8. Coagulapathies Flashcards
what is the most common hereditary bleeding disorder?
vWD. 1% of population.
vWD is synthesized as proteins of how many units? what happens subsequently?
synth as monomers. motidied and turned into mulitmers, then cleaved into multimers of various sizes by ADAMTS13.
three functions of vWD?
- tethers platelets to subendo in vascular injury
- chaperones/protects FVIII in blood, lengthens half-life
- localizes FVIII at site of injury
three categories of vWD?
type 1: low levels of wWD
Type 2: qualitative problem with protein. abnormal structure so doesn’t work well. normal QUANTITY of vWD
Type 3: complete absence of protein
Acquired: antibody against it
Type 1, 2, 3, acquired vWD: what is most common?
Type 1
what pattern/type of bleeding is most common with vWD?
muco-cutaneous. epistaxis, gums, bruising
PT, PTT tests normal or abnl with vWD?
PT normal
PTT can be normal or prolonged
Platelet function tests abnl or nl with vWD?
abnormal. prolonged PFA-100, prolonged bleeding time, abnl aggregation with stimulation by ristocetin
what is DDAVP? what does it do?
desmopressin.
stimulates release of vWF and FVIII from endothelial cells
how is DDAVP delivered?
intranasally or by IV.
should we use DDAVP in Type 2 vWD?
NO because you’d just stimulate release of more abnormal/nonfunctional platelets
will DDAVP work for Type 3 vWD?
no, you don’t have any vWF at all. give replacement factor.
in the female carrier state of hemophilia A of B, what symptom is common?
menorrhagia
Mild Hemophilia A: factor level? PTT? bleeding?
factor level: 5-40%
PTT may be normal
bleeding with trauma, surgery
Moderate Hemo A: factor level? PTT? bleeding?
factor level: 2-5%
PTT prolonged
bleeding sometimes spontaneous
Severe Hemo A: factor level? PTT? bleeding?
factor level: <1%
PTT prolonged
bleeding: spontaneous = common
why may bleeding be delayed in Hemophilia?
can form primary platelet plug, cannot form secondary coagulation/stabilization
what is the biggest problem with the clotting cascade in Hem A or B?
The Thrombin Burst is diminished, can’t make a good fibrin clot.
Labs for Hem A and B: PT? will PTT correct with a mixing study?
PT normal
PTT will correct with a mixing study
Tx of hemophilia?
recombinant VIII and IX
what other treatment might FVIII def respond to?
DDAVP
what is an inhibitor?
antibody to the coag factor that is being replaced.
in what cases is prophylactic factor replacement used with?
severe hemophilia only.
how is an inhibitor treated?
use of bypassing agents, ie FVIIa, trying to drive the extrinsic pathway by mass action.
labs in acquired hemophilia or with an inhibitor: PFA-100, bleeding time? PT? PTT? mixing study? FVIII level?
- PFA and bleeding time will be normal
- PT normal
- PTT prolonged
- mixing study does NOT correct
- FVIII level low
what is fibrinolytic bleeding?
bleeding is delayed (12-24 hrs) because clot/fibrin is broken down prematurely by PLASMIN. bleeding is often mucocutaneous/oropharyngeal
what are some of the causes of fibrinolytic bleeding?
hereditary causes are very rare. more common = cancer, lifer disease, DIC, release of plasminogen factors from prostate surg.
fibrinolytic bleeding: lab results: PT? PTT? D-Dimer?
PT may be prolonged
PTT may be prolonged
D-Dimer may be increased
what is D-Dimer?
breakdown product when plasmin breaks down fibrin (ie clot breakdown)
why is d-dimer elevated in DIC but not disorders of fibrinolysis?
for disorders of fibrinolysis, it is the fibrinogen in the blood that is broken down, not the fibrin in clots. fibrinogen does not yield D-dimer as a breakdown product. with DIC, it is the FIBRIN clots that are broken down. yields D-Dimer.
why is vitamin K deficiency a problem?
it is required for gamma-carboxylation of coag factors, makes coag binding more efficient.
what is the relationship between Vit K and warfarin?
warfarin blocks epoxide reductase, so Vit K is not activated, and coag factors are not gamma-carboxylated, don’t work as well.
generally, what does Vit K def lead to?
bleeding disorder
what does warfarin do?
anticoagulation
labs in Vit K deficiency: PT? PTT? mixing study? platelet function studies? levels of F 2, 7, 9, 10? level of FV?
PT prolonged PTT prolonged mixing study will correct platelet function studies normal 2, 7, 9, 10 levels decreased FV level normal
how can we tell the difference between Vit K def and liver failure?
FV level: normal with Vit K def, and low with liver failure
Treatment of Vit K def?
give Vit K (oral, IV)
fresh frozen plasma + vit K (emergency)
Prothrombin complex: F2, 7, 9, 10
where are coag factors synthesized?
liver
in addn to liver, where is FVIII also synthesized?
vasc endothelial cells. so FVIII preserved with liver dz.
where are fibrinolytic factor inh synthesized?
liver
in general, liver disease results in bleeding or clotting?
bleeding often predominates but there can also be clotting. Forces in both directions, overall clotting diathesis.
in terms of what is happening to synthesis and clearance of factors, liver disease causes what?
liver disease will lead to decr synthesis of anticoagulant and fibrinolytic factors as well as decr clearance of activated coag factors
what anticoag and fibrinolytic factors are synth by the liver?
Protein C, S, antithrombin, plasminogen. also, activated coag factors are cleared by liver
Define DIC
acquired coag disorder that occurs when the normal hemostatic balance is disturbed, primarily resulting in excessive thrombin formation
in DIC, what does intravascular thrombin generation lead to?
conversion of fibrinogen to fibrin in the systemic circulation, activation of platelets
DIC: once fibrinogen has been converted to fibrin in systemic circ and platelets have been activated, what are compensatory reactions?
activation of protein C
incr in plasmin and fibrinolysis
