Hemophilia
INTRODUCTION:
- Group of hereditary genetic disorders that impair body’s ability to control blood clotting or coagulation.
TYPES:
1. Based on clotting factor affected:
| 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 |
2. Based on severity of condition:
| Classification |
Distribution |
Clotting factor activity |
|
Severe hemophilia |
50% |
<1% |
|
Moderate hemophilia |
10% |
1-5% |
|
Mild hemophilia |
30-40% |
5-40% |
ETIOLOGY:
Are sex-linked –
- Mainly X chromosome disorder.
- Manifested almost entirely in males.
- Females mostly are carriers & inherited from either mother/father.
Haemophilia A –
- Due to lack of functional clotting Factor VIII.
- Bleeding due to lack of reaction accelerator during factor X activation in coagulation cascade.
Haemophilia B –
- Bleeding due to lack of functional clotting factor IX.
- More severe yet, less common than Hemophilia A.
Haemophilia C –
- Autosomal recessive genetic disorder.
- Bleeding due to lack of functional clotting Factor XI.
HEMOPHILIA A:
- Represents 90% of hemophilia cases.
Based on severity:
- Mild: 6 – 50 % of normal factor VIII level.
- Moderate : 1 -5 %
- Severe: < 1% – Hence, presents with joint synovitis, hemophilic arthropathies, intramuscular bleeding & hemorrhagic cyst.
CLINICAL MANIFESTATIONS:
- Bleeding can happen anywhere in body following an injury/surgery or spontaneous.
Effects on muscles:
- Musculoskeletal bleeding
- Deep bleeding into joints and muscles – Hallmark finding.
- Begin when child reaches toddler age.
- In toddlers, ankle is the most common site.
- Later, knees & elbow become most common sites.
- Preceded by an aura.
- Develops “Compartment syndrome” –
- Hematomas into muscles of distal part of limbs lead to external compression of arteries, veins or nerves that can evolve into “Compartment syndrome”.
Hemorrhages:
- Presents with “Exsanguinating” hemorrhage involving almost most regions.
Iliopsoas bleeding:
- Vague abdominal & upper thigh discomfort.
- Characteristic gait with hip is flexed & internally rotated.
- Intracranial hemorrhage- Bleeding into & around oropharyngeal spaces.
- Retroperitoneal hemorrhages accumulate large quantities of blood with formation of masses with calcification & inflammatory tissue reaction(Pseudomotor syndrome).
Hematuria- May arise spontaneously.
Effects on bone:
- Most common cause of fracture in hemophilic patient – Osteoporosis & Restricted Joint Movement
- Develops “Hemophilic arthropathy”:
- When factor VIII< 5%.
- Also develops, Chronic proliferative synovitis.
Long-term sequelae of multiple bouts of hemarthrosis results in
- Cartilage damage
- Subarticular cysts
- Osteopenia
- Enlarged epiphyses.
- Combination of intercondylar notch widening & widened epiphysis – Characteristics of hemophilia & juvenile rheumatoid arthritis (JRA).
INVESTIGATIONS:
BASIC:
- Complete hemogram:
- TLC – normal
- DLC – normal
- Platelet count – normal
- Coagulation time: Prolonged
- Hb count – decreased
- Bleeding time: Normal.
- Note: Prolonged in von Willebrand disease.
- PT – Usually normal.
- APTT – Prolonged to 2–3 times.
- X-ray of joint: Knee joint, Elbow joint & Ankle joint
SPECIAL:
- Factor VIII assay
- Synovial Fluid Investigation
- Carrier state genetic testing
Liver biopsy:
- Multiple blood transfusions increase total iron load on body resulting in accumulation of iron-containing pigment in liver.
Prenatal diagnosis:
- Termination of pregnancy considered if fetus affected.
- Obtain chorionic villi samples in 10th – 11th gestational week and perform direct genotype testing by PCR.
- Test duration – 1wk / 2wk.
TREATMENT:
Basis of management –
- Mainly aims for prevention or as part of treating acute bleeding.
Replacement therapy-
- Replacement of factor VIII or IX to hemostatically adequate plasma levels.
Treatment on demand:
- For mild to moderate haemorrhages –
- Achieve factor VIII levels – 30-40 U/dL
- Factor IX levels to 30 U/dL.
- DDAVP(ADH preparation) – Drug used in mild hemophilia.
- By acting on V2 receptors causing increased factor VIII & vWF release from endothelium.
For life-threatening haemorrhages –
- Immediately correct factor level to 100-150 U/dL.
- Also, maintain level between 80-100 U/dL for 5-7 days followed by vigorous maintenance.
Prophylactic factor VIII therapy:
- Administered by subcutaneous access port of central venous line.
- Dose of 20-40 U/kg of factor VIII administered every other day or thrice weekly.
- Dose and rate adjusted to ensure maintenance before next infusion by >1U/dL
- Prevents spontaneous bleeding.
- Haemorrhages caused by trauma require additional replacement.
In Hemophilia with rheumatoid arthritis –
- Analgesic of choice – Acetaminophen.
Exam Question
- Increased total body iron concentration within liver.
- Biopsy showing large amounts of granular golden- brown pigment which stains blue with Prussian blue stain is suggestive of haemophilia.
- Haemophilia causes an overgrowth of epiphyses.
- Prenatal diagnosis of Hemophilia is best done by PCR
- Prolong APTT with normal PT, BT & platelets with postpartum haemorrhage is suggestive of acquired haemophilia 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 <5%.
- The most common manifestation of moderate /severe Hemophilia A is Recurrent Hemarthrosis.
- The most common cause of fracture in a patient with Hemophilia is Osteoporosis and Restricted Joint Movement.
- Females 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
