Coagulation Question Notes (Book) Flashcards
What is the treatment of choice for
congenital Factor VII deficiency ?
- recombinant Factor VIIa
- In the past FFP or Prothrombin complex concentrates were used
- but since both are plasma derived there is risk of infection
- large volumes of plasma are also needed to replace the factor, because it has a short half life
What is the composition of
prothrombin complex concentrate?
- Factors II, VII, IX and X
- all vitamin K dependant
What is a potential complication of
treating patients with recombinant Factor VII for a while ?
- they can develop autoantibodies to Factor VII which may cause the PT mix to remain long after mixing and complicate therapy
- this should be considered if the patient stops responding to Factor VII
What is the inheritance pattern of
Factor VII deficiency and clinical presentation ?
- Autosomal recessive
- affects males and females
- > 250 gene mutations have been identified
- IMP
- in contrast to hemophilia A and hemophilia B, the level of factor VII in patients with congenital deficiency does not correlate well with the clinical severity of bleeding symptoms
At what factor level would significant
bleeding in Factor VII deficiency be expected ?
- if activity is <1%
What are common types of bleeding
symptoms seen in Factor VII deficiency ?
- easy bruising
- epistaxis
- soft tissue hemorrhage
- menorrhagia
- bleeding with trauma
- postoperative bleeding
Note:
- postpartum and intracranial hemorrhage may be seen in severely affected patients
What is something that is frequently seen
in patient’s with Factor VII deficiency ?
- paradoxical thromboembolism
- both arterial and venous
- this would complicate measuring levels
What is the characteristic presentation of hemophilia
in a newborn ?
- circumcision bleeding
Note: Hemophilia A and B are indistinguishable clinically, but the majority of patients have Hemophilia B
What is the clinical differential diagnosis
for Hemophilia ?
- defect in primary hemostsasis
- vWD
- disorder of platelet function
- IMP:
- disorders of primary hemostasis do not usually present with circumcision bleeding but rather with oral bleeding, epistaxis, and gastrointestinal bleeding
What is a particular issue when measure factor
levels in newborns ?
- there may be normal mildly decreased factor levels
- due to newborn liver
- affects factors produced in liver (not Factor V)
- this may lead to a mildly prolonged PT
- a factor level of 30% may be normal for a newborn so do not overcall
- levels around 1-5% are never normal
What is the appropriate management of
severe hemophilia ?
- initiate factor replacement with VIII or IX
- treatment must be continued until the bleeding stops
If there is a family history of hemophilia
when do pregnant women get tested ?
- tested in the 8th month of pregnancy
- this is to help with the delivery and obtain baby’s cord blood for testing
What is the inheritance pattern
of Hemophilia A ?
- for both Hemophilia A and B
- sex-linked recessive
- affect males with carrier females
- A > B 4:1 ratio
- up to 1/3 of hemophilia cases arise as spontaneous mutations
- defective gene is on mother’s X chromosome
- 1/2 of cases have a signature mutation
- intron 22 inversion
- easily can be assessed by PCR
What is the accepted treatment of Hemophilia A ?
- in order to prevent joint bleeding or damage
- prophylactic infusions of Factor VIII (3x per week)
IMP: these children tend to develop autoantibodies to the infused Factor VIII and they become not responsive to treatment
What is the differential diagnosis for
decreased Factor VIII in a woman ?
- Hemophilia A carrier
- von Willebrand disease
- both
Note: a woman may have hemophilia if she inherits two abnormal chromsomes (from mom and dad or if she has Turners)
What is the mechanism of action of
DDAVP and possible issue with it’s use in treating
Hemophilia A ?
- DDAVP induces release of Factor VIII and vWF from endothelial cell Weibel-Palade bodies
- problem:
- with continued use of DDAVP the stores are depleted within 3 days so patients may bleed
- need to treat ongoing bleeding with Factor VIII concentrates
What sort of medications are
contraindicated in patients with bleeding disorders ?
- drugs inhibiting platelet function (primary hemostasis)
- vWD and Hemophilia are secondary hemostasis
What is the differential diagnosis for
Hemophilia B ?
- Factor VIII deficiency
- Factor IX deficiency (hemophilia B)
- von Willebrand disease
- Congenital deficiency of Factor XI
What can possibly be tried to
reduce an anti-Factor IX or VIII inhibitor?
- trying larger doses of clotting factor to overwhelm the antibody or induce immune tolerance
- especially by trying daily dosing of the recombinant factor
How are Factor VIII and IX deficiencies graded ?
- Severe: <1%
- Moderate: 2-5%
- Mild: >5%
Note: Hemophilia B is extremely common in the Amish community
What clinical presentation is common in
Hemophilia A and B ?
- LACK of menorrhagia
- this type of bleeding is considered mucosal and more likely to be seen with platelet disorders and vWD
For carrier patients of Hemophilia A and B, what
is the amount of time they must receive recombinant factor
in anticipation of surgery or delivery ?
- 4 days of factor minimum
When there is prolongation of both
PT and PTT what should be
suspected?
- a common pathway issue
- if there is no correction with mixing studies then an inhibitor should be suspected
- Common pathway factors
- II
- V
- X
- can evaluated specific factors using direct assays for them
What are available treatments for
common pathway inhibitors ?
- general approach is immunosuppression
- steroids, IVIG, and various chemotherapeutic agents
- Rituximab could be considered in refractory cases
- plasma transfusions
- unlikely to overcome a high titer antibody
- may result in fluid overload
- anti-fibrinolytics
- can control the bleeding
- plasmapharesis
What common scenario have factor V
inhibitors been described in ?
- contaminated bovine thrombin used topically
- leads to an acquired factor V inhibitor
- factor V inhibitors are the second most common factor inhibitors
- factor VIII is the most common
