clotting disorders part 1 Flashcards
What are vitamin K dependent factors
2,7,9 and 10
What is Hemophilia A
congenital factor VIII (8) deficiency: clotting disorder - prolonged time or inability to clot
most common
x-linked recessive disorder - mostly affects males
what are the results of Hemophilia A
lack of factor VIII disrupts the cascade downstream
results in weak platelet plug
leads to weak/delayed fibrin clot
prone to developing antibody inhibitors to exogenous factor VIII
what is Hemophilia B
congenital factor IX (9)
also x-linked recessive (mostly males)
less common them Hem A
no racial differences
what are the results of Hemophilia B
lack of factor IX still disrupts the cascade
also results in weak platelet plug
leads to weak/delayed fibrin clot
AKA Christmas Disease (named after first known)
What is Hemophilia C
Factor XI (11) deficiency
hereditary but not x-linked
M = F
primarily jewish/ashkenazi/eastern european pts
what is the presentation of hemophilia
clinically indistinguishable
characterized by multiple episodes of ‘abnormal’ bleeding
*Hemarthrosis - bleeding into a joint
Mucous membrane bleeding
epistaxis
soft tissue hematomas
hematuria
internal hemorrhages
how is hemophilia worked up
prolonged activated partial thromboplastin time (aPTT)
thrombin time and prothrombin time (PT) / (PT/INR) are normal
definitive diagnosis with specific factor activity assay
what is a higher aPTT and PT/PT/INR indicative of
worse at clotting (higher number) - measure how long it takes to clot
how is hemophilia treated
mainstay is factor replacement with factor concentrate (prevention and treatment)
alternative for Hemophilia A is desmopressin (DDAVP)
- synthetic vasopressin - stimulates vWF production, only for mild to moderate disease- severe does not respond
What is the treatment for patients with hemophilia that develop antibody inhibitors
factor VII concentrate
this bypasses the defunct intrinsic pathway
increase production of factor X from other side - common pathway continues uninterrupted
what are general adjunctive treatments to AVOID in patients with hemophilia
avoid:
NSAIDs, anticoagulants (including ASA), and anti-platelet agents
what is hemophilia health maintenance
prenatal counseling/testing routinely done
primarily for mom with +FH and affected dad
done via gene sequencing on Male offspring
females generally not sequenced (Rare)
need to connect with HTC, travel with documentation
conferences and camps for families
what is Von Willebrands Disease (VWD)
deficiency in vWF
most common inherited coagulation disorder
autosomal dominant and recessive inheritance
M=F (F more symptomatic)
most not diagnosed until adulthood
what is the effect of VWD
vWF main role is to bind factor VIII to extends its half-life
promotes platelet aggregation and adhesion - binds vessel wall at site of injury
also activated factor X
what are the different types of VWD
Type 1, 2 and 3
Quantitative and Qualitative
what is Quantitative VWD
reduced levels of vWF that is present is still functional
Type 1 - autosomal dominant
Type 3 - most severe form - autosomal recessive
what is qualitiative VWD
total vWF levels normal but structure/function is not
Type 2vWFD - mostly autosomal dominant
what is Acquired vWD
secondary to some other disease process
mostly over age 40
Multiple myeloma, lymphoproliferative DO, autoimmune, Malignancy, DM
how is vWD screened
International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH - BAT)
- cant separate between types
- looks at 14 bleeding domains
what is the presentation of VWD
hemarthrosis much more rare*
mucuocutaneous bleeding more prominent*
nose bleeds
easy bruising
heavy menstruation*
GI bleeding
Excessive bleeding with injury/surgery
petechiae/purpura
internal bleeding rare
how is VWD worked up
CBC often to r/o other causes
PT and aPTT often normal (aPTT may be prolonged, factor 8 still present and functional)
definitive diagnosis by looking at clotting factor function
what is the treatment of type 1 VWD
DDAVP (desmopressin)
causes release of stored vWF and factor 8
used for episodic bleeding - with procedures
shouldn’t be given long term due to SE
not everyone responds well - usually evaluate prior to regulat use
what is the treatment of VWD if DDAVP is failed and acute bleeding, undergoing longer procedures or type 3
replacement of vWF
vWF concentrate comes as vWF -containing factor 8 concentrate
