HIT Flashcards
HIT results from an autoantibody directed against endogenous platelet factor 4 (PF4) in complex with heparin, it Usually requires exposure of _____ for several days
heparin
HIT’s autoantibody activates platelets and can cause _____.
catastrophic arterial and venous thrombosis
mortality rate of HIT
2-20%
Once HIT antibodies bind to PF4 on platelet surface, their Fc region is captured by Fc receptors on surface of same or adjacent platelets.
This creates a positive feedback loop of further ______.
platelet activation
HIT: Thrombocytopenia is Mainly caused by ?
removal of IgG-coated platelets by macrophages of the reticuloendothelial system (e.g., spleen, liver, bone marrow)
HIT: Thrombosis potential causes
o Release of procoagulant substances from activated platelets
o Release of platelet microparticles (i.e., fragments derived from the platelet membrane) that can catalyze clot formation
o Endothelial cell activation
o Endothelial cell injury induced by binding of HIT antibodies to heparan sulfate on endothelial cell surfaces, leading to increased tissue factor and thrombin generation
o Endothelial cell release of adhesion molecules (e.g., interleukin-6, von Willebrand factor)
o Activation of monocytes by HIT antibodies
o Alteration of other aspects of the coagulation cascade by HIT antibodies (e.g., reduced generation of activated protein C)
what heparin dose is needed for HIT to occur?
HIT can occur with any heparin dose, schedule, and administration route
Ultralarge complexes form most efficiently with what kind of heparin?
unfractionated heparin
HIT IS Reported in up to WHAT PERCENT of patients exposed to heparin for more than four days?
5%
Risk factors for HIT
Ð UFH (~3%) v. LMWH (<1%) in surgical patients (not proved in medical patients) Ð Higher doses Ð Female gender Ð Surgery Ð Older age
most common manifestation of HIT
thrombocytopenia
thrombocytopenia occurs when platelet count is
<150,000/microL or
A platelet count drop of >50% of baseline
is bleeding common with Thrombocytopenia
- Bleeding is rare because the platelet count nadir typically does not drop below 20,000/microL
HIT- Thrombocytopenia Onset typically occurs _____ after the initiation of heparin therapy
5 to 10 days
Early onset of HIT (i.e., thrombocytopenia within the first 24 hours of exposure) may be seen if the patient has been exposed to heparin in the previous one to three months and has circulating______.
HIT antibodies
- The resolution of thrombocytopenia following withdrawal of heparin typically occurs within__.
7 days
Delayed-onset HIT: rarely (but with increasing frequency) thrombocytopenia and thrombosis can occur___ after heparin has been withdrawn (need thorough medication history in patients developing S/Sx)
1-2 weeks
HIT: Thrombosis
Occurs in up to what percentage of individuals with HIT
50%
Common sites of venous thrombosis include______.
leg veins, cardiac vessels, and skin
Arterial thrombosis has been reported in the ______.
heart, central nervous system, limbs, and internal organs
- Complications of thrombosis include ?
skin necrosis, limb gangrene (sometimes requiring amputation), and organ infarction
Acute systemic anaphylactic reactions have been described in patients with HIT, and these can be fatal. Affected patients may have what symptoms?
fever, respiratory compromise, and/or hypertension
HIT: Monitoring
- Frequent (daily or every 2d) PLT count
- If at high risk ) then enzyme immunoassays for antibodies to PF4-heparin complexes or heparin-dependent platelet activation can be ordered
- EIAs should be ordered before treatment if patient is high risk but should NOT delay therapy
____ has the potential to prevent thrombotic events, which are the major cause of morbidity and mortality in patients with HIT
early intervention
HIT: Treatment Overview
- Stop and avoid all heparin products- forever
- Give a non-heparin alternative anticoagulant
- Postpone warfarin pending substantial PLT count recovery
- Test for HIT antibodies
- Investigate for lower limb DVT
- Avoid prophylactic PLT transfusion
To reduce thrombotic complications, administer a different, non-vitamin K-dependant anticoagulant such as _______.
argatroban, bivalirudin, or fondaparinux until PLT >150/mcL
Warfarin should not be used as the initial anticoagulant since warfarin therapy may increase the risk of?
increase the risk of venous limb gangrene in patients with deep vein thrombosis through its rapid lowering of protein C levels
Warfarin should be started in a patient with HIT only when both of the following have been accomplished
o The patient has been stably anticoagulated with an alternative anticoagulant
o The platelet count has increased to at least 150,000/microL
- The starting dose of warfarin should be a low maintenance dose of ≤5 mg/day rather than a high initial or loading dose (e.g., ≥10 mg/day), to minimize the transient hypercoagulable state induced by the rapid decline in______
protein C levels
Warfarin must be monitored by the prothrombin time (PT) with international normalized ratio (INR)
The target range for anticoagulation should be an INR in the range of ___ to ____.
There should be a minimum of ___ of overlapping therapy before the alternative anticoagulant is discontinued
2.0 to 3.0
5 days
- Patients diagnosed with HIT based on clinical and laboratory data should avoid ____ for life
heparin
Sources of heparin include
o Heparin flushes (e.g., for arterial lines or heparin locks)
o Heparin-bonded catheters
o Heparin-containing medications (e.g., some forms of prothrombin complex concentrates [PCCs])
o LMWHs (e.g., enoxaparin, dalteparin, tinzaparin) and UFH
