B3-068 Big Case: Hemophilia Flashcards
1
Q
quantitative types of vWD
A
1 and 3
2
Q
qualitative types of vWD
A
type 2
3
Q
platelet plug
A
primary hemostasis
4
Q
fibrin meshwork stabilized by cross linking
A
secondary hemostasis
5
Q
extrinsic pathway
A
tissue factor
factor VII
6
Q
intrinsic pathway
A
prekallikrein
HMWK
XII
XI
IX
VIII
7
Q
common pathway
A
X
V
II (prothrombin)
I (fibrinogen)
8
Q
fibrin stabilization
A
XIII
9
Q
PFA-100 screens for
A
primary hemostasis
-vWF
-platelets
10
Q
PTT screen for
A
intrinsic pathway
-XII, XI, IX, VIII
11
Q
PT screens for
A
extrinsic pathway
VII, tissue factor
12
Q
D-dimer screens for
A
fibrinolysis
13
Q
skin/mucosal bleeds indicates issue with
A
primary hemostasis
14
Q
purpura, petechiae, ecchymosis indicate issue with
A
primary hemostasis
15
Q
spontaneous bleeding indicates issue with
A
primary hemostasis
16
Q
bleeds into soft tissue, muscle, joints indicate issue with
A
secondary hemostasis
17
Q
hemarthrosis indicates issue with
A
secondary hemostasis
18
Q
bleeding with trauma indicates issue with
A
secondary hemostasis
19
Q
acquired factor deficiencies
secondary hemostasis
A
liver
DIC
vitamin K deficiency
20
Q
factor inhibitors
secondary hemostasis
A
lupus anticoagulant
heparin therapy
specific factor inhibitors
21
Q
factor VIII comes from the
A
liver
22
Q
half life of unbound VIII
A
2.4 h
23
Q
half life of factor VIII if bound to vWF
A
12 hrs
24
Q
VIII is a cofactor for
A
factor IX
form Xase complex
25
VIII is a cofactor for
factor IX
| form Xase complex
26
factor VIII can be measured via
PTT
FVIII clotting assay
27
vWF comes from
endothelial cells and megakaryocytes
28
vWF can be measured via
PFA-100 (screen)
vWF antigen (quantify)
vWF activity (quality)
29
hemophilla A is caused by decreased
factor VIII
30
hemophillia B is caused by decreased
factor IX
31
hemophilia A is [more/less] common than B
more
32
Hemophilia A and B inheritance pattern
X linked recessive
33
30% of hemophilia A and B are caused by
new mutations, no family hx
34
spontaneous or traumatic bleeding into joints, soft tissue, or muscle
hemophilia A/B
35
hemophilia A and B can cause life threatening bleeding into
CNS, oropharyngeal space, retroperitoneal space
36
self-limited hematuria
hemophilia A/B
37
contractures, joint deformaties secondary to hemarthrosis
hemophilia A/B
38
hemophilia can be diagnosed via
prolonged PTT
decreased factor VIII or IX level
| extent of prolongation does not correlated with factor level
39
only way to distinguish hemophilia A from B
decreased factor VIII or IX level
40
disease severity of hemophilia is associated with
residual factor level
41
severe hemophilia
<1%
| risk of spontaneous bleeding
42
moderate hemophilia
1-5%
43
mild hemophilia
6-30%
| usually only have bleeds in relation to trauma
44
what products should never be used to treat hemophilia
cryoprecipitate
45
leading causes of death in hemophilia patients prior to 1980s
HIV and HCV
| due to transfusion with contaminated blood products
## Footnote
exceedingly rare now
46
treatment for hemophilia
factor VIII or IX concentrates
supportive: DDAVP, antifibrinolytics
| DDAVP increases vWF, severe will not respond to this
## Footnote
DDAVP=desmopressin
47
Dose calculation for factor VIII concentrate
(target FVIII level- baseline FVIII level) x body weight (kg) x 0.5 (unit/kg)
48
dosing for factor VIII concentrate
twice daily or continuous
49
dose calculation for factor IX concentrate
(target FIX level- baseline FIX level) x body weight (kg) x 1 (unit/kg)
50
dosing for factor IX concentrate
once daily or continuous
51
target factor levels for primary prophylaxis
1%
52
target factor level: surgical prophylaxis
100% for 7-10 days, then tapered based on risk of bleeding
53
target factor level: mild bleeding
30-50% for several days
54
target factor level: severe bleeding
100% for several days
55
incidence of antibodies to FVIII
5-10% of all cases
20% of severe cases
56
incidence of antibodies to FIX
3-5% of all cases
57
risk factors for FVIII or FIX inhibitors
severe deficiency
family hx
african descent
large gene deletions or rearrangements
intensive therapy
58
hemophilia due to inhibitors shows a
lack of response to therapeutic dose of factor concentrates
59
hemophilia due to factor inhibitors will develop ..... in life
early
60
laboratory testing of hemophilia inhibitors
PTT 1:1 mixing study
bethesda assay
61
<5 BU
low responder
62
.>10 BU
high responder
| more difficult to treat, use bypass agents like FVIIa to activate X
63
1 BU
amount of inhibitor that neutralized 50% factor activity at 2 hr
64
management of acute bleeding in low responders
high dose recombinant human or porcine factor concetrate
65
management of acute bleeding in high responder
bypass agents (prothrombin complex concentrates) or recombinant factor VIIa
| bypasses need for FVIII and FIX, but extremely difficult to titrate
66
treatments for inhibitor reduction in hemophilia
immune tolerance induction
immunosuppression, anti CD20 (rituximab)
| not super effective
67
FXII, HMWK, prekallikrein deficiencies cause
prolonged PTT but no bleeding tendency
68
FXI deficiency causes
variable bleeding tendency
| depends on severity of mutation
69
combined FV and FVIII deficiency is caused by
lack or dysfunction of chaperone protein
70
hemophilia A is due to deficiency in factor
8
71
in hemophilia A, deficiency of factor 8 risrupts the
intrinsic and common pathways
| causes decreased factor X
72
hemarthroses
hemophilia A
73
dental procedures could cause hemorrhage
hemophilia A
74
hemophilia A leads to prolonged [PT/PTT]
PTT
75
desomopressin can be used to treat
hemophilia A
| induces platelets and endothelial cells to release factor 8
76
inheritance pattern: hemophilia
X linked recessive
77
hemophilia B is due to deficiency of
factor IX
78
SLE can be associated with
hemophilia B
79
factor deficiencies that show **no bleeding tendencies**
Factor XII
HMWK
prekallikrein
80
inherited clotting disorders are generally
uncommon
81
deficiency of common factors is more likely to impact [PTT/PT]
PTT
82
when treating factor deficiencies, always opt for ...... as they are not infectious
concentrated producted
| blood products are more commonly infectious
83
Factor VIII catalyes the reaction of
FX to FXa
84
screening test for VIII deficiency
PTT
85
definitive test for FVIII deficiency
FVIII clotting assay
| normal 50-150%
86
screening test for vWF deficiency
PFA-100
87
in type 2 vWD, the patient will have low levels of
VIII
| 2.4 hour half life without vWF
88
how would you distinguish vWD normandy (type 2) from FVIII deficiency?
vWF normandy is autosomally inherited
FVIII is X linked recessive
89
hemophilia is symptomatic at ....% functionality
30
90
should hemphilia be excluded from the differential without family hx?
no; 30% of hemophilia cases are caused by de novo mutations
