Defects of Coagulation mechanism Flashcards
What are the 3 main types of bleeding disorders?
acquired platelet defects
inherited bleeding disorders
acquired coagulopathy
What is hemostasis?
process that prevents blood loss form damaged blood vessels
What is thrombosis?
pathological formation of a ‘hemostatic’ plug within the vascularture in the absence of bleeding
(excesive hemostasis)
What important factor is needed for platelet adhesion? Receptor?
vWF
GPIbalpha
What important factor is needed for platelet aggregation? Receptor?
Fibrinogen
GPIIb/IIIa
What is contained in dense granules in the platelet?
ADP, ATP
seratonin
calcium
What does calcium release lead to?
integrin activation
granule secretion
What are the 2 binding domains on vWF?
Gp1b
GPIIb/IIIa
What does binding of vWF with GP1b cause?
braking/activation of the platelet
What does binding of vWF ith GPIIb/IIIa cause?
arrest of the platelet
What does platelet granule release lead to?
signals other platelets
What does platelet membrane coagulant expression lead do?
thrombin and clot
Initiation phase of cell based coagulation
activaion of IXa & Xa
Xa converts II to IIa (thrombin)
Amplification phase of cell based coagulation
thrombin activated Va, VIIIa, XIa and platelets
Propagation of cell based coagulation
IXa catalyzing further thrombin formation
XIa augments by driving further IXa formation
Thrombin driven pahse of cell based coagulation
transformation of fibrinogen to fibrin and cross linking
What are the vitamin K dependent pro coagulant factors?
II, VII, IX, X
What are the vitamin K dependent anti coagulant factors?
Proteins C & S
What does thrombin activate?
Fibrinogen to fibrin
Factor XIIIz
TAF1
What does an intrinsic pathway deficiency lead to?
increased PTT
What does an extrinsic pathway deficiency lead to?
increased PT
What enzymes are important for the fibrinolytic system?
t-PA
Plasminogen
alpha-antiplasmin
D-dimer
What does active protein C do?
proteolysis of factors Va and VIIa
What does mucosal bleeding usually indicate?
platelet defect of vWF
What does deep tissue bleeding usually indicate?
factor deficiency
Generalized oozing at venipuncture sites is indicative of?
DIC
What are screening tests done for platelet phase problems?
platelet count
PFA-100
What are screening tests done for coagulation phase problems?
PT
PTT
Fibrinogen
Inhibitor screening (1:1 mix)
How do we check for quantitative defects of platelets?
peripheral blood film
Vit B12, PF4 ELISA
What causes decreased platelet production?
vit B12 deficiency
marrow failure or disease
What are peripheral destruction syndromes that can cause thrombocytopenia?
DIC (non-immune) Immune -Fab mediated (ITP) -Non-Fab mediated (heparin induced, TTP) -innate immunity (sepsis)
ITP types and features
childhood-abrupt, viral syndrome, autoantibody to platelet surface glycoproteins, most patients recover
adult-insidious, only 5% spontaneous recovery
both have large platelets
HIT (heparin induced thrombocytopenia) features
immune disease, neo epitope (heparin:PF4) causes transient autoimmune disease (4-14 days into heparin tx)
moderate thrombocytopenia
associated with thrombotic events
confirm w/PF4-Heparin elisa
stop heparin, begin alternate anticoag tx
Thrombotic microangiopathies
microangiopathic blood films
- TTP
- HUS
- DIC
- Sepsis
TTP features
microangiopathic hemolytic anemia thrombocytopenia renal failure mental status change fever ADAMTS13
What is the role of ADAMTS13?
regulates vWF/platelet interaction (cleaves vWF)
How do you treat TTP?
plasma exchange
What does PFA-100 screen for? measure?
screens for platelet and vWF function
measures occlusion time
sensitivity/specificity lower than desireable
What are the functions of vWF?
supports platelet adhesion
carrier for factor VIII
abnormalities lead to long PTT
Screening for vWF disease?
PFA-100
PTT
assay vWF
What is bernard soulier syndrome?
congenital absence of GPIb
platelet function defect
What is Glanzman’s thrombasthenia?
congenital absences of GPIIb/IIIa
platelet function defects
How is a PT test performed?
Tissue factor, phospholipid and Ca2+ are added to citrated plasma and clotting time is measured
What is INR?
normalized PT so that result is comparable across labs
intended for warfarin monitoring
(pts PT/mean normal PT)^ISI
What is the 1:1 mix test?
pt plasma is mixed with normal plasma with all factors, clotting time is performed on mixed sample
if clotting time corrects to normal: factor def likely
if clotting time remains prolonged: “inhibitor” likely
DDX of isolated long PTT?
Factor deficiency inhibitors present (heparin, lupus anticoag, specific factor inhibitor)
DDX of isolated long PT?
Factor deficiency
-VII
_vit K defic, oral anticoag, liver disease
What factors are not tested by screens?
Factor XIII
Anticoagulants (Proteins C&S, factor V leiden)
Prolonged PT and PTT DDX?
factor deficiency (isolated or combo [liver disease, vit K defic, DIC]) inhibitors present (isolated factor inhibitor, drugs, lupus inhibitor)
What factor is deficient in Hemophilia A?
VIII
What factor is deficient in Hemophilia B (christmas disease)?
IX
How is hemophilia inherited?
X linked
Sx of hemophilia?
hemarthrosis & deep muscle bleeds
prolonged PTT (corrects on 1:1 mix)
sx correleate with level
Problems causing vitamin K deficiency?
drugs-oral anticoags (warfarin), antibiotics that decreased bowel flora (less vit K synthesis)
malabsorption or dietary deficiency
liver disease
newborns
What occurs with liver disease in regard to anticoagulation?
deficiency of multiple coag factors -pro: II, VII, IX, X & V -anti:antithrombin, protein C, protein S thrombocytopenia -hypersplenism -decreased TPO production
