RBC II Putthoff, Bleeding Disorders from defective platelet functions Flashcards
What are the classes of inherited disorders of platelet function
defects of adhesion
defects of aggregation
disorders of platelet secretion
What is Bernard Soulier syndrome
defective adhesion of platelets to subendothelial matrix
Where is the defect in Bernard Soulier
glycoprotein complex Ib-IX
R for vWF
What is disorder has bleeding from defective platelet aggregation
Glanzmann thrombasthenia
inheritance of glanzmann thrombasthenia
autosomal recessive
Where is the defect in glanzmann thrombasthenia
dysfunction of glycoprotein IIb IIIA
does not aggregate in response to ADP, collagen, epinephrine, thrombin
disorders of platelet secretion are chanracterized by what
defective release of certain mediators of platelet activation like thromboxane and ADP
what are the 2 significant types of acquired defects of platelet function
aspirin and NSAID caused
related to uremia
what activates fibrinogen to form clots
thrombin
What factors are involved in intrinsic clotting pathyway
XII XI IX
X
thrombin and fibrin
what factors are involved in extrinsic clotting pathway
VII TF
X
thrombin, fibrin
how do most patients with from coagulation factor defects present?
large post-traumatic ecchymoses or hematomas or prolonged bleeding
where are sites of bleeding from factor defect
GI and urinary tracts
weight bearing joints
What are the most common inherited disorders of coagulation pathway
VIII (hemophilia A)
IX (hemophilia B)
vWF
what is characteristic of acquired deficiencies of coagulation factors
multiple factors
decreased protein synthesis or shortened half life
vit K deficiency affects coagulation how
impaired synthesis of factors II, VII IX X and protein C
how does liver disease affect coagulation factors
many are made in the liver
how are coagulation factors affected in DIC
multiple coagulation factors are consumed and deficient
what cause single factor acquired deficiency
autoAb
very rare
Where is factor VIII made
sinusoidal endothelial cells and kupffer cells in the liver
where is vWF produced
endothelial cells and megakaryocytes
what is the role of vWF
binds factor VIII and increases its circulation half life
promotes adhesion of platelets to subendothelial matrix thorugh GpIb-IX
where is vWF stored
alpha granules of megakaryocyts
what is the most common inherited bleeding disorder of humans in US
vWF disease
what are signs of vw disease
mild bleeding
spontaneous bleeding from mucous membranes, excessive wound bleeding or menorrhagia
what is inheritance pattern of vw disease
autosomal dominant but some are autosomal recessive
what else can vWF bind to besides VIII
GpIIb IIIa intefrins
how is vwF measured
ristocetin agglutination test
measured with aggregaometer
What types vw are assoc with quantitative defects in vwF
type I and III
characteristics type I VW disease
autosomal dominant
mild to mod deficiency
describe type III VW disease
autosomal recessive with very low levels vWF and severe manifestations
what causes type 3 VW disease
deletions or frameshift mutations involving both alleles
is type 2 VW disease characterized by quantitative or qualitative defects
qualitative
what is most common subtype type 2 VW disease
2A
inheritance 2A VW disease
autosomal dominant
missense mutations
how common is type 2 VW disease
25% of all cases assoc with mild-moderate bleeding
are platelet counts low in VW disease
no
what will vwD cause a deficiency in
factor VIII levels
are PT and PTT normal in vw D
prolonged PTT in type I and 3
what is Tx for mild vwD
desmospressin which stimulates vWF release
or infusions of VIII and vWF
