Inherited Bleeding Disorders

Question 1

deficiencies that cause bleeding

Answer 1

1,2,5,7,8,9,10,11

Question 2

hemophilia A

Answer 2

deficiency in factor 8

Question 3

hemophilia B

Answer 3

deficiency in factor 9

Question 4

hemophila C

Answer 4

deficiency in factor 11

Question 5

deficiency in factor 13

Answer 5

delayed bleeding. re-bleed much later after first bleed is controlled

Question 6

inherited defects of platelet function (broad)

Answer 6

secretion (granules), recruitment (ADP receptor, TxA2 synthesis), cohesion (Glanzmann), adhesion (VWF)

Question 7

bleeding phenotype associated with platelet defect

Answer 7

petechiae & ecchymoses, epistaxis & menorrhagia, skin & mucus membrane bleeding, immediate bleeding from failure to form platelet plug

Question 8

bleeding phenotype associated with coagulation defects

Answer 8

deep spreading hematomas, hemarthrosis, retroperitoneal bleeding, delayed bleeding when an inadequate fibrin clot breaks down prematurely

Question 9

aggregation study

Answer 9

tests for increased aggregation of platelets and increased secretion (downwards)

Question 10

glanzmann’s thrombasthenia

Answer 10

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

Question 11

von Willebrand factor (VWF)

Answer 11

accessory molecule that sticks platelets to collagen. how rapid moving platelets in arteries are stopped at site of vascular injury

Question 12

deficiency in VWF

Answer 12

bleeding disorder that looks like a platelet defect even though platelets are totally normal. they just won’t aggregate at site of trauma

Question 13

structure of VWF

Answer 13

multimeric protein with genes for factor 8 binding, platelet binding, and collagen binding

Question 14

function of VWF

Answer 14

facilitates platelet adhesion to injured epithelium, binds and carries factor 8 in plasma

Question 15

where is VWF synthesized?

Answer 15

vascular endothelial cells and megakaryocytes

Question 16

what is VWF secreted in?

Answer 16

weibel palade bodies

Question 17

structure of circulating VWF

Answer 17

folded in on itself so that it physically occludes its platelet binding sites. doesn’t spontaneously bind to platelets

Question 18

VWF relationship to Factor 8

Answer 18

VWF stabilizes circulating factor 8 and increases its half life, helping to maintain higher plasma levels. VWF is a carrier of factor 8

Question 19

how is VWF secreted from weibel-palade bodies?

Answer 19

as large multimers

Question 20

what proteolytic enzyme breaks down the ultra large VWF multimers?

Answer 20

ADAMTS13

Question 21

deficiency in ADAMTS13

Answer 21

thrombocytopenic purpura (TTP)

Question 22

TTP

Answer 22

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

Question 23

TTP treatment

Answer 23

plasmaphoresis. steroids, rituximab

Question 24

VWD (von Willebrand’s disease)

Answer 24

autosomal dominant disease in which VWF is deficient. most commonly inherited bleeding disorder. symptoms: bruising easily.

Question 25

type 1 VWD

Answer 25

decreased amounts of normal VWF

Question 26

type 2 VWD

Answer 26

decreased amounts of abnormal VWF

Question 27

type 3 VWD

Answer 27

severely decreased VWF concentration and activity

Question 28

lab tests for VWD

Answer 28

VWF antigen tests, VWF multimer gel electrophoresis, increased aPTT if factor 8 is affected, normal PT

Question 29

VWD treatment

Answer 29

DDAVP (vasopressin receptor agonist) causes release of VWF from endothelial cells & antifibrinolytic agents

Question 30

hemophilia inheritance

Answer 30

x linked recessive

Question 31

hemophilia clinical symptoms

Answer 31

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

Question 32

factor 8 deficiency

Answer 32

hemophila a

Question 33

factor 9 deficiency

Answer 33

hemophilia b

Question 34

tests for hemophilia

Answer 34

prolonged aPTT, specific factor assays,

Question 35

treatment for hemophilia

Answer 35

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