Inherited Bleeding Disorders Flashcards Preview

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Flashcards in Inherited Bleeding Disorders Deck (35):
1

deficiencies that cause bleeding

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

2

hemophilia A

deficiency in factor 8

3

hemophilia B

deficiency in factor 9

4

hemophila C

deficiency in factor 11

5

deficiency in factor 13

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

6

inherited defects of platelet function (broad)

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

7

bleeding phenotype associated with platelet defect

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

8

bleeding phenotype associated with coagulation defects

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

9

aggregation study

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

10

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

11

von Willebrand factor (VWF)

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

12

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

13

structure of VWF

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

14

function of VWF

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

15

where is VWF synthesized?

vascular endothelial cells and megakaryocytes

16

what is VWF secreted in?

weibel palade bodies

17

structure of circulating VWF

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

18

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

19

how is VWF secreted from weibel-palade bodies?

as large multimers

20

what proteolytic enzyme breaks down the ultra large VWF multimers?

ADAMTS13

21

deficiency in ADAMTS13

thrombocytopenic purpura (TTP)

22

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

23

TTP treatment

plasmaphoresis. steroids, rituximab

24

VWD (von Willebrand's disease)

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

25

type 1 VWD

decreased amounts of normal VWF

26

type 2 VWD

decreased amounts of abnormal VWF

27

type 3 VWD

severely decreased VWF concentration and activity

28

lab tests for VWD

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

29

VWD treatment

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

30

hemophilia inheritance

x linked recessive

31

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

32

factor 8 deficiency

hemophila a

33

factor 9 deficiency

hemophilia b

34

tests for hemophilia

prolonged aPTT, specific factor assays,

35

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