The document discusses various bleeding disorders including their causes, presentations, and treatments. It covers platelet disorders, coagulation factor deficiencies, von Willebrand disease, hemophilia A and B, disseminated intravascular coagulation (DIC), and liver disease. Treatment options discussed include cryoprecipitate, factor concentrates, DDAVP, vitamin K, fresh frozen plasma, and recombinant factor VIIa.
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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
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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
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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
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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
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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
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
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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
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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
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
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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)
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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
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
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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
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.
