Bleeding Disorders Flashcards
genetics of vWF
autosomal dominant
vWF function
tethers platlets to subendo in vascular injury–>localizes and holds factor 8 to site of injury
vWF type 1
most common
low levels of vWF activity
vWF type 2
normal levels of vWF protein, but reduced activity due to abnormal molecule or decreased high molecular weight multimers
vWF type 3
absent vWF activity
aspirin and bleeding disorder
makes it worse!
lab testing in vWF
prolonged aPTT but normal PT
decreased or normal factor VIII fx
prolonged PFA-100
abnormal ristocetin test
DDAVP
desmopression;synthetic vasopression
stimulates release of vWF and favtor VIII from endothelial cells
good for type I, but not really type II because if no functional protein doesnt matter if you pump out more
other treatments for vw def
vw factor replacement- humate P, alphanate, cryoprecipitate
antifibronlytic therapy
contraceptives
medic alert bracelets
x linked recessive hemophilia
hemo A
hemo B
autosomal recessive hemophilia
hemo C
parahemophilia
heterozygotes of hemo
will have low levels but will generally not bleed (except maybe C)
hemo A
factor VIII def
hemo B
factor IX def (christmas disease)
hemo C
factor XI def
parahemophilia
factor V def
factor levels for different severities
mild: 5-40%
moderate 2-5%
severe: less than or equal to 1%
joint disease in hemophilia
bleeding into joing–>Fe causes synovial proliferation–> chronic synovitis–>arthritis–>joint destruction
labs in hemo
aptt prolonged
treatment of hemo
coagulation factor concentrations on demand
prophylaxis to reduce bleeding episodes
complications with hemophilia
chronic arthropathy
infectious diseases- hiv, hep c
inhibitors to missing coag factors (can complicate treatment)
Coagulation Factor Inhibitor disease
acquired hemophilia- spontaneous autoantibody to factor VIII
lab studies in aquired hemophilia
aPTT will be prolonged, but will NOT correct with mixing study
bethesda assay is used to measure antibody titer: if less than or equal to 5 BUs, may correct temporarily
treatment methodology of bleeding disorders
treat bleeding and do something about antibody
if low BU titer,
treat with high doses of factor VIII concentrate
if titer high
treat with bypass agent
–recombinant factor VII, FEIBA, porcine factor VIII
you can also do this for acquired hemophilia
immunosuppresion
hereditary fibrinolytic defects
deficient inhibitors
overexpression of plasminogen activator
deficinet inhibitor diseases
alpha 2 antiplasmin
plasminogen activator inhibitor deficiency
overexpression of plasminogen activator
quebec platelet disorder
acquired fibrinolytic defects
cancer
liver disease
DIC
local relase plasminogen activators from prostate surgery
lab results of fibrinolytic diseases
prolonged PTT and PT
increased d-dimers
treatment of fibrinolytic disorders
supportive with plasma infusions antifibrinolytic drugs (if NO DIC)
antifibrinolytic drugs
epsilon aminocaproic acid
tranexamic acid
DIC labs
prolonged PT, aPTT
elevated d-dimers
decreased fibrinogen, platlet count, rbcs, antithrombin, protein c, protein S
presence of schistocytes
treatment DIC
plasma to replace coagulation factors and anticoagulants
cryoprecipitate (to replace fibrinogen)
platelets, RBC
**heparin will stop DIC, but may lead to bleeding
liver disease parameters
bleeding due to decreased synthesis of coagulation factors, fibronlytic factor inhibitors
clotting due to decreased clearance of activated coagulation factors
liver disease labs
prolonged PTT and PT, but this doesnt correspond with bleeding
low factor levels except VIII
treatment of liver disease
transplant; everything else is only temporary
vitamin K is required for
gamma-carboxylation of coagulation factors which improves coagulation factor binding to phospholipid surface of platelet
ways to get vitamin K def
dietary-poor intake, malabsorption due to pancreatic or small-bowel disease, alcoholism
medications
warfarin!
lab studies vitamin k def
prolonged PT, PTT factor 2, 7, 9, 10 decreased normal 5 (so we know it's not liver disease)
treatment vitamin k def
give vitamin K
fresh frozen plasma can get you out of a quick bind, but not long lasting
must give vitamin K concurrently because
short half life of factor VII in plasma
