CLINICAL NEWS
HIT or Miss: Is a Gel Immunoassay Better Than the 4Ts Score?
A fraction of patients taking the
anticoagulant heparin will develop
heparin-induced thrombocytopenia
(HIT) – an adverse drug reaction
caused by IgG platelet-activating
antibodies that bind to platelet factor
4-heparin (PF4-H) complexes on
platelets’ surfaces that can trigger
devastating venous and arterial
thromboembolic complications.
Rapidly determining whether
or not a patient has HIT is critical in identifying patients who can
continue to receive heparin or who
need alternative anticoagulation
therapies. The current standard for
this determination is the 4Ts score,
which rates patients’ likelihood of
developing HIT based on four criteria: thrombocytopenia, timing of
platelet count fall, thrombosis, and
other potential causes of thrombocytopenia. The ASH Choosing Wisely®
campaign recommends not testing
or treating for suspected HIT in
patients who have a low 4Ts score,
based on its high negative predictive
value (99.8%).
According to a team of Canadian
investigators, though, a low 4Ts
score may be insufficient to exclude
HIT; instead the researchers, led by
lead investigator Lori-Ann Linkins,
MD, of McMaster University in
Hamilton, Ontario, have developed
an alternative algorithm that rules
TABLE 2.
out HIT,” the researchers wrote.
Dr. Linkins’ group conducted
a prospective management study
in 526 patients suspected of having
HIT (mean age = 66.5 years) who
presented at one of four hospitals
from January 2008 to February 2013.
All patients were evaluated for their
4Ts score, then underwent a PF4-H/
PaGIA test and the standard test that
evaluates for HIT, the serotoninrelease assay (SRA).
While waiting for the SRA
results to either confirm or rule
out HIT, all participants, including those with a low 4Ts score
(regardless of PF4-H/PaGIA result)
or intermediate 4Ts score plus a
negative PF4-H/PaGIA result,
received alternative anticoagulant
therapy: prophylactic danaparoid or
fondaparinux (26.2%), danaparoid
or fondaparinux therapeutic dose
(13.5%), argatroban (1.9%), and
“other” (i.e., warfarin, rivaroxaban;
2.7%). After SRA results were returned, patients with confirmed HIT
continued to be treated with one of
these alternative anticoagulant strategies, while those with negative SRA
results were switched to heparin.
Thirty-two patients (6.1%) were
confirmed HIT-positive (based on a
positive SRA result). The frequency
of SRA-confirmed HIT according
to heparin exposure was 4.9 percent
A positive PF4/H-PaGIA result,
on the other hand, increased the
pretest probability of HIT to 15.4
percent (95% CI 5.9-30.5%), 42.3
percent (95% CI 23.4-63.1%), and
88.2 percent (95% CI 63.6-98.5%) in
each of the groups, respectively.
Based on these results, Dr.
Linkins and colleagues developed
a treatment algorithm to guide
therapy according to 4Ts score and
PF4/H-PaGIA result (TABLE 2).
The primary outcome of the
study was the frequency of management failure, defined as SRA-based,
HIT-positive patients who had one
of the following combinations of
results: low 4Ts score and negative
PF4/H-PaGIA result, low 4Ts score
and positive PF4/H-PaGIA result, or
intermediate 4Ts score and negative
PF4/H-PaGIA result. Six patients
(1.1%) were identified as management failures – all of whom had a
low 4Ts score and a positive PF4-H/
PaGIA result. Reasons for failure
included incorrect 4Ts scor H[