8. Coagulapathies Flashcards by Jennifer Cromwell

what is the most common hereditary bleeding disorder?

vWD. 1% of population.

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Type 1, 2, 3, acquired vWD: what is most common?

Type 1

How well did you know this?

Not at all

Perfectly

what pattern/type of bleeding is most common with vWD?

muco-cutaneous. epistaxis, gums, bruising

How well did you know this?

Not at all

Perfectly

PT, PTT tests normal or abnl with vWD?

PT normal

PTT can be normal or prolonged

How well did you know this?

Not at all

Perfectly

Platelet function tests abnl or nl with vWD?

abnormal. prolonged PFA-100, prolonged bleeding time, abnl aggregation with stimulation by ristocetin

How well did you know this?

Not at all

Perfectly

what is DDAVP? what does it do?

desmopressin.

stimulates release of vWF and FVIII from endothelial cells

How well did you know this?

Not at all

Perfectly

how is DDAVP delivered?

intranasally or by IV.

How well did you know this?

Not at all

Perfectly

should we use DDAVP in Type 2 vWD?

NO because you’d just stimulate release of more abnormal/nonfunctional platelets

How well did you know this?

Not at all

Perfectly

will DDAVP work for Type 3 vWD?

no, you don’t have any vWF at all. give replacement factor.

How well did you know this?

Not at all

Perfectly

in the female carrier state of hemophilia A of B, what symptom is common?

menorrhagia

How well did you know this?

Not at all

Perfectly

Mild Hemophilia A: factor level? PTT? bleeding?

factor level: 5-40%
PTT may be normal
bleeding with trauma, surgery

How well did you know this?

Not at all

Perfectly

Moderate Hemo A: factor level? PTT? bleeding?

factor level: 2-5%
PTT prolonged
bleeding sometimes spontaneous

How well did you know this?

Not at all

Perfectly

Severe Hemo A: factor level? PTT? bleeding?

factor level: <1%
PTT prolonged
bleeding: spontaneous = common

How well did you know this?

Not at all

Perfectly

why may bleeding be delayed in Hemophilia?

can form primary platelet plug, cannot form secondary coagulation/stabilization

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

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