This document discusses haemophilia, a bleeding disorder caused by deficiencies in coagulation factors VIII or IX. It defines haemostasis and the causes of bleeding disorders. Haemophilia A is caused by a mutation in the F8 gene resulting in decreased factor VIII levels, while haemophilia B is caused by a mutation in the F9 gene decreasing factor IX levels. Clinical features, laboratory findings, and treatment options involving factor replacement therapy are described. Complications like inhibitor development and chronic joint damage are also summarized.

1. HAEMOPHILIA
DR. MANISH KUMAR YADAV
JUNIOR RESIDENT III
INTERNAL MEDICINE

2. MODERATOR
Dr. Ajeet Kumar Chaurasia
(MD)
PG Deptt Of Medicine
MLNMC , PRAYAGRAJ

3. HAEMOSTASIS
• BLOOD MUST BE MAINTAINED IN A FLUID STATE IN ORDER TO
FUNCTION AS TRANSPORT SYSTEM ,BUT MUST BE ABLE TO SOLIDIFY
TO FORM A CLOT FOLLOWING VASCULAR INJURY IN ORDER TO
PREVENT EXCESSIVE BLEEDING ,A PROCESS KNOWN AS HAEMOSTASIS

8. BLEEDING DISORDER
CAUSES
 VESSEL WALL ABNORMALITIES
PLATELETS DEFECT
 COAGULATION DEFECT

9. VESSELS WALL ABNORMALITIES
• CONGENITAL e.g.
Hereditary haemorrhagic telangiectasia
Ehlers Danlos Disease
• AQUIRED e.g.
Vasculitis
Scurvy

11. COAGULATION DISORDER
PRIMARY
 HAEMOPHILIA A
HAEMOPHILIA B
HAEMOPHILIA C
 VON WILLEBRAND FACTOR DISEASE
 SECONDARY
 DIC
ANTICOAGULANTS
VITAMIN K DEFICIENCY
LIVER DS
RENAL DS
RAT POISON

17. HAEMOPHILIA
X LINKED RECESSIVE DS (A AND B)
MUTATION IN F8 GENE CAUSE HAEMOPHILIA A
MUTATION IN F9 GENE CAUSE HAEMOPHILIA B
HAEMOPHILIA AFFECT 1 IN 10,000 MALE
HAEMOPHILIA A AFFECT 80% OF ALL CASES
 FAMILY HISTORY OF DS IS ABSENT IN 30% OF CASES
80% MOTHERS ARE CARRIER OF MUTATED ALLELE
CLINICALLY HAEMOPHILIA A AND B ARE INDISTINGUISHABLE

18. CLINICAL FEATURES
HAEMOPHILIA SHOULD BE SUSPECTED IN PATIENTS WITH HISTORY OF
EASY BRUISING IN EARLY CHILDHOOD
SPONTANEOUS BLEEDING (APPARENTLY NO REASONS PREVIOUSLY)
IN JOINT ,MUSCLES AND SOFT TISSUE
EXCESSIVE BLEEDING AFTER TRAUMA OR SURGERY
 FAMILY HISTORY OF BLEEDING OBTAINED IN 2/3 OF ALL PATIENTS
SEVERITY OF BLEEDING IS GENERALY CORRELATED WITH CLOTTING
FACTOR LEVEL

21. LABORATORY FINDING IN HAEMOPHILIA A
APTT: PROLONGED CORRECTED BY ADSORBED PLASMA
PT AND BT :NORMAL
TT AND FIBRINOGEN : NORMAL
PLT :NORMAL
FACTOR VIII ACTIVITY :DECREASED
DNA ANALYSIS ANTENATAL DIAGNOSIS AND CARRIER DETECTION

22. TREATMENT FOR HAEMOPHILIA A
• FVIII REPLACEMENT THERAPY
CRYOPRECIPITATE
FVIII CONCENTRATE
RECOMBINANT VIII

23. LABORATORY FINDING IN HAEMOPHILIA B
APTT: PROLONGED CORRECTED BY AGED PLASMA
PT AND BT :NORMAL
TT AND FIBRINOGEN : NORMAL
PLT :NORMAL
FACTOR IX ACTIVITY :DECREASED
DNA ANALYSIS ANTENATAL DIAGNOSIS AND CARRIER DETECTION

24. TREATMENT FOR HAEMOPHILIA B
• FIX REPLACEMENT THERAPY
FFP
FIX CONCENTRATE
RECOMBINANT IX

30. • FVIII dose (IU)=TARGET FACTOR VIII LEVELS-FACTOR VIII BASELINE
LEVELS X BODY WT IN KG X .5UNIT/KG
• FIX dose (IU)=TARGET FACTOR IX LEVELS-FACTOR IXBASELINE LEVELS X
BODY WT IN KG

31. NONTRANSFUSION THEREPY IN
HAEMOPHILIA
• DDAVP
• SYNTHETIC VASOPRESSIN
• CAUSE RISE IN FVIII AND VWF
• DOSE .3MICRO GRAM/KG BODY WT OVER 20 MIN
• CAUSE RISE IN 2-3 TIMES RISE
• USES IN MILD TO MODERTAE HAEMOPHILIA

32. ANTIFIBRINOLYTICS
• EPSILON AMINO CAPROIC ACID
DOSE LOADING 200mg/KG (MAX 10G)
MAINTENANCE 100mg/kg /dose every 6 hourly
• TRANEXEMIC ACID
 DOSE 25mg/KG QID
• CONTRAINDICATED IN HAEMATURIA DUE TO CLOT FORMATION IN
GENITOURINARY TRACT

34. COMPLICATIONS
• INHIBITORS
• ALLOANTIBODY AGAINST FVIII AND FIX
5-10 % IN HAEMOPHILIA A
3-5 % IN HAEMOPHILIA B
• HIGH RISK GROUP
• SEVERE DEFICIENCY OF FACTOR
• FAMILY HISTORY OF INHIBITORS
• AFRICANS DESCENDENT
• USUALLY APEAR IN EARLY IN LIFE MEDIAN AGE 2 YRS

35. • INTENSIVE REPLACEMENT THERAPY SUCH AS MAJOR SURGERY , INTRA
CRANIAL BLEED, TRAUMA
• TREAMENT
• RECOMBINANT FACTOR VIIa
ENHANCES TF –DRIVEN THROMBIN FORMATION
• FEIBA(FACTOR EIGHT INHIBITOR BYPASS AGENT)
MIXTURE OF PARTIALLY ACTIVATED VITAMIN K DEPENDENT CLOTTING
PROTEASEINCLUDING FACTOR VIIa
• INDUCTION OF TOLERANCE BY DAILY INFUSION
OF FACTOR VIII

36. • CHRONIC JOINT DEFORMITIES BY FROM RECURRENT BLEEDING
• HCV INFECTION AND RELATED MALIGNANCY
• HIV INFECTION

37. MANAGEMENT IN CARRIERS OF
HAEMOPHILIA
USUALLY HAEMOPHILIA CARRIERS WITH FACTOR LEVEL OF 50%
NORMAL
DURING PREGNANCY BOTH FVIII AND FIX INCREASES 2 -3 TIMES
AND RAPID FALL AFTER DELIVERY LEADS TO RISK OF BLEEDING AND
PREVENTED BY INFUSION OF FACTOR CONCENTRATE TO LEVEL 50-
70% FOR 3 DAYS IN VAGINAL DELIVERY AND 5 DAYS IN CAESERIAN
SECTION
 IN MILD CASE BY ANTIFIBRINOLYTIC