<20IU = homozygote/compound heterozygotye a compound heterozygote is someone who has inherited to different mutant polymorphisms <10IU = homozygote Type 1 disorder = absence. Type 2 disorder = dysfunction The concentration of coagulation factor required for haemostasis to occur is much lower than the lowest boundary of the normal range. Hence bleeding severity vary rarely correlates with deficiency (except for fibrinogen, f10, f13), bleeding patterns are variable, and heterozygotes/carriers may still have bleeding problems. The majority of rare coagulation disorders follow an autosomal recessive inheritance and demonstrate largely unpredictable bleeding patterns Factor Deficiencies Result of Bleeding PT APTT TT ‘pattern’ absence Fibrinogen Type 2> Type 1; Not fatal Umbilical cord, oral, - - + (AD) majority of Type 2 are muscle/joint, nose, acquired eg dx periods. Thrombosis if mutation near to thrombin cleavage site PT/F2 Rarest of them all Always Nose, periods, oral, + + - muscle/joint F5 Type 1> type 2 Always fatal Nose, periods, oral + + - F5+F8* Nose, periods, oral + + - (mild) F7 Commonest of them all Nose, periods, oral + - - (Arg353G mutation & environmental influences cited) F10 Always Joints, GI/urinary + + - F11 (AI) Particularly common in Genitourinary, oral, - + - Ashkenazi jews (f7 nose, tonsils (injury levels low in liver dx, related; mild) preg) F13 Umbilical, intracranial, - - - miscarriages, impaired healing *Combined F5/F8 deficiency is not due to mutations in the genes but due to problems in intracellular traifficking The management of rare bleeding disorder is difficult Rare disease = limited expertise and resources Haemophilia centres will usually cover these patients FFP/Promthrombinase concentrates (PCC )are usually the only resource, recombinant factors are being developed but they are expensive and the market is very narrow. Adjuvants like TAFI, DDAVP, OCP, IUCD can be used
<20IU = homozygote/compound heterozygotye a compound heterozygote is someone who has inherited to different mutant polymorphisms <10IU = homozygote Type 1 disorder = absence. Type 2 disorder = dysfunction The concentration of coagulation factor required for haemostasis to occur is much lower than the lowest boundary of the normal range. Hence bleeding severity vary rarely correlates with deficiency (except for fibrinogen, f10, f13), bleeding patterns are variable, and heterozygotes/carriers may still have bleeding problems. The majority of rare coagulation disorders follow an autosomal recessive inheritance and demonstrate largely unpredictable bleeding patterns Factor Deficiencies Result of absence Bleeding ‘pattern’ PT APTT TT Fibrinogen (AD) Type 2> Type 1; majority of Type 2 are acquired eg dx Not fatal Umbilical cord, oral, muscle/joint, nose, periods. Thrombosis if mutation near to thrombin cleavage site - - + PT/F2 Rarest of them all Always Nose, periods, oral, muscle/joint + + - F5 Type 1> type 2 Always fatal Nose, periods, oral + + - F5+F8* Nose, periods, oral (mild) + + - F7 Commonest of them all (Arg353G mutation & environmental influences cited) Nose, periods, oral + - - F10 Always Joints, GI/urinary + + - F11 (AI) Particularly common in Ashkenazi jews (f7 levels low in liver dx, preg) Genitourinary, oral, nose, tonsils (injury related; mild) - + - F13 Umbilical, intracranial, miscarriages, impaired healing - - - *Combined F5/F8 deficiency is not due to mutations in the genes but due to problems in intracellular traifficking The management of rare bleeding disorder is difficult Rare disease = limited expertise and resources Haemophilia centres will usually cover these patients FFP/Promthrombinase concentrates (PCC )are usually the only resource, recombinant factors are being developed but they are expensive and the market is very narrow. Adjuvants like TAFI, DDAVP, OCP, IUCD can be used