1

PLASMAPHERESIS IN THE TREATMENT OF ANTOPHOSPHOLIPID SYNDROME

V.A.Voinov
First Pavlov State Medical University of St. Petersburg, Russia.

The development of many diseases associated with various autoimmune

processes, and in particular, with a large group of antiphospholipid antibodies. Depend
on them, many vascular diseases, early heart attacks and strokes, pulmonary
embolism. In addition, also are often complications of pregnancy with recurrent
miscarriage. In all these cases, standard medical therapy is not always ensure success.
The most pathogenetically indicated are courses of plasmapheresis.
Keywords: antiphospholipid syndrome, heart attack, stroke, pulmonary embolism,
recurrent miscarriage.

1. Antiphospholipid syndrome in general somatic practice

Recently, there is growing interest in this autoimmune vascular disease that

manifests itself in the development of recurrent thrombosis of the venous and arterial
systems of various organs [1]. The frequency of pulmonary embolism as a result of
deep vein thrombosis reaches 500,000 cases per year, most of which are fatal.
Insidiousness of these complications is almost completely asymptomatic during their up
to the time of thromboembolism in 50% of patients [2]. Deep vein thrombosis is often
(up to 29%) develop also after surgery, and after surgery for malignant tumors the
frequency reaches 66% [3].
Most often it is a question of antiphospholipid syndrome, first described in 1983
G.R.Hughes [4]. Antiphospholipid (aPL) antibodies are heterogenous group of
autoantibodies with different properties, including different specific phospholipid-
associated proteins, as well as reactive phospholipid molecules. There are basic
proteins, which are considered as antigens 2-glycoprotein I, prothrombin, protein C,
protein S, kininogen, annexin V. The various mechanisms involved in the pathogenesis
of aPL syndrome, including the effect of aPL autoantibodies to protein C system and
antithrombin III, as well as platelets, endothelial cells and monocytes [5, 6].
In particular, these antibodies disrupt the interaction of platelets with the
endothelium of blood vessels [7]. It was experimentally demonstrated that isolated from
patients with aPL syndrome antibodies bind phospholipids and 2-glycoprotein 1
membrane of vascular endothelial cells and platelets, leading to their activation and the
subsequent predisposes to thrombosis in such exposure [8]. Elevated levels of
antibodies to the antigen ANCA component of the cytoplasm of neutrophils and
 2
endothelial cells promotes the development of vasculopathies of different types with an
increased tendency to thrombosis [9].
Endothelial cells play a central role in preventing unwanted activation of the
coagulation cascade in intact vessels. Antiphospholipid antibodies of sera from patients
with systemic lupus erythematosus in the presence of low doses of TNF- stimulate
procoagulant activity of the culture of endothelial cells [10]. Endothelial damage
contributes to the release of large amounts of von Willebrand factor and fibronectin, that
due to lower natural anticoagulant activity of antithrombin III also contributes to a
hypercoagulable [11]. The sharp increase in factor VIII and vWF with common venous
thrombosis also noted S.A.Vasilev et al. (12).
That's why a lot of connections between these autoantibodies and coagulation
disorders, including the impact on co-factors, 2-glycoprotein I, which regulate the
processes of blood clotting. The nature of such relations is unclear, but apparently their
influence on immunodependent mechanisms of coagulation. These patients have a
higher risk of thrombosis and their recurrence.
There is the most dangerous thrombosis of cerebral vessels with the appearance
of strokes [13]. In 25% of young patients with stroke it can be found anticardiolipin
antibodies [14, 15]. It is also conceivable that some of the manifestations of migraine
could be explained by vascular disorders for the same reasons. In particular, there may
be repeated episodes of transient ischemic brain disorders, accompanied by headaches
[16]. There can communicate aPL syndrome with amyloid deposits in the walls of
cerebral vessels with a local weakening of the mechanical properties of their way to
tears, is the cause of hemorrhagic stroke in 10-15% of cases [17].
It is believed that the age of onset of cerebral ischemia associated with aPL
antibodies, a few tens of years younger than in the population of a typical cerebral
ischemia. Perhaps there are development the venous sinus thrombosis also. It can not
be excluded due to vascular dementia disorders caused by aPL antibodies. The same
applies to cases of late-onset epilepsy, which once again highlights the need for an
immunological study of patients with neurological symptoms, especially young women
[18]. Neurological disorders are described in the background of an increased level of
anticardiolipin antibodies without causing visible vascular lesions [19]. There relations is
possible also of some mental disorders with aPL syndrome [20].
Antiphospholipid antibodies may be the cause of coronary heart disease and
myocardial infarction, hepatic lesions [21, 22, 23]. In this case, myocardial infarction
due to coronary artery damage as well as on the background of coagulation disorders of
 3
lipid metabolism and hypercholesterolemia, can occur even in young adults [24. It
describes the development of myocardial infarction and during pregnancy in women
with aPL syndrome caused miscarriage also, although not excluded fetal antigen
immunization [25]. Anticardiolipin antibodies are detected in more than 70% of patients
with coronary artery disease at a young age.
Impact of aPL antibodies on 2-glycoprotein I, which is anti-atherogenic factor may
play a complementary role in promoting atherosclerosis in patients with aPL syndrome
[26]. Patients with antiphospholipid syndrome have a greater tendency to atherogenesis
[27, 28]. Oxidation of plasma proteins and endothelial damage oxidant-dependent
reduce physiological anticoagulant endothelial function [29]. Antiprothrombin antibodies
increase the risk of myocardial infarction, and antibodies against 2-glycoprotein I
contribute to increasing platelet aggregation. It is possible that aPL antibodies occur as
a result of systemic arterial inflammatory process and are the part of an autoimmune
response to the appearance of different antigens, modified atherosclerotic vascular wall
[6].
Thrombosis in patients with systemic lupus erythematosus are also associated
with aPL antibodies, with antibodies to 2-glycoprotein I is much more commonly
associated with such clinical manifestations of aPL syndrome than anticardiolipin
antibodies [30]. Antiprothrombin autoantibodies, even without other antiphospholipid
antibodies, may be to blame for the development of portal vein thrombosis [31].
Thrombosis occur in the kidneys also - thrombotic microangiopathy [32].
Glomerular capillary thrombosis passes into glomerulosclerosis with chronic renal
failure. It perhaps the development the nephrotic syndrome also.
Similar processes in the liver contribute to the development of Budd-Chiari
syndrome thrombosis of the hepatic veins with hepatomegaly, ascites, hepatic
congestion in the sinuses, hepatocellular necrosis and subsequent fibrosis. No less
dangerous are also the mesenteric arterial thrombosis, both arteries and veins,
accompanied by catastrophic complications. Ischemic neuropathy of the optic nerve and
retinal vascular occlusion may also be consequences of antiphospholipid syndrome
[33, 34].
Level rise antiphospholipid antibodies can also be observed in patients with
cancer, up to the development of symptoms of multiple organ failure with high hospital
mortality rate of up to 72% [35].
In some cases, it may develop catastrophic antiphospholipid syndrome, first
described R.A.Asherson in 1992 (36), when there are arise vascular occlusion of many
 4
organs in a short period of time from a few hours to several days, leading to acute
respiratory distress syndrome, CNS lesions, myocardial and intestine infarction with the
development of severe organ failure and death [11, 37, 38, 39]. With the help of
plasmapheresis on the background of glucocorticoids and low molecular weight heparin
it is possible to relief also such a serious complications.
Separately there is differentiated Sneddon syndrome, which is also characteristic
of ischemic strokes, peripheral thrombosis with specific manifestations - skin livedo
thrombosis of small dermal vessels traveling in the form of spider veins on the surface
of the skin, usually of the lower limbs. Histological study identifies noninflammatory
thrombosis of small arteries and veins of the skin and subcutaneous tissue. Cerebral
manifestations are characterized by headaches, focal neurologic symptoms,
progressive dementia [41]. Cutaneous manifestations may be the first symptoms of aPL
syndrome. In 37% of these patients subsequently develop systemic thrombosis. At the
same time, along with the lupus anticoagulant and anticardiolipin antibodies are
detected to the vascular endothelium also [42].
Antiphospholipid syndrome can be primary or secondary, combined with systemic
lupus erythematosus, Raynaud's phenomenon, Sjogren's syndrome, Behcet's uveitis
and iridocyclitis, as well as malignant neoplasms. Since one of the aPL antibodies is
lupus anticoagulant, it is not surprising that patients with systemic lupus
erythematosus are prone to thrombotic complications occurring in children, even in 17%
of cases [43]. The main manifestations are thrombotic vascular lesions of glomeruli
("non-inflammatory renal microangiopathy", lupus vasculitis or angiitis) with vascular
intimal hyperplasia, which leads to hypertension in antiphospholipid syndrome. There
are frequent concomitant valvular lesions and peripheral vascular disease by type of
Raynaud's phenomenon [44].
Antiphospholipid antibodies affect platelet membrane phospholipids with the
excitation of aggregation, leading to thrombocytopenia and trigger mechanisms for the
development of DIC. On the other hand, these antibodies act on phospholipid
membranes of vascular endothelial cells, promoting their degradation and thrombosis.
Furthermore, it is inhibited plasminogen activators [45]. The first sign of antiphospholipid
syndrome occurs unexplained time of activated partial thromboplastin time, which
requires a more in-depth research, which can help you identify also increase the
content of anticardiolipin antibodies, which, of course, is more sensitive and specific test
of this pathology [46] .
 5
Therefore, among the therapeutic measures it predominate methods impact on the
mechanisms of coagulation. There are used anticoagulants such as heparin,
acetylsalicylic acid (reducing agent of platelet aggregation), ticlopidine, dipyridamole.
However, cases are described also the progression of thrombosis with gangrene of
limbs during treatment with heparin or warfarin, which is associated with the
development of heparin-induced thrombocytopenia (in 1-3% of cases) about the 5th day
of heparin therapy.
Platelet activation under the influence of heparin leads to the formation heparin-
dependent IgG-antibodies to damage the vascular wall of arteries as well as veins, and
small vessel thrombosis developed with the advent of surface skin necrosis [47]. In the
past 50 years, heparin is widely used in the treatment of pulmonary embolism and
coronary thrombosis in coronary heart disease and other indications, but these facts
require caution in the use of heparin, especially in cases of aPL syndrome.
Recently, more and more are used such drugs as low molecular weight heparin
(dalteparin sodium, enoxaparin sodium), administered by the patients themselves
subcutaneously twice a day with little or no laboratory monitoring [48]. These drugs do
not cause serious thrombocytopenia, and therefore safer, including for self-
administration at home [2].
Thrombotic complications in aPL syndrome stimulated activation of lipid
peroxidation, as seen by the increase in the level of isoprostanes (markers of oxidative
stress). So is justified also the take of antioxidants [49].
Nevertheless, given the autoimmune nature of the disease, most pathogenetically
justified is plasmapheresis with removal of the course up to 3.8 liters of plasma, which
reduces the frequency of recurrent thrombosis [50]. A.P. Elchaninov et al. (51) in 41
patients with acute central neuroischemic processes on the background of identified
features of aPL syndrome was able to make more rapid regression of brain disorders
using plasmapheresis, compared with the control group of patients treated only with the
help of instenon. Plasmapheresis with the success has been used for the relief of
cerebellar ataxia on the background of aPL syndrome [19]. Plasmapheresis has proved
effective in the treatment of widespread thrombosis in the background of an increased
level of lupus anticoagulant and also factor VIII and von Willebrand factor [12 Vasiliev
S.A. et al. 2001]. Plasmapheresis is especially shown during a catastrophic
antiphospholipid syndrome with multiple organ failure [11, 37, 38, 39 ].
We must assume that in cases of pulmonary embolism, especially in the chronic
course of recurrent episodes, what matters is not so much true thromboembolism, as
 6
pulmonary vascular thrombosis in situ with the progression of pulmonary hypertension.
There is the primary factor in vascular endothelial injury, which can further lead to
thrombosis also in such places. And plasmapheresis pathogenetically is more justified
than only anticoagulant therapy, because it can prevent such primary vascular damage.
And this tactic has its confirmation.
Thus E.B.Orel et al. (40) report on the use of plasma exchange in patients with
acute pulmonary embolism with subtotal (90%) thrombosis of the inferior vena cava,
which was held on 29 (!!!) plasmapheresis procedures (10 inpatient, 19 outpatient).
After the treatment there were normalized levels of factors VIII and W, fibrinogen
content. Recurrent thrombotic events were observed for 13 months. A similar positive
result of plasmapheresis in a patient with pulmonary embolism on a background of
widespread thrombosis of the jugular, subclavian vein and the other described
V.Ya.Rudakova et al. (52). The use of plasmapheresis led to recanalization of previously
thrombosed veins of the lower extremities with the restoration of the microcirculation in
the lungs after pulmonary thromboembolism.
S. Otsudo et al. (53) cited a case where the use of warfarin and prednisone was
not able to arrest the thrombotic symptoms and only after cascade plasmapheresis
decreased titers of antibodies to beta2-glycoprotein 1 and anticardiolipin IgG-antibodies.

2. Antiphospholipid syndrome in obstetrics.

In addition to deep-vein thrombosis there are observed and spontaneous abortions

("habitual miscarriage"). This problem is one of the most pressing problems in
obstetrics. Their frequency is 15-20% of all pregnancies, and the incidence of infertility
in 5-11% of marriages [54]. In 30-40% of these abortions are "unexplained [55].
And among the causes of miscarriage play an important role antiphospholipid
autoantibodies (aPL). Known for their association with habitual spontaneous abortion,
intrauterine growth retardation, "missed abortion", preeclampsia, thrombocytopenia [56].
Antiphospholipid most often include two types of autoantibodies anticardiolipin and
lupus anticoagulant. Their detected at about 2% of women with normal pregnancy. At
the same time, in pregnant women with preeclampsia incidence of antiphospholipid
antibodies reaches 63.5% [57], and the combination of intrauterine growth retardation
with hypertensive disorders in pregnancy, this rate reaches 90% [58].
Non-organ specific autoantibodies and, especially, aPL, are one of the causes of
recurrent miscarriage. Immunopathogenetic mechanism which leads to early
 7
miscarriage in patients with APA may be determined utero-placental thrombosis and
vasoconstriction due to the coupling of antibodies to the phospholipid membrane, as
well as endothelial cells and platelets. This reduces the production of prostacyclin by
endothelial cells, increased platelet thromboxane production, reduced the activity of S-
protein, which is a physiological anticoagulant, inactivating procoagulants factor Va
and VIIIa [55]. This leads to instability of the membrane, increased platelet aggregation
and inhibition of endothelial prostacyclin synthesis. In addition, the process can cause
inhibition of prekallikrein and release endothelial plasminogen. It may also affect the
process of embryo implantation in the endometrium.
N. Gleicher et al. (59) also examined the relationship between unexplained
infertility and miscarriages with autoimmune disorders. Autoantibodies were detected
such as lupus anticoagulant, anti-cardiolipin, anti-phosphatidylserine, anti-
phosphatidylethanolamine, histones, against DNA, and poly-dioksitimidil acid 88% of
infertile patients and 70.8% with miscarriages. They reported also about the unusual
frequency gammopathy (type IgM) in 38.5% and 45.8% of these patients, respectively.
They concluded that some patients with unexplained infertility and miscarriages suffer
polyclonal activation of B-lymphocytes and thus confirmed the causal relationship of
autoimmune disorders with this obstetric pathology. Even in cases where the
autoantibodies for whatever reason can not be determined, increased by 1.5-2 times
the level of the CIC indirectly, may also indicate an autoimmune nature of the
"unexplained" infertility [60].
Many researchers believe the leading anti-2-glycoprotein I in the genesis of
thrombophilia [61]. There is the most frequent and more severe in also preeclampsia
[62]. R.Roubey (63) considered the detection of antibodies to 2-glycoprotein I the most
reliable and early sign of the presence of antiphospholipid syndrome.
It is usually assumed that the spontaneous abortions in the first trimester of
pregnancy are the result of a chromosomal abnormality. However, damage to the aPL
antibody phospholipids of cell membranes villous trophoblast "discovers" them for the
impact of cytotoxic immune cells mother in the first trimester, to the 8th week of
pregnancy [64]. Circulation of aPL antibodies is often detected in the group of early
miscarriage in 43.1% of patients, and even in the group of early pre-embryo losses
(35.7%) than in the group of late miscarriages (22.4%). Characteristically, the majority of
these women initially treated for infertility, while 15% of them have been repeated
attempts to in vitro fertilization [65].
 8
Clinical studies have shown that in the early miscarriages reasons were not
anticardiolipin or anti-phosphatidil serine, and anti-phosphatidilethanolamine antibody.
Phosphatidylethanolamine is one of the major components for both peripheral and inner
layers of the cell membranes. However, these specific antibodies contribute not so
much direct damage phosphatidylethanolamine as much damage high molecular weight
kininogen, factor XI or prekallikrein. Thus kininogen-dependent antibodies stimulate
anti-phosphatidylethanolamine thrombin induced platelet aggregation [66].
Histologically identified salient features peri-villous thrombosis, vascular desolation
of terminal villi, their chronic inflammation. In addition to thrombosis and hemorrhage
there are detected in the intervillous spaces, retroplacental hematoma, extensive
infarction and necrosis of the placenta [48]. This leads to early thrombosis of
uteroplacental vessels with fetal malnutrition and death of the embryo.
Besides influence violations receptors of endothelial cells and trophoblast function,
as well as the impact of intrauterine autoantibodies that affect embryonic development
of the fetus that are the cause of repeated implantation failures, which are not rightly
interpreted as infertility [67]. In addition to blood supply and nutrition disorders of the
fetus, it can occur also direct effects of antiphospholipid autoantibodies. So, L.F.Akanli
et al. (68) described 5 cases of cerebral infarcts in neonates whose mothers showed
increased concentrations of anticardiolipin antibodies.
Antiphospholipid antibodies can bind to the trophoblast cells and damage them in
violation of the placental barrier, which becomes passable for CIC, viruses, bacteria,
and iso-immune auto-antibodies. Antiphospholipid antibodies are a class of IgG-globulin
and cross the placenta, giving the fetus the same effect as in the mother's body [61].
Transplacental transfer of maternal antibodies to the fetus can cause vascular
thrombosis of any location, including the aorta, renal arteries, cerebral arteries, the
superior sagittal sinus and into the portal system. In this case, aPL antibodies in the
blood of the newborn may be delayed for a period of 3-6 months. On the other hand, in
the "reverse" direction through impaired placental barrier can penetrate fetal antigens of
the fetus, the mother contribute to sensitization with the development of fetal antibodies,
which further exacerbates the development of the fetus. [48].
The surface of the apical membrane of placental villi, converted to the uterine
intervillous circulation, normally covered with a special anticoagulant protein Annexin-
V. In studying these villi in the placenta, a checked for caesarean section, J.H.Rand et
al. (69) found that in patients with aPL syndrome content Annexin-V is much less than
in healthy women. Upon incubation of tissue culture placental villi of normal placentas
 9
with aPL IgG for 24 hours showed a significant reduction of apical annexin-V.
Furthermore, inhibition of cell proliferation observed human umbilical vein endothelial
cell in culture, containing anticardiolipin antibodies [70].
Available block Annexin V specific anti-annexin-V antibodies are described in
connection with recurrent miscarriage and systemic lupus erythematosus. These
antibodies can facilitate the transition of anionic phospholipids on the inner and outer
shell membranes promote apoptosis umbilical vein endothelial cells. When this occurs
and the yield on the membrane surface of procoagulant phospholipid
phosphatidylserine [71]. Such "externalizing" phosphatidylserine upon activation of
platelets and macrophages leads to activation of their surface coagulation factors X and
V, and also prothrombin [72].
Removing annexin V under the influence of aPL antibodies on the surface of
trophoblast makes it procoagulant. In addition, they inhibit the formation of syncytia,
hormone production and invasion of the decidua. This results in a placental
insufficiency, leading to stop development of the fetus, preeclampsia and abortion [73,
74]. In aPL syndrome prematurity observed in 2.5 times more often, in 3 times more
common the malnutrition in newborns and wasting all cases of malnutrition III level [57].
Antiphospholipid syndrome predisposes to severe preeclampsia also [75]. In
addition, there is possible development also the so-called catastrophic aPL syndrome
with severe progressive multiple organ failure [76]. In preeclampsia on the background
of aPL syndrome in 71.5% of cases there were signs of placental insufficiency with
intrauterine growth retardation [77].
Failure of implantation of fertilized embryos extracorporeal B.Fisch et al. (78)
explained the possible effect of ovarian hyperstimulation stimulating effect of high
doses of estrogen on the development of autoantibodies. They determined the level of
AFA during the early follicular phase, during the expected peak level of E2 and 14 days
after the egg retrieval. But these findings show also high initial level and AFA before
treatment.
As in the pathogenesis of complications of pregnancy in aPL syndrome plays a
certain role hypercoagulation, there are widely used anticoagulant and disaggregants
on the background of corticosteroids [79]. Nevertheless, the conventional therapy with
corticosteroids suppress immunological reactivity and correction of hemostatic disorders
of anticoagulants and antiplatelet agents are not always effective and fraught with acute
exacerbation of chronic endometritis with the risk of intrauterine infection of the fetus.
Moreover, there is evidence that glucocorticoids administered to a pregnant woman can
 10
cause a delay of growth and development of the fetus, which was confirmed in special
experiments on animals [80].
Antiphospholipid syndrome, in addition to the danger of recurrent miscarriage, may
be accompanied also by pulmonary vessels thromboembolism in the development of
deep vein thrombophlebitis of the lower limbs and pelvis, the frequency of which varies
from 1.5 to 2.7 per 1,000 pregnant women and from 2.8 to 18.3% in of maternal
mortality [81].
C.A. Laskin et al. (82) attempted to use prednisone and acetylsalicylic acid in
pregnant women with APA and do not succeed, because the frequency of live births did
not increase significantly, but the premature in the study group was 62% compared with
17% in the control. In addition, there is information on the effects of aspirin on the fetus,
causing hemorrhagic condition in newborns. Furthermore, more likely there are
developed hypertension (13% vs. 5%) and diabetes (15% versus 5% in control group).
S. Cowchock (83), leaving the possibility of the use of heparin in the presence of
signs of thrombosis, urged caution with the appointment of prednisone and
immunosuppressive therapy (including immunoglobulins) in pregnancy.
It should be emphasized the dangers of hormone therapy during pregnancy yet.
Thus, G. Celsi et al. (84) have shown that the penetration of glucocorticoids across the
placenta contributes to slowing the growth of the fetus and the appearance of
hypertension in them as adults. There is described dysfunction of the hypothalamic-
pituitary-adrenal system in children whose mothers received during pregnancy hormone
therapy.
This was confirmed in the experiments where the use of dexamethasone in
pregnant animals led to a decrease in body weight infants, malnutrition and reducing
renal glomeruli compared to the control. It is believed that the reduction in the number
of nephrons decrease in glomerular filtration area, which contributes to the development
of essential hypertension. Obviously this explains the higher levels of blood pressure
(130 4 vs. 107 1 mmHg in the control) in the experimental animals were born.
G. Framton et al in 1987 (85) described a case of when, after 10 unsuccessful
attempts to continue the pregnancy only after the introduction of plasmapheresis in the
complex of therapeutic measures it was managed to prolong pregnancy up to 34 weeks
with the healthy delivery. Later D. Fulcher et al (86), also after repeated unsuccessful
attempts to save the pregnancy and fetal life with the help of prednisone and aspirin,
have been successful only with the help of six sessions plasma exchange, which led to
 11
a significant reduction of anticardiolipin antibodies and stabilized the level of placental
blood flow, followed by the birth of a living child.
Experience of the Scientific Center for Obstetrics, Gynecology and Perinatology of
Russian Academy of Sciences [74, 87] in the treatment of 147 patients using
plasmapheresis sessions showed the possibility to obtain a reduction of activity of the
autoimmune process with a significant reduction, up to complete disappearance of
lupus anticoagulant, CIC levels (26%), and immunoglobulin E, M, G (for 16-21%),
normalization hemostasiogram, the disappearance of DIC markers. There are
normalized indicators of oxygen transport, PaO2 and hemoglobin oxygen saturation. In
76% of these patients took timely delivery, and 6% at term 32-34 weeks weighing 2.6-
3.9 kg newborn, and all the children were alive [88].
Moreover, it was useful to introduce a course of plasmapheresis (three-fold in a
day) also in the scheme of preparation for in vitro fertilization (IVF) and embryo transfer
in 62 women with tubal-peritoneal infertility. Percentage of pregnancy is based on one
embryo transfer at the same time was 51.6%, while in the comparison group (50 women
who have had a drug therapy only) 42% (p <0.05). Of the pregnancies there was
resulted in births of 84.4% (with 71.4% in the control group, p <0.05), with the birth of
viable children in 100% of patients. After the preparation for IVF using plasmapheresis
incidence of ovarian hyperstimulation syndrome was 8%, while in the comparison
group, it developed three times more likely (28%) [89, 90].
In Ukraine, the Donetsk regional center of maternity and childhood courses of
plasmapheresis were performed in 80 pregnant women with aPL syndrome who have
managed to get the 78 (97.5%) of viable children, while in the comparison group (60)
had been 14 pregnancies (23, 3%) in the I trimester, 10 (16.67%) in the II trimester, 5
neonates died from respiratory distress syndrome and cerebral blood flow disorders
[91].
Moreover, courses of plasmapheresis in 33 women with preeclampsia on the
background of aPL syndrome contributed to relief of hypercoagulable syndrome with
decreased fibrinogen levels by 17%, the normalization of prothrombin ratio, activated
thrombin time, a decrease in the degree of platelet aggregation by 18%, a decrease in
levels of markers of DIC D dimers and fibrin monomer complexes in the 2.5-3 times,
while in the comparison group (30 women with traditional drug therapy) was observed in
only a trend towards normalization of these parameters [48]
K. Abou-Nassar (92) in a patient with systemic lupus erythematosus
plasmapheresis used prophylactically during pregnancy every month with the birth of a
 12
healthy baby. In such patients found the use of immunosorption also [93] Positives
results plasmapheresis noted by other authors [77, 94, 95], as well as on our
experience of own [96, 97].

CONCLUSION
All these facts show that the antiphospholipid syndrome occurs much more
frequently than it is usually fixed, and this leads to the use of the most belated
pathogenetically justified plasmapheresis, or even ignored. This problem is still waiting
for its decision and further research.
In our opinion, if you suspect the possibility of such autoimmune disorders there is
requires its timely verification and confirmation when it is advisable to perform
plasmapheresis without waiting for its manifesting symptoms.

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