Clotting Cascade Flashcards
What factors make up the extrinsic clot pathway?
VII
X
II (thrombin)
fibrinogen–> fibrin
What factors are invovled in the Intrinsic pathway?
PK to XII
XI
IX
X (and VIII)
II (and V)
fibrinogen–> fibrin
What is the role of Vit K in the clotting cascade?
(glutamate—>carboxylated–> glutamic acid) and need it to make
X, IX, VII, and II
PC and S
diSCo in 1972
Where do the two pathways meet?
at factor X
intrinsic has IX activate X
Extrinxic has VII activate X
What is the partial thromboblastin time a measure of? (aPTT)
What is the Pro-Thrombin time measuring?
aPTT measure of the intrinsic pathway
PT measures the extrinsic pathway
High Molecular Weight Kininogen deficiency Prekallikrein deficiency
- *FXII** deficiency
- *FXI** deficiency
- *FIX** deficiency
- *FVIII** deficiency
Passovoy Deficiency
Lupus anticoagulant
All cause
Isolated prolongued aPTT
What causes isolated PT pronlongation?
Factor FVII defiency
What can cause both a prolongued aPTT and PT
FX deficiency
FV deficiency
FII deficiency
Fibrinogen deficiency
What can cause a long TCT
Dys/hyper/hypo/A fibrinogenima
FDPs, immunoglobins, heparin
What disorders will we see bleeding but they have normal screens
Mild factor deficiency
Thrombocytopenia
Thrombocytopathia Vascular abnormality (scurvy)
FXIII deficiency
Antiplasmin deficiency
Post op 5 yo boy tonsils out, can’t get them to stop bleeding, no sig medical, family hx and ROS no history of bleeding or bruising and normal PE
WBC= 10.1 (nml 5.0-14.0) Hemoglobin = 13.0 g/dL (nml 11.5-15.5)
Platelet count = 210 (nml 150-450)
Prothrombin time= 11 (nml 11-13.5)
INR= 1.0
Activated partial thromboplastin time (PTT)= 41sec (nml 25-32)
next step?
get a Partial thromboplastin time with 1:1 mixing
if it corrects then we know its a cloting factor deficiency
if it doesn’t, we know its some sort of inhibition
How do you manage a pt that has bleeding in the throat that needs to be stopped but you are unsure of the cause of the bleed?
– Assessment of the patient’s airway with intubation if required
– IV fluids
– Type and cross for blood transfusion
– Surgical hemostasis
– Further lab studies
You have a pt with prolonged aPTT of 42 secs (normal is 25-32) which corrected after a 1:1 mixing
What could be cause?
This is factor deficency in the INTRINSIC path
could be : VIII, IX, XI, XII as most likely
What is hemophelia A and how is it inherited?
What about hemophelia B?
Hemophilia is an inherited bleeding disorder in which there is a deficiency or lack of factor VIII (hemophilia A) or factor IX (hemophilia B)
What is the inheritance pattern for hemophelia?
how does it affect males and females?
What is the severity level?
- Hemophilia A and B are X-linked recessive disorders
- Hemophilia is typically expressed in males and carried by females
- Severity level is consistent between family members
- ~30 % of cases of hemophilia are new mutations
What are common complications in pts with hemophelia?
Joint bleeds and hemarthrosis or deep tissue bleeds (non mucocutaneous)
need to use rFVIII prior to procedures
What is a concern when using recomb FVIII?
development of inhibitor (antibody) against VIII
you would see that by performing a 1:1 mix study and the PTT would NOT correct anymore
Describe process of developing antibodies to fVIII or fIX
Polyclonal high affinity IgG Ab that neutralize the procoagulant function of fVIII or fIX
Factor replacement therapy becomes ineffective unless antibody is removed
Most serious complication of factor replacement therapy
Presents major economic and clinical challenges.
• Formation of a fibrin clot (secondary hemostasis) requires initiation of the coagulation cascade by ____ for intrisic and ____through the extrinsic pathway
tissue factor (TF)
factor VIIa
Fibrin clot is propagated by the
instrinsic pathway
Deficiencies in _______ result in prolongation of aPTT with normal PT
factors VIII, IX, and XI
Correction of a coagulation study (aPTT or PT) on a 1:1 mix is diagnostic of
a deficiency of clotting factor
Hemophilia is an ____ disorder
• Bleeding pattern in hemophilia is characterized by :
X-linked
joint, muscle and soft tissue bleeding
