taking.

40. Physical examination.

41. Signs of bleeding (petechiae and purpura).

42. Mucosal bleeding.

43. Investigations.

44. Full blood count.

45. Low platelet count.

46. Histological findings.

47. Platelets are normal in size or may appear larger than normal.

48. Normal red blood cells morphology.

49. Normal white blood cells morphology.

50. Coagulation tests.

51. Prolong bleeding time, normal PT and PTT.Not all children with acute ITP need hospitalization.Treatment is indicated if there is:Life threatening bleeding episode (e.g. ICH) regardless of platelet count.Platelet count < 20,000/mm³ with mucosal bleeding.Platelet count < 10,000/mm³with any bleeding.Choice of treatment:Oral prednisolone - 4 mg/kg/day for 7 days, taper and discontinue at 21 days.

52. IV Methylprednisolone - 30 mg/kg/day for 3 days.

53. IV Immunoglobulin - 0.8 g/kg/dose for 1 day OR 250 mg/kg for 2 days.

54. IV Anti-Rh(D) immunoglobulin - (50 – 75 µ/kg) in Rhesus positive patients – may cause haemolytic anaemia.TREATMENT & MANAGEMENT

55. Splenectomy is only for life threatening in acute ITPFor chronic ITP:Repeated treatment with IV immunoglobulin or IV anti-D or high dose pulse steroids are effective in delaying the need for splenectomy

56. Splenectomy is effective in inducing remission in 70-80% of childhood chronic ITPCOMPLICATIONIntracranial hemorrhage - 50% mortality rate.Risk of ICH highest in:Platelet count < 20 000/mm³.

57. History of head trauma.

58. Uses of aspirin (inhibitor of platelet aggregation).

59. Presence of cerebral arteriovenous malformation.50% of all ICH occurs after 1 month of presentation, 30% after 6 months.

60. 2. Hemolytic Uremic Syndrome (HUS)Related to TTP in which the number of platelets suddenly decreases, RBC are destroyed and the kidney stop functioningHUS is rare, but can occur with certain bacterial infection (E.coli or shigelladysenteriae) and with the use some drugs (quinine, cyclosporine, mitomycin C)Toxin producing organism such as E.coli cause endothelial damage that activates localized clotting, leading to platelet aggregation and consumption Common in infants, young children and pregnant women

61. 3.Thrombotic Thrombocytopenic Purpura (TTP)Resembles hemolytic uremic syndrome but occur more commonly in adults than in children

62. Spontaneous aggregation of platelets and activation of coagulation in small blood vessels

63. In TTP, platelet consumption, precipitated by a congenital or acquired deficiency of metalloproteinase that cleaves vWFTHROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) HEMOLYTIC – UREMIC SYNDROME (HUS) Severe deficiency of the vWF – cleavage protease Platelet activation Platelet thrombi formation.

64. 4.Marrow infiltration eg: leukemiaA progressive, malignant disease of the blood forming organs, marked by distorted proliferation and development of leukocytes and their precursors in the blood and the bone marrowOverproduction of these white cells, which are immature or abnormal forms, suppresses the production of normal WBC, RBC and plateletsLead to increase susceptibility to infection,anemia and bleeding

65. Clinical presentationResult from infiltration of bone marrow or other organs with leukemic blast cellsMostly presents insidiously over several weeks with some or all of following signs and symptoms:Malaise

66. Infections

67. Pallor

68. Abnormal bruising

69. Hepatosplenomegaly

70. Lymphadenopathy

71. Bone painProgress rapidly in some childrenBlood count is abnormal, low hemoglobin,thrombocytopenia and evidence of circulating blast cells in most childrenBone marrow examination to confirm the diagnosis

72. 5.Disseminated Intravascular Coagulation (DIC) Disorder characterized by coagulation pathway activation leading to diffuse fibrin deposition in the microvasculature and consumption of coagulation factors and platelets.

73. Occurs as secondary complication of variety diseases.

74. Caused by the systemic activation of coagulation pathways, leading to formation of thrombi throughout the microcirculation and widespread thromboses. There is consumption of platelets and coagulation factors and secondarily activation of fibrinolysis. As consequence, there is depletion of the elements required for hemostasis ( consumptive coagulopathy)

75. May be acute or chronic.

76. Initiated through the tissue factor pathway.The commonest causes of activation of coagulation are severe sepsis or shock due to circulatory collapse, e.g in meningococcal septicemia or extensive tissue damage from trauma or burn.InfectiousMeningococcemia

77. Other gram –vebact (Salmonella, E.coli, Haemophilus)

78. Virus (CMV, herpes, hemorrhagic fevers)

79. Rickettsia, Malaria and fungus Tissue injuryCNS trauma, crush injury

80. Multiple fracture with fat emboli

81. Profound shock of asphyxia

82. Hypothermia/hyperthermia

83. Massive burnsMalignancyAcute promyelocytic leukemia

84. Acute monoblastic or myelocytic leukemia

85. widespread malignancies (neuroblastoma)Causes ofDICVenom/ toxinSnake bites

86. Insect bitesMicroangiopathic disorder Severe TTP/ hemolytic uremic syndrome

87. Giant hemangiomaHereditary thrombotic disordersAntithrombin iii def.

88. Homozygous protein C def.GIT disorderFulminant hepatitis

89. severe IBD

90. Reye syndromeNewbornMaternal toxemia