1 / 43

COAGULOPATHIES

BY : DR.SHAINA KALRA MODERATOR : DR.VIJAY KUMAR. COAGULOPATHIES. www.anaesthesia.co.in anaesthesia.co.in@gmail.com. INHERITED DISORDERS OF HEMOSTASIS. Hemophilia A (FVIII), Hemophilia B (FIX ), Hemophilia C (FXI ) Von Willebrand Disease Deficiencies of factors X ,

saeran
Download Presentation

COAGULOPATHIES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. BY : DR.SHAINA KALRA MODERATOR : DR.VIJAY KUMAR COAGULOPATHIES www.anaesthesia.co.inanaesthesia.co.in@gmail.com

  2. INHERITED DISORDERS OF HEMOSTASIS • Hemophilia A (FVIII), • HemophiliaB (FIX), • HemophiliaC (FXI) • Von Willebrand Disease • Deficiencies of factors X, • Deficiencies of factors V, • Deficiencies of factor VII • Deficiencies Prothrombin • Afibrinogenemia • Dysfibrinogenemia

  3. Hemophilia A • Inheritance is X-linked • Deficiency of Factor VIII • Clinical presentation : • 90% of bleeding episodes occur into the joints (knees and elbows predominantly) • Intramuscular, intracranial, & gastrointestinal

  4. Severity of bleeding depends on levels of FVIII Mild: activity levels between 5-25% Have significant bleeding after major trauma or surgery but generally go undetected until abnormal APTT is found Moderate: activity levels between 2-5% Bleeding is precipitated by trauma or surgery Severe: less than 1% activity Present with recurrent hemorrhages that occur spontaneously or after minor trauma/surgery

  5. Diagnosis • Severe : • shortly after birth • Extensive cephalhematoma • Profuse bleeding at circumcision • Moderate : • Bleed when they begin to walk or crawl • Mild : • Diagnosed at adult age

  6. Treatment • Treatment goal (at present) is to replace FVIII • Since cryoprecipitate (containing FVIII, VWF, & Fibrinogen) is not virally attenuated, it should only be used for urgent replacement. • Plasma-derived concentrates that contain intermediate to high activities of FVIII • Monoclonal antibody purified products that contain extremely high quantities of FVIII • Genetically engineered FVIII

  7. Mild :DDAVP (desmopressin) increases FVIII level transiently safe causes hyponatremia ppt thrombosis in elderly • Uncomplicated episode of soft tissue bleed one infusion of FVIII concentrate to raise the FVIII level by 15 – 20 % • More extensive hemarthrosis continous infusion of FVIII to keep level of 25-50% for atleast 72hours

  8. Life threatening bleeding into CNS require therapy for 2 weeks to keep the level at 50 % of normal

  9. 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

  10. 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)

  11. 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

  12. Hemophilia B • Inheritance is X-linked • Deficiency of Factor IX • Factor IX require vit.K for its biological activity • Treatment : • fresh frozen plasma • plasma enriched in prothrombin complex protein • recombinant Factor IX

  13. 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

  14. Hemophilia C • Autosomal recessive inheritance • Deficiency of Factor XI • Homozygotes : Factor XI conc < 4% • Heterozygotes : Factor XI conc 15 – 65% • Found predominantly in individuals of Ashkenazi Jewish descent • Treatment : FFP • Factor XI concentrates can be given but they are thrombogenic and Factor XI has a v long life

  15. Von Willebrand Disease (VWD) • von Willebrand factor Carrier of factor VWF Anchors platelets to subendothelium . Bridge between platelets • Inheritance Autosomal dominant • Incidence 1/10,000

  16. Types of bleeding Mucocutaneous bleeding • Epistaxis , menorrhagia , ecchymoses & hematomas, gingival and gastrointestinal bleeding • Results from defect in primary hemostasis Soft tissue bleeding (after trauma/injury) • Dental extraction, wounds, post-operatively, post-partum • Results from defect in secondary hemostasis – VWF is carrier (protector) protein for FVIII

  17. vonWillebrand type Assay 1 2 3 vWF antigen ß Normal ßß vWF activity ßßßß Multimer analysis Normal Normal Absent Laboratory evaluation Classification • Type 1 Partial quantitative deficiency • Type 2 Qualitative deficiency • Type 3 Total quantitative deficiency • Diagnostic tests: Assay 1 2 3 vWF antigen ß Normal ßß vWF activity ßßßß Multimer analysis Normal Normal Absent

  18. Screening Tests for VWD • APTT (degree of prolongation depends on FVIII levels) • PFA closure time (“in vitro” bleeding time) PFA-100™ instrument measures the time required to stop the flow of blood (by occluding a small hole in a collagen coated membrane) in a high shear environment when exposed to physiologic agonists such as ADP or epinephrine • Platelet count • ABO blood group

  19. Specific Tests for VWD • Factor VIII procoagulant activity (FVIII:C) Low plasma levels seen in Hemophilia A and VWD • VWF antigen (VWF:Ag) level • Ristocetin Cofactor (VWF:RCo) activity of VWF Determines VWF function

  20. Treatment for VWD • Desmopressin (DDAVP) – Synthetic analog of vasopression that releases endogenous stores of VWF from endothelial cells – VWD types 1, 2A, 2M, some 2B • Factor VIII concentrates – Must contain both FVIII and VWF since both defects necessitate correction – Useful in all VWD types

  21. Treatment • 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

  22. AcquiredHemorrhagic Disorders • Vitamin K deficiency • Liver Disease • Immune coagulopathies • Disseminated intravascular coagulation (DIC) • Pharmacologic overdosing • Acquired platelet defects due to : Uremia, myeloproliferative disorders, antiplatelet antibodies, drugs that inhibit platelet function

  23. 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

  24. Vitamin K deficiency due to warfarinoverdose:Managing high INR 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)

  25. INR >9; no bleeding Omit dose; vitamin K 3-5 mg po ; repeat as necessary Resume therapy at lower dose when INR therapeutic • 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

  26. Disseminated Intravascular Coagulation

  27. DIC is characterized by excessive deposition of fibrin throughout the vascular tree • Simultaneous depression of inhibitory mechanism of coagulation and impaired fibrin degradation

  28. Common causes of DIC • Sepsis • Trauma • Head injury • Fat embolism • Malignancy • Obstetrical complications • Amniotic fluid embolism • Abruptioplacentae • Vascular disorders • Reaction to toxin (e.g. snake venom, drugs) • Immunologic disorders • Severe allergic reaction • Transplant rejection

  29. Clinical picture • Skin and mucous membrane bleeding. • Hemorrage from • Surgical incision • Venipuncture less common features : • Peripheral acrocyanosis • Thrombosis • Pregenrenous changes in digits , genitalia and nose

  30. Lab manifestations • Thrombocytopenia • Schistiocytes • Prolonged PT and APTT • Prolonged TT • Decreased fibrinogen levels • Raised FDP • d Dimer assay

  31. 3P test Plasma-Protamine-procoagulation test • Relatively specific test • Tests for the presence of soluble complexes composed of fibrin monomers and FDPs • Addition of protamine desolubilises these complexes resultin in precipitate formation

  32. Treatment approaches • Treatment of underlying disorder • Anticoagulation with heparin : if thrombosis is problematic • Cryoprecipitate : hypofibrinogenmeia • Platelet transfusion : if platelet <50,000 • Fresh frozen plasma : if factor deficiency • APC(activated protein C) :decreases mortality and organ failure

  33. Antithrombin III : may reverse the DIC process in septicaemia • Prostacyclin : where platelet activation is the primary cause • Aprotinin : where the primary cause is fibrinolysis

  34. Liver Disease • Decreased synthesis of II, VII, IX, X, XI, and Fibrinogen . Prolongation of PT, aPTT and Thrombin Time • Treatment Fresh-frozen plasma infusion (immediate but temporary effect)

  35. laboratory Evaluation of Bleeding CBC and smearPlatelet count Thrombocytopenia RBC and platelet morphology TTP, DIC, etc. CoagulationProthrombin time Extrinsic/comm pathways Partial thromboplastin time Intrinsic/comm pathways Coagulation factor assays Specific factor def 50:50 mix Inhibitors (e.g., abs) Fibrinogen assay Decreased fibrinogen Thrombin time Qualitative/quantitative fibrinogen defects FDPs or D-dimerFibrinolysis (DIC) Platelet functionvon Willebrand factorvWD In vivo test (non-sp) Platelet function analyzer (PFA) Qualitative plat disorders Bleeding time and vWD Platelet function tests Qualitative platelet disorders

  36. 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

  37. 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

  38. Aminocaproic acid (Amicar) • Mechanism • Prevent activation plaminogen -> plasmin • Dose • 50mg/kg po or IV q 4 hr • Uses • Primary menorrhagia • Oral bleeding • Bleeding in patients with thrombocytopenia • Blood loss during cardiac surgery • Side effects • GI toxicity • Thrombi formation

  39. Desmopressin (DDAVP) • Mechanism • Increased release of VWF from endothelium • Dose • 0.3µg/kg IV q12 hrs • 150mg intranasal q12hrs • Uses • Most patients with von Willebrand disease • Mild hemophilia A • Side effects • Facial flushing and headache • Water retention and hyponatremia

  40. Recombinant human factor VIIa(rhVIIa; Novoseven) • Mechanism • Activates coagulation system through extrinsic pathway • Approved Use • Factor VIII inhibitors in hemophiliacs • Dose: (1.2 mg/vial) • 90 µg/kg q 2 hr • “Adjust as clinically indicated” • Cost (70 kg person) @ $1/µg • ~$5,000/dose or $60,000/day

  41. Recombinant human factor VIIain non-approved settings • Surgery or trauma with profuse bleeding • Consider in patients with excessive bleeding without apparent surgical source and no response to other components • Dose: 50-100ug/kg for 1-2 doses • Risk of thrombotic complications not well defined • Anticoagulation therapy with bleeding • 20ug/kg with FFP if life or limb at risk; repeat if needed for bleeding www.anaesthesia.co.inanaesthesia.co.in@gmail.com

More Related