Coagulation factor disorders

1. Coagulation factor disorders Dr. Maji Jose

2. 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

3. HAEMOPHILIA Also called as BLEEDER’S DISEASE,DISEASE OF HAPSBURG,DISEASE OF KINGS. Disease has been known since ancient times but SCHONLEIN in 1839 gave this ‘bleeders disease’ the name HAEMOPHILIA. Its 2nd most common hereditary coagulation disorder.

4. THREE FORMS OF HAEMOPHILIA SEEN Haemophilia A(Classic haemophilia) Haemophilia B(Christmas disease) Haemophilia C

5. TYPE CLOTTING FACTOR DEFICIENCY Haemophilia A Plasma thromboplastinogen (AHG,antihaemophilicglobulin, Factor VIII) Haemophilia B Plasmathromboplastin component (PTC,Factor IX) Haemophilia C Plasmathromboplastin antecedant(PTA,Factor XI)

6. Its inherited as sex (X) linked recessive trait and therefore manifested in males,while females are carriers. Occassional women carriers of haemophilia may produce factorVIII levels far below 50% and become symptomatic carriers. True female haemophilis-due to consanguinity within family-rare Transmitted through an unaffected daughter to a grandson.

7. Sons of haemophilic are normal and not carriers of the trait. Heterogenous daughters carry the defect to half of their sons and as recessive trait to half of their daughters.

9. Frequency of haemophilias varies in different races,highest incidence being in population of Britain,NorthernEurope,Australia. Occurs in 1 in 10,000 male births Interesting factor-occurrence of this disorder in royal blood of Great Britain and European royal families.

10. HAEMOPHILIA A Most common type of haemophilia. Due to deficiency of factor VIII

11. ETIOLOGY Genes for factor VIII and factor IX located on long arm of X-chromosome in bands q28 and q27. Haemophilia A result from inversion mutation-45% Haemophilia A caused by quantitative reduction of factor VIII in 90% cases,10% cases has normal or increased levels of factor VIII with reduced activity Normal haemostasis requires 25% of factor VIII activity,symptomatic haemophilic patients have factor VIII levels below 5%.

13. HAEMOPHILIA B Haemophilia B-several mutations like partial and total deletions,missense mutations that result in decrease or absence of factor IX .1 in 50,000 males HAEMOPHILIA C Factor XI gene located on chromosome 4 Mutation of factor XI gene cause failure ,reduced production of active protein and rarely production of an abnormal molecule result in factor XI deficiency.

14. CLASSIFICATION CLASSIFICATION FACTOR CAUSE OF ACTIVITY HAEMORHAGE MILD >5 MAJOR TRAUMA MODERATE 1-5 MILD TO MODERA TE TRAUMA SEVERE <1 SPONTANEOUS HAEMARTHROSIS, SOFT TISSUE BLEEDING

15. Clinical features Persistent bleeding after mild trauma. Haemorrhage into subcutaneous tissues internal organs and joints is a common feature and result in haematomas. Its present from birth,but may not become clinically apparent for years. 30-50% of patients with severe haemophilia present with manifestations of neonatal bleeding such as prolonged bleeding from umblical cord.

16. Spontaneous cyclic remissions and exacerbations of haemophilia are common Petechiae usually do not occur in patients with haemophilia because they are manifestations of capillary blood leaking,which is result of vasculitis or abnormalities in number or functions of platelets. Haemophilia C – distinguished from A and B by absence of bleeding into joints and muscles and by its occurrence in individuals of either gender

17. ORAL MANIFESTATIONS Gingival haemorrhage massive and prolonged Physiologic process of tooth eruption and exfoliation maybe attended with severe prolonged haemorrhage. Mandibular ‘pseudotumours’-a condition in which there is subperiosteal bleeding ,with reactive new bone formation causing tumour like expansion of bone.-STONEMAN and BEIERL

18. Dental extraction difficult-pre-medication Use of rubber bands-its placed around neck of the tooth and allowed to migrate apically causing exfoliation of tooth through pressure necrosis of Periodontal ligament

20. LAB FINDINGS Coagulation time-prolonged Bleeding time –normal Prothrobin time and platelet aggregation-normal Activated partial thromboplastin time-prolonged Functional assay of factors useful in diagnosing haemophilia caused due to dysfunction of coagulation factors.

21. Combination of low factorVIII and low Von Willebrands factor indicate Von Willebrands disease. In vitro,the deficiency of clot promoting factors in the plasma of haemophilics impairs clotting because it appears to retard development of substance responsiblefor conversion of prothrombin to thrombin

22. A small percentage of haemophilics have circulating anticoagulant,probably an antibody,which specifically inactivates antihaemophilicfactor,negating effects of transfusion Prognosis-variable and many affected person die during chilhood.

23. TREATMENT No surgical cure. Tooth extraction in hospitals. Preoperative transfusion of whole blood and administration of antihaemophilic factor concentrate recommended.

24. VON WILLEBRANDS DISEASE PSUEDOHAEMOPHILIA,VASCULAR HAEMOPHILIA,VASCULAR PURPURA It’s a disease characterised by the tendency to excessive bleeding in patients who have normal platelet count ,normal clotting time,normal serum fibrinogen and prothrombin time. BT-prolonged

25. It was 1st described by-Erik Adolf Von Willebrand 1st common hereditary disorder Inherited as AD trait transmitted by and manifested in both males and females. More in females 1 in 1000 persons

26. ETIOLOGY vWdisease is due to an abnormality either quantitative or qualitative of vWF ,which is large multimeric glycoprotein that functions as the carrier protein for factor VIII. A gene on chromosome 12p codes for the synthesis of this macromolecule. A variety of point mutations,insertions and deletion at vWF locus vWf –required for normal adhesion of platelet. It functions in both primary and secondary haemostasis.

27. CLASSIFICATION : Type I : characterised by partial quantitative decrease of normal vWF and factor VIII Type II : A variant of disease with primarily qualitative defects of vWF. It can be either AD or AR Type III : Severe and rarest form. In homogenous patients type III vW disease is charecterised by marked deficiencies of both vWFand factor VIII in plasma .

28. Absence of vW F from both platelets and endothelial cells and lack of secondary transfusion response. This type is characterised by severe clinical bleeding and is inherited as AR trait. And common in case of consanguinous marriage. In heterozygous disease is less severe.

29. CLINICAL FEATURES. Many children are asyptomatic – diagnosed as a result of positive family history of during routine pre-operative screening. Excessive bleeding either spontaniously or following a minor trauma. Sites of bleeding- nose ,skin ,gingiva Bleeding into GIT, severe menorrahagia, spontaneous nose bleeds and cutaneousecchymosis is seen. Hemarthrosis is rare. Bleeding tendency- cyclic or sporadic.

30. ORAL MANIFESTATIONS : Gingival bleeding- spontaneous or after brushing of teeth. Bleeding after dental extraction result in unmanagable flow. LABORATORY FINDINGS BT- range from several minutes to 1 hour. PT – Normal aPTT- Increased. CT – Normal but may be slightly prolonged. Capillary fragiliy – increased with +vetorniquet test. Clot retraction --normal

31. TREATMENT : Transfusion of plasma and antihemophilic factor and by local control of hemostasis.

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