Sunday, May 5, 2024

Factor XI

 April 2024

Factor XI deficiency

  • Rare prevelance is 1/1 million Caucasian/ Ashkenzi Jews
  • However among rare bleeding disorders, it tops the list
  • Deficiency - two types- quantitative and qualitative
  • Severe disease if homozygous or compound heterozygous
  • Severe def if factor XI levels < 15 to 20 IU/dl
  • Clinical manifestations- due to injury, increased bleeding with circumcision, tonsillectomy, increased menstrual and post partum bleeding
  • If no personal hx of bleeding, that was the best predictor of low risk. Also if levels > 40 IU
  • Older pt- factor XI remains the same. Can use anticoagulation for Afib if no bleeding hx or def is not severe. Using factor XI / VII a to counteract bleeding after surgery can lead to thrombosis in rare cases.
  • May develop inhibitors to Factor XI but don't get spontaneous bleeding
  • No standard prophylaxis even if levels < 1%
  • High risk surgery e.g neurosurgery- tranexamic acid, FFP, FXI concentrate, off label factor 7a
  • Gross hematuria in GU surgery contraindication to antifibrinolytic such as tranexamic acid
  • Minor surgery : 3-5 days TXA or EACA 
  • Major surgery: 7-10 days of TXA or EACA, FFP, Factor XI and off label factor 7a recombinant( mostly for those with factor XI inhibitors from prior FFP)
  • Dose of FFP 20 ml /kg q 24
  • Dose of Factor XI 10-20 IU/kg repeat q 48 hr
  • Dose of Novo Seven- single dose 10-15 microgram /kg

Factor XI inhibitors for VTE prevention
  • Three categories- Monoclonal Ab, small molecule oral agents, DNA antisense oligonucleotide
  • While Factor XI inhibitors reduced risk of VTE esp post op, these drugs were not effective in secondary stroke reduction
  • Inferior efficacy compared to DOAC in Afib and stroke reduction
  • These drugs caused less  bleeding than DOAC
Interesting MCQ question for ASH: Name the gene variation associated with gestational thrombocytopenia?
Ans: PEAR1 ( plt endothelial aggregation receptor)

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