Allergy Asthma and Immunological Studies

Plasmapheresis in the treatment of antiphospholipid syndrome

*VA Voinov
Department Of Therapeutic Apheresis, Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation

*Corresponding Author:
VA Voinov
Department Of Therapeutic Apheresis, Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation

Published on: 2019-01-04


In recent years there is a growing interest to the whole group of diseases, having common pathogenetic developmental mechanisms. We are talking about the antiphospholipid syndrome, which has been well studied in obstetric practice, because it is accompanied by disorders of fetal development and habitual miscarriages. Nevertheless, in general somatic practice it plays one of the leading roles in vascular pathology, both in the venous circulation, leading to deep vein thrombosis and thromboembolism of the pulmonary vessels and in the arterial circulation that results in occlusive complications, including myocardial infarction and ischemic strokes. Symptomatic drug therapy and anticoagulants are commonly used, ignoring the primary cause of the vascular wall lesion induced by antibodies. Plasmapheresis should be considered to be the most pathogenically justified therapy, aimed to remove antiphospholipid autoantibodies, which are the primary factors of such conditions.


antiphospholipid syndrome, thrombophilia, venous thrombosis, thromboembolism pulmonary vessels, myocardial infarction, stroke, habitual miscarriage, infertility

Copyright: © 2019 VA Voinov


The development of many diseases associated with various autoimmune processes, and in particular, with a large group of antiphospholipid antibodies. Depend on them, there are many vascular diseases, early heart attacks, and strokes, pulmonary embolism. In addition, there are often complications of pregnancy with recurrent miscarriage also. In all these cases, standard medical therapy is not always ensure success, as no medicines, an organism is able to remove the antibodies which are large molecular immunoglobulin’s which kidneys don’t remove and mechanisms of biotransformationthem don’t destroy. At the same time, most pathogenetic the plasma exchange courses allowing to remove them together with plasma are reasonable.

The main point of application of these antibodies is phospholipid components of the vessels endothelium membranes. At the same time, it is possible to select two main groups of the arising deterioration - damages of vessels of the most different bodies and also areas of uterine and placental blood circulation, therefore, we also will examine them separately.

 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 by 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 β2-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 blood vessels endothelium [7]. It was experimentally demonstrated that isolated from patients with aPL syndrome antibodies bind phospholipids and β2-glycoprotein I 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 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 TNFα 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 sudden increase in factor VIII and WF with common venous thrombosis also noted S.A.Vasilev et al. [12].

That’s why there are a lot of connections between these autoantibodies and coagulation disorders, including the impact on co-factors, β2-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 developed the venous sinus thrombosis also. It cannot 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 neurolog-ical 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 are 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 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 β2-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 oxidant-dependent endothelial damage reduce physiological anticoagulant endothelial function [29]. Antiprothrombin antibodies increase the risk of myocardial infarction, and antibodies against β2-glycoprotein Icontribute 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 β2-glycoprotein I are 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 by R.A.Asherson in 1992 [36], when there are arise vascular occlusion of many 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 infarctions with the development of severe organ failure and death [11, 37, 38]. 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 [39, 40]. 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 no inflammatory 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] .

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. Plasmapheresis is especially indicated during a catastrophic antiphospholipid syndrome with multiple organ failure [37-40 ]. 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 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. [52] 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. 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 β2-glycoprotein I and anticardiolipin IgG-antibodies.

Antiphospholipid Syndrome In Obstetrics.

In addition to deep-vein thrombosis there are observed and spontaneous abortions (“habitual miscarriage”), stiibirth, fetal grows restriction and premature birth. 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% 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 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-deoxythymidine 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 cannot be determined may also indicate an autoimmune nature of the “unexplained” infertility [60].

Many researchers believe the leading anti-β2-glycoprotein I in the genesis of thrombophilia [61]. There is the most frequent and more severe in preeclampsia also [62]. R.Roubey [63] considered the detection of antibodies to β2-glycoprotein I the most reliable and early sign of the presence of the 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 trophoblast villous cell membranes “discovers” them for the impact of mothers cytotoxic immune cells 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]. Clinical studies have shown that in the early miscarriages reasons were not anticardiolipin or anti-phosphatidil serine, and anti-phosphatidylethanolamine 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]. There are histologically identified expressed features peri-villous thrombosis, vascular emptiness 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 [58]. This leads to early thrombosis of utero-placental vessels with fetal malnutrition and death of the embryo. Besides influence damages 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, there were described 5 cases of cerebral infarcts in neonates whose mothers showed increased concentrations of anticardiolipin antibodies [68]. Antiphospholipid antibodies can bind to the trophoblast cells and damage them in disorder 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 [58]. 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. [58]. 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, it was 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 with aPL IgG for 24 hours showed a significantreduction of apical annexin-V [69]. 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 cell 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 prothrombin also [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 fetation of the embryo, 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 APA during the early follicular phase, during the expected peak level of E2 and 14 days after the egg retrieval. But these findings show the high initial level and APA before treatment also. As in the pathogenesis of complications of pregnancy in aPL syndrome plays a certain role hypercoagulation, there are widely used anticoagulant and desaggregants 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 cause a delay of growth and fetation of the embryo, 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 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 interrupted 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. 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 [91]

K. Abou-Nassar [92] in a patient with systemic lupus erythematosus plasmapheresis used prophylactically during pregnancy every month with the birth of a healthy baby. In such patients found the use of immunosorption also [93] Positives results plasmapheresis noted by other authors [94, 95], as well as on our own experience [96, 97, 98].


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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