Page 364 - Concise Pathology for Exam Preparation ( PDFDrive )

12 Haematology 349

Incidence

Incidence of hemophilia is 1 in 20,000 persons.

Pathophysiology
• Factor VIII normally circulates in the plasma bound to a much larger molecule VWF
(VIII C along with VWF is called Factor VIII complex).
• Functional attribute of Factor VIII is VIII C.
• Examination of haemophilia genes has revealed seven different mutations.

Carrier Detection
• Demonstration of subnormal levels of Factor VIII C by immunoassays
• Ratio of VIII C to VWF normally 0.74–2.2; in carriers, 0.18–0.9
• Abnormally low ratios of VIIIC/VWF may be seen in stress
• Falsely high ratios of VIII C/VWF are seen in pregnancy, oral contraceptive intake and
contamination of plasma samples with thrombin or proteolytic enzymes
Haemophilia in Females
• Minority of heterozygous carriers in whom X-chromosome inactivation has occurred
• Mating between affected male and carrier female
• Due to a new mutant gene in a carrier

Clinical Manifestations
• Excessive haemorrhage from a trivial injury
• Haemarthrosis most common and debilitating manifestation; usually preceded by ‘Aura’
(tingling before haemarthrosis)
• Haemorrhage n organization and inflammation n chronic proliferative synovitis n
chronic haemophilic arthropathy (may lead to fibrous or bony ankylosis)
• Pain, muscle spasm and limitation of mobility
• Subcutaneous, intramuscular haematomas, psoas and retroperitoneal haematomas
• Gastrointestinal and genitourinary bleeding
• Splenomegaly (40% patients)

Laboratory Diagnosis

• Anaemia with neutrophilia
• Megakaryocytes are normal or increased in number
• PTT is prolonged; abnormal results of PTT only when Factor VIII C levels fall to ,20–25%
of normal.
• Biological or immunological assays are used to determine the levels of factor VIII.
Factor VIII C level deficiency is classified as:
• Severe deficiency: Factor VIII C level ,0–2 U/dL
• Moderate deficiency: Factor VIII C level 2–5 U/dL
• Mild deficiency: Factor VIII C level .5 U/dL
• BT, CT abnormal

Q. Write briefly on von Willebrand disease.
Ans. von Willebrand disease is also called angiohaemophilia and pseudohaemophilia.
It is second only to haemophilia A in frequency.

Genetics
• Classified into types I–III and a platelet type
• Types IIC and Type III are autosomal recessive
• Rest are autosomal dominant

mebooksfree.com