10. Rare Bleeding Disorders - Human Haemostatic Knock Outs Flashcards
List some rare bleeding disorders.
How are they different from e.g. haemophilia?
Factor XI, X, VII, II (prothrombin) deficiency. Factor XIII (fibrin stabilising factor) and fibrinogen. Combined V + VIII, kit K dependant factor deficiency. Severe platelet disorders - Bernard-Soulier, Glanzmanns.
Affect men and women, less life/limb threatening, bleed risk less frequent, mucosal bleeding, mennorhagia in 50%
What abnormal factors (A, B and C) would the following abnormalities result in?
- *A:** VII
- *B:** FVIII, FIX, FXI, FXII
- *C:** Fibrinogen, FII, FV, FV + VIII, FX
What is haemophilia C?
How is it treated?
What would you be worried about if an INR was >16?
Factor XI deficiency, Askenazi Jew predisposition. Complicated genetics: dominant negative effects. Surgery site important e.g. mucosal and urogenital more likely to bleed
Factor concentrate. Tranexamic acid used alone for simple proceedures. Aim low to normal levels + long half life (possible to overdose on FXI)
Over anticoagulated, worry about bleeding risk
How would you distinguish a factor VII deficiency from too much warfarin, since both would show a high INR?
Factor VII deficiency is recessive and rare. How is it treated?
How does pregnancy affect FVII?
Warfarin reduces vitamin K dependant factors 2, 7, 9 and 10 so APTT and PT would be affected too. If it’s a factor 7 deficiency then just INR and PT will be affected
Low dose recombinant FVIIa
Levels may rise in pregnancy, possible compensation by other clotting factors,
How is factor 5 deficiency treated?
What is FV + FVIII deficiency?
How is it treated?
Mild phenotype, don’t need much for haemostasis. TX: no concentrate available, plasma - solvent detergent fresh frozen plasma.
Generally mild phenotype, normal VII and V genetics, abnormal cellular transport (proteins homologous in tertiary strucuture, share transport mechanism out of endoplasmic reticulum, error in mechanism = deficiency)
VIII concentrate, DDAVP, plasma
What are the different types of fibrinogen deficiency?
What is fibrinogen deficiency and how is it managed?
How is it managed during pregnancy?
Quantitative (afibrinogenaemia/hypofibrinogenaemia), qualitative (dysfibrinogenaemia), coexist (hypodysfibrinogenaemia)
Potential severe bleeding phenotype, umbilical cord bleeding. Tx: fibrinogen concentrate or cryoprecipitate (both plasma derived but cryo not pathogen inactivated)
May cause recurrent miscarriage, abruption and PPH. Tx: fibrinogen replacement b/c clearance increases during pregnancy
What is factor II (thrombin) deficiency?
How is it managed?
What results APTT/PT/TT results would you see on someone with suppresed factor X?
How is it managed?
Variable phenotype, can be in isolation or all vit K dependant factors
Prothrombin complex concentrate, plasma, symptomatic manouvres e.g. Mirena coil
Gross derangment of APTT and PT. Some bleeding correlation with severity level
Prothrombin complex concentrate, plasma
What is factor XIII?
And if you are deficient?
What are the vitamin K dependant factors? How is their deficiency managed?
Fibrin stabilising factor - enzyme that crosslinks fibrin - final glue
Bleeding symptoms from birth - often diagnosed then, poor wound healing, conventional bleeding test doesn’t detect (PT/APTT/TT ok)
II, VII, IX, and X.
Prothrombin concentrate, plasma, vit K given as neonate (or else haemorrhagic disease of the newborn)
Where is a mutation for rare bleeding disorders normally found? What are the execeptions?
What are 3 severe primary haemostasis defects?
In corresponding clotting factor gene. Exceptions: combined FV + FVIII deficiency, vitamin K dependant factor deficiency. Often kindred specific, autosoma recessive: homozygous/compound hetrozygous
Bernard-Soulier syndrome (GpIb deficiency), Glanzmann’s, von Willebrand disease (vWF deficiency)
What are the following, and how are they detected and treated?
a) Glanzmann’s
b) Bernard-Soulier
Absent IIb/IIIa receptor on platelet surface. Platelets morphologically and numerically normal. Demonstrate absence with flow cytometry, abnormal platelet function assay, and platelet aggregometry.
Absent Ib/IX/V receptor on platelet surface, platelets large and fewer. Demonstrate absence with flow cytometry, abnormal platelet function assay, and platelet aggregometry.
Tx for both: HLA matched platelets, tranexamic acid for minor injury, recombinant FVIIa, bone marrow transplant, COCP
Care around menarche, gynae clinic!, contraception, iron deficiency - bleeding/dietary
