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Homestasis Surgery

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  • 35
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  • Delayed bleeding due to preservation of platelet function
  • – fibrinogen - abN reflected in PTT and INR, as it is a constituent of the common pathway Also an acute phase reactant; up in infection, pregnancy & malignancy
  • May combine corticosteroids with either IgG or anti-D if significant bleeding
  • Autosomal dominant – severe form (1/1000000) Mucosal bleeding – recurrent epistaxis, monorrhagia, and excessive bleeding following tooth extraction
  • Do not give DDAVP to type II – may result in abnormal polymers
  • Normal hemostatic mechanisms are vascular response, plt plug formation and activation of coagulation factors with fibrin formation to stabilize the plt plug.
  • Transcript

    • 1. Notable Quote: Smile ………..Is the key for every one S-----------Smile M------------Make shack hand I-------------Introduce your self L---------------- Learn your partner Name E------------Eye contact
    • 2. Haemostasis &Bleeding disorders BY Prof.Dr . Mervat Atfy Mohamed
    • 3. Objectives/Outline
      • Definitions
      • Review pathophysiology of bleeding Provide a framework for differential diagnosis of purpura
      • Brief discussion of some of the more common presentations and their management
    • 4. Purpura
      • Hemorrhage into skin or mucous membrane
      • Due to:
      • Loss of vascular integrity
      • Platelet problems
        • Number
        • Function
      • Clotting factor deficiency
    • 5. Purpuric lesions
      • Petechiae
        • capillary hemorrhages, purple macular lesions
        •  2mm
        • develop in areas of increased venous pressure
      • Purpura – 2mm-1cm
      • Ecchymoses – > 1cm, often tender
      • Non-blanching, may be raised
    • 6. Platelet platelet count bleeding time < 8 min Platelet function Coagulation ACT PT aPTT thrombin time fibrinogen 90-130 sec 12-15 sec 35-45 sec < 14 sec 250-500 mg/dL Monitor heparin Extrinsic & final Intrinsic & final Final common ↓ in DIC Fibrinolysis FDP d-dimer ↑ during fibrinolysis
    • 7. Hemostasis requires normal:
      • vessels
      • platelets
      • coagulation pathway components
    • 8. Coagulation factor disorders
      • Inherited bleeding disorders
        • Hemophilia A and B
        • vonWillebrands disease
        • Other factor deficiencies
      • Acquired bleeding disorders
        • Liver disease
        • Vitamin K deficiency/warfarin overdose
        • DIC
    • 9. Hemostasis
      • Arteriolar vasoconstriction
      • Formation of platelet plug
      • Activation of coagulation cascade
      • Formation of permanent plug
      Secondary Hemostasis Primary Hemostasis
    • 10.  
    • 11.  
    • 12. Four reasons for Cell based model
      • 1. Congenital deficiency of XII, HMW kininogen and pre-kallikrein have prolonged PTT but NO BLEEDING PHENOTYPE.
      • 2. These components are NOT required for hemostasis in vivo
      • 3. TF/VIIa activates not only X but also VIII and IX
      • 4. XI deficiency is not associated with bleeding phenotype
    • 13. Cell Based coagulation model
      • TF bearing cells
        • Adventital cells
        • Myo-epithelial cells
        • Endothelial cells
      • 3 phases
        • Initiation
        • Priming
        • Propagation
    • 14. Initiation
      • TF bearing cells exposed to plasma
      • VII binds to TF and is activated
        • VIIa  Xa
        • TF/VIIa  IXa
      • TF/VIIa/Xa binds Va  converts Prothrombin to Thrombin
      • Small amount of Thrombin
        • Activate platelets
        • accelerant
    • 15. Priming
      • Release of granules containing V
      • Cleaved to Va
      • Formation of VIIIa
      Propagation
      • Activated platelets rapidly bind V/VIII/IX
      • Formation of VIII/IXa complex
      • MAJOR activator of X
      • Major prothrombin activator
    • 16. Screening tests for bleeding disorders
      • Prothrombin time
        • Measures function of VII, X, Prothrombin, fibrinogen
        • Prolonged when V, VII, X fall below 50%
        • And when prothrombin level falls to <30%
        • Vit K dependent proteins:
          • Prothrombin, V, VII, X, Proteins C and S
        • Warfarin, Liver Failure
    • 17. Screening tests for bleeding disorders
      • aPTT
        • Detects decrease in
        • XII, XI, IX, VIII AS WELL AS
        • Fibrinogen, prothrombin, V and X
        • Heparin
    • 18. Hemophilia
      • X linked recessive
      • Deficiency of Factor VIII
      • Degrees of severity:
        • Mild : 5% - 30%
        • Moderate : 2% - 5%
        • Severe : <2%
      • Prolonged PTT. Normal PT, vWf, BT
    • 19. Hemophilia A and B Hemophilia A Hemophilia B Coagulation factor deficiency Factor VIII Factor IX Inheritance X-linked X-linked recessive recessive Incidence 1/10,000 males 1/50,000 males Severity Related to factor level <1% - Severe - spontaneous bleeding 1-5% - Moderate - bleeding with mild injury 5-25% - Mild - bleeding with surgery or trauma Complications Soft tissue bleeding
    • 20. Hemophilia
      • Clinical manifestations (hemophilia A & B indistinguishable)
        • Hemarthrosis (most common)
          • Fixed joints
        • Soft tissue hematomas (e.g., muscle)
          • Muscle atrophy
          • Shortened tendons
        • Other sites of bleeding
          • Urinary tract
          • CNS, neck (may be life-threatening)
        • Prolonged bleeding after surgery or dental extractions
    • 21. Treatment of hemophilia A
      • Intermediate purity plasma products
        • Virucidally treated
        • May contain von Willebrand factor
      • High purity (monoclonal) plasma products
        • Virucidally treated
        • No functional von Willebrand factor
      • Recombinant factor VIII
        • Virus free/No apparent risk
        • No functional von Willebrand factor
    • 22. Dosing guidelines for hemophilia A
      • Mild bleeding
        • Target: 30% dosing q8-12h; 1-2 days (15U/kg)
        • Hemarthrosis, oropharyngeal or dental, epistaxis, hematuria
      • Major bleeding
        • Target: 80-100% q8-12h; 7-14 days (50U/kg)
        • CNS trauma, hemorrhage, lumbar puncture
        • Surgery
        • Retroperitoneal hemorrhage
        • GI bleeding
      • Adjunctive therapy
        •  amino caproic acid (Amicar) or DDAVP (for mild disease only)
    • 23. Complications of therapy
      • Formation of inhibitors (antibodies)
        • 10-15% of severe hemophilia A patients
        • 1-2% of severe hemophilia B patients
      • Viral infections
        • Hepatitis B Human parvovirus
        • Hepatitis C Hepatitis A
        • HIV Other
    • 24. Treatment of hemophilia B
      • Agent
        • High purity factor IX
        • Recombinant human factor IX
      • Dose
        • Initial dose: 100U/kg
        • Subsequent: 50 U/kg every 24 hours
    • 25. Von Willebrand disease
      • Most common congenital bleeding disorder
      • Bleeding is usually mild
      • Etiology of bleeding
        • Platelet aggregation
        • Major carrier for VIII
      • Types
    • 26. von Willebrand Disease Clinical features
      • von Willebrand factor Carrier of factor VIII Anchors platelets to subendothelium Bridge between platelets
      • Inheritance Autosomal dominant
      • Incidence 1/10,000
      • Clinical features Mucocutaneous bleeding
    • 27. Laboratory evaluation of von Willebrand disease
      • Classification
        • Type 1 Partial quantitative deficiency
        • Type 2 Qualitative deficiency
        • Type 3 Total quantitative deficiency
      • Diagnostic tests:
      vonWillebrand type Assay 1 2 3 vWF antigen  Normal  vWF activity    Multimer analysis Normal Normal Absent
    • 28. Treatment of von Willebrand disease Varies by Classification
      • Cryoprecipitate
        • Source of fibrinogen, factor VIII and VWF
        • Only plasma fraction that consistently contains VWF multimers
        • Correction of bleeding time is variable
      • DDAVP (Deamino-8-arginine vasopressin)
        • Increases plasma VWF levels by stimulating secretion from endothelium
        • Duration of response is variable
        • Used for type 1 disease
        • Dosage 0.3 µg/kg q 12 hr IV
      • Factor VIII concentrate (Humate-P)
        • Virally inactivated product
        • Used for type 2 and 3
    • 29. Type I vW disease
      • Autosomal dominant
      • Normal vWF
      • Quantitative decrease
      • Normal PT
      • Mildly prolonged aPTT
    • 30. Rx of vW disease
      • DDAVP
      • Cryoprecipitate
      • Monitor VIII levels
    • 31. DDAVP
      • 1-Deamino, 8 D-arginine vasopressin
      • Rx for mild Hemophilia A , vW disease
      • Increases plasma fVIII, vWf from endogenous sorces
      • Amount of increase = factor transfusion
      • Useful for platelet dysfunction secondary to aspirin, dextran, ticlopidine
      • 0.3- 0.4 mcg/kg
      • Onset 30 min, peak 90-120 min
    • 32. Cryoprecipitate
      • useful in treating factor deficiency (hemophilia A), von Willebrand's disease, and hypofibrinogenemia
      • uremic bleeding
      • Each 5- to 15-mL unit contains more than 80 units of factor VIII and about 200 mg of fibrinogen.
      • Because the proteins mentioned previously are in relatively high concentration, a smaller volume may be given than would be required if plasma were used. Cryoprecipitate is usually administered as a transfusion of 10 single units.
    • 33. NovoSeven
      • Recombinant f VIIa
      • Activates X and IX (conversion of prothrombin to thrombin)
      • $$$$
      • Not FDA approved
      • Anecdotal miraculous rescues
    • 34.  
    • 35. Heparin
      • Blocks Xa by binding to AT-III and thrombin.
      • Load 80 mg/kg
      • Infusion 18 mg/kg
      • Cleared from blood in 6hrs
      • Neutralized by protamine
      • 100u of Heparin = 1mg of protamine
    • 36. HIT
      • Heparin induced thrombocytopenia
      • Formation of IgG against Heparin- PF4 complexes
      • Upto 5% of patients
      • Onset 4-5 days, but earlier if prior exposure
      • Can occur with flushes, heparin bonded catheters also
    • 37. LMW Heparins
      • More selective anti-Xa activity
      • Less bleeding complications
      • Do not affect PT
      • Measure anti Xa activity
      • <1% incidence of HIT
    • 38. Enoxaparin
      • LMW heparin
      • Porcine intestinal submucosa
      • Binds to and accelerates AT-III activity
    • 39. Fondaparinux (Erixtra)
      • Synthetic pentasaccharide
      • 5 sugar AT-III binding site similar to Heparin
      • 1000x more potent
      • Very low- no incidence of HIT
      • Cannot be given in CRI
    • 40. Vitamin K
      • Necessary for addition of carboxyglutamate residues to the clotting factors synthesized in the liver.
      • Sites of Calcium binding
      • Prothrombin, VII, IX, X
      • drugs- cephalosporins, quinolones
      • 5mg iv slowly corrects deficit in 6 hrs
      • 10-25 mcg /day sq or im x 3days
    • 41. Vitamin K deficiency
      • Source of vitamin K Green vegetables Synthesized by intestinal flora
      • Required for synthesis Factors II, VII, IX ,X Protein C and S
      • Causes of deficiency Malnutrition Biliary obstruction Malabsorption Antibiotic therapy
      • Treatment Vitamin K Fresh frozen plasma
    • 42. Vitamin K deficiency due to warfarin overdose Managing high INR values Clinical situation Guidelines INR therapeutic-5 Lower or omit next dose; Resume therapy when INR is therapeutic INR 5-9; no bleeding Lower or omit next dose; Resume therapy when INR is therapeutic Omit dose and give vitamin K (1-2.5mg po) Rapid reversal: vitamin K 2-4 mg po (repeat) INR >9; no bleeding Omit dose; vitamin K 3-5 mg po; repeat as necessary Resume therapy at lower dose when INR therapeutic Chest 2001:119;22-38s (supplement)
    • 43. Vitamin K deficiency due to warfarin overdose Managing high INR values in bleeding patients Clinical situation Guidelines INR > 20; serious bleeding Omit warfarin Any life-threatening bleeding Vitamin K 10 mg slow IV infusion FFP ± factor rhVIIa (depending on urgency) Repeat vitamin K injections every 12 hrs as needed
    • 44. DIC Warfarin
      • Consumption coagulopathy
      • Systemic thromb-hemorrhagic disorder
      • Etiology:
        • Gram negative sepsis, crush injuries, amniotic fluid embolism, hemolysis, massive transfusion
      • Activation of clotting and fibrinolysis
      • Microvascular thrombosis, sequestration of platelets
    • 45. Pathogenesis of DIC Coagulation Fibrinolysis Fibrinogen Fibrin Monomers Fibrin Clot (intravascular) Fibrin(ogen) Degradation Products Plasmin Thrombin Plasmin Release of thromboplastic material into circulation Consumption of coagulation factors; presence of FDPs  aPTT  PT  TT  Fibrinogen Presence of plasmin  FDP Intravascular clot  Platelets Schistocytes
    • 46. Common clinical conditions associated with DIC
      • Sepsis
      • Trauma
        • Head injury
        • Fat embolism
      • Malignancy
      • Obstetrical complications
        • Amniotic fluid embolism
        • Abruptio placentae
      • Vascular disorders
      • Reaction to toxin (e.g. snake venom, drugs)
      • Immunologic disorders
        • Severe allergic reaction
        • Transplant rejection
    • 47. DIC
      • Low fibrinogen
      • High FDP
      • Low platelets
      • Elevated D-dimer
    • 48. Disseminated Intravascular Coagulation (DIC) Mechanism Systemic activation of coagulation Intravascular deposition of fibrin Depletion of platelets and coagulation factors Bleeding Thrombosis of small and midsize vessels with organ failure
    • 49. DIC Treatment approaches
      • Treatment of underlying disorder
      • Anticoagulation with heparin
      • Platelet transfusion
      • Fresh frozen plasma
    • 50. Liver Disease
      • Decreased synthesis of II, VII, IX, X, XI, and fibrinogen
        • Prolongation of PT, aPTT and Thrombin Time
      • Often complicated by
        • Gastritis, esophageal varices, DIC
      • Treatment
        • Fresh-frozen plasma infusion (immediate but temporary effect)
        • Vitamin K (usually ineffective)
    • 51. Stopping the bleeding
      • Direct pressure.
      • More direct pressure. Pack. Pack. Pack.
      • Electrocautery.
      • Ligate vessel
    • 52. Methylcellulose
      • Gelfoam
        • Absorbable
        • Liquefies in 2-5 days
        • Serves as a scaffold for coagulation
    • 53. Microfibrillar collagen
      • Decellularized bovine source
      • Stimulates latelet adhesion
      • Stops venous ooze
      • Absorbed in 90 days
    • 54. Thrombin + Gelfoam + CaCl
      • Thrombin for cleavage/activation
      • Gelfoam as matrix
      • Very useful in vascular surgery
    • 55. Fibrin glue
      • Tiseel
      • FDA approved in 1998
      • Concentrated fibrinogen and f VIII
      • Thrombin and calcium
      • Aprotinin to prevent clot dissolution
      • Takes time to prepare
      • Good for diffuse oozing, needle punctures, parenchymal injuries
    • 56. Hemostasis:
      • Lab Tests
      • CBC- Plt
      • BT ,(CT)
      • PT
      • PTT
      Plt Study Morphology Function Antibody BV Injury Platelet Aggregation Platelet Activation Blood Vessel Constriction Coagulation Cascade Stable Hemostatic Plug Fibrin formation Reduced Blood flow Tissue Factor Primary hemostatic plug Neural
    • 57. Hemostasis
      • 1. Vascular phase : vasoconstriction, immediately
      • 2. Platelet phase : adhesion & aggregation, several seconds after
      • 3. Coagulation phase : later, contains extrinsic & intrinsic pathways
      • 4. Metabolic (fibrinolytic) phase: release antithrombotic agent
      primary secondary
    • 58. Hemostasis
      • The intrinsic pathway :
      • Initiated through surface contact activation of factor XII by exposed subendothelial tissues--collagen
      • The extrinsic pathway :
      • Initiated through tissue thromboplastin released by injured tissue, which activates factor VII
      Antihemophilic factor; von Willebrand factor, VWF Plasma thromboplastin component , PTC; Christmas factor
    • 59.  
    • 60. Antihemophilic factor; von Willebrand factor, VWF
    • 61. Gla domain: activated by vit. K and NADH
    • 62. Antithrombotic agent
      • Postaglandin: secretion by endothelial cell
      • Antithrombin III (AT III): main Antithrombotic agent
      • Protein C: inactivate factor V and VIII with protein S
      • Plasmin: activated by urokinase and streptokinase from plasminogen
      primary secondary
    • 63. Etiology of bleeding disorder
      • 1. Nonthrombocytopenia
      • 2. Thrombocytopenia purpuras
      • 3. Disorders of coagulation
    • 64. Etiology of bleeding disorder
      • Nonthrombocytopenia
      • 1. vascular wall alteration : infection, chemical, allergy
      • 2. Disorder of platelet function :
      • Genetic defects (bernard-soulier disease: glycoprotein, GP-Ib dysfunction with VWF )
      • Aspirin, NSAIDs, broad-spectrum antibiotics(Ampicillin, Penicillin, Gentamycin, Vancomycin)
      • Autoimmue disease
    • 65. Adjunctive drug therapy for bleeding
      • Fresh frozen plasma
      • Cryoprecipitate
      • Epsilon-amino-caproic acid (Amicar)
      • DDAVP
      • Recombinant human factor VIIa (Novoseven)
    • 66. Clinical Features of Bleeding Disorders Platelet Coagulation disorders factor disorders Site of bleeding Skin Deep in soft tissues Mucous membranes (joints, muscles) (epistaxis, gum, vaginal, GI tract) Petechiae Yes No Ecchymoses (“bruises”) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed (1-2 days), usually mild often severe
    • 67.  
    • 68. Correct surgical bleeding ACT elevated normal Protamine 25-50mg PLT 0.1 u/kg ACT elevated normal Heparin level yes no protamine Coagulation profile FDP >32mcg/kg TEG abnormal clot lysis fibrinolysis FFP 5-10ml/kg CP 0.2-0.4u/kg EACA PLT<70000 thrombocytopenia PLT 0.1u/kg bleeding time >20min PLT dysfunction Fibrinogen < 100mg/dL TEG abnormal hypofibrinogenemia FFP 5-10ml/kg CP 0.2-0.4u/kg aPTT >1.3x PT >1.5x Anesthesiologist ’ s manual of surgical procedures
    • 69. Fresh frozen plasma
      • Content - plasma (decreased factor V and VIII)
      • Indications
        • Multiple coagulation deficiencies (liver disease, trauma)
        • DIC
        • Warfarin reversal
        • Coagulation deficiency (factor XI or VII)
      • Dose (225 ml/unit)
        • 10-15 ml/kg
      • Note
        • Viral screened product
        • ABO compatible
    • 70. Cryoprecipitate
      • Prepared from FFP
      • Content
        • Factor VIII, von Willebrand factor, fibrinogen
      • Indications
        • Fibrinogen deficiency
        • Uremia
        • von Willebrand disease
      • Dose (1 unit = 1 bag)
        • 1-2 units/10 kg body weight
    • 71. Etiology of bleeding disorders
      • Thrombotic Thrombocytopenia purpuras (TTP) : 血栓性血小板低下紫斑
      • 1. primary
      • 2. secondary : Chemicals, ex: mitomycin C
      • Physical agent (radiation)
      • Systemic disease (leukemia )
      • Character:
      • 1.Thrombocytopenia 2. Micro-angiopathic hemolytic anemia(MAHA) 3. Fever 4. Hyporenal function 5. Neural systemic desturbance due to ischemic
      • Considered to be an emergency
      • Tx: plasma exchange ( 血漿置換術 ) and glucocortisone application
    • 72. Etiology of bleeding disorders
      • Disorders of coagulation
      • 1. Inherited : Hemophilia A
      • Christmas disease
      • von Willebrandis Disease
      • 2. Acquired : Liver disease
      • Vitamin K deficiency
      • Anticoagulation drugs (heparin, coumarin)
      • Anemia
    • 73. Etiology of bleeding disorders
      • Thrombotic Thrombocytopenia purpuras (TTP) : 血栓性血小板低下紫斑
      • 1. primary
      • 2. secondary : Chemicals, ex: mitomycin C
      • Physical agent (radiation)
      • Systemic disease (leukemia )
      • Character:
      • 1.Thrombocytopenia 2. Micro-angiopathic hemolytic anemia(MAHA) 3. Fever 4. Hyporenal function 5. Neural systemic desturbance due to ischemic
      • Considered to be an emergency
      • Tx: plasma exchange ( 血漿置換術 ) and glucocortisone application
    • 74. Evaluation of bleeding disorders
      • 1. Take history
      • 2. Physical examination
      • 3. Screening clinical laboratory tests
      • 4. Observation of excessive bleeding following a surgical
      • procedure
    • 75. Physical examination
      • Jaundice ( 黃疸 )
      • Petechiae ( 淤點 ) : < 0.2 cm
      • Purpura ( 紫斑 ) : 0.2 cm-1 cm
      • Eccymoses ( 淤斑 ) : > 1 cm
      • Spider angioma ( 蜘蛛斑 )
      • Oral ulcer
      • Hyperplasia of gingiva
      • Hemarthrosis ( 關節血腫 )
    • 76. Platelet count
      • Test platelet phase: evaluation of platelet function
      • Normal (140,000 to 400,000/mm3)
      • Thrombocytopenia : < 140,000/mm3
      • Clinical bleeding problem : <50,000/mm3
      • Spontaneous bleeding with life theartening : <20,000/mm3
    • 77. PT (Prothrombin Time)
      • Activated by tissue thromboplastin
      • Tests extrinsic ( factor VII ) and common ( I,II,V,X ) pathways
      • Normal ( 11-15sec )
      • Coumarin therapy- PT at 1.5 to 2.5 time
      • International normalized ratio= INR, (1) surgery can be done under INR< 3.0 (2) when INR=3.0-3.5, consultation is needed (3) delay surgery when INR>3.5
    • 78. Activated PTT (aPTT)
      • Activated by contact activator (kaolin)
      • Tests intrinsic and common pathway
      • Normal ( 25-35 sec )
      • Heparin therapy- PTT in 50-65 sec range by promote AT III
    • 79. TT (Thrombin Time)
      • Activated by thrombin
      • Tests ability to form initial clot from fibrinogen
      • Normal ( 9 to 13 seconds )
    • 80. 1. No historical bleeding problem 3. Aspirin therapy 4. Coumarin therapy 6. Possible liver disease 7. Chronic leukemia 8. Long term antibiotic therapy 5. Renal dialysis (heparin) 2. History bleeding problem 9. Vascular wall alteration 10. Cancer (fibrinogenolysis) Following surgical procedure PT, aPTT, TT, BT BT, aPTT PT aPTT BT, PT BT PT BT TT Dental management of the medically compromised patient
    • 81. condition 8. thrombocytopenia 2. Coumarin therapy 4. Liver disease 7. Vascular wall defect 9. hemophilia 1. Aspirin therapy Platelet count 5. leukemia 6. Long term antibiotic 3. Heparin therapy 10. fibrinogenolysis + - + + + - - ++ - - BT + - + + + - + ++ - - PTT + ++ ++ ++ - ++ - - ++ + PT + ++ - ++ - ++ - - - + TT - - - ++ - ++ - - - ++ -: normal, +: may be abnormal, ++: abnormal
    • 82. Patient at low risk
      • 1. patient with no history of bleeding disorders, normal
      • examinations, no medications associated with bleeding
      • disorders and normal bleeding parameters
      • 2. patients with nonspecific history of excessive bleeding
      • with normal bleeding parameters (PT, PTT, BT,
      • platelet count, are within normal time)
    • 83. Patient at moderate risk
      • 1. patients in chronic oral anticoagulant therapy
      • (coumadin)
      • 2. patients on chronic aspirin therapy
    • 84. Patient at high risk
      • 1. patients with known bleeding disorders
      • Thrombocytopenia
      • Thrombocytopathy
      • Clotting factor defects
      • 2. Patient without known bleeding disorders found to
      • have abnormal , platelet count, BT, PT, PTT
    • 85. Dental management of bleeding disorders
      • Replacement therapy :
      • 1. platelet concentrate : thrombocytopenia ( 1 unit= 30,000/ uL enough for 1 day )
      • 2. Fresh frozen plasma : liver disease, Hemophilia B, vWD type III
      • 3. Factor VIII,IX concentrate : Hemophilia A ( 1 unit /kg can add 2%, so 50 unit /kg add 100% )
      • 4. Factor IX concentrate : Hemophilia B
      • 5. 1-desamino-8-darginine vesopressin (DDAVP) : Hemophilia A, vWD type I, II
      • Antifibrinolytic therapy:
      • 1. E-aminocaproic acid (EACA, Plaslloid)
      • 2. Tranexamic acid (AMCA, Transamin)
    • 86. Heparin (anticoagulant)
      • Complex inhibited ( IXa, Xa, XIa, XIIa )
      • Used in deep vein thrombosis , renal dialysis
      • Rapid onset, Duration 4-6hrs ( given IV )
      • Monitoring by aPTT: 50-65 sec
      • Discontinue 6 hrs before surgery then reinstituting therapy 6-12hrs post –op
      • Protamine sulfate can reverse the effect
    • 87. Coumarin (Vit k anatagonist)
      • Inhibit Vit K action (Factor II,VII,IX,X)
      • Used venous thrombosis, cerebrovascular disease
      • Duration haft-life 40hrs
      • Monitored by PT : INR 1.5-2.5
      • PT>2.5, reduction coumarin dosage ( 2-3 days )
      • Vit. K can reverse the effect
    • 88. Local hemostatic methods
      • splints, pressure packs, sutures; gelfoam with thrombin, surgicel, oxycel, microfibrillar collagen(avitene), topical AHF
    • 89. Aspirin (antiplatelet)
      • Inhibit cycloxygenase, TxA2 formation
      • Analgesic drug impairs platelet function
      • Aterial thrombosis, MI
      • Tests-BT, aPTT
      • If tests are abnormal , MD should be consulted before dental surgery is done
      • Stop aspirin for 5 days , substitute alternative drug in consultation with MD
    • 90. Thrombocytopenia
      • Disease in number of circulation platelets
      • Idiopathic thrombocytopenia, secondary thrombocytopenia
      • TX : is none indicated unless
      • platelets<20000/mm3, or excessive bleeding
      • TX : Steroid, platelet transfusion
    • 91. Von Willebrandis Disease
      • Gene mutation on Von Willebrandis factor; most common Inherited disease in America ( 1% )
      • Type I : 70%-80%, partial loss on quantity
      • Type II : poor on quality
      • Type III : severe loss on quantity, inactive to DDAVP
    • 92. Laboratory evaluation of von Willebrand disease
      • Classification
        • Type 1 Partial quantitative deficiency
        • Type 2 Qualitative deficiency
        • Type 3 Total quantitative deficiency
      • Diagnostic tests:
      vonWillebrand type Assay 1 2 3 vWF antigen  Normal  vWF activity    Multimer analysis Normal Normal Absent
    • 93. Hemophilia
      • Sex-linked recessive trait, X chromosome, male > female
      • Prolong aPTT, normal BT,PT
      • Hemophilia A (factor VIII deficiency)
      • Hemophilia B or Christmas disease (factor IX deficiency)
      • Severity of disorder : severe<1%, moderate 1-5%,
      • mild 6-30%
      • TX : Replacement factors, antifibrinilytic agents, steroids
    • 94. Hemophilia-dental management
      • Preventive dentistry
      • 1. tooth brushing, flossing, rubber cup prophylaxis &
      • topical fluoride, supragingival scaling
      • 2. without prior replacement therapy
      • Pain control
      • 1. block anesthesia: factor level>50%
      • 2. Avoid aspirin, NSAIDs
    • 95. Hemophilia-dental management
      • Orthodontic treatment :
      • 1. no contraindication in well-motivated patients
      • 2. care with placement of bands and wires
      • Operative dentistry
      • 1. rubber dam to protect tissue against accidental
      • laceration
      • 2. wedges should be place to protect and retract
      • papilla
    • 96. Hemophilia-dental management
      • Pulp therapy
      • 1. Preferable to extraction
      • 2. Avoid overinstrumentation and overfilling
      • Periodontal therapy
      • 1. no contraindication of probing and supragingival
      • scaling
      • 2. deep scaling, curettage, surgery need replacement
      • therapy
    • 97. Hemophilia-dental management
      • Oral surgery :
      • 1. Dental extraction: 40%-50% level
      • 2. Maxillofacial surgery (including surgery
      • extraction of impaction teeth): 80-100%
      • 3. Antifribrinilytic therapy & local hemastatic
      • measure
      • 4. do not open lingual tissue in lower molar regions to
      • avoid hemorrhage track down a endanger airway
    • 98. Summary
      • History, PE, Lab data
      • Consultation with physician
      • Antibiotics to prevent post-op infection
      • Avoid aspirin and NSAIDs
      • Local hemostatic measure is very important
    • 99. Haemostasis
    • 100. Hemostasis
      • 1° hemostasis
        • Vasoconstriction & retraction of cut ends of blood vessels
        • Release of FVIII-vWF
        • Platelets adhere to endothelium
        • granules release ADP, Ca & ThromboplastinA 2  aggregation
        • Stabilization of platelet plug
    • 101.  
    • 102.  
    • 103.  
    • 104.  
    • 105.  
    • 106.  
    • 107.  
    • 108. Coagulation Cascade: Intrinsic Path (12,11,9,8) Extrinsic Path (7) Fibrinogen  Fibrin Common Path (5,2) (PT) (aPTT) (TT) (F & FDP) (Factor 10) (Thrombin)
    • 109. Coagulation cascade Vitamin K dependant factors XIIa IIa Intrinsic system (surface contact) XII XI XIa Tissue factor IX IXa VIIa VII VIII VIIIa Extrinsic system (tissue damage) X V Va II Fibrinogen Fibrin (Thrombin) IIa Xa
    • 110. Laboratory Evaluation of the Coagulation Pathways Partial thromboplastin time (PTT) Prothrombin time (PT) Intrinsic pathway Extrinsic pathway Common pathway Thrombin time Thrombin Surface activating agent (Ellagic acid, kaolin) Phospholipid Calcium Thromboplastin Tissue factor Phospholipid Calcium Fibrin clot
    • 111. Pre-analytic errors
      • Problems with blue-top tube
        • Partial fill tubes
        • Vacuum leak and citrate evaporation
      • Problems with phlebotomy
        • Heparin contamination
        • Wrong label
        • Slow fill
        • Underfill
        • Vigorous shaking
      • Biological effects
        • Hct ≥55 or ≤15
        • Lipemia, hyperbilirubinemia, hemolysis
      • Laboratory errors
        • Delay in testing
        • Prolonged incubation at 37°C
        • Freeze/thaw deterioration
    • 112. Initial Evaluation of a Bleeding Patient - 1 Normal PT Normal PTT Consider evaluating for: Mild factor deficiency Monoclonal gammopathy Abnormal fibrinolysis Platelet disorder (  2 anti-plasmin def) Vascular disorder Elevated FDPs Urea solubility Normal Abnormal Factor XIII deficiency
    • 113. Initial Evaluation of a Bleeding Patient - 2 Normal PT Abnormal PTT Test for factor deficiency: Isolated deficiency in intrinsic pathway (factors VIII, IX, XI) Multiple factor deficiencies (rare) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific factors: VIII,IX, XI Non-specific (anti-phospholipid Ab)
    • 114. Abnormal PT Normal PTT Test for factor deficiency: Isolated deficiency of factor VII (rare) Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific: Factor VII (rare) Non-specific: Anti-phospholipid (rare)
    • 115. Initial Evaluation of a Bleeding Patient - 4 Abnormal PT Abnormal PTT Test for factor deficiency: Isolated deficiency in common pathway: Factors V, X, Prothrombin, Fibrinogen Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC) Repeat with 50:50 mix 50:50 mix is normal 50:50 mix is abnormal Test for inhibitor activity: Specific : Factors V, X, Prothrombin, fibrinogen (rare) Non-specific: anti-phospholipid (common)
    • 116. Coagulation factor deficiencies Summary
      • Sex-linked recessive
      •  Factors VIII and IX deficiencies cause bleeding
          • Prolonged PTT; PT normal
      • Autosomal recessive (rare)
        •  Factors II, V, VII, X, XI, fibrinogen deficiencies cause bleeding
          • Prolonged PT and/or PTT
        •  Factor XIII deficiency is associated with bleeding and
        • impaired wound healing
          • PT/ PTT normal; clot solubility abnormal
        •  Factor XII, prekallikrein, HMWK deficiencies
        • do not cause bleeding
    • 117. Disorders of Hemostasis
      • Vascular disorders
        • Scurvy, easy bruising,
      • Platelet disorders
        • Low Number or abnormal function
      • Coagulation disorders
        • Factor deficiency.
      • Mixed/Consumption: DIC
    • 118. Purpura - Manifestations
      • Platelet
        • petechiae, mucosal bleeding
        • CNS bleeding in severe cases
      • Coagulation disorders
        • ecchymoses or hemarthroses
      • Vascular
        • contusion, ecchymosis, hemorrhage
        • palpable purpura
    • 119. Clinical manifestations of disordered hemostasis Clinical Characteristic Platelet defect Clotting factor deficiency Site of bleeding Skin, mucous membranes Deep in soft tissues Bleeding after minor cuts Yes Unusual Petechiae Yes No Ecchymoses Small, superficial Large, palpable Hemarthroses, muscle hematomas Rare Common Bleeding after surgery Immediate, mild Delayed, severe
    • 120. Platelet Coagulation Petechiae, Purpura Hematoma, Hemarthrosis
    • 121. Thrombocytopenias
      • Decreased production
      • Platelet pooling and splenic sequestration
      • Increased destruction
        • Plt <100 000
        • Spontaneous bleeding uncommmon with plt > 20 000
        • Bleeding time prolonged, PT/PTT normal
    • 122. Sites of bleeding in thrombocytopenia
      • Skin and mucous membranes
        • Petechiae
        • Ecchymosis
        • Hemorrhagic vesicles
        • Gingival bleeding and epistaxis
      • Menorrhagia
      • Gastrointestinal bleeding
      • Intracranial bleeding
    • 123. Classification of platelet disorders
      • Quantitative disorders
        • Abnormal distribution
        • Dilution effect
        • Decreased production
        • Increased destruction
      • Qualitative disorders
        • Inherited disorders (rare)
        • Acquired disorders
          • Medications
          • Chronic renal failure
          • Cardiopulmonary bypass
    • 124.
      • Associated with bleeding
        • Immune-mediated thrombocytopenia (ITP)
        • Most drug-induced thrombocytopenias
        • Most others
      • Associated with thrombosis
        • Thrombotic thrombocytopenic purpura
        • DIC
        • Trousseau’s syndrome
        • Heparin-associated thrombocytopenia
      Acquired thrombocytopenia with shortened platelet survival
    • 125. Approach to the thrombocytopenic patient
      • History
        • Is the patient bleeding?
        • Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease)
        • Is there a history of medications, alcohol use, or recent transfusion?
        • Are there risk factors for HIV infection?
        • Is there a family history of thrombocytopenia?
        • Do the sites of bleeding suggest a platelet defect?
      • Assess the number and function of platelets
        • CBC with peripheral smear
        • Platelet function study
    • 126. Platelet function screen Results Epi ADP Interpretation Normal Normal Normal platelet function Abnormal Normal “Aspirin effect” Abnormal Abnormal Abnormal platelet function Valvular heart disease Renal failure Von Willebrand disease
    • 127. Platelet transfusions
      • Source
        • Platelet concentrate (Random donor)
        • Each donor unit should increase platelet count ~10,000 /µl
        • Pheresis platelets (Single donor)
      • Storage
        • Up to 5 days at room temperature
      • “ Platelet trigger”
        • Bone marrow suppressed patient (>10-20,000/µl)
        • Bleeding/surgical patient (>50,000/µl)
    • 128. Platelet transfusions - complications
      • Transfusion reactions
        • Higher incidence than in RBC transfusions
        • Related to length of storage/leukocytes/RBC mismatch
        • Bacterial contamination
      • Platelet transfusion refractoriness
        • Alloimmune destruction of platelets (HLA antigens)
        • Non-immune refractoriness
          • Microangiopathic hemolytic anemia
          • Coagulopathy
          • Splenic sequestration
          • Fever and infection
          • Medications (Amphotericin, vancomycin, ATG, Interferons)
    • 129. Laboratory Evaluation of Bleeding Overview CBC and smear Platelet count Thrombocytopenia RBC and platelet morphology TTP, DIC, etc. Coagulation Prothrombin time Extrinsic/common pathways Partial thromboplastin time Intrinsic/common pathways Coagulation factor assays Specific factor deficiencies 50:50 mix Inhibitors (e.g., antibodies) Fibrinogen assay Decreased fibrinogen Thrombin time Qualitative/quantitative fibrinogen defects FDPs or D-dimer Fibrinolysis (DIC) Platelet function von Willebrand factor vWD Bleeding time In vivo test (non-specific) Platelet function analyzer (PFA) Qualitative platelet disorders and vWD Platelet function tests Qualitative platelet disorders
    • 130. Decreased Production
      • Malignancies (leukemia, lymphoma, neuroblastoma)
      • Bone marrow suppression
        • Drug-related (aplastic anemia)
        • Infection
      • Congenital
        • Fanconi anemia
        • TAR syndrome
        • Wiscott-Aldrich
        • Glycogen storage diseases
    • 131. Platelet Dysfunction
      • Congenital
        • Glanzmanns thrombasthenia (GP 11b/IIIa deficiency)
        • Bernard Soulier (vWF receptor deficiency)
      • Acquired
        • Drugs (ASA/NSAIDs, lasix, nitrofurantoin)
        • Renal disease
        • Liver disease
    • 132. Increased Platelet Destruction
      • Immunologic
        • ITP
        • SLE
        • Isoimmunization (post-transfusion, neonatal)
        • Drug related (heparin, quinine, dig, sulphonamides, phenytoin)
      • Infection
        • Sepsis
      • Mechanical
        • DIC
        • HUS-TTP
        • Giant hemangioma (Kasabach-Merritt)
        • Burns
        • Trauma
    • 133. Thrombocytopenia (cont’d)
      • Sequestration
        • Hypersplenism
        • Sickle cell anemia
      • Dilutional
        • Massive transfusion
    • 134. Loss of Vascular Integrity
      • Congenital
        • Disorders of connective tissue
          • Ehlers-Danlos syndrome
          • Osteogenesis imperfecta
          • Marfan’s
        • Disorders of blood vessels
          • Hemorrhagic telangiectasia
      • Acquired
        • Trauma/NAI
        • Scurvy
        • Steroid induced
        • Increased intravascular pressure
          • coughing
          • vomiting
          • straining
    • 135. Vasculitis
      • Drug-related
      • Infection
        • Viral
          • Coxsackie A9, B3
          • Echoviruses 4,9
          • Atypical measles
        • Bacterial
          • Meningococcemia
          • Streptococcal pharyngitis
          • Septic emboli
          • SBE
          • Gonococcus
        • Rickettsial
          • Rocky Mountain spotted fever
      • Immune-mediated
        • HSP
        • SLE
        • Serum sickness
        • Dysgammaglobulinemia
    • 136. Coagulation Factor Deficiency
      • Usually cause larger ecchymoses, deep tissue hemorrhage, and mucosal bleeding
      • Clotting factor deficiencies
        • Congenital
          • von Willebrand’s disease
          • Hemophilias
          • Protein C and S deficiencies
        • Acquired
          • Vitamin K deficiency
            • Liver disease
            • Malabsorption
    • 137. Diagnosis
      • Careful history and focused physical exam are keys to diagnosis
      • Laboratory tests are confirmatory
    • 138. History
      • Present history
        • Onset
        • Location
        • Associated symptoms
          • Fever
          • Abdominal pain
          • Arthralgias/joint swelling
          • meningismus
    • 139. History
      • Recent
        • Viral illness
        • Ill contacts
        • Trauma
        • Medications
        • Immunization
        • Travel
      • Past history
        • Easy bruising or bleeding
        • Epistaxis, menorrhagia
        • Excessive bleeding following circumcision or dental extraction
      • Family History
        • Bleeding disorders
    • 140. Physical Exam
      • Sick vs. not sick
      • Fever
      • Lymph nodes
      • Liver, spleen
      • Joints – arthritis, hemarthrosis
    • 141. Physical exam - Skin
      • Are lesions petechial, purpuric or ecchymotic?
      • Palpable purpura
        • Vasculitis – HSP, RMSF, SLE
        • Embolic lesions, meningococcemia, bacterial endocarditis
      • Location
        • Isolated petechiae above nipple line often associated with crying, coughing, vomiting
        • Purpura in dependent areas with HSP
        • Ecchymoses on upper extremities,, or with recognizable pattern –
    • 142. Investigations - initial
      • CBC, peripheral smear
        • Hgb - Blood loss, hemolysis
        • Plt - thrombocytopenia
        • WBC - Sepsis, leukemia
      • Prothrombin Time
        • extrinsic and common pathway
        • Factors II, V, VII , X
      • PTT
        • intrinsic and common pathway
        • all factors except VII and XIII
    • 143. Specific tests
      • Factor Level Assays
      • Fibrin, FSP, D-dimer
      • Bleeding time - test of platelet function
      • platelet aggregation - ADP, epinephrine, collagen, and ristocetin
    • 144. Cases
    • 145. Case1 - 2 year old presents with purpuric rash
      • Acting otherwise well, eating normally
      • No fever, no weight loss, no systemic Sx
      • Recovered from a URI
      • Rash is not itchy and is flat
      • No regular medications
      • No hospitalizations or chronic illnesses
    • 146. Idiopathic Thrombocytopenic Purpura
      • Most common platelet disorder in children (5/100,000 prevalence)
      • Isolated thrombocytopenia (often < 20 000)
      • No associated conditions that may cause thrombocytopenia
      • Peak age 2-4
      • Male = female
    • 147. ITP -pathophysiology
      • Development of IgG Abs to plt membrane glycoproteins as a result of an unbalanced response to an infectious agent or autoimmunity
      • Sequestration by splenic macrophages
      • 70% cases occur 1-4 weeks following viral illness
      • VZV, EBV, influenza common causes
    • 148. ITP - Clinical presentation
      • Usually acute, sudden onset with history of viral illness in the several weeks preceeding onset
      • Petechiae, purpura, and easy bruising
      • Epistaxis, gingival bleeding and menorrhagia are common
      • ICH very rare
    • 149. Diagnosis
      • Hx, PE, CBC and peripheral smear
      • Isolated thrombocytopenia
        • Bone marrow ex will show megakaryocytes hyperplasia (increased plt production)
    • 150. Clinical course
      • Self limiting in 80-90% cases
        • Normalize within months
        • ↑ plt 5-7 days
      • Serious bleeding in 2-4%
        • Epistaxis, GI, hematuria, menorrhagia
        • ICH - 0.1-0.5%
          • Plt<10,000, NSAIDs, head trauma,
      • Chronic 10-20%
    • 151. ED Management – if severe bleeding
      • No controlled studies to guide management
      • Transfusions of PRBC to HGB > 10
      • Transfusions of platelets (0.2unit/ kg)
      • Corticosteroids
        • Prednisone 1-2mg/kg/d x 1-2wk, then taper
        • Methylprednisolone 30mg/kg (max 1g) IV over 30 min QD x3
      • IgG
        • IvIG 1g/kg/d over 3 hrs x 2days
      • Anti-Rh D (only if Rh+)
        • Rhogam 40-80ug/kg single dose over 5 min
      • Splenectomy
    • 152. Management if not bleeding
      • 80% resolve spontaneously
      • Treatment does shorten duration of profound thrombocytopenia, but doesn’t alter clinical course
    • 153. HSP
      • Vasculitis
    • 154. Case 2
      • 6 yo boy c/o periumbilical abdominal pain and rash x 2/7
      • Also c/o knee and ankle pain
      • Recently recovered from Grp A Strep infection
    • 155. Henoch Sch ö nlein Purpura
      • Palpable purpura
      • Arthritis
      • Abdominal pain
      • +/-Glomerulonephritis
      • Most common in spring
      • 75% cases occur between ages 2-11
      • Often follows URI (grp A strep, mycoplasma, VZV, EBV, parvovirus B19)
      • Insect stings
    • 156. HSP - pathophysiology
      • Exact cause unknown
      • IgA mediated systemic vasculitis of small vessels of skin, GIT, kidneys, synovium
    • 157. HSP – Clinical features
      • Gradual or acute onset
      • Blanching macules or papules on buttocks and lower extremities that evolve into palpable purpura
      • Younger children - face, torso and extremities
      • Arthritis of large joints (65-85%)
      • 50% will have GI symptoms
        • Crampy abdominal pain +/- hematochezia
        • Intussusception, bowel infarct, pancreatitis
      • 25-50% develop glomerulonephritis
        • Self limited, CRF in 1%
    • 158. HSP - Diagnosis
      • Clinical diagnosis
      • CBC, Urea, Cr, urine analysis
      • DDx
        • Meningococcemia
        • Rheumatic fever
        • Rocky Mountain spotted fever
        • Bacterial endocarditis
        • Juvenile rheumatoid arthritis
        • Systemic lupus erythematosis
        • Reactive arthritis
    • 159. HSP- Treatment
      • No specific Tx
      • Majority resolve over 2-4 wks
      • Symptomatic treatment of arthritis, malaise, fever – acetaminophen or NSAIDs*
      • If severe abdo pain:
        • prednisone 1-2mg/kg/d
    • 160. Case 3
      • 13 year boy c/o fever,, myalgias
      • Developed rash that started on hands and feet, now all over
      • Recent travel to camp in Colorado
    • 161. Rocky Mountain Spotted Fever
      • 1-2 weeks after bite by tick infected with Rickettsia rickettsii
      • fever, headache, myalgias, nausea, vomiting
      • petechial rash that begins on day 2-6 of fever
      • Starts on palms and soles and spreads centripedally over the torso within hours
      • Vasculitis 2º to rickettsial invasion of endothelial cells
    • 162. RMSF - Epidemiology
      • SE and South Central US
      • Between April and October
      • Most common in under 15 yrs
      • Not contagious
    • 163. RMSF - Treatment
      • Tx based on clinical suspicion
      • Abx, supportive care, +/- steroids
        • <8 chloramphenicol 50mg/kg/day x 7-10 d
        •  8 doxycycline 100mg PO BID x 7-10 d
      • Delayed treatment may result in DIC, shock, encephalopathy, gastrointestinal bleeding and myocarditis
    • 164. Meningococcemia
      • most often seen in children younger than 5 years old
      • peak attack rate in infants < 6 months
      • gram-negative diplococcus
      • spread by respiratory droplets
      • outbreaks are common after index case exposes others
      • day care centers, schools, and colleges
    • 165. Meningococcemia
      • begins abruptly with fever, lethargy, and rash
      • Initially the rash may be maculopapular or urticarial
      • Rapidly becomes purpuric as the disease progresses
      • 15-25% of patients -purpura fulminans
        • syndrome characterized by very large purpuric lesions secondary to cutaneous hemorrhage and necrosis with DIC
    • 166. Meningococcemia -Treatment
      • ABCs, supportive care
      • Abx:
        • Ceftriaxone 200mg/kg/d IV q6H
        • Vancomycin 60 mg/kg/d IV q6H
        • If severe B-lactam allergy:
        • Chloramphenicol 75-100mg/kg/d IV q6H
        • Vancomycin 60 mg/kg/d IV q6H
    • 167. Case 4
      • 5yo male with 3/7 hx watery diarrhea after attending a birthday party
      • Today developed fever and petechial rash
      • Looks unwell
    • 168. Hemolytic Uremic Syndrome
      • Acute renal failure
      • Microangiopathic hemolytic anemia
      • Thrombocytopenia
      • Fever
      • 90% of cases follow a diarrheal illness
        • Most often E. coli 0157:H7
        • Also Shigella, Salmonella, Yersinia , and Campylobacter species
        • From undercooked meats, unpasteurized dairy
    • 169. HUS - pathophysiology
      • Verotoxins from bacteria  endothelial cell injury  cascade of events leading to hyaline microthrombi formation and consumptive thrombocytopenia
      • TTP seems to have similar pathophysiology but has predominately CNS effects cf predominately renal involvement with HUS
    • 170. HUS-Tx
      • Diagnosis is clinical with supportive lab investigations
        • CBC and smear - MAHA, thrombocytopenia
        • PT/PTT, fibrinogen – normal
        • Elevated BUN, Cr
        • E. coli 0157:H7 on stool culture
      • Treatment -
        • consultation with hematology and nephrology
        • early dialysis, plasma exchange, treatment of hypertension
      • Mortality 5-15%
    • 171.
      • Disorders of Coagulation
    • 172. von Willebrand’s Disease
      • Most common inherited bleeding disorder
      • 2 functions of vWF:
        • plt aggregation at site of injury
        • carrier protein for FVIII
      • 3 phenotypes:
        • Type I - ↓ amount vWF (60-80% cases)
        • Type II – vWF abnormal (10-30%)
        • Type III – no vWF (1-5%)
      • patients typically present with bruising, menorrhagia, epistaxis or excessive bleeding after surgical procedures
    • 173. von Willebrand’s Disease
      • Difficult to diagnose
      • Platelets normal
      • Prolonged bleeding time
      • PTT – may be prolonged
      • vWF activity, levels
      • Factor VIII levels
    • 174. von Willebrand’s Disease - Tx
      • DDAVP
        • 0.3 ugkg IV over 30 min or SC
        • 150ug nasal inh
        • Releases FVIII and vWF from endothelial cells (3-5x ↑ level)*
      • Factor VIII/vWF concentrates
      • Cryoprecipitate 1 bag/ 10kg
      • Aminocaproic acid (Amicar®)
      • Tranexamic acid (Cyclokapron®)
    • 175. Hemophilia A and B
      • X-linked recessive
      • Deficiency factor VIII (A) and IX (B)
      • Multiple cutaneous bruises, muscular bleeding and hemarthroses
      • Prolonged PTT but normal PT and bleeding time
      • Tx - FFP or factor replacement – Life long
    • 176. Summary
      • Bleeding caused by vascular, platelet or clotting factor problems
      • Broad differential diagnosis
        • Relatively benign to potentially fatal
      • Most causes can be diagnosed by good history, physical exam and simple laboratory tests
    • 177. Infections
      • Viral
        • Atypical measles
        • Congenital rubella
        • Cytomegalovirus
        • Enterovirus
        • HIV
        • Hemorrhagic varicella
      • Bacterial
        • Meningococcemia
        • Gonnococcemia
        • Pneumococcal sepsis
        • Haemophilus influenzae sepsis
        • Pseudomonas aeruginosa sepsis
      • Rickettsial
        • Rocky Mountain spotted fever
      • Protozoal
        • Malaria
    • 178. BV Injury Platelet Aggregation Platelet Activation Blood Vessel Constriction Coagulation Cascade Stable Hemostatic Plug Fibrin formation Reduced Blood flow Contact/ Tissue Factor Primary hemostatic plug Neural
    • 179. Questions?
    • 180.  
    • 181.
      • 1. What is the mechanism for the thrombocytopenia in ITP?
      • 2. What is the classic triad associated with hemolytic uremic syndrome?
      • 3. How is hemophilia inherited?
      • 4. Describe some indications for factor VIII administration in a patient with hemophilia A.
      • 5. What are the functions of von Willebrand factor?
    • 182.
      • 6. What combination of laboratory tests are good screening studies for von Willebrand disease?
      • 7. Why is it important to test for blood type in a person with suspected von Willebrand disease?
      • 8. Name the vitamin K dependent factors.
      • 9. Explain why the addition of normal plasma to a patient's PTT test, will help to identify a circulating anticoagulant such as the lupus anticoagulant.
    • 183.
      • 1. True/False: Newborns with Down syndrome and elevated white counts and immature forms frequently progress to leukemia.
      • 2. True/False: Factor VIII deficiency is on the vitamin K dependent factors leading to Hemorrhagic disease of the newborn.
      • 3. Rh antibodies in mothers can result from: . . . . . a. previous mismatched transfusions . . . . . b. prior miscarriages . . . . . c. fetal maternal transfusion . . . . . d. all of the above.
    • 184.
      • 4. True/False: Red cell problems are usually seen with abnormalities of white cells and platelets.
      • 5. True/False: Neonatal immune thrombocytopenia can result from maternal auto sensitization or fetal maternal transfusion.
      • 6. True/False: Thalassemia and hemoglobinopathies can present in the neonatal period with severe anemia.
    • 185.  
    • 186.