Coag U4 - Hemorrhagic Disorders

Question 1

hemorrhage

Answer 1

excessive bleeding that needs medical or physical intervention

Question 2

localized bleeding

Answer 2

bleeding from one location, like from an injury, infection, or tumor

Question 3

what are some examples of localized bleeding?

Answer 3

ineffective sutured surgical site or arteriovenous malformations (AMV)

Question 4

generalized bleeding

Answer 4

bleeding from multiple sites, spontaneous/recurring bleeds, or hemorrhaging that needs physical intervention

Question 5

what is an example of generalized bleeding?

Answer 5

disorders relating to primary or secondary hemostasis

Question 6

mucocutaneous hemorrhaging

Answer 6

bleeding in the skin or at a body orifice

Question 7

what are some examples of mucocutaneous bleeds?

Answer 7

petechiae, purpura, ecchymoses, defects of primary hemostasis

Question 8

anatomic hemorrhaging

Answer 8

bleeding in the soft tissue, muscles, joints, or deep in the tissues

Question 9

what are some examples of anatomical bleeds?

Answer 9

after minor trauma, dental extractions, surgery
internal bleeds within the joints, body cavities, muscles
defects of secondary hemostasis

Question 10

what is the difference between congenital and acquired bleeding disorders?

Answer 10

congenital is genetic, the first sign is bleeding from the umbilical cord
acquired develops after a disease or physical trauma

Question 11

in order, what are the most common congenital deficiencies?

Answer 11

VWF, factor 8 (hemophilia A), factor 9 (hemophilia B)

Question 12

trauma-induced coagulopathy (TIC)

Answer 12

accounts for most instances of fatal hemorrhage

Question 13

what is the first coag factor that decreases activity in liver disease?

Answer 13

factor 7

prolonged PT is an early marker for liver disease because it is sensitive

Question 14

what does decrease in factor 10 mean?

Answer 14

another marker for liver disease

more specific indicator because it is not vitamin K dependent

Question 15

what would the presence of fibrinogen mean in liver disease?

Answer 15

increases in early mild liver disease and is an acute phase reactant

Question 16

dysfibrinogenemia

Answer 16

fibrinogen coated with excessive sialic acid, fibrinogen functions poorly

Question 17

what would you expect to happen to VWF, factor 8, factor 13 in liver disease?

Answer 17

will be unaffected or elevated in mild/moderate liver disease, are acute phase reactants

Question 18

what do the presence of factor 10 and factor 12 do in liver disease?

Answer 18

helps in differentiating liver disease from vitamin K deficiency

both factors are decreased in liver disease
factor 10 - normal in vitamin K deficiency
factor 12 - decrease in vitamin K deficiency

Question 19

what test confirms dysfibrinogenemia?

Answer 19

reptilase time test

Question 20

what is chronic renal failure associated with?

Answer 20

associated with PLT dysfunction and mucocutaneous bleeding

PLT adhesion and aggregation are suppressed

Question 21

dialysis

Answer 21

temporarily activates PLTs and improves PLT function

Question 22

desmopressin acetate

Answer 22

increase VWF multimers which aids PLT adhesion and aggregation

Question 23

coumadin/warfarin

Answer 23

disrupts enzymes involved in vitamin K activation of coag factors

Question 24

what does proteins induced by vitamin K antagonists (PIVKA) do?

Answer 24

inactivate factors 2, 7, 9, 10, and proteins C, S, Z

Question 25

how does vitamin K deficiency lead to bleeding issues?

Answer 25

activates coag factors → fibrin → fibrin clot

Question 26

what is autoanti-factor 8 most commonly seen in? what is it also known as?

Answer 26

acquired hemophilia, a factor inhibitor

Question 27

what are some notable associations with acquired hemophilia?

Answer 27

patients older than 60 associated with RA, IBD, SLE patients prescribed immunosuppressive therapy those who experience sudden and severe bleeding in soft tissues, GI, genitourinary tract

Question 28

type 1 VWD

Answer 28

quantitative deficiency makes up 40-70% of VWF cases - therefore most common mild to moderate systemic bleeding and menorrhagia

Question 29

type 2 VWD

Answer 29

qualitative VWF abnormalities (five types 2A, 2B, 2M, 2N, 3) VWF function consistently reduced

Question 30

in VWF, how do CBC and PT and PTT play a role?

Answer 30

CBC - rules out thrombocytopenia PT and PTT - assess coag cascade to rule out other coag factor deficiencies

Question 31

VWF: RCo

Answer 31

add to patient plasma → unfolds the VWF molecule and reduces repelled negative charges → HMW-VWF multimers bind reagent PLT membrane GPIb/IX/V receptors

Question 32

VWF: Ag assay

Answer 32

most important in VWF lab profile EIA methodology, LIA/Stago methodology, CLIA technology

Question 33

factor 8 assay

Answer 33

markedly reduced in VWF (for subtype 2N)

Question 34

what will lead to VWF collagen-binding (VWF:CB) assay?

Answer 34

poor reproducibility of VWF: RCo

Question 35

hemophilias

Answer 35

deficiencies associated with anatomic soft tissue bleeding the second most common congenital bleeding disorder mostly occurring in males

Question 36

what is hemophilia A a deficiency for?

Answer 36

factor 8, aka Classic hemophilia

Question 37

why does factor 8 deficiency lead to hemorrhagic results?

Answer 37

it significantly slows the coag pathway’s production of thrombin

Question 38

structure of factor 8

Answer 38

two-chained, 285,000-Dalton protein translated on the X chromosome

Question 39

normal function of factor 8

Answer 39

thrombin cleaves factor VIII → B domain large polypeptide is released → calcium-dependent heterodimer is left behind that detaches from VWF to create the tenase complex → massive activation of factor X

Question 40

genetics of hemophilia A

Answer 40

located on the X chromosome affected males will experience anatomic bleeding female carriers/heterozygotes do not experience bleeding approximately 30% of newly diagnosed patients have no family history of hemophilia A

Question 41

what are the genotypes of an carrier mother and an unaffected father?

Answer 41

25% unaffected daughter 25% carrier/heterozygote daughter 25% unaffected son 25% affected/hemophilic son

Question 42

what are the genotypes of an unaffected mother and an affected (with hemophilia A) father?

Answer 42

50% carrier/heterozygote daughters 50% unaffected sons

Question 43

anatomical bleeds of hemophilia A

Answer 43

deep muscle and joint hemorrhages, hematomas, wounds oozing after trauma or surgery, bleeding into CNS, peritoneum, GI tract, and kidneys

Question 44

diagnosing newborns

Answer 44

perform lab testing on babies with mothers that have a history of hemophilia abnormal bleeding (easy bruising, bleeding from umbilical stump, hematuria, intracranial bleed) is suspicious for hemophilia

Question 45

complications with hemophilia A

Answer 45

debilitate and progressive musculoskeletal lesions and deformities neurologic deficiencies leading to intracranial hemorrhage

Question 46

in hemophilia A, what do the screening tests look like?

Answer 46

PT, FBG, TT - normal PTT - prolonged

Question 47

hemophilia A therapy/treatment

Answer 47

use self-administered desmopressin acetate (DDAVP) "on-demand" treatment - raise FVIII activity when a patient suspects a bleed or anticipates a hemostatic challenge

Question 48

Nijmegen-Bethesda assay (titer)

Answer 48

quantitative inhibitor

Question 49

which population is most affected by hemophilia A and why?

Answer 49

males because they only have one X chromosome, making them more likely to be affected

Question 50

what is hemophilia B a deficiency for?

Answer 50

factor 9, aka Christmas Disease

Question 51

pathophysiology of hemophilia B

Answer 51

reduces thrombin production, causing soft tissue anatomic bleeding

Question 52

lab tests of hemophilia B

Answer 52

PT, FBG, TT - normal PTT - prolonged

Question 53

treatment of hemophilia B

Answer 53

purified factor 9 concentrates, repeat doses every 24 hours

Question 54

in what percentage of patients have inhibitors?

Answer 54

3%

Question 55

what is hemophilia C a deficiency for?

Answer 55

factor 11, aka Rosenthal syndrome

Question 56

facts about hemophilia C

Answer 56

autosomal dominant mild to moderate bleeding symptoms more than half cases seen in Ashkenazi Jews

Question 57

lab tests of hemophilia C

Answer 57

PT - normal PTT - prolonged

Question 58

treatment of hemophilia C

Answer 58

frequent plasma infusions

Question 59

VWF primary function

Answer 59

mediate PLT adhesion to subendothelial collagen in areas of high flow rate and shear force

Question 60

review question: which factors are associated with the intrinsic pathway?

Answer 60

XII, XI, IX, VIII

Question 61

review question: which factors are associated with the extrinsic pathway?

Answer 61

VII

Question 62

review question: which factors are associated with the common pathway?

Answer 62

I, II, V, X