Bleeding Disorders Flashcards
What is Haemophilia A?
Factor VIII deficiency, Sex linked recessive, missense or frameshift mutations or deletions
What is Haemophilia B?
Factor IX deficiency
Where is Factor VII synthesized?
Liver and endothelial cells
Which mutation leads to the more severe form of Haemophillia A?
Flip tip inversion in the Factor VIII gene?
What are the clinical features of Haemophilia A?
- Recurrent painful Haemarthroses
- Muscle haematomas
- Can progress to joint deformity
- Prolonged bleeding after dental procedures
- Spontaneous G.I bleeds and haematuria
What are Haemophilic pseudotumours?
Large encapsulated haematomas withh progressive cystic swelling from repeated hemorrhage. Best visualized by MRI
What are the treatments available for haemophilia A patients?
- Bleeding episodes are treated with Factor VIII replacement therapy.
- Recombinant factor VII and plasma derived factor VII preparations are available for clinical use
- 1-Diamino-8-D-Arginine vasopressin (DDAVP) provides an alternative means of increasing the plasma factor VIII level in milder haemophiliacs
What is a side effect of DDAVP?
Antidiuretic action
2.Avoid in the elserly
What recommendation is made to Haemophiliacs?
Have regular conservative dental care.
What is one of the most serious complications with haemophilia treatment?
The development of antibodies to to infused Factor VIII (occurs in 30-40% of patients)
How can the antibody development to infused Factor VIII be countered?
Immunosupression
What is the difference in the synthesis of factor VIII and IX?
Factor IX synthesis is dependent on vitamin K
What test are abnormal in a patient with Haemophilis B.
- PTT
2. Factor IX clotting assay
What is von Willebrand disease?
A disorder in which there are low levels or abnormal function of VWF stemming from a missense mutation or null mutation
Where is VWF produced?
- Endothelial cells
2. Platelets
What are the 2 functions of VWF?
- Promotes platelet adhesion to subendothelium at high shear rates
- It is the carrier molecule for Factor VIII protecting it from premature destruction
What other factor is reduced in von Willebrand disease?
Factor VIII
What is the most inherited bleeding disorder?
Von Willebrand factor disease
What is the usual inheritance patern for Von Willebrand disease?
Autosomal Dominant
Which gender is generally worse affected at a given VWF level?
Women
Lab findings?
1.Factor VIII - Low
2.PTT elevated
3.VWF levels low
.Platelet count normal except intype 2B disease
Is senile purpura a bleeding disorder?
No, comes with aging
What is andiodysplasia?
Structural insufficiency of blood vessel (small) generally leads to G.I bleeding
What is Hereditary hemmorhagic telangiectasia?
Structural deficiency of blood vessels these can be spotted around the lips and nose.
When can a diagnosis on Henoch-Schonlein purpura be made?
When a perpuric rash is associated with fever, malaise, polyarthralgia and colicky abdominal pain.
2.Thought to be an immune mediated vasculitis
What kind bleeding would one expect with “production failure” thrombocytopenia?
Superficial/Surface i.e petechiae etc
What usually precedes ITP in children.
Viral infection
What is the treatment for ITP in children?
Self Limiting, goes away within weeks
Is ITP in adults preceded by viral infection?
NO
What is the treatment for ITP in adults?
Immunosuppresion
What is HIT?
Heparin induce thrombocytopenia
What is the pathogenesis of HIT?
- Antibodies develop to Heparin-PF4 complex
- Antibody+complex binds to the platelets FC receptor
- causes platelet activation and aggregation
What is the classic presentation for HIT?
1.Thrombosis
2.Thrombocytopenia from increased use of platelets
Platelets are the only abnormal cell
How can diagnosis be made?
Ru ELISA to test for Heparin-P4 antibody
What is (TTP) Thrombotic Thrombocytopenic purpura?
Inherited or acquired deficiency of ADAMTS13
2.Aquired is an IgG antibody against ADAMTS13
What is the pathogenesis?
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
What is the presentation of TTP?
- Renal insufficiency
- thrombocytopenia
- Microangipathic hemolytic anemia
- neurological changes
- fever
What is another blood smear finding indicative of TTP?
Schistocytes Increased LDH
What is the treatment for TTP?
Plasma exchange NOT PLATELETS.
Injuries around the face of a Haemophiliac are particularly worrisome because?
Continued bleeding into tissue could obstruct the larynx and kill the patient.
