Coagulation Question Notes (Book)

Question 1

What is the treatment of choice for

congenital Factor VII deficiency ?

Answer 1

• 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

Question 2

What is the composition of

prothrombin complex concentrate?

Answer 2

• Factors II, VII, IX and X
  
  • all vitamin K dependant

Question 3

What is a potential complication of

treating patients with recombinant Factor VII for a while ?

Answer 3

• 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

Question 4

What is the inheritance pattern of

Factor VII deficiency and clinical presentation ?

Answer 4

• 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

Question 5

At what factor level would significant

bleeding in Factor VII deficiency be expected ?

Answer 5

• if activity is <1%

Question 6

What are common types of bleeding

symptoms seen in Factor VII deficiency ?

Answer 6

• easy bruising
• epistaxis
• soft tissue hemorrhage
• menorrhagia
• bleeding with trauma
• postoperative bleeding

Note:

• postpartum and intracranial hemorrhage may be seen in severely affected patients

Question 7

What is something that is frequently seen

in patient’s with Factor VII deficiency ?

Answer 7

• paradoxical thromboembolism
  
  • both arterial and venous
  • this would complicate measuring levels

Question 8

What is the characteristic presentation of hemophilia

in a newborn ?

Answer 8

• circumcision bleeding

Note: Hemophilia A and B are indistinguishable clinically, but the majority of patients have Hemophilia B

Question 9

What is the clinical differential diagnosis

for Hemophilia ?

Answer 9

• 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

Question 10

What is a particular issue when measure factor

levels in newborns ?

Answer 10

• 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

Question 11

What is the appropriate management of

severe hemophilia ?

Answer 11

• initiate factor replacement with VIII or IX
  
  • treatment must be continued until the bleeding stops

Question 12

If there is a family history of hemophilia

when do pregnant women get tested ?

Answer 12

• tested in the 8th month of pregnancy
  
  • this is to help with the delivery and obtain baby’s cord blood for testing

Question 13

What is the inheritance pattern

of Hemophilia A ?

Answer 13

• 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

Question 14

What is the accepted treatment of Hemophilia A ?

Answer 14

• 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

Question 15

What is the differential diagnosis for

decreased Factor VIII in a woman ?

Answer 15

• 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)

Question 16

What is the mechanism of action of

DDAVP and possible issue with it’s use in treating

Hemophilia A ?

Answer 16

• 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

Question 17

What sort of medications are

contraindicated in patients with bleeding disorders ?

Answer 17

• drugs inhibiting platelet function (primary hemostasis)
• vWD and Hemophilia are secondary hemostasis

Question 18

What is the differential diagnosis for

Hemophilia B ?

Answer 18

• Factor VIII deficiency
• Factor IX deficiency (hemophilia B)
• von Willebrand disease
• Congenital deficiency of Factor XI

Question 19

What can possibly be tried to

reduce an anti-Factor IX or VIII inhibitor?

Answer 19

• trying larger doses of clotting factor to overwhelm the antibody or induce immune tolerance
  
  • especially by trying daily dosing of the recombinant factor

Question 20

How are Factor VIII and IX deficiencies graded ?

Answer 20

• Severe: <1%
• Moderate: 2-5%
• Mild: >5%

Note: Hemophilia B is extremely common in the Amish community

Question 21

What clinical presentation is common in

Hemophilia A and B ?

Answer 21

• LACK of menorrhagia
  
  • this type of bleeding is considered mucosal and more likely to be seen with platelet disorders and vWD

Question 22

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 ?

Answer 22

• 4 days of factor minimum

Question 23

When there is prolongation of both

PT and PTT what should be

suspected?

Answer 23

• 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

Question 24

What are available treatments for

common pathway inhibitors ?

Answer 24

• 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

Question 25

What common scenario have factor V inhibitors been described in ?

Answer 25

* 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