Thrombolytic Agents

Question 1

What population is most affected by thromboembolic events?

Answer 1

neonates; most affected age group with an incidence of 41:100k per year

Question 2

What are indications for prophylaxis thrombolytic agent use in children?

Answer 2

central venous catheters, prosthetic heart valves, blalock-taussig shunt, endovascular stents, fontan procedure, atrial fibrillation, continuous arteriovenous hemofiltration, hemodialysis, ECMO and kawasaki dz

Question 3

What are indications for treatment with thrombolytic agent use in children?

Answer 3

DVT, PE, arterial thromboembolism, venous thromboembolism and nonhemorrhagic stroke

Question 4

what are the typical events in the NICU requiring intervention by a thromblytic agent?

Answer 4

catheter does not function, cannot infuse/draw from line; less commonly, thromboembolic phenomenon is due to an inherited or acquired thrombophilia

Question 5

what is an example of an inherited thrombophilia disease state?

Answer 5

heterozygous factor V protein C or protein S deficiency

Question 6

what is an example of an acquired thrombophilia disease state?

Answer 6

CMV is a rare cause of neonatal aortic thrombosis

Question 7

what is the definition of a thrombus?

Answer 7

a BLOOD CLOT formation in an artery or vein. this clot formation can cause partial or complete obstruction

Question 8

what is the definition of an embolus?

Answer 8

a clot that is MOBILE and lodges in a blood vessel. this may cause obstruction or vasospasm

Question 9

what is the definition of a vasospasm?

Answer 9

a muscular contraction of an arterial vessel. cardinal sign: COLOR ∆ in the affected extremity

Question 10

What are the characteristics of color ∆ accompanying vasospasm?

Answer 10

color ∆ is blue or white; may extend to buttocks or abdomen; ∆ may be transient of persistent

Question 11

what can induce color ∆ and vasospasm?

Answer 11

prior injection of medication, a manifestation of a thromboembolism or thromboembolitic phenomena

Question 12

what can be a predisposing factor to vasospasm?

Answer 12

arterial blood sampling

Question 13

what is a cause of venous thrombosis?

Answer 13

indwelling venous catheters or renal vein thrombosis

Question 14

what are the signs and symptoms a/w a venous thrombosis?

Answer 14

the extremities are swollen, discolored, superificial veins are distended

Question 15

what are the signs and symptoms a/w renal venous thrombosis?

Answer 15

hematuria, HTN, thrombocytopenia and/or a flank mass

Question 16

If a pt p/w absent pulses, what diagnosis should you consider?

Answer 16

aortic thrombosis

Question 17

what are the signs and symptoms a/w an arterial thrombosis?

Answer 17

decreased perfusion and color ∆ of the lower extremities, loss of pulses, blood pressure difference between UE and LE, oliguria, HTN and hematuria

Question 18

What is aortic thrombosis with absent arterial pulses considered?

Answer 18

a medical emergency

Question 19

what labs are indicated for a suspected thromboembolic w/u?

Answer 19

thrombin time, PTT, PT/INR, PCV (hct), Plt count, Fibrinogen, genetic tests and CMV r/o

Question 20

what is the most common diagnostic study used?

Answer 20

US; can be unreliable (underestimates # of art/ven throbuses and has a significant # of false positives)

Question 21

when is an US a helpful tool?

Answer 21

to monitor progress of thrombus over time

Question 22

what is the gold standard diagnostic study used?

Answer 22

angiography; performed via umbi line

Question 23

When is a total w/u indicated?

Answer 23

when a thrombus is suspected and dissolving medication used; not necessary in the presence of an independent vasospasm

Question 24

what are the general guidelines in the treatment of a thromboembolic event?

Answer 24

prompt removal of offending catheter (take access into account), tx vol depletion, replete electrolyte abnormalities, sepsis, thrombocytopenia and anemia; evaluate for IVH; s/p major surgery w/i 10d; investigate for other causes of increased bleeding (GI, pulm, intercranial, etc..); anticoag and thromobolytic tx is NOT recommended in these circumstances

Question 25

why is tx with thrombolytic agents controversial?

Answer 25

no studies have been done with preterm infants

Question 26

what are general tx guidelines when administering thrombolytic agents?

Answer 26

maintain plt >50k & fibrinogen >100 md/dL, monitor PT/PTT/Fibrinogen; can administer medications via catheter unless obstructed in which case systemic tx can be used

Question 27

what products are indicated for tx of an infant with a plt count <50k?

Answer 27

plt or cryo tx

Question 28

what is the thrombolytic agent of choice?

Answer 28

recombinant tissue plaminogen activator (rTPA)

Question 29

why has rTPA become the thrombolytic agent of choice?

Answer 29

lowest risk of allergies, shortest 1/2 life and less manufacturing concerns, minimal antigenicity, lack of inhibition by a2-antitrypsin and a local and specific action on plasminogen bound fibrin

Question 30

what is the mechanism of action for rTPA?

Answer 30

enhances the conversion of plasminogen to plasmin, which then cleaves fibrin, fibrinogen, factor V and factor VIII- resulting in clot issolution

Question 31

how should rTPA be administered?

Answer 31

dilute the desired dose in NS to the vol needed to “fill” the catheter; instill into lumen of catheter very slowly and carefully to ensure that the medication is not released into systemic circulation; dwell time is 2-4 hours

Question 32

when is systemic use of rTPA contraindicated?

Answer 32

with preexisting IVH or cerebral ischemic ∆

Question 33

what should be done prior to rTPA use?

Answer 33

correct preexisting HTN

Question 34

what are complications of rTPA administration?

Answer 34

severe bleeding, if central venous catheter is occluded bleeding may occur if excessive use of rTPA reaching systemic circulation, excessive pressure may release clot into circulation; even greater risk of bleeding is on warfarin, indomethacin or heparin

Question 35

what are more recent trends of rTPA use in the NICU population?

Answer 35

infused via cont gtt for lysis of intracardiac or large vessel thrombus; some practices may use concomitant low dose heparin to prevent reoccurence of the thrombus

Question 36

what are complications of continuous rTPA infusion?

Answer 36

IVH, allergic rx (very rare)