Bleeding Disorders

Question 1

What is Haemophilia A?

Answer 1

Factor VIII deficiency, Sex linked recessive, missense or frameshift mutations or deletions

Question 2

What is Haemophilia B?

Answer 2

Factor IX deficiency

Question 3

Where is Factor VII synthesized?

Answer 3

Liver and endothelial cells

Question 4

Which mutation leads to the more severe form of Haemophillia A?

Answer 4

Flip tip inversion in the Factor VIII gene?

Question 5

What are the clinical features of Haemophilia A?

Answer 5

1. Recurrent painful Haemarthroses
2. Muscle haematomas
3. Can progress to joint deformity
4. Prolonged bleeding after dental procedures
5. Spontaneous G.I bleeds and haematuria

Question 6

What are Haemophilic pseudotumours?

Answer 6

Large encapsulated haematomas withh progressive cystic swelling from repeated hemorrhage. Best visualized by MRI

Question 7

What are the treatments available for haemophilia A patients?

Answer 7

1. Bleeding episodes are treated with Factor VIII replacement therapy.
2. Recombinant factor VII and plasma derived factor VII preparations are available for clinical use
3. 1-Diamino-8-D-Arginine vasopressin (DDAVP) provides an alternative means of increasing the plasma factor VIII level in milder haemophiliacs

Question 8

What is a side effect of DDAVP?

Answer 8

Antidiuretic action

2.Avoid in the elserly

Question 9

What recommendation is made to Haemophiliacs?

Answer 9

Have regular conservative dental care.

Question 10

What is one of the most serious complications with haemophilia treatment?

Answer 10

The development of antibodies to to infused Factor VIII (occurs in 30-40% of patients)

Question 11

How can the antibody development to infused Factor VIII be countered?

Answer 11

Immunosupression

Question 12

What is the difference in the synthesis of factor VIII and IX?

Answer 12

Factor IX synthesis is dependent on vitamin K

Question 13

What test are abnormal in a patient with Haemophilis B.

Answer 13

1. PTT

2. Factor IX clotting assay

Question 14

What is von Willebrand disease?

Answer 14

A disorder in which there are low levels or abnormal function of VWF stemming from a missense mutation or null mutation

Question 15

Where is VWF produced?

Answer 15

1. Endothelial cells

2. Platelets

Question 16

What are the 2 functions of VWF?

Answer 16

1. Promotes platelet adhesion to subendothelium at high shear rates
2. It is the carrier molecule for Factor VIII protecting it from premature destruction

Question 17

What other factor is reduced in von Willebrand disease?

Answer 17

Factor VIII

Question 18

What is the most inherited bleeding disorder?

Answer 18

Von Willebrand factor disease

Question 19

What is the usual inheritance patern for Von Willebrand disease?

Answer 19

Autosomal Dominant

Question 20

Which gender is generally worse affected at a given VWF level?

Answer 20

Women

Question 21

Lab findings?

Answer 21

1.Factor VIII - Low
2.PTT elevated
3.VWF levels low
.Platelet count normal except intype 2B disease

Question 22

Is senile purpura a bleeding disorder?

Answer 22

No, comes with aging

Question 23

What is andiodysplasia?

Answer 23

Structural insufficiency of blood vessel (small) generally leads to G.I bleeding

Question 24

What is Hereditary hemmorhagic telangiectasia?

Answer 24

Structural deficiency of blood vessels these can be spotted around the lips and nose.

Question 25

When can a diagnosis on Henoch-Schonlein purpura be made?

Answer 25

When a perpuric rash is associated with fever, malaise, polyarthralgia and colicky abdominal pain. 2.Thought to be an immune mediated vasculitis

Question 26

What kind bleeding would one expect with "production failure" thrombocytopenia?

Answer 26

Superficial/Surface i.e petechiae etc

Question 27

What usually precedes ITP in children.

Answer 27

Viral infection

Question 28

What is the treatment for ITP in children?

Answer 28

Self Limiting, goes away within weeks

Question 29

Is ITP in adults preceded by viral infection?

Answer 29

NO

Question 30

What is the treatment for ITP in adults?

Answer 30

Immunosuppresion

Question 31

What is HIT?

Answer 31

Heparin induce thrombocytopenia

Question 32

What is the pathogenesis of HIT?

Answer 32

1. Antibodies develop to Heparin-PF4 complex 2. Antibody+complex binds to the platelets FC receptor 3. causes platelet activation and aggregation

Question 33

What is the classic presentation for HIT?

Answer 33

1.Thrombosis 2.Thrombocytopenia from increased use of platelets Platelets are the only abnormal cell

Question 34

How can diagnosis be made?

Answer 34

Ru ELISA to test for Heparin-P4 antibody

Question 35

What is (TTP) Thrombotic Thrombocytopenic purpura?

Answer 35

Inherited or acquired deficiency of ADAMTS13 2.Aquired is an IgG antibody against ADAMTS13

Question 36

What is the pathogenesis?

Answer 36

ULVWF not able to be cleaved which binds platelets via Ib+IIb/IIIa which leads to occlusion due to platelet aggregation which leads to microangiopathic anemia

Question 37

What is the presentation of TTP?

Answer 37

1. Renal insufficiency 2. thrombocytopenia 3. Microangipathic hemolytic anemia 4. neurological changes 5. fever

Question 38

What is another blood smear finding indicative of TTP?

Answer 38

Schistocytes Increased LDH

Question 39

What is the treatment for TTP?

Answer 39

Plasma exchange NOT PLATELETS.

Question 40

Injuries around the face of a Haemophiliac are particularly worrisome because?

Answer 40

Continued bleeding into tissue could obstruct the larynx and kill the patient.