Case Report
A 51-year-old woman was admitted to
the internal medicine department in a state of shock of unclear etiology. She
was hypotensive, tachycardic, and dyspneic, with incipient blue mask. On ECG
the typical signs of pulmonary embolism were detected (Figure 1) and according
to the CT-pulmo-angiographic examination, bilateral massive pulmonary embolism
was clearly confirmed (Figure 2). The shock was immediately treated with volume
expanders (Gelafundine 500 ml intravenously 6 times) and vasoactive therapy
(Noradrenaline 8 mg in 5% glucose 500 ml, 1ml/hour intravenously) was begun.
After getting the patient´s
condition under control, thrombolytic therapy was initiated. According to
current guidelines, the thrombolytic therapy was started with an intravenous
bolus of alteplase 10 mg and then 40 mg intravenously during the first hour and
50 mg intravenously during the second hour. Intravenous anticoagulation with
heparin was initiated after alteplase treatment to complete the treatment
(Heparin 10 000 j. bolus and consequently 1000 units/hour intravenously). This
therapy was administrated with a positive effect and led to the stabilization
of patient´s condition. After stabilization of patient´s condition, the cause
of pulmonary embolism was investigated, but there was nothing in the history
suggesting a cause. The patient was normostenic, with BMI 23, a non-smoker,
without hormonal therapy or contraception.
Except of a simple infection of the
upper airways last month, she was healthy, without any history of serious
internal diseases, trauma, or surgery. According to the differential diagnosis
of pulmonary embolism, the patient underwent deep venous system
ultrasonography, but no thrombosis was found. To exclude inflammation as an
etiologic agent, a search for all focuses was subsequently conducted.
The patient was examined by a
stomatologist and an otorhinolaryngologist; cultivation of nasal and throat
swabs was done and gastrofibroscopy was also preformed, but no pathology was
found. Gynecological examination was without any pathological finding, except
for a hematoma of the right breast as a side effect of thrombolysis. Screening
for oncologic diseases (hemoccult testing of stool, onco markers – CA 19-9,
125, 15-3, CEA, alpha-phetoprotein, CT of lungs and abdomen) was also negative;
therefore, after this step the complete hematological examination for excluding
the hereditary coagulation disorder was performed, but all results were normal
(Table 1). Only a slight elevation of coagulation factor VIII was detected, but
was most likely reactive. In DNA analysis, only the heterozygote form of MTHFR
mutation was found.
Fig
1 : ECG of patient
Fig
2: Spiral CT angiography shoing Bilateral PE
showed bilateral PE
Table 1
Haematological screening for the thrombophilic state.
|
PCR DNA analysis
|
Coagulation factors function
|
Natural coagulation inhibitors
|
|
|
Methyl
Tetrahydrofolate Reductase C677T: C/T
Factor V Leiden R506Q: G/G
Factor II ntG20210A: G/G
CYP4V2 p.Q259K: K/K (*cytochrome P450, family 4, subfamily
V, polypeptide 2)
Factor XI: c.56-282T>c: C/T
Factor XI: c.1481-188C>T: C/T
|
Factor
VIII function: 1,883 IU/ml
Factor XI function: 1,35 IU/ml
|
Antithrombin
III function: 104,2%
Protein C function: 135%
Protein S function: 84%
|
|
|
|
Screening for antiphospholipid syndrome
|
|
|
|
1.)
Anti-β2-glycoprotein I: 1,8 IU/ml 2.) Kaolin clotting time - ratio: 0,87 3.)
Dilute Russell’s Viper Venom Time - ratio: 1,12
|
4.)
Tissue thromboplastin inhibition (TTI) * TTI 1: 50 ratio: 1,28 * TTI 1: 500 ratio: 1,62
|
5.)
Partial thromboplastin time - lag time (PTT-LT) * PTT – LT control: 33s * PTT - LT patient: 35s * PTT – LT ratio: 1,061
|
6.)
Partial thromboplastin time – lupus anticoagulans (PTT-LA) * PTT – LA control: 30s * PTT – LA patient: 34,4s * PTT-LA ratio: 1,14
|
*DNA CYP4 and DNA factor XI were examined just in frame of the research
of importance of these polymorphisms for venous thrombembolism incidence.
After completion of all screening examinations to clarify
the etiology of pulmonary embolism, we decided to examine the platelet
aggregometry. Although SPS does not typical cause pulmonary embolism, in our
patient we confirmed SPS type I using optical aggregometry
Discussion: SPS is a hereditary thrombophilia, first
described in the literature in 1983, but for a long time it has been primarily
just a theoretical term with little practical basis. In 1995 it was proposed as
a possible cause of unexplained arterial and venous thromboses [
1].
According to Bick et al. [
1]
SPS is responsible for 21% of arterial and 13.2% of venous thromboembolic
events that are otherwise unexplainable. However, in the literature it is
predominantly known as a hematologic disorder connected with arterial
thrombosis. There are just a few publications about the venous complications of
this syndrome.
This hereditary, probably autosomally dominant, platelet
disorder can be diagnosed by using platelet aggregometry, which makes
confirmation easy if the hyperaggregability of platelets is induced by
subliminal concentrations of adenosine diphosphate (ADP) and epinephrine (type
I), epinephrine alone (type II), or ADP alone (type III) [
2,
5].
After activated protein C resistance, it is the second most frequent hereditary
thrombophilia, and it has been suggested that it is connected with other
hereditary thrombophilic states [
3].
Clinically, patients may present with symptoms of acute coronary syndrome,
transient cerebral ischemic attacks, stroke, retinal thrombosis, peripheral
arterial thrombosis, and venous thrombosis [
5].
In this case, the SPS was also the only found risk factor
explaining why a quite healthy young woman with no coagulation-influencing
treatment had a highly fatal pulmonary embolism. After stabilizing the
patient’s condition and providing thrombolytic therapy, we started to search
for the etiology of the thromboembolic event. But all basal examinations –
exclusion of inflammatory and oncologic disease, and deep vein thrombosis –
were negative. We continued with the screening of hereditary thrombophilia. A
slight elevation of coagulation factor VIII was detected, which was most likely
reactive (factor VIII is the reactant of acute phase reaction) [
10],
and its role as an important risk factor for venous thromboembolism is not
generally accepted [
11].
DNA analysis revealed the heterozygote form of methylenetetrahydrofolate
reductase (MTHFR) mutation. This hereditary disorder is often connected to
folic acid and vitamin B12 metabolism, and if patient has a normal level of
homocysteine it is not clinically significant for the hemostatic disorder [
12,
13].
Nowadays, the examination of SPS is a standard part of
thrombophilic screening in some hemostasis and thrombosis centres, especially
in patients under age 35 years after an attack of arterial thrombosis and in
patients with repeated or progressive occurrence of vein thrombosis despite
anticoagulation therapy [
5].
These requirements were not met by our patient
But when all performed examinations seemed to yield negative
results, we decided to try platelet aggregometry, with a positive result for
SPS type I. In the literature, the combination of SPS with other hereditary
thrombophilic states has been described in patients with arterial and venous
thrombosis, but in our case a single SPS seems to have caused the
thromboembolic event.
Conclusions
Although sticky platelets syndrome has been known since 1983
[
1],
it is still a new phenomenon, and few clinicians have practical experience in
dealing with it. Clinically, this syndrome can be silent, or it can be
presented by stroke, transient cerebral ischemic attacks, acute coronary
syndrome, and arterial or venous thrombosis [
5].
Although some previous reports found that SPS can be responsible for 21% of
arterial thrombosis and 13.2% of venous thrombosis unexplainable by another
reason, most data in the literature associates it with arterial thromboembolism
[
1,
14].
However, the results from recently a published study suggest that it may be a
more frequent cause of venous thrombosis/pulmonary embolism than is
traditionally thought [
15].
The criteria for its screening are limited and include only patients under age
35 and who have had arterial thrombosis, as well as patients with repeating or
progressive occurrence of vein thrombosis despite anticoagulation therapy [
5].
In the routine hematological screening of hereditary thrombophilia, this
examination is not included. SPS testing is known and easy, but perhaps due to
lack of practical experience with this thrombophilia, it is not part of the
routine examination of hereditary thrombophilia. Despite this lack of clinical
experience, SPS is serious risk factor for patient health and thus the benefit
of SPS testing for the standard screening of thrombophilia deserves
consideration.
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