Discussion
The incidence of HIT is estimated to be about 0.1-5% of patients
exposed to heparin. However, despite the low incidence of HIT, it is
considered a life-threatening condition with high morbidity and
mortality, as demonstrated by our case report (11,12). The pathogenesis
of HIT has been researched in depth over the years. It results from
autoantibodies IgG directed against PF4 complexes with heparin.
Thrombocytopenia (Platelets <150000) with or without
thrombosis is the most common feature of HIT, occurring in 90-95% of
patients (10,11,13). 5-10% of patients diagnosed with HIT do not
present with absolute thrombocytopenia, but have relative
thrombocytopenia, which means platelet count drop between 30-50% from
baseline (10).
The 4Ts Pretest probability has been widely implemented in patients with
suspected HIT since 2006 to identify HIT (14,15). It is a point-based
test, with points assigned for thrombocytopenia, the timing of platelet
count drip, thrombosis, and other causes of thrombocytopenia.
Furthermore, this test has high negative predictive values with low
probability scores (9). Our patient’s platelet levels fell from 241 on
day one of heparin exposure to 190 on day ten. Despite this drop, levels
remained above 150 and were less than a 30% drop from admission. Also,
platelets count on day seven, and eight were 271,253 respectively,
contradicting the pathophysiology of HIT that includes platelet
consumption. With a low pretest probability with the 4Ts score and no
initial clinical suspicion for HIT, testing was not indicated nor
recommended (9,15,16). Hence, our patient developed multiple
life-threatening thromboembolic events, including massive occipital
infractions while on heparin, and continued despite its discontinuation.
The error, in this case, was to rely on the high negative predictive
value and sensitivity of low 4T pretesting that could exceed 98% (9).
The reliance on the pretest probability of the 4Ts also deferred the
Hematology and Pharmacy teams from further investigation into HIT. The
medical team did discuss testing for HIT when the anticoagulation
serologies were initially sent. However, they were detracted by the
specialists and pharmacists. Therefore, the discontinuation of heparin
was delayed leading to more fatal thrombosis. In brief, our patient
never had neither absolute nor relative thrombocytopenia, contradicting
current guidelines for HIT.
To our knowledge, limited studies have investigated the occurrence of
HIT without thrombocytopenia. Busche, Marc Nicolai, et al., published in
a case report published in 2009, showed a 26-year-old in a burn ICU who
developed thrombotic events after 13 days of heparin infusion without
thrombocytopenia (17). Heparin was stopped, and the HFP4 test was
positive, later confirmed by ELISA. This finding is consistent with our
report that HIT could occur without a fall in platelet count and could
be associated with major thromboembolic events. However, in this
patient, thrombosis occurred after 13 days of heparin compared to our
case, which occurred within 5-10 days of heparin infusion. In another
case report titled “Heparin associated thrombosis without
thrombocytopenia,” Phelan Brian demonstrated a 64-year-old who
developed a series of thromboembolic complications after the initiation
of heparin drip (18). He reported that these events were associated with
platelets of 187, which did not show absolute thrombocytopenia. However,
the platelets baseline, in this case, was 365 before the start of the
heparin drip. Hence, there was relative thrombocytopenia due to a more
than 50% fall in platelet counts. This finding contradicts the case
title and supports the current guidelines’ definition of HIT. Moreover,
Greinacher, Andreas, et al., in a retrospective analysis of 408 patients
aiming to identify risk factors for developing HIT-associated
thrombosis, illustrated that 4.4 % of patients diagnosed with HIT did
not have thrombocytopenia. At the time of clinical diagnosis of HIT, a
decrease in platelet counts of at least 50% occurred in 271/319
(84.9%) patients. Of the remaining 48 patients, HIT was suspected in 14
patients because new thrombosis without a platelet count fall greater
than 30% (4.4%). (19)
Further research into current recommendations of the 4Ts mentions using
the pretest probability in conjunction with clinical judgment, as
clinical judgment and assessment is required for evaluating the
likelihood of HIT. In addition, evidence-based algorithms describe that
there may be extremely rare cases of HIT with a low pretest probability.
Additionally, the 4 Ts score has yet to be validated on patients
receiving prophylactic dose of heparin. However, many institutions use
this score to guide testing and at times, strongly discourage testing
for HIT unless the 4Ts score is intermediate or high.
Our case touches on not relying blindly on guidelines but using them as
therapeutic guides and tools to aid in our clinical diagnosis and
treatment of patients. As Physicians, we cannot blindly diagnose or
treat diseases. As many of us were taught, diseases do not follow the
textbook. Therefore, the physician must remember to trust their clinical
judgment and use evidence-based medicine to guide the diagnosis and
treatment. Medicine is both a science and an art, and being an artist is
human.