Abstract:
We described a rare case of nadroparin-induced skin necrosis with
thrombocytopenia.LMWH therapy is used in thrombosis prophylaxis, it is
important to recognize that skin necrosis can be a part of HIT early in
its course and change heparin or LMWH to non-heparin anticoagulants such
as director thrombin III inhibitors.
A 75-yr-old obese woman developed one 20 cm area of nonpalpable purpura
with surrounding erythema and hemorrhagic vesicles on the central
abdominal part (Fig. 1). These occurred 8 days after nadroparin 2850 U
injection for thromboembolic prophylaxis because of deep vein thrombosis
and concomitant metastatic neoplasia of liver and intrahepatic ducts.
There was no pruritus or surrounding pain. The platelet count decreased
from 217 000/microl at hospitalization to 68 000/microl when the skin
necrosis developed. Protein S, protein C, prothrombin time, and thrombin
time were normal. PF4/heparin antibodies were positive 1:32. Based on
the clinical picture nadroparin-induced skin necrosis was diagnosed. We
also clinically suspected a high probability of type II heparin-induced
thrombocytopaenia (HIT) as a score of 8 points according to the 4T’s HIT
score system was calculated. All contact with heparin (including
catheter washing) and LMWH were stopped. Lower extremity Doppler
ultrasound confirmed acute iliofemoral thrombosis of the right leg, thus
anticoagulation was required. After changing nadroparin to fondaparinux
and later on to oral apixaban, the lesions improved and eventually
healed. Thrombocyte count returned to normal 11 days after
discontinuation of nadroparin.
Skin necrosis is a rare complication of low molecular weight heparin
(LMWH), although for heparin injections it is a well-described
complication. In the literature dalteparin and enoxaparin are mostly
described LMWH which cause HIT, 1 nadroparin induced
skin necrosis is rarely published.2-4 Skin necrosis
immediately suggests the presence of HIT5 as this
develops due to intradermal microvascular thromboses. The absolute risk
for HIT is 0.2% with LMWH and 2.6% with unfractionated
heparin.6 Often the first manifestation of HIT is
thrombocytopenia, occurring in up to 90% of those affected. Thrombosis
occurs in up to 50%7 of patients, more frequently due
to venous than to arterial thrombi, and can lead to skin necrosis and
organ infarction. Mortality from HIT, mostly due to thrombosis, can be
as high as 20%, and approximately 10% of patients require amputations
or suffer other major morbidities.8-10 Protein C and S
deficiencies greatly increase the risk of skin necrosis and should be
measured if skin necrosis follows LMWH injection.
Heparin or LMWH induced skin necrosis is generally a benign condition,
which resolves after stopping the culprit drug, but skin necrosis can
just be part of a clinical spectrum of thrombotic complications, which
are potentially life-threatening.1 The decisive
diagnostic procedure in heparin-induced necrosis is HIT antibody
testing, histological examination if necessary and the chronological
connection between the initiation of heparin/LMWH and appearance of skin
necrosis, thrombocytopenia, which usually occurs 5–10 days later at the
site of injection (although there are the description of distant lesions
development).
Acknowledgment: The patients in this manuscript have given
written informed consent to publication of their case details.
Author contribution : Author 1: conception and design, writing
the manuscript, revising and final approval of the version to be
published.
Author 2:drafting the manuscript, final approval of the version to be
published.
Author 3: analysis and interpretation of data, final approval of the
version to be published.
Author 4:acquisition of data, final approval of the version to be
published.
Each author participated sufficiently in the work to take public
responsibility for appropriate portions of the content.
Data availability statement: Data sharing not applicable to
this article as no datasets were generated or analysed during the
current study.
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Figure 1. Skin necrosis on the abdomen at the site of nadroparine
injection, which developed after 8 days of treatment