Although not part of the original study protocol, HIT antibody was checked by the treating clinician

1
Heparin Does Not Contribute to Intra-Aortic
Balloon Pump-Associated Thrombocytopenia
Edward W. Howard MD PhD1, Sion K. Roy MD1, Julio
A. Panza MD2, Howard A. Cooper MD2
1Department of Medicine, Georgetown University
Hospital, Washington, DC 2Coronary Care Unit,
Washington Hospital Center, Washington, DC
Georgetown University
Abstract
Introduction
Multivariate analysis
Introduction- Intra-aortic balloon
counterpulsation pumps (IABP) are frequently used
in critically ill patients on the coronary care
unit. However, their use is often limited by the
development of thrombocytopenia and its perceived
associated risk of bleeding. While other authors
have shown that IABP use induces
thrombocytopenia, in all previous studies
patients were routinely anticoagulated with
heparin, a medication known to be associated with
thrombocytopenia. Our group recently demonstrated
that heparin does not prevent thrombo-embolic
complications of IABP therapy, and should not be
used routinely unless there is another indication
for its use. Therefore, the contribution of
heparin and other medications to the development
of thrombocytopenia after IABP use has not been
previously reported, and this was the goal of our
study. Methods- Using a series of 252
consecutive patients at the Washington Hospital
Center who received treatment with IABP, of whom
70 received heparin and 182 did not, we studied
the prevalence, severity and duration of
thrombocytopenia. We also studied the
relationship of other medications with
thrombocytopenia, including aspirin and
clopidogrel. Results- Heparin use was not
associated with thrombocytopenia, with mean
platelet nadirs of 237100.2 and 219.284.9 in
heparin and non-heparin groups respectively.
Heparin also did not affect the speed of platelet
recovery after IABP discontinuation. Patients
with heparin induced thrombocytopenia (HIT) were
included in the analysis. Aspirin and clopidogrel
were also studied, and were demonstrated not to
be independent predictive factors of
thrombocytopenia. Conclusion- Although
thrombocytopenia is a common occurrence in IABP
therapy, it is not associated with heparin or
antiplatelet therapies and these should not be
taken into consideration in the decision to
continue or discontinue IABP therapy in patients
with thrombocytopenia.
Intra aortic balloon pumps (IABP), first
developed at the Cleveland Clinic in the 1960s,
are the most common circulatory assist devices
used in the United States. 1 Thrombocytopenia
is a recognized effect of IABP use- and it has
been widely theorized, although never
experimentally established, that this is due to
the shear effect of the device on platelets 2.
Other unknown contributory factors to this
IABP-induced thrombocytopenia may also exist.
Recent data from our center indicating that
heparin use is not mandatory in CCU patients
undergoing IABP presented us with the opportunity
to establish whether heparin was an independent
cause of thrombocytopenia 3.
Since thrombocytopenia may be induced by various
factors in addition to IABP insertion, many of
which bear a poor prognosis independently, and to
further study the clinical significance of the
thrombocytopenia induced by IABP insertion,
multivariate analysis was performed. Significant
independent predictors of clinical
thrombocytopenia in our patient population were
duration of IABP insertion (p0.019), the
presence of cardiogenic shock (p0.036) and low
body weight (p0.01). Neither heparin use,
aspirin use of clopidogrel use was associated
with thrombocytopenia independently (p0.76, 0.54
and 0.34 respectively).
Discussion
The effect of Heparin on Platelet Trends
Recent data among patients undergoing IABP in
the coronary care unit suggests that heparin
anticoagulation does not reduce the rate of limb
ischemia, and therefore may not be mandatory in
this patient population where there is no other
indications for its use 3. In this study we
tested the hypothesis that heparin is a
contributor to the thrombocytopenia observed
after IABP deployment. Heparin did not affect the
nadir platelet count, the number of patients who
became thrombocytopenic or the dynamics of
platelet recovery. HIT positive patients were not
excluded from the analysis, so cannot be used to
explain the lack of difference between the two
groups. Aspirin and clopidogrel use had been
studied previously and our results support the
recorded data that they do not influence the
development of thrombocytopenia. This data may
be useful for clinical decision-making in that we
have established that heparin is not a factor in
IABP associated thrombocytopenia. Although HIT
should be considered in all patients on heparin
as a possible cause of thrombocytopenia, the
heparin group as a whole did not show a
significant drop in platelets, and HIT was also
not a significant factor in the group as a whole.
In summary, heparin is not a significant factor
in IABP-associated thrombocytopenia and further
research into IABP technology will be required
to reduce its thrombocytopenic effects.
Figure 1a Platelet trend after IABP insertion
We studied the effect of heparin on platelet
trend, testing the hypothesis that heparin may
induce or worsen the thrombocytopenia associated
with IABP use. The combined data for all IABP
patients regardless of heparin usage is shown in
Figure 1a, and the data separated by heparin
treatment protocol is shown in Figure 1b. The
heparin and non-heparin cohorts started with
similar platelet counts (mean of 237100.2 and
219.284.9 respectively). As can be seen in
Figure 1b, the use of heparin did not affect the
platelet count , with nadir counts expressed as a
percent of initial platelet counts of 65.923.7
and 70.223.7 in heparin and non-heparin groups
respectively. Furthermore, the use of heparin did
not appear to affect platelet recovery times, and
did not affect the platelet count regardless of
the duration of IABP use (data not shown).
Conclusions
Heparin Induced Thrombocytopenia
Although thrombocytopenia is a common occurrence
in IABP therapy, it is not associated with
heparin or antiplatelet therapies and these
should not be taken into consideration in the
decision to continue or discontinue IABP therapy
in patients with thrombocytopenia.
Although not part of the original study protocol,
HIT antibody was checked by the treating
clinicians on the basis of clinical suspicion. Of
the study population, 53 of the total 252
patients underwent testing for HIT. Factors
involved in this decision were studied. The
decision to test HIT antibody was strongly
predicted by lower platelet nadir, higher percent
platelet reduction and longer duration of IABP
use (plt0.01 in each case), as well as by longer
duration of hospital stay (plt0.001) and length of
stay in the CCU (p0.018) and larger patient
weight (p0.008). Of the 53 patients in whom
HIT antibody was checked, 11 patients (20.8) had
positive tests. Presence of HIT antibody in this
sample however did not predict mortality or major
bleeding when compared either to patients whose
HIT antibody was negative or to all patients who
did NOT have a positive HIT test (p0.71 and 1.00
respectively for mortality and p0.24 and 0.51
respectively for major bleeds).
References

• Moulopoulos SD et al. Extracorporeal assistance
  to the circulation and intraaortic ballon
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• 2) Bream-Rouwenhorst H et al. Thrombocytopenia in
  patients with heparin, combination antiplatelet
  therapy, and intra-aortic balloon pump
  counterpulsation therapy. Journal of
  Interventional CardiologyVol. 2008- Vol 21, 4
  350-56.
• 3) Cooper HA, Thompson E, Panza JA. The role of
  heparin anticoagulation during intra-aortic
  balloon counterpulsation in the coronary care
  unit. Acute Cardiac Care 200810214-220.