Coagulation Disorders

1. Coagulation Disorders

2. HEMOSTASIS BV Injury Neural Damage/contact. Contact Coagulation Cascade Blood Vessel Constriction Platelet Aggregation Primary hemostatic plug Reduced Blood flow Platelet Activation Fibrin formation Stable Hemostatic Plug

3. COAGULATION CASCADE

4. DISORDERS OF HEMOSTASIS • Disorders of Blood vessels • Scurvy, senile purpura, cushing’s syndrome, connective tissue disorders, HENOCH-SEHONLEIN Purpura • Disorders of Platelets • Thrombocytopenia-impaired production, hyper splenism, accelarated destruction • Functional-Thrombasthenia,Bernard –Soulier, VON WILLEBRAND’s disease • Platlete release defect-Aspirin, NSAID, Uremia • DISORDERS OF COAGULATION

5. COAGULATION DISORDERS • Inherited disorders • Hemophilia A and B • Other factor deficiencies[V,VII,X,II,XIII] • Acquired disorders • Liver disease • Vitamin K deficiency/warfarin overdose • DIC

6. HAEMOPHILI A • Hemophilia was known as the “Royal disease” because it spread to the royal families of Europe through Britain Queen Victoria’s descendants

7. HAEMOPHILIA

8. INHERITANCE

9. Clinical manifestations • Hemophilia A & B indistinguishable • Hemarthrosis (most common) Acute or chronic • Fixed joints(target joints) • Mainly affect knees, elbows, ankles, shoulders, and hips • Soft tissue hematomas • Muscle atrophy • Shortened tendons • Other sites of bleeding • Urinary tract • CNS • Retroperitoneal bleed • Prolonged bleeding after surgery or dental extractions

10. HEMARTHOSES

11. Bleeding and clotting disorders

12. LAB INVESTIGATIONS • Normal bleeding time and platelets • Normal prothrombin time • Isolated APTT prolongation • Measurement of factor levels

13. TREATMENT OF HEMOPHILIA A Recombinant factor VIII • One unit of F VIII increases the plasma F VIII level by 2% • The FVIII half-life of 8–12 h ;requires injections twice a day • Dose: 15-50 IU/d depending on the severity Cryoprecipitate • Contains half of the FVIII activity in 1/10th volume

14. TREATMENT Desmopressin “DDAVP” • Synthetic vasopressin analogue • Transient rise in FVIII and von Willebrand factor (vWF), through a mechanism involving release from endothelial cells • useful in mild haemophilia ANTIFIBRINOLYTIC DRUGS • Aminocaproic acid (EACA) or tranexamic acid

15. TREATMENT OF HEMOPHILIA B • Recombinant factor IX plasma t1/2 24 hours 50-100 IU/Kg/day • FFP

16. VITAMIN K • 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

17. SOURCES OF VITAMIN K

18. VITAMIN K CYCLE

19. LAB INVESTIGATIONS • Normal platelets • Prolonged prothrombin time • Normal bleeding time • Prolongation of APTT

20. TREATMENT Vitamin K Fresh frozen plasma

21. LIVER DISEASE • Decreased synthesis of II, VII, IX, X, XI, and fibrinogen • Often complicated by • Gastritis, esophageal varices, DIC • Treatment • Fresh-frozen plasma infusion (immediate but temporary effect) • Vitamin K (usually ineffective)

22. Disseminated Intravascular Coagulation (DIC) • Clinicopathologic syndrome characterized by widespread intravascular fibrin formation in response to excessive blood protease activity that overcomes the natural anticoagulant mechanisms

23. CAUSES • 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 • Drugs • Liver disease

24. MECHANISM Systemic activation of coagulation Depletion of platelets and coagulation factors Intravascular deposition of fibrin Thrombosis of small and midsize vessels with organ failure Bleeding

25. CLINICAL MANIFESTATIONS • Bleeding tendency in presence of widespread coagulation • Acute D.I.C.= dominated by a bleeding • seen in obstetrical complications and trauma • Chronic D.I.C.= presents with Thrombotic complications • seen in cancers

26. CLINICAL MANIFESTATIONS • Organ damage due to Micro thrombi • Kidney : Microinfarcts in the renal cortex • In severe cases = bilateral renal cortical necrosis • Adrenals : Bilateral adrenal hemorrhage • resembles Waterhouse - Friderichsen syndrome • Brain : Microinfarcts surrounded by foci of hemorrhage • Heart and anterior pituitary: show similar changes

27. LAB INVESTIGATIONS • Decreased platelets • Prolonged prothrombin time • Prolonged bleeding time • Prolongation of APTT • Elevated D dimer • Elevated fibrin degaradation products(FDP)

28. TREATMENT • Treatment of underlying disorder • Anticoagulation with heparin • Platelet transfusion • Fresh frozen plasma

29. COAGULATION CASCADE AND LAB INTERPRETATION

30. HMWK VII XII PK XI APTT PT IX VIII X PT -  APTT, TT, PLC - N V TT II I • Factor VII deficiency • Anticoagulant therapy • Early vitamin k deficiency

31. HMWK VII XII PK XI APTT PT IX VIII X APTT -  PT, TT, PLC - N V TT II I • Factor deficiency • Inhibitors • Heparin therapy

32. HMWK VII XII PK XI APTT PT IX VIII X V PT, APTT -  TT, PLC - N TT II I • Common Pathway Factor deficiency • Vitamin K deficiency-late • Oral anticoagulant therapy • Liver disease

33. HMWK VII XII PK XI APTT PT IX VIII X V PT, APTT, TT -  PLC - N TT II I • Hypo / dysfibrinogenemia • Heparin • Liver disease • Systemic hyperfibrinolysis

34. HMWK VII XII PK XI APTT PT IX VIII X APTT, PT,TT all  PLC - low V TT II I • DIC • - FDP (fibrin degradation product) • - D-dimer • - Fibrin monomer

35. Platelet, BT,PT, APTT- NORMAL Causes • Factor XIII deficiency • Thrombasthenia (disorder of platelets) • congenital • drug induced • Disorders of vascular hemostasis

36. Factor XIII deficiency • Factor XIII- clot stabilizing factor • Diagnosed by clot solubility test (5 M urea solution)

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