BIOLOGY 2F03 Lecture Notes - Lecture 8: Haemophilia B, Antihemorrhagic, Haemophilia A
19 May 2018
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HAEMOPHILIA
1. There are broad patterns of bleeding concerning primary and secondary haemostatic defects
Primary haemostatic defects essentially cover platelet disorders and vWD
• Vessel wall & collagen disorders are also in this bracket, but are comparatively rare
• Bleeding is from sall essels, ioles o delay ad doest stop
Secondary haemostatic defects are usually due to procoagulant deficiencies
• Haemophilia is the commonest
• Heaprin therapy may produce a similar type of bleeding
• Bleeding is from deep structures, involves a delay (the time in which the plug is stable; before it
breaks apart) ad doest stop fro the o
Fibrinolytic disorders are rare
2. The genetic basis of haemophilia concerns an inversion mutation of chromosome X
Female carriers are not safe
• Circulating factor levels in women are extremely variable
• A carrier may display very low circulating F8 and then experience symptoms
• Conversely, a female may have high circulating F8 but is obviously not homozygous for the
disease.
The inversion mutation causes 45% of severe haemophilia A cases
• The mutation tends to occur in spermatogenesis
• Essentially, two homologus regions on the X chromosome recombine to give a gene that is
subsequently un-transcribable
• A number of other polymorphisms have been implicated in haemophilia A & B (B is not
associated with the inversion phenomenon)
• Some patients produce antibodies against F8/9
3. The pathogenesis of haemophilia involves the inability to generate a thrombin burst
Lack of either factor 8/9 means that the propagation stage of coagulation cannot occur
Failure of a throi urst i haeophilia
• slow thrombin generation = weak, unstable platelet aggregate
• The platelet aggregate will break due to lack of fibrin production
• NO factor 13 cross linking = any fibrin generated is insecure
• NO TAFI activation = any fibrin generated is more prone to fibrinolysis
4. Haemophilia is particularly prone to bleeding in joints and muscles
Haemophilia A & B are clinically indistinguishable. It was discovered thatthey were different diseases
whe two patiets oe A oe B ould ure eah others’ lottig aorality.
Classification of bleeding in Haemophilia
• Severe (factor level <1%)
o Spontaneous bleeding, from joints/muscles, which is delayed but prolonged.
• Moderate (factor level 2-5%)
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Document Summary
Haemophilia: there are broad patterns of bleeding concerning primary and secondary haemostatic defects. Primary haemostatic defects essentially cover platelet disorders and vwd: vessel wall & collagen disorders are also in this bracket, but are comparatively rare, bleeding is from s(cid:373)all (cid:448)essels, i(cid:374)(cid:448)ol(cid:448)es (cid:374)o delay a(cid:374)d does(cid:374)(cid:859)t stop. Fibrinolytic disorders are rare: the genetic basis of haemophilia concerns an inversion mutation of chromosome x. Lack of either factor 8/9 means that the propagation stage of coagulation cannot occur. It was discovered thatthey were different diseases whe(cid:374) two patie(cid:374)ts (cid:894)o(cid:374)e a o(cid:374)e b(cid:895) (cid:272)ould (cid:272)ure ea(cid:272)h others" (cid:272)lotti(cid:374)g a(cid:271)(cid:374)or(cid:373)ality. Haemarthrosis is a vicious cycle and a hallmark of haemophilia. Muscle bleeds in haemophilia may result from exertion. The psoas muscle is commonly involved bleeding in this muscle may result in compression of the femoral nerve and/or a compartment syndrome: the treatment of haemophilia is switching to a prophylactic scheme.
