Inherited Bleeding Disorders Flashcards
deficiencies that cause bleeding
1,2,5,7,8,9,10,11
hemophilia A
deficiency in factor 8
hemophilia B
deficiency in factor 9
hemophila C
deficiency in factor 11
deficiency in factor 13
delayed bleeding. re-bleed much later after first bleed is controlled
inherited defects of platelet function (broad)
secretion (granules), recruitment (ADP receptor, TxA2 synthesis), cohesion (Glanzmann), adhesion (VWF)
bleeding phenotype associated with platelet defect
petechiae & ecchymoses, epistaxis & menorrhagia, skin & mucus membrane bleeding, immediate bleeding from failure to form platelet plug
bleeding phenotype associated with coagulation defects
deep spreading hematomas, hemarthrosis, retroperitoneal bleeding, delayed bleeding when an inadequate fibrin clot breaks down prematurely
aggregation study
tests for increased aggregation of platelets and increased secretion (downwards)
glanzmann’s thrombasthenia
fibrinogen receptor deficiency (alpha2beta3) resulting in a failure of platelet aggregation. autosomal recessive bleeding disorder. causes easy bruising, epistaxis, menorrhagia, requires platelet transfusions before surgery
von Willebrand factor (VWF)
accessory molecule that sticks platelets to collagen. how rapid moving platelets in arteries are stopped at site of vascular injury
deficiency in VWF
bleeding disorder that looks like a platelet defect even though platelets are totally normal. they just won’t aggregate at site of trauma
structure of VWF
multimeric protein with genes for factor 8 binding, platelet binding, and collagen binding
function of VWF
facilitates platelet adhesion to injured epithelium, binds and carries factor 8 in plasma
where is VWF synthesized?
vascular endothelial cells and megakaryocytes
what is VWF secreted in?
weibel palade bodies
structure of circulating VWF
folded in on itself so that it physically occludes its platelet binding sites. doesn’t spontaneously bind to platelets
VWF relationship to Factor 8
VWF stabilizes circulating factor 8 and increases its half life, helping to maintain higher plasma levels. VWF is a carrier of factor 8
how is VWF secreted from weibel-palade bodies?
as large multimers
what proteolytic enzyme breaks down the ultra large VWF multimers?
ADAMTS13
deficiency in ADAMTS13
thrombocytopenic purpura (TTP)
TTP
autoantibodies to ADAMTS13. prothrombotic state. small clumps of platelets because they spontaneously stick to each other when exposed to large VWF multimers that don’t require the typical shear forces and anchoring that typically activates platelets
TTP treatment
plasmaphoresis. steroids, rituximab
VWD (von Willebrand’s disease)
autosomal dominant disease in which VWF is deficient. most commonly inherited bleeding disorder. symptoms: bruising easily.
type 1 VWD
decreased amounts of normal VWF
type 2 VWD
decreased amounts of abnormal VWF
type 3 VWD
severely decreased VWF concentration and activity
lab tests for VWD
VWF antigen tests, VWF multimer gel electrophoresis, increased aPTT if factor 8 is affected, normal PT
VWD treatment
DDAVP (vasopressin receptor agonist) causes release of VWF from endothelial cells & antifibrinolytic agents
hemophilia inheritance
x linked recessive
hemophilia clinical symptoms
CNS bleeding, pharyngeal, most commonly in joints. spontaneous bleeding episodes and excessive bleeding following surgery, dental procedures, or trauma. delayed bleeding due to normal platelets but premature clot dissolution
factor 8 deficiency
hemophila a
factor 9 deficiency
hemophilia b
tests for hemophilia
prolonged aPTT, specific factor assays,
treatment for hemophilia
episodic infusion of clotting factor in response to bleeding episodes, prophylaxis, plasma derived factor concentrates, recombinant 8,9 & 7(drives thrombin production circumventing 8,9), gene therapy
