Heparin-induced thrombocytopenia occurs in 0.2 to 2%
of cases of open heart surgery.[
1,
5,
6] Suspecting HIT is
the first step in diagnosis of the disease in cardiac
surgical patients.[
7] Taking into account for the other
causes that may lead to drop in platelets, clinican
should suspect for HIT in the findings which are
unexplained thrombocytopenia, venous or arterial
thrombosis in the presence of thrombocytopenia,
necrotic skin lesions at heparin injection sites and acute
anaphylactoid reactions after IV boluses of heparin.[
7]
Unlike cases with previous history of HIT, it can be
more challenging to diagnose and establish a standard
protocol for those with postoperative worsening of
hemodynamic parameters.
In our case, HIT diagnosis was based on the clinical
and laboratory findings. The 4Ts scoring system[8]
was used in the clinical evaluation. The patient had
a low-risk score of three, platelet nadir <10,000,
1 point; non-necrotizing widespread skin lesions,
1 point; and possible other causes of thrombocytopenia
(rheumatoid arthritis), 1 point. The anti-PF4/heparine
antibody was positive. Although pretest scores were
low, clinical and routine laboratory findings with
confirmed antibody positivity suggested HIT.
In addition, several conditions may cause or aggravate
thrombocytopenia including extended total perfusion
time, dialysis treatment, and history of rheumatoid
arthritis requiring immunosuppressive treatment as in
our patient. However, the decrease in the platelet counts
during postoperative period was beyond expectations
in our case who was on heparin treatment. The
preoperative platelet count was 310,000/μL, whereas
it was 48,000, 36,000, 16,000, and 10,000/μL in the first, second, third, and fourth postoperative days,
respectively. Simultaneously, ecchymotic eruptions
appeared in the arms and neck around the catheter
sites, which disseminated to the legs, chest, and
abdomen over the next days. The patient's response
to the treatment also supported the diagnosis of HIT.
Following the discontinuation of heparin treatment,
low-molecular-weight heparin treatment was
initiated. Also, after plasmapheresis and intravenous
immunoglobulin treatment, hemodynamic, laboratory,
and clinical findings showed a rapid improvement. The
amount of drainage was negligible and no massive blood
transfusion was required. The thrombocyte count was
10,000/μL in the fourth postoperative day. However,
after low-molecular-weight heparin was initiated, it
increased to 57,000, 66,000, and 71,000 in the sixth,
seventh, and eighth postoperative days, respectively. The
clinical presentation of the patient and her responsiveness
to the treatment, altogether, suggested HIT. Based on
the anti-PF4/heparine antibody positivity, the condition
was confirmed as HIT.
In the literature, some authors advocate that HIT
diagnosis should not be eliminated in patients with
low 4Ts scores[9,10] In a study in which surgical ICU
patients were analyzed, the rate of HIT positivity was
8.6% in patients with a 4T score between 0 and 3,
while the rate of HIT negativity was 57% among
those with a score higher than 3[11] These results may
raise a question on the reliability of the 4Ts scoring
system.[11] Although both pretests and laboratory
findings have some limitations, it is rare that both
fail simultaneously.[9] In all patients with clinically
suspected HIT, the detection of the anti-PF4/heparine
antibody is required.[12]
In our case, we administered plasmapheresis in
the fourth postoperative day, as the clinical worsening
was apparent. Plasmapheresis was repeated on the
following day. Treatment was followed by improved
hemodynamic parameters and arrest of bleeding. In
general, plasmapheresis recommendations for HIT
following open heart surgery involve the postoperative
period.[13] There is, however, no established treatment
protocol. In a study, 11 patients with history of HIT
underwent intraoperative plasmapheresis to reduce
the antibody load.[2] Plasmapheresis was followed
by the placement, under cardiopulmonary bypass,
of a permanent left ventricular assist device in a
patient with hemodynamic instability and acute viral
myocarditis was reported in another case.[14] Therefore,
we believe that the postoperative administration of plasmapheresis might play a critical role for the
improved status of our case.
Furthermore, unfractionated heparin was
substituted by fondaparinux in the fourth postoperative
day due to worsened hemodynamic status and HITtargeted
treatment was, then, initiated. The platelet
count increased within 17 days of treatment and no
bleeding occurred. Bedside echocardiography showed
no valvular problems. Current guidelines also indicate
that fondaparinux may be used as an alternative
agent in HIT treatment.[15] Fondaparinux doesn't
enhance the platelet activation effect of HIT sera and
could be used as a treatment for HIT.[16] In addition,
a successful therapeutic use of fondaparinux was
previously reported in a HIT case following the
implantation of a left ventricular assist device.[17] We,
therefore, suggest that fondaparinux may be used as an
alternative intravenous anticoagulation agent in cases
of HIT following mechanical valve replacement.
After consulting to a hematologist, we
administered intravenous immunoglobulin in the
sixth and seventh postoperative days. Intravenous
immunoglobulin is often considered to be safe
and effective, when used in open heart surgery
cases with immune dysfunction accompanied by
thrombocytopenia.[18] Similarly, we believe that
the administration of intravenous immunoglobulin
following plasmapheresis might contribute to the
improved clinical status of our case.
In conclusion, the substitution of fondaparinux
for unfractionated heparin and treatment with
plasmapheresis and intravenous immunoglobulin may
improve clinical and laboratory findings. Considering
the long-term anticoagulant efficacy of fondaparinux
and possible merits of plasmapheresis and intravenous
immunoglobulin, the treatment which we used
may be applicable for those with heparin-induced
thrombocytopenia accompanied by compromised
hemodynamics following mechanical heart valve
replacement.
Declaration of conflicting interests
The authors declared no conflicts of interest with
respect to the authorship and/or publication of this
article.
Funding
The authors received no financial support for the
research and/or authorship of this article.