117 Heparin-Induced Thrombocytopenia Flashcards
A complication of heparin therapy that leads to a fall in platelet count and a high incidence of arterial and/or venous thromboembolic complications
Heparin-induced thrombocytopenia (HIT)
Types of HIT
HIT type I: a benign nonimmune condition associated with a mild, immediate, and transient drop in platelet count and no increased risk of thrombosis
HIT type II: the classic immune-mediated prothrombotic disease
HIT antibodies activated both platelets and endothelial cells
Heparin is bound to this platelet-specific chemokine
Platelet factor 4 (PF4, CXCL4)
The most important determinant of risk for HIT
Whether the patient is exposed to unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH)
Table of risk factors
Heparin-Induced Thrombocytopenia Risk Factors
Patient-Specific Factors
* Age (older individuals > pediatrics > neonates)
* Patient population (surgical > medical > obstetric)
* Intervention (cardiopulmonary bypass surgery, hemodialysis, trauma, hip and knee arthroscopy)
* Major trauma > minor trauma
* Sex (female > male)
* Bacterial infection ( urinary tract infection, pneumonia, periodontal/ gingival disease)
Heparin-Specific Factors
* Type of heparin (unfractionated heparin > lowmolecular-weight heparin)
* Duration of heparin (~5 days > shorter courses)
The presence of periodontal/gingival disease, which has been shown to increase the risk of developing naturally occurring anti-PF4/heparin antibodies, has also been linked to an increased risk of developing HIT, with an incidence in affected patients nearly twice as high as the overall rate in hospitalized patients.
Etiology and pathogenesis of HIT
The primary immune response in HIT is nonclassical in that antibodies appear as IgG without IgM precedence or class switching.
The secondary immune response in HIT is also weak and antibodies typically disappear after a few months and may not reappear with heparin reexposure.
A 7.8-kDa protein synthesized by megakaryocytes and packaged into platelet α granules as a tetrameric complex bound to the intracellular proteoglycan serglycin
PF4
Upon platelet activation, PF4 is released into the circulation where it rapidly binds to polyanionic GAGs found on the surface of hematopoietic and vascular cell types.
Anticoagulant that is a synthetic heparin pentasaccharide, is shorter than LMWH and contains fewer negatively-charged side chains
Fondaparinux
It does not form large complexes with PF4,explaining the negligible incidence of HIT with this agent and supporting its potential utility in the prevention or treatment of HIT.
TRUE OR FALSE
Although platelets are central to the pathophysiology of HIT, PF4 interacts with other cells to contribute to the high risk of thrombosis.
TRUE
Although platelets are central to the pathophysiology of HIT, PF4 interacts with other cells to contribute to the high risk of thrombosis.
ULCs form preferentially on monocytes as a result of their high expression of surface heparan sulfate that binds PF4 more avidly than the chondroitin sulfate GAG side chains that predominate on the platelet surface.
Neutrophils, which may be affected directly by HIT antibodies,PF4/heparin immune complexes, or cross-talk with activated platelets, become incorporated into thrombi where they can release NETs that contribute to thrombus growth by capturing red cells and platelets.
The clinical hallmark of HIT
Development of thrombocytopenia after a proximate heparin exposure
The combination of thrombocytopenia and heparin exposure in hospitalized patients is common and has poor specificity for HIT.
Other clinical clues must be sought to estimate the clinical likelihood of developing HIT:
- Timing
- Degree of platelet count fall
- Nadir platelet count
- Presence of thromboembolism or hemorrhage
- The likelihood of other causes of thrombocytopenia
The platelet count in HIT characteristically begins to fall ______ days after initial heparin exposure
5–10 days
Exceptions to this rule:
* Rapid onset HIT: 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
* Delayed-onset HIT: clinical manifestations develop a median of 10–14 days after heparin is discontinued
Both delayed-onset HIT and spontaneous HIT occur in the absence of circulating heparin and are termed
Autoimmune HIT
May exhibit atypical clinical features including more severe or prolonged
How is the percentage fall in platelet count measured
From the peak platelet count after initiation of heparin to the nadir platelet count
TRUE OR FALSE
The nadir platelet count is approximately 60 X 109/L and rarely falls below 20 X 109/L in the absence of concomitant DIC.
TRUE
The nadir platelet count is approximately 60 X 109/L and rarely falls below 20 X 109/L in the absence of concomitant DIC.
Most patients with HIT see a 50% or greater fall in platelet count; a more modest decline (30–50%) occurs in approximately 10% of patients
Thus, as opposed to other forms of drug-induced immune thrombocytopenia, the decrease in platelet count in HIT is characteristically mild or moderate.
TRUE OR FALSE
The nadir platelet count in HIT needs to meet the traditional definition of thrombocytopenia (<150 x 109/L).
FALSE
The nadir platelet count in HIT does not need to meet the traditional definition of thrombocytopenia: less than 150 x 109/L
The most common thrombotic manifestations of HIT
Lower-extremity deep vein thrombosis and pulmonary embolism
Outnumbering arterial events by approximately 2:1
Thromboembolism is the presenting feature in up to 25% of patients with HIT and develops in half of all cases.
TRUE OR FALSE
Spontaneous hemorrhage is common in HIT, specially when thrombocytopenia is severe.
FALSE
Spontaneous hemorrhage is rare in HIT, even when thrombocytopenia is severe.
Although the risk of bleeding is lower in HIT than other immune thrombocytopenias, the prothrombotic nature of HIT is not protective against hemorrhage
Clinical scoring system for HIT composed of:
* Thrombocytopenia
* Timing
* Thrombosis or other sequelae
* Other causes of Thrombocytopenia
4T score
Scores of 0–3, 4–5, and 6–8 are classified as low, intermediate, and high probability, respectively.
