Hemophilia

INTRODUCTION:
  • A group of hereditarygenetic disorders that impair the body's ability to control blood clotting or coagulation .
  • The effects of this sex-linked, X chromosome disorder are manifested almost entirely in males
  • Females are almost exclusively carriers of the disorder, and may have inherited it from either their mother or father.
ETIOLOGY:
  • Haemophilia A is an X-linked genetic disorder involving a lack of functional clotting Factor VIII and represents 90% of hemophilia cases.
  • Patients with hemophilia A have bleeding disorder because of Lack of reaction accelerator during activation of factor X in coagulation cascade
  • Haemophilia B is an X-linked genetic disorder involving a lack of functional clotting Factor IX It is more severe but less common than Hemophilia A. Haemophilia C is an autosomal recessive genetic disorder involving a lack of functional clotting Factor XI.
HEMOPHILIA A:
  • Mild : 6 – 50 % of normal factor viii level
  • Moderate : 1 -5 %
  • Severe : < 1% ( joint synovitis , hemophilic arthropathies , IM bleeding, hemarrhagic cyst)
HEMOPHILIA B:
  • Genetic bckgrnd , factor level, clinical symptoms are same as HEM A
  • specific factor concentrate
Hemophilia A → Deficiency of factor VIII C
Hemophilia B(Christmas disease)   Deficiency of factor IX (X-linked)
Hemophilia C   Deficiency of factor XI (autosomal inherited defect)
Parahemophilia  Deficiency of factor V
Von Willebrand's disease   Deficiency of v WF along with VIIIC
     
Distribution

Clotting factor activity
Severe hemophilia
50%
Moderate hemophilia
10%
Mild hemophilia 30-40%
5-40%
CLINICAL MANIFESTATIONS:
  • Bleeding can happen anywhere in the body following an injury / surgery or spontaneous.
  • Musculoskeletal bleeding
  1. Deep bleeding into joints and muscles is the hallmark.
  2. Begin when the child reaches the toddler age.
  3. In toddlers ankle is the most common site.
  4. Later knees and elbow become the most common sites.
  5. Preceded by an aura.
  6. Hematomas into muscles of distal part of limbs leads to external compression of arteries, veins or nerves that can evolve to a compertment syndrome. Iliopsoas bleeding
  7. Vague abdominal and upper thigh discomfort and a characteristic gait (hip is flexed and internally rotated).
  8. Intracranial haemorrhage, bleeding into and around the oropharyngeal spaces and exsanguinating haemorrhage.
  9. Retroperitonial hemorrhages can accumulate large quantities of blood with formation of masses with calcification & inflammatory tissue reaction ( Pseudomotor syndrome) Hematuria- May arise spontaneously.
  10. The most common cause of fracture in a patient with Hemophilia is Osteoporosis and Restricted Joint Movement
  11. Hemophilic arthropathy:(factor VIII< 5%)Chronic proliferative synovitis, Chronic hemophilic arthropathy
  12. Long-term sequelae of multiple bouts of hemarthrosis include cartilage damage, subarticular cysts, osteopenia, and enlarged epiphyses.The combination of intercondylar notch widening and widened epiphysis is seen only in haemophilia and juvenile rheumatoid arthritis (JRA).
INVESTIGATIONS:
  • BASIC:
  1. Complete hemogram:
  2. Hb count – decreased
  3. TLC – normal
  4. DLC – normal
  • Platelet count – normal
  1. Coagulation time:Prolonged
  2. Bleeding time: normal ( prolong in von Willebrand disease)
  3. PT(Usually normal) & APTT(prolonged to 2-3 times )
  4. X-ray of joint:Knee joint ,Elbow joint & Ankle joint
  • SPECIAL:
  1. Factor VIII assay
  2. Synovial Fluid Investigation
  3. Carrier state genetic testing
  4. Liver biopsy:multiple blood transfusions increases the total iron load on the body resulting in accumulation of iron-containing pigment in his liver
  •  Prenatal diagnosis
  1. Offered when termination of pregnancy would be considered if affected fetus identified.
  2. Obtain chorionic villi samples in 10th-11th gestational week and perform direct genotype testing.
  3. Test duration. 1wk / 2wk
  4. Done by PCR
  5. TREATMENT:
  • Replacement therapy- Replacement of FVIII or IX to hemostatically adequate plasma levels for prevention or treatment of acute bleeding is the basis of the management of hemophilia Treatment on demand:
  • For mild to moderate haemorrhages, achieve FVIII levels of 30-40 U/dL or FIX levels of 30 U/dL.
  1. For life threatening haemorrhages, immediately correct factor level to 100-150 U/dL and maintain level between 80-100 U/dL for 5-7 days followed by vigorous maintenance. Prophylactic factor VIII therapy
  2. Administered by subcutaneous access port of a central venous line.
  • Prevents spontaneous bleeding; haemorrhages caused by trauma may still require additional replacement.
  • Dose of 20-40 U/kg of FVIII administered every other day or thrice weekly. Dose and rate adjusted to ensure that nadir before next infusion is >1U/dL. DDAVP(ADH preparation) is the drug used in mild hemophilia
    1. It acts on V2 receptors to cause increased release of factor VIII and vWF from the endothelium
    2. In Hemophilia with Rheumatoid arthritis, analgesic of choice is Acetaminophen
Exam Question
  • Prenatal diagnosis of Hemophilia is best done byPCR
  • Prolong APTT with normal PT,BT & platelets with post partum hemorrhage is suggestive of acquired hemophlia A
  • Normal platelets,Deficient factor VIII & IX are suggestive findings of hemophilia
  • Hemophilia is associated with X chromosome
  • Hemophilia B is due to deficiency of clotting Factor IX
  • Patients with hemophilia A have bleeding disorder because of Lack of reaction accelerator during activation of factor X in coagulation cascade
  • DDAVP is the drug used in mild hemophilia
  • A child who bleeds from gums and has swollen knee-probably due to hemophilia
  • Spontaneous muscle bleeding is typically seen in hemophilia
  • Bleeding time may be used to differentiate hemophilia A from von Willebrand disease
  • Recurrent Spontaneous Hemarthrosis is commonly seen in patients with Hemophilia when factor VIII levels are The most common manifestation of moderate /severe Hemophilia A is Recurrent
  • HemarthrosisThe most common cause of fracture in a patient with Hemophilia is Osteoporosis and Restricted Joint
  •  MovementFemales are mostly carriers and all males are affected in hemophilia
  • In Hemophilia with Rheumatoid arthritis, analgesic of choice is Acetaminophen
Don't Forget to Solve all the previous Year Question asked on Hemophilia