Disorders of Plasma Clotting Factors

1. Disorders of Plasma Clotting Factors Kaur, 2006

2. Fibrinogen

3. Prothrombin –Factor 2

4. Clotting Factors Defects • Decreased Synthesis • Production of abnormal molecules • Loss of consumption of Coagulation factors • Inactivation of factors by inhitors or antibodies

5. Transmission of Clotting Factors Disorders Inherited • Sex linked Acquired • Vitamin K deficiency • Liver disease • Hemorrhage • DIC

6. FACTOR DEFICIENCIES Table 25-1, p496

7. Von Willebrand’s Disease • Autosomal • Consistently prolonged bleeding time • Mucocutaneous bleeding

8. Production • Megakaryocytes and endothelial cells • Found in plasma • Stored in plasma granules and endothelial cells • Combines with VIII as VIII:vW • Allows VIII:C to concentrate at site of injury

9. Correction • Normal plasma

10. Signs and Symptoms • Mucocutaneous bleeding • Epistaxis • Ecchymosis • Easy bruising • GI bleeding • Menorrhagia • hemorrhage

11. Function • Carrier protein for VIII:C • Inability of the platelet to adhere to the subendothelial surface

12. LABORATORY ASSAYS • PT – Normal • APTT – Prolonged -corrects with pooled plasma • Platelets count – normal • Bleeding time – abnormal • Factor VIII:C activity • vWF-Ag concentration • Ristocetin aggregation

13. TREATMENT • CONCENTRATES OF fviii • CRYOPRECIPITATE • vWF • DESMOPRESSIN

14. HEMOPHILIA A • Most common hereditary coagulation disorder • Sex linked • Absence of VIII:C (procoagulant factor) • vWF:Ag is normal

15. INHERITANCE • X-linked (only one chromosome carries the gene for active VIII) • Males inherit from mothers • Daughters carriers • Mutation or silent carriers

16. Signs and Symptoms • Less than 1% have severe hemorrhage • Hemathrosis

17. Characteristics of Factor • Acute phase reactant • Minor portion is linked as VIII:C • Major portion is VIII:vW

18. Laboratory Findings • APTT – prolonged • PT – normal • Bleeding time – normal • Mixing studies with pooled plasma or adsorbed plasma corrects • APTT - Functional activity

19. TREATMENT • Concentrates of Human Plasma • Purified heat treated lyophilized FVIII (most accepted) • Recombinant-DNA FVIII

21. FACTOR IX – Christmas Factor/Plasma Thromboplastin Component • Synthesized in the liver • Vitamin k dependent • Intrinsic pathway activated by factor Xia and calcium ions • Activated by Russell viper venom

22. AGED SERUM Aged serum is prepared by incubating normal serum for 24 hours at 37°C. Lacks • fibrinogen (I), • prothrombin (II), • Factor V, • Factor VIII. Present • Factors VII, • IX, • X, • XI, • XII

23. ADSORBED PLASMA Platelet-poor plasma that is adsorbed with either barium sulfate or aluminum hydroxide Lacks the coagulation factors • factors II, VII, IX, X (the prothrombin group). Present • Factors V, VIII, XI, XII, and fibrinogen (I)

24. Hemophilia B (Christmas Disease) • Factor IX deficiency • Sex linked • Acquired • Liver disease • Vitamin K deficiency • Oral anticoagulant therapy

25. Serious complication • Development of antibodies (differs from Hemophillia A)

26. Laboratory Findings • PT – Normal • Thrombin Time – Normal • Bleeding Time – Normal • APTT – prolonged • Correction of APTT with pooled normal plasma or aged serum

27. Factor X