test 7 Flashcards

Question

Hepcon vs ACT

Answer 1

use both if available

Answer 2

 Prime ECC with 5 units of heparin per milliliter of pump prime  Initial dose 350-400 u/kg IV  Draw sample for ACT 2 to 5 minutes after infusion  Give additional heparin as needed to achieve ACT above 400 seconds before initiation of bypass  Give additional heparin as needed to maintain ACT above 400 seconds during normothermic bypass  Give additional heparin as needed to maintain ACT above 480 seconds during hypothermic bypass (24o to 30o C)  Monitor ACT every 30 minutes during bypass or more frequently if patient shows heparin resistance

Answer 3

 Heparin binds to platelets  No specific binding site yet determined  Binding decreases with decreased MW (i.e.. LMWH)  Transient decrease in platelet count  Prolonged bleeding time  Insufficient heparinization on bypass causes consumption of clotting factors.  Bleeding Due to heparin rebound

Answer 4

 Need for higher than normal heparin doses to induce sufficient anticoagulation for the safe conduct of bypass.  When more than 600u/kg given and ACT still is <300 seconds

Answer 5

```  ATIII Deficiency  Familial/ Congenital  Acquired  Extreme thrombocytosis  Platelet count > 500,000  Septicemia (rare)  Hypereosinophilic Syndrome (rare)  Nitroglycerin (rare) ```

Answer 6

 Autosomal dominant  1/2000 to 20,000 people  Usually ATIII < 50% normal  Presents @ 15-30 years old with low limb venous thrombosis or Pulmonary Embolism

Answer 7

 Life long antithrombotic therapy after diagnosis  Decreases incidence of thromboembolic events by 65%  Heparin resistance can occur even when therapeutic levels of plasma heparin concentration has been reached  Inability of Heparin to suppress the activity of thrombin

Answer 8

- blocks the thrombin | - if levels low, high thrombin levels leading to more clotting

Answer 9

-They have heparin resistance -they have 60-80% of ATIII than adults because their systems are immature Newborns don’t have thrombotic activity like adults do. Studies show that ATIII levels above 65% are less likely to exhibit embolic events like that which occur when levels reach less than 50% -this is why they don't have problems  @ 3 months: 90% of adult levels  Explains heparin resistance of newborns

Answer 10

 More common than Familial ATIII Deficiency.  Occurs when patients are on Heparin pre-op  Decrease ATIII levels ~5-7%/day  Plateau around 60% of normal

Answer 11

1. Give additional Heparin 2. ATIII supplementation with FFP 3. ATIII supplementation with ATIII concentrate 4. No treatment – just go on bypass

Answer 12

 Account for increased protein binding  Ceiling effect at 4.0 u/mL Higher concentration unlikely to increase ACT further  **Caution  Heparin rebound (Treat with Protamine)

Answer 13

```  2 units Appx 1 unit ATIII / 1 mL FFP 2 units FFP = 500 mL FFP = 500 units ATIII  **Time delay to thaw  **Transfusion risk ```

Answer 14

 Ex: Atryn – recombinant AT, Thrombate – Human purified AT  Sometimes not available due to $$  Offers targeted approach  Less volume  Less transfusion related complications – TRALI

Answer 15

 Fear of sub-therapeutic anticoagulation  Protocol:  Heparin Concentration to 4.0+ or >600 u/kg heparin given  ACT <400 sec Assume ATIII deficiency  Give 500-1000 units ATIII

Answer 16

Heparin Induced Thrombocytopenia

Answer 17

 Clinical condition characterized by a drop in platelet counts to <100,000 or 50% reduction from baseline  Typically occurs between 2-10 days after initiation of heparin therapy, but can be w/in hours.  Seen in 5-28% of patients receiving heparin  Plt counts return to baseline 4 days after d/c heparin  Less common with LMWH, and porcine mucosal

Answer 18

Separate and distinct conditions Type I Type II

Answer 19

 Mild decrease in platelet count  Due to the pro-aggregatory effects of heparin  Normalizes with continued therapy  Appears within first 2 days of exposure to heparin  As long as platelet count isn’t too low, can receive heparin for CPB

Answer 20

```  Aka. The “big hit”  More severe / life threatening  0.5-4% of patients on heparin therapy  Develops w/in 5-10 days, or upon re-exposure to heparin w/in 6 months.  **IMMUNE MEDIATED**  Moderate to severe drop in platelet count  Does not spontaneously resolve  Potentially life-threatening!!! ```

Answer 21

 Heparin exposure -> formation of Antibody (IgG)  Fc part binds to heparin-PF4 complex on surface of platelet  Fab part causes platelet activation , renders hypercoagulable

Answer 22

 Characterized by severe thrombocytopenia (<50,000) and formation of thrombus in 75% of patients  Can lead to stroke, MI, PE, limb threatening ischemia.  Patient history vital in determining re-exposure

Answer 23

 Just because the patient has the antibody does NOT mean they have HIT  MOST patients with HIT antibodies DO NOT have HIT syndrome  Detection of HIT antibodies alone is highly sensitive and specific for HIT, but has a poor positive predictive value

Answer 24

-measures how many antibodies there are

Answer 25

 Functional test (tells you funciton of the antibodies)  Measures what happens to the antibodies in the presence of that heparin platelet factor 4 complex -needs to be used in conjunction with other more sensitive test -slow turn around time

Answer 26

– measures serotonin released by platelets activated by the HIT antibodies  Considered “gold standard”  Expensive, slow turn around

Answer 27

 Newer, quicker than serotonin release assay

Answer 28

- Do they have thrombocytopenia? - timing - how early the onset is gives them a higher score - do they have thrombosis - any other causes for thrombocytopenia

Answer 29

 Consider HIT  Run tests – don’t assume! -Get a hematologist involved!!

Answer 30

 Antibodies become undetectable several weeks after d/c of heparin  Reaction doesn’t occur with every exposure  HIT 1: Can get heparin  HITT 2 with undetected antibodies + 90 days w/o heparin exposure: can get heparin  HITT 2 and a recent exposure to heparin: Heparin alternative OR Profound platelet-inhibiting drug

Answer 31

 Low Molecular Weight Heparins  Defibrinogenating Agents (Not discussing)  Ancrod  Direct Thrombin Inhibitors (don’t require cofactors like ATIII)  Hirudin  Bivalirudin/ Angiomax  Argatroban

Answer 32

 Short heparin chains have lower affinity for platelets (don't have the sequence to bind with thrombin)  Bind less to plasma proteins  Do not bind endothelial cells in culture (less heparin rebound)  Increase bioavailablity  More constant dose-response curve  Reduced ability to inhibit thrombin, but are potent inhibitors of factor Xa.  Longer half life than unfractionated heparin.  110-200 minutes  Renal excretion elimination  Less bleeding complications  Less likely to cause HIT (illicit less immune response)  Problematic for use on bypass b/c Xa inhibition is less responsive to Protamine neutralization than thrombin inhibition.  Hard to measure

Answer 33

o Obtained from salivary glands of leeches o Inhibits thrombin independent of ATIII o Inhibits clot-bound and circulating thrombin o T1/2 = 30-60mins with normal renal function o Renal Clearance o Ecarin Clotting Time (ECT) required for monitoring. Values of 300s have been shown to be adequate for CBP o Bolus followed by continuous infusion (b/c half life is so short) -doesn't need a cofactor

Answer 34

 Also a direct thrombin inhibitor like Hirudin  Synthetic derivative of Hirudin  Binds fluid and clot-bound thrombin  Enzymatic action cleaves thrombin and bivalirudin -cleaves itself so you don't need to worry about reversal agents  Inhibits activity of bivalirudin  Constant infusion  T1/2 ~ 24min  need to avoid stasis in CPB circuit and patient (chest cavity)  Linear dose response to ACT’s up to 300s  MINIMUM ACT 2.5x baseline accepted as therapeutic

Answer 35

 Inhibits thrombin by only binding to it’s catalytic site  Approved for use on HIT patients  Inhibits circulating and clot bound thrombin  Half life of 40 minutes  Liver metabolism  Good for RI patients -good for renal dysfunction -problems with bleeding and clotting in the same patient because it inhibits some activity and activates others

Answer 36

DON’T USE HEPARIN!!! | -CPD instead

Answer 37

 Whole blood clotting time accelerated by using celite or kaolin activator (XII, XI)

Answer 38

o When a baseline value is correlated to an ACT, this concentration can be an anticoagulation endpoint since it is not affected by outside values

Answer 39

o Tests Intrinsic coagulation pathway (VIII, IX, XI) | o Very sensitive to heparin. Not useful during CPB

Answer 40

o Tests extrinsic pathway (VII) o Normal values ~ 10-13s o Less sensitive to heparin

Answer 41

o Specific for common pathway o Normal values are <17s o Sensitive to effects of heparin

Answer 42

o Quantity only – NO functional testing

Answer 43

o Product of clot lysis