Understanding Heparin Induced Thrombocytopenia (HIT) / Test 3/3 Flashcards
1
Q
Heparin was discovered by
A
1916 Dr. Maclean
2
Q
Heparin is a member of heterogeneous family of
A
glycosaminoglycans
3
Q
Molecular weight of Heparin ?
A
3,000 - 30,000 daltons
4
Q
Heparin is negatively charged, binds to a variety of ?
A
Plasma Proteins
5
Q
Synthesized endogeneously and stored in basophilic granules of __________ cells. (High concentrations in lung & intestines)
A
Mast
6
Q
Product Sources:
Porcine ?
Bovine ?
A
Porcine = Intestines Bovine = Lungs
7
Q
Does renal nor hepatic dysfunction have any significant effect on heparin elimination?
A
No
8
Q
Heparins primary action is to bind reversibly to natural circulating ?
A
ATIII
1,000-4,000 fold acceleration
9
Q
What happens Following the blockade and inactivation of thrombin ?
A
heparin is released
10
Q
Heparins Limited anticoagulant action is that it is unable to dissolve an ?
A
Existing thrombus directly
11
Q
Heparins Effectiveness occurs immediately, how long after the heparin bolus do we test ?
A
3 min
12
Q
Heparin is associated with what ?
A
Deranged platelet function
13
Q
HIT is a result of what ?
A
Immune and non-Immune responses.
14
Q
In regards to heparin and inflammation, heparin can bind to what ?
A
chemokines,
cytotoxic peptides, &
tissue destructive enzymes
15
Q
In regards to heparin and malignancy ?
A
Heparin contains Anti metastatic action
16
Q
Inhibition of adrenal aldosterone which is generated by heparin may produce what?
A
hyperkalemia
17
Q
In regards to heparin and metabolism, Heparin activates what ?
A
lipoprotein lipase
18
Q
Abnormal thyroid function tests may occur with
A
heparin admistration
19
Q
Long-term heparin therapy can cause the development of what?
A
osteoporosis
20
Q
Studies find that this heparin preparation is more likely to yield immune HIT.
A
Bovine Lung
21
Q
Many cases of HIT could be avoided simply by usingwhat?
A
porcine GUT UFH
22
Q
Prophylactic dose
Therapeutic dose
Flushes
Heparin-coated devices
Fall under what type of heparin ?
Associated Incidence of HIT?
A
Unfractionated Heparin
Highest
23
Q
Prophylactic dose
Therapeutic dose
Fall under what type of heparin ?
Associated Incidence of HIT?
A
Low Molecular Weight Heparin
Medium
24
Q
Pentosan polysulfate
Hypersulfated chondroitin sulfate
PI-88 (anti-angiogenic drug)
Fall under what type of heparin ?
Associated Incidence of HIT?
A
Highly sulfated polysaccharides
Low
25
Clinical events associated with HIT include:
-Venous thromboembolism
-Arterial thromboembolism
-Skin lesions
-Disseminated Coagulation
(DIC)
26
DVT and pulmonary embolism are strongly associated with ?
HIT (1,2,)
27
Arterial thromboembolic events include ?
peripheral arterial occlusion, acute myocardial infarction, and stroke.
28
The ratio of venous to arterial thrombotic events in a large retrospective study of serologically confirmed HIT was approximately
4:1
29
Pulmonary embolism occurred in about ___ of all patients diagnosed with HIT, which was more frequent than all arterial thrombotic events combined
25%
30
Skin lesions associated with HIT include?
Skin necrosis and/or erythematous plaques
31
Acute Systemic reactions associated with HIT include?
Acute inflammatory – fevers, chills
| Cardiorespiratory – hypertension, tachycardia
32
For the last 60 years, heparin has been widely used as an anticoagulant drug for the treatment and prevention of thromboembolic disorders
during CPB & Cath Lab procedures. Heparin may cause what?
Immune thrombocytopenia (a reduction in platelet count), or HIT
33
HIT can cause ___ threatening thromboses
Life or Limb
34
HIT Type 2 also known as ?
- White Clot Syndrome &
| - Heparin-associated thrombocytopenia (HAT)
35
If heparin-dependent antibodies are detectable, this tell the perfusionist what?
HIT Type 2
We need to dig a little further to see if this will be a problem .
36
Non-immune heparin-associated thrombocytopenia
| Also known as what ?
HIT Type 1
| (non-immune) HAT
37
Denotes absence of heparin-dependent antibodies and the potential role for other factors in causing thrombocytopenia
non-immune HAT
AKA
HIT Type 1
38
Denotes demonstrable role of heparin in “inducing” thrombocytopenia (ie, heparin-dependent antibodies are detectable)
HIT Type 2 patient
39
Clinical Conditions/Causes of Non-immune
| Thrombocytopenia (HIT Type 1 )?
-Septicemia/Inflammation
-Disseminated intravascular
coagulation
-Thrombotic thrombocytopenic purpura
40
Clinical Conditions/Causes of Immune
| Thrombocytopenia (HIT Type 2 )?
```
Alloimune:
- post-transfusion purpura
Drug-induced:
-Prothrombic (heparin),
-Prohemorrhagic (quinine, quinidine, gold, sulfa antibiotics, rifampin, vancomycin, NSAIDs, many others)
```
41
HIT Type 1 Characteristics:
```
Frequency:
Timing of onset:
Nadir platelet count:
Antibody mediated:
Thromboembolic sequelae:
Treatment:
```
```
Frequency: 10 - 20%
Timing of onset: 2 - 3 days
Nadir Platelet count: 100,000
Antibody mediated: No
Thromboembolic sequelae: none
Treatment: Observe patient
```
42
HIT Type 2 Characteristics:
```
Frequency:
Timing of onset:
Nadir platelet count:
Antibody mediated:
Thromboembolic sequelae:
```
```
Frequency: 1 - 3 %
Timing of onset: 5 - 10 days
Nadir Platelet count: 10,000 - 20,000
Antibody mediated: yes
Thromboembolic sequelae: 30-80%
```
43
Treatment for HIT Type 2 ?
Discontinue heparin by all routes, select other anticoagulation, adjunctive therapy.
44
What to do During HIT Type I and Cardiopulmonary Bypass ?
- Continue Heparin if indicated.
- Patients with non-immune HAT are asymptomatic; platelet counts should return to normal during continuation of heparin therapy.
- No additional risk of thrombosis
45
Frequency of HIT related to Bovine Lung?
1.9 - 30.8%
46
Frequency of HIT related to Porcine intestines?
1.3 - 8%
47
Frequency of HIT related to full dose heparin?
0 - 30%
48
5 T’s …. Approach to diagnose HIT
1.) Thrombocytopenia = >50%
2.) Timing = 5-14 days after
starting heparin
3.) Thrombosis (unusual thromboembolism, skin lesions, anaphylaxis)
4.) OTher cause not apparent
5.) Test for HIT antibodies is
positive
49
HIT is a clinicopathologic syndrome, i.e. the diagnosis is based on both
clinical and laboratory prerequisites:
50
HIT antibody seroconversion occurs as a result of
heparin exposure
51
Recent exposure to heparin (within ~100 days) may be associated with a more rapid response and is usually associated with ?
persistence of the HIT antibodies
52
HIT antibodies may develop in patients who do not develop the HIT Syndrome, i.e.
thrombocytopenia +/- thrombosis
53
Patients with HIT seroconversion without thrombocytopenia or other clinical sequelae should
not be diagnosed as having HIT
54
Although in occurs much less frequently in patients receiving low molecular weight heparins (LMWH) the possibility of the diagnosis must always be considered particularly in those patients who may have received ?
unfractionated heparin in the past
55
What must we monitor in all patients receiving heparin ?
Platelet counts.
Changes in platelet count should increase the level of suspicion and the intensity of observation for evidence of occult thrombosis increased
56
Extension or failure of the thrombotic to respond during prescribed heparin therapy should also raise the possibility of ?
HIT
57
It is essential that the diagnosis is confirmed early in the process by specific HIT serology if possible but the management decision to suspend heparin therapy and institute substitution antithrombotic therapy should ?
not be delayed for this if there is strong clinical confirmation of the diagnosis
58
5 Clinical events associated with HIT:
Venous Thrombosis ?
30 - 70%
- (DVT)
- (PE)
- Adrenal necrosis (adrenal
vein thrombosis)
- Cerebral venous (sinus)
thrombosis
- Venous limb gangrene (VKA
associated)
59
3 Clinical events associated with HIT:
Arterial Thrombosis ?
15-30%
- Limb artery thrombosis
- Stroke
- Myocardial infarction
60
Clinical events associated with HIT:
Skin lesions at heparin injection sites ?
10%
Skin necrosis
Erythematous plaques
61
Clinical events associated with HIT:
| Acute reactions after i.v. heparin bolus ?
10%
62
Clinical events associated with HIT:
| Disseminated intravascular coagulation (DIC) ?
10%
63
The following Acute Systemic Reactions can occur in patients sensitized to heparin within 5–30 minutes:
```
Fever, chills
Tachycardia, hypertension
Flushing, headache
Chest pain, dyspnea
Nausea, vomiting, large-volume diarrhea
Sudden Anaphylactic shock
Transient global amnesia
```
64
Heparin interacts (mild activation) with platelets causing release of proteins (chemokines) including ______from alpha granules
PF4
65
PF4 & heparin form an antigen complex which induces the formation of anti-heparin-PF4 complex IgG antibodies that bind to
FcIIa (gamma) receptors on platelet surface membrane
66
Binding causes strong platelet activation and release of
| ______ that promotes thrombin formation.
Microparticles
67
Microparticles are
intensely procoagulant
68
HIT antibodies also bind to endogenous PF4-endothelial
| heparan-sulfate complexes (endo activation) which leads to what ?
Increased amounts of Thrombin
69
Thrombin = platelet aggregation =
cross linking w/fibrinogen
70
14C-serotonin-release assay (SRA) &
The Heparin-induced Platelet Aggregation Assay (HIPAA)
Sensitivity % ?
Early Thrombocytopenia Specificity %
Late Thrombocytopenia Specificity %
Sensitivity: 90%
Specificity (%)
Early Thrombocytopenia: > 95%
Late Thrombocytopenia: 80-95%
71
Platelet-rich plasma (PRP) aggregation
Sensitivity % ?
Early Thrombocytopenia Specificity %
Late Thrombocytopenia Specificity %
Sensitivity: 35-85%
Specificity (%)
Early Thrombocytopenia: 90%
Late Thrombocytopenia: 82%
72
PF4 Antigen Assays
Sensitivity % ?
Early Thrombocytopenia Specificity %
Late Thrombocytopenia Specificity %
Sensitivity: > 90%
Specificity (%)
Early Thrombocytopenia: > 95
Late Thrombocytopenia: 50-93%
73
This assay can detect IgG, IgM, and IgA antibodies with a sensitivity of approximately 80-90% (5,6).
Sensitivity is less than 100% because the test does not recognize antigens other than
PF4 Antigen Assays
heparin-PF4 complex
74
Combination of:
Heparin-induced platelet activation assay &
PF4 antigen EIA
Sensitivity:
Early Thrombocytopenia:
Late Thrombocytopenia:
Sensitivity: 100%
Early Thrombocytopenia: > 95%
Late Thrombocytopenia: 80-97%
75
How should Cardiac surgery in patients with previous HIT episode be addressed ?
- Delay surgery until the (transient) antibodies are undetectable. (usually decline to zero in 100 days.
- Use UFH, but avoid pre-operative heparin completely.
- Remove any heparin-coated products from circuitry
76
Bypass pharmacology options while pumping a patient with HIT ?
```
- Argatroban : Dorect thrombin
inhibitor
- Iloprost : prostacyclin analog,
reversibly inhibits platelet
aggregation.
- Lepirudin: leach saliva;
Monitor ECT
```
77
defibrinogenating agent (pit viper venom)
Ancrod
78
Danaparoid sodium
(hepariniod)
79
Prostacyclin Analogues
Act as natural vasodilators
| Inhibit platelet aggregation
80
Advantages of Prostacyclin Analogues ?
-Platelet activation blocked in
patients with HIT
-Short half-life (15–30 minutes)
permits ease of control
81
Disadvantage of Prostacyclin Analogues ?
Adverse reactions, such as hypotension, may limit usefulness
82
Treatment of HIT should be initiated before?
laboratory confirmation
