CH 117 HEPARIN-INDUCED THROMBOCYTOPENIA Flashcards
The incidence of HIT ranges from
less than 0.1% to 7.0%,
The most important determinant of risk factor for HIT
exposure to unfractionated heparin (UFH) or low-molecular-weight- heparin (LMWH)
Note:
incidence of HIT with UFH and LMWH was 2.6% and 0.2%, respectively.
True or False:
The duration of heparin exposure also influences the risk of HIT.
True
True or False:
Advancing age is a major risk factor for HIT
Advancing age is a major risk factor for HIT with a nearly negligible risk in children and
rising rates in adults with each decade beyond 50 years.
Gender at risk for HIT
Female sex was also found to be a risk factor for HIT.
True or False:
Medical patients have consistently been found to have a higher risk of HIT than surgical or trauma patients.
False
Medical patients have consis- tently been found to have a lower risk of HIT than surgical or trauma patients.
Procedures at greater risk for HIT
CABG, ECMO, LVAD
Patients who require cardiopulmonary bypass (CPB) or other major arterial surgery, heart/lung transplantation, extracorporeal mem- brane oxygenation (ECMO), or ventricular assist devices are among those with an elevated incidence of HIT.
True or False
Infection can increase the frequency of HIT
True
Patient-Specific Factors for Heparin-Induced Thrombocytopenia
1) Age (older individuals > pediatrics > neonates)
2) Patient population (surgical > medical > obstetric)
3) Intervention (cardiopulmonary bypass surgery, hemodialysis, trauma, hip and knee arthroscopy)
4) Major trauma > minor trauma
5) Sex (female > male)
6) Bacterial infection ( urinary tract infection, pneumonia, periodontal/ gingival disease)
Heparin-Specific Factors for Heparin-Induced Thrombocytopenia
Type of heparin (unfractionated heparin > low- molecular-weight heparin)
Duration of heparin
(~5 days > shorter courses)
the only FDA-approved drug for treatment of HIT available in the United States
Argatroban
a hirudin analogue
It is approved for patients with and without HIT undergoing percutaneous vascular procedures.
Bivalirudin
HIT is rare (<0.1%) in pregnant women exposed to heparin.
When it does occur, what is the recommended anticoagulant?
Danaparoid
- does not cross the placenta
- no measurable anti-Xa activity in the cord blood of six neonates who were tested after delivery.
If danaparoid is unavailable, fondaparinux may be considered
- but partial transplacental passage has been demonstrated
True or False
Ongoing heparin exposure during dialysis in patients with a history of HIT is contraindicated.
True - Ongoing heparin exposure during dialysis in patients with a history of HIT is contraindicated.
p 2135
In general, heparin reexposure should be avoided in patients with history of HIT because of the risk of reoccurrence.
An exception to this rule is the use of intraoperative heparin in patients with ______
a history of HIT who are undergoing cardiovascular surgery.
Patients with HIT-associated thromboembolism are typically treated with therapeutic anticoagulation for
3–6 months
True or False:
The optimal duration of anticoagulation in patients with HIT without thrombosis is unknown.
But it generally accepted that anticoagulation be continued in patients with HIT until platelet count recovery.
TRUE (p.2135)
Platelet Transfusion in HIT
T/F
Transfusion may be considered in the setting of clinically significant bleeding, high bleeding risk, or diagnos- tic uncertainty.
TRUE
The HIT immune response wanes over time.
Functional assays become negative at a median of __ days after heparin cessation
Anti-PF4/heparin antibody titers decline more slowly and are no longer detectable in 60% of patients by day ____.
50
100
True or False
Patients with a negative immunologic and functional assay may safely receive UFH during surgery.
True
True or False
Heparin should be avoided in patients with a positive functional assay
True
Appropriate intraoperative anticoagulation of patients with a functional assay that is negative, but an immunologic assay that remains positive:
UNCERTAIN
True or False
Heparin should be discontinued and a nonheparin anticoagulant initiated in patients with an intermediate- or high-probability 4T score until the results of HIT laboratory testing become available.
TRUE
The clinical hallmark of HIT
development of thrombocytopenia after a proximate heparin exposure.
The platelet count in HIT characteristically begins to fall_____days after initial heparin exposure.
5–10
Type of HIT
where patients with heparin exposure in the past 90 days who have recently formed anti-PF4/heparin IgG antibodies, experience a fall in platelet count immediately upon heparin reexposure.
rapid-onset HIT
clinical manifestations develop a median of 10–14 days after heparin is discontinued
delayed-onset HIT
Both delayed-onset HIT and spontaneous HIT occur in the absence of circulating heparin and are termed
autoimmune HIT
These patients present with a thrombotic thrombocytopenic disorder reminiscent of HIT in the absence of recognized heparin exposure.
spontaneous HIT
The percentage fall in platelet count is measured from the peak platelet count _________
after initiation of heparin to the nadir platelet count
The nadir platelet count is approximately ___ × 109/L and rarely falls below 20 × 109/L in the absence of concomitant DIC
60
Most patients with HIT see a ___% or greater fall in platelet count;
50
the most common thrombotic manifestations in HIT
Lower-extremity deep vein thrombosis and pulmonary embolism
T/F
In contrast to other forms of drug-induced immune thrombocytopenia, spontaneous hemorrhage is rare in HIT, even when thrombocytopenia is severe.
True
Rare sequelae of HIT include
anaphylactoid reactions after IV heparin bolus,
transient global amnesia, and
skin necrosis at subcutaneous heparin injection sites
Non-necrotizing erythematous injection site lesions are generally caused by _____hypersensitivity rather than by HIT.
delayed type IV
Components of 4T score
Thrombocytopenia, Timing, Thrombosis or other sequelaeand the likelihood of other causes of Thrombocytopenia
An alternative scoring system for HIT
the HIT Expert Probability (HEP) Score
True or False
Surgical and trauma patients receiving postoperative UFH are classified as high-risk and should have platelet counts drawn every other day
True
Management for Intermediate- or high-risk patients include those receiving postoperative UFH or those receiving LMWH after major surgery or trauma.
platelet counts drawn every 2–3 days from days 4 through 14,
although monitoring should begin earlier in those with heparin exposure in the 30 days preceding surgery or trauma.
detect the presence of circulating anti-PF4/heparin antibodies, irrespective of whether they are able to activate platelets and cause disease
Immunoassays
T/F
False-positive results are common in immunoassays and may result from detection of non- pathogenic anti-PF4/heparin antibodies.
TRUE
T/F
ELISA specificity may be improved by raising the optical density (OD) cutoff. OD is directly associated with the 4T and HEP scores, the like- lihood of a positive functional assay, and the risk of thrombosis.
TRUE
4T score
Scores of
0–3,
4–5,
6–8 are classified as respectively
Scores of 0–3, 4–5, and 6–8 are classified as low, intermediate, and high probability, respectively.9
T/F
All functional assays operate under the same principle: Plasma or serum from HIT patients are incubated with platelets from healthy donors in the presence of UFH and the resulting platelet activation is measured.
True
are more specific than commercial immunoassays because they detect antibodies capable of inducing platelet activation in a heparin-dependent manner
FUNCTIONAL ASSAYS
The prototypical functional assays are the
14C-serotonin release assay (SRA) and
the heparin-induced platelet-activation assay (HIPA).
The various concentrations of heparin and heat-inactivated patient serum are added to washed donor platelets radiolabeled with 14C.
A positive test is signified by heparin-dependent release of 14C-serotonin.
SRA
visualizes plate- let aggregation as an end point
HIPA
True or False
Another limitation of the SRA is that certain drugs can interfere with the test and yield false-positive results, including danaparoid, which impairs the formation of PF4/heparin complexes128 and P2Y12 antagonist, ticagrelor, which blocks platelet activation.
False
Another limitation of the SRA is that certain drugs can interfere with the test and yield false-NEGATIVE results, including danaparoid, which impairs the formation of PF4/heparin complexes128 and P2Y12 antagonist, ticagrelor, which blocks platelet activation.
Current guidelines for the treatment of HIT divide the disorder into five distinct phases: suspected HIT, acute HIT, subacute HIT A, subacute HIT B, and remote HIT.
Patients with _____ are those who are thought to have HIT based on clinical grounds for which confirmatory test results have not yet been obtained.
suspected HIT
Current guidelines for the treatment of HIT divide the disorder into five distinct phases: suspected HIT, acute HIT, subacute HIT A, subacute HIT B, and remote HIT.
Immediately after laboratory testing has confirmed the diagnosis, a patient is said to have _____, a highly prothrombotic phase that lasts until platelet count recovery.
acute HIT
is the interval after platelet recovery during which the functional assay and the immunoassay remain positive
Subacute HIT A
is the phase that occurs after the functional assay becomes negative but the immunoassay remains positive.
Subacute HIT B
PF4/heparinantibodies are no longer detectable by immunoassay
Remote HIT
Dose of Argatroban
Mode of Monitoring
Clearance
Bolus: None
Continuous infusion:
* Normal organ function → 2 mcg/kg/min
* Liver dysfunction (total bilirubin >1.5 mg/dL), heart failure, postcardiac surgery, anasarca → 0.5–1.2 mcg/kg/min
Adjust dose to aPTT of 1.5–3.0 × patient baseline
Hepatobiliary (40–50 min)
Dose of Bivalirudin
Mode of Monitoring
Clearance
Bolus: None
Continuous infusion:
* Normal organ function → 0.15 mg/kg/h
* Renal or hepatic insufficiency → consider dose reduction
Adjust dose to aPTT of 1.5–2.5 × patient baseline
Enzymatic and renal (25 min)
Warfarin and other vitamin K antagonists should not be prescribed as the initial anticoagulant in patients with acute HIT because their use increases the risk of venous limb gangrene as a result of ______
rapidly lowering of protein C and protein S activity
Management
For patients receiving a vitamin K antagonist at the time HIT is diagnosed, the vitamin K antagonist should be
discontinued immediately and its effects reversed with vitamin K.
In subacute HIT A, after the platelet count has recovered to a stable plateau, a vitamin K antagonist may be initiated. Large loading doses (eg, warfarin >5 mg/day) should be avoided.
At this time, many practitioners choose _____ in the treatment of HIT because it is the agent on which most published clinical data are available.
rivaroxaban
in large-scale anticoagulation trials, ____ is the DOAC associated the lowest risk of major bleeding and is commonly chosen in patients with HIT deemed to be at a higher risk of bleeding, including those with recent surgery or with creatinine clearance below 30 mL/min.
apixaban
NCCN Question
Duration of therapy:
HITwithout thrombosis:
HIT with thrombosis:
HITwithout thrombosis: At least 4 weeks (in the absence of serious bleeding risk)
HIT with thrombosis: At least 3 months as indicated for thrombotic event
