Rare inherited bleeding disorders in pregnancy

Question 1

what is the incidence of factor 11 deficiency in the general population?

Answer 1

1 in 1 million

Question 2

what is the incidence of factor 11 deficiency in Ashkenazi Jews?

Answer 2

8% homozygous

0.2-0.5% heterozygous

Question 3

What is the inheritance and phenotype of a factor 11 deficiency?

Answer 3

Autosomal dominant or recessive
spontaneous bleeding rare - most commonly with invasive procedures typically mucosal membranes
variable phenotype - bleeding risk may be high or low

Question 4

Which blood group increases the risk of bleeding with factor 11 deficiency?

Answer 4

Blood group O

Question 5

What are the risks to the mother with a factor 11 deficiency?

Answer 5

Bleeding - PPH, heavy bleeding with miscarriage, bleeding with invasive procedures
If bleeding phenotype, or unknown phenotype epidural typically not recommended?

Question 6

What are the risks to the fetus when a mother has factor 11 deficiency?

Answer 6

Risks are low
No ICH has been recorded
Prenatal diagnosis not recommended

Question 7

When should clotting factors be measured in women with factor 11 deficiency?

Answer 7

Booking, third trimester, before invasive procedures

Include vwf and platelets as can contribute to bleeding

Question 8

What are the treatment options for factor 11 deficiency?

Answer 8

Expectant
Tranexamic acid (don’t use with clotting factor)
Recombinant factor 11
Fresh frozen plasma (should be solvent detergent type)
Off label use of factor 7a sometimes used but cant be used if there are inhibitors to recombinant factor 11

Question 9

What are the risks with giving recombinant factor 11?

Answer 9

IF given with TXA can cause blood clots
Patients can develop inhibitors
Risk of blood clots if factor levels rise above 0.7
Can have get transfusion reaction and transfusion-transmitted infection

Question 10

What are the risks of giving fresh frozen plasma to factor 11 deficient patients?

Answer 10

Transfusion reaction
Transfusion-transmitted infection
Develop inhibitors
Risk of blood clots

Question 11

How do factor 11 levels change in pregnancy?

Answer 11

They do not increase

Question 12

Which rare inherited bleeding disorders are treated with prothrombin complex concentrate?

Answer 12

Prothombin (factor 2) deficiency
Factor X (10) deficiency

Question 13

Which rare inherited bleeding disorders are treated with SD-FFP?

Answer 13

Factor V (factor 5) deficiency
Combined factor V and VIII deficiency

Question 14

Which rare inherited bleeding disorders are treated with their factor replacement?

Answer 14

Prothombin (factor 2) deficiency - treated with prothrombin complex concentrate
Factor VII (factor 7) deficiency - treated with Factor VIIa
Factor XIII (factor 13) deficiency - treated with Factor XIII

Question 15

What are the different phenotypes of fibrinogen deficiency?

Answer 15

Severe deficiency leading to bleeding
Mild deficiency - variable bleeding but also thrombosis risk
Qualitative deficiency -variable bleeding but also thrombosis risk

Question 16

How is severe fibrinogen deficiency treated in pregnancy?

Answer 16

fibrinogen concentrate replacement (derived from plasma)
OR if not available cryoprecipitate
N.B fibrinogen replacement is not reliable to safely insert an epidural

Question 17

What are the risks associated with fibrinogen deficiency and pregnancy?

Answer 17

Different phenotypes include increased risk of bleeding, increased risk of pregnancy loss, increased risk of thrombosis and abruption

Question 18

What is the inheritance of Bernard Soulier Syndrome and what does the condition result in?

Answer 18

BSS is autosomal recessive causing a platelet disorder due to deficiency (qualitative or quantitative) of Gp-Ib-IX-V complex

Question 19

How is Bernard Soulier Syndrome treated to prevent severe bleeding in labour and c-section?

Answer 19

Platelet transfusions and tranexamic acid

N.B> DDAVP does not work

Question 20

What is the inheritance of Glanzmann’s thrombocytasthenia and what does the condition result in?

Answer 20

GT is autosomal recessive condition causing platelet deficiency disorder due to dysfunctioning GpIIb/IIIa

Question 21

How is Glanzmann’s thrombocytasthenia treated to prevent severe bleeding in labour and c-section?

Answer 21

Platelet transfusions and tranexamic acid +/- recombinant factor VIIa
N.B. DDAVP does not work