Platelet disorder can cause microhemorrhage and result in which of the following: petechiae, purpura, epistaxis
All three! Basically think continuous bleeding because platelet can’t adhere to the subendothelial layer
T/F: hemarthrosis (bleeding into joints) and muscle hematomas are present in primary hemostatic disorders
False; these are signs of secondary hemostasis which results in delayed deep bleeding. Vs Primary hemostasis results in prolonged bleeding time and PE shows petechiae and purpura
Which glycoprotein has the function of stabilizing Factor VIII in the circulation, maintaining it inactive and protecting it from proteolytic degradation?
Von Willebrand Factor
vWF also mediates platelet adhesion to damaged subendothelium via Gp1b
vWF is stored in _____ in the _____ cells
Weibel-Palade bodies
Endothelial cells
What do weibel-palade bodies store?
Store and release vWF and P-selectin
In von Willebrand disease, which clotting factor is affected and how is PT/PTT time changed, if any?
Factor VIII decreases
vWF decreases
Bleeding time increased
PT is normal
PTT is either unchanged or increased (PTT is intrinsic, and factor VIII is involved in that pathway)
What is inheritance pattern of von Willebrand disease?
Autosomal dominant
High variability of penetrance
How does von Willebrand disease cause platelet and coagulation defect?
Low vWF cannot adhere platelets to site of endothelial injury
Low vWF cannot protect factor VIII
What is Bernard-Soulier syndrome?
Large platelets which leads to increased bleeding time and thrombocytopenia
What causes the mutation in Bernard-Soulier syndrome?
Mutations in the GP1b gene in which vWF cannot bind to
What is changed, if any, in PT and PTT in Bernard-Soulier syndrome?
PT and PTT usually normal
No clotting factors affected here, just platelets cannot adhere to injury so no platelet aggregation causing increased bleeding time
What is the inheritance pattern of Bernard-Soulier syndrome?
Autosomal recessive
Large platelets bleeding disorder? Think:
Bernard-Soulier syndrome
In what two organelles is the vWF processed through?
ER and golgi apparatus
Which platelet disorder fail/have abnormal ristocetin assay?
Von Willebrand disease and Bernard-Soulier syndrome
Which platelet disorder fails platelet aggregation test with addition of either ADP, collagen , epinephrine or arachidonic acid?
Glanzmann thrombasthenia
What is Glanzmann thrombasthenia?
No platelet aggregation with normal platelet count due to mutations in GpIIb-IIIa integrin receptor preventing platelet to platelet aggregation
What is GPIIb-IIIa, and when the gene coding for it is mutated, what results?
It is receptor for fibrinogen and vWF, which aids in platelet activation
Mutation of it leads to Glanzmann thrombasthenia
What is inheritance pattern of Glanzmann?
Autosomal recessive
T/F: all three of these congential coagulation disorder have autosomal recessive inheritance pattern
False; von Willebrand disease is autosomal dominant while the other two are autosomal recessive
How is GPIIb-IIIa activated?
By ADP, epinephrine, collagen, arachidonic acid or thrombin will activate this receptor which will lead to platelet aggregation
von Willebrand disease having to do with _____, Bernard-Soulier syndrome having to do with _____, and increased ______ time, with decreased ______. Glanzmann thrombasthenia is mutation in ______, which leads to platelet aggregation problem, leading to increased ____ time.
