Introduction.

The problem of preventing miscarriage remains one of the primary goals of modern obstetrics [1, 6]. An important meaning in pathegonesis of pregnancy losses refers to trombophilic complications [4]. It is known that physiological flow of gestation process is complicated by an increase in coagulation potential of blood due to development of fetoplacental complex, hormone, hemodynamic, and hypervolemic alterations [4, 5]. At the same time, emergence of any pathologic process provides for disturbances of hemostatic potential of blood, thus complicating the flow of main disease and pregnancy [5].

Appendicitis is one of the most widespread acute surgical disease of stomach organs among the pregnant (0,05 – 0,12% to 5,2%) that requires urgent surgery treatment [1, 2]. Regardless of significant number of publications, devoted to diagnostics and variants of surgery treatment of appendicitis among pregnant women, prevention of gestation complications after appendectomy remains unsolved problem so far [8, 9, 10]. According to bibliographic data, potential losses under non-complicates appendicitis vary from 2 to 17%, growing to 19,4 – 50% in case of perforation of sprout, and achieving 90% in case of development of peritonitis [2, 8, 10]. Difficulties of diagnosing surgery pathology under pregnancy provide for a growth of destructive forms of appendicitis that increases a part of gestation complications.

Research objective: studying an impact of hemostatic disturbances over a flow and outcome of pregnancy under development of appendicitis and evaluating efficiency of using discreet plasma exchange within a complex of treatment measures of post–surgical period.

Materials and methods of research.

Complex investigation of 78 pregnant women who were treated with a surgery on acute appendicitis with gestation period from 4 to 30 weeks, has been carried out. During post-surgical period all patients were given treatment, aimed to prolong pregnancy and prevent purulent-septic complications. The main group (n=36) was treated with discreet plasma exchange on days 3 and 5 after appendectomy apart from general spasmolytic and anti-bacterial therapy (penicillins or cephalosporins) for detoxication and correction of hemostasiological disturbances. Patients of comparison group (n=42) received standard amount of treatment-preventive measures after the surgery. Control group (n=42) was formed of pregnant women with physiological flow of gestation.

All women were taken to a complex of laboratory and instrumental research. Evaluation of initial condition of the system of hemostasis was carried while the women were entering a hospital, on days 2-3 and 5-7 after the treatment. Study of the system of hemostasis was carried out with test-tube method, and also with a plane-table set for express-diagnostics. Analysis of platelet link of the system of hemostasis was based on evaluating quantity and aggregation ability of platelets. These indexes were found according to 2-channel laser analyser of platelet aggregation «Biola»-LA 230 (Russia), connected through an interface to IBM-compatible computer. Adenosine diphosphate, produced by the firm “Technology-Standard” in concentration of 2,5 mmole/l was used for aggregation induction. In order to study coagulation hemostasis, we have used the following methods: time of blood coagulation according to Lee-White (Lee R.J., White P.D., 1913); prothrombin index (PTI), activated partial thrombo-plast time (APTT) in modification of Z.S. Barkagan (1980). APTT was defined with sets, supplied by medical scientific-practical center “Technology” (Barnaul) on turbidmetric hemocoagulometer C GL 2110 (Belarus); contents of fibrogen in plasma was defined according to kinetic method (Clauss A., 1957). Quantitative express-method was used to define a level of thromb emergence markers – dimer with usage of partable facility Cardiac Reader. A state of the system of fibrinolysis was evaluated through studying indexes of fibrinolytic activity of blood cells according to the time of lysis of euglobulin fraction clots (G.F. Eremin, A.G. Archipov, 1979).

Statistic processing of the research results was carried out with usage of applied program pack (APP) ) Statgraphics (Statistical Graphics System), developed by “STSC Inc.”, with introduction of M+m percent, logarithmic averages (x) with 95% of trust interval and difference reliability (P) according to the criterion of Student.

Research results and discussion.

Patients of all groups were comparable according to age and terms of pregnancy. Age of patients varied from 19 to 32 years, average age of the main group equaled 24,5±4,7 years, of comparison group - 25,3±4,4 years, of control group - 24,2±5,6 (Р>0.05). Gestation term of patients at the moment of entering hospital in most of cases (40,5% – 41,7%) was within the limits from 4 to 12 weeks, that corresponds to the pinion of the most authors on the highest frequency of acute appendicitis development (up to 75%) in the first half of pregnancy [1, 2, 8]. First delivery awaited 34 women of the main group (94,4%) and 40 women of the comparison group (95,2%). Detail study of obstetric-gynaecological anamnesis allowed us to reveal a high percent of chronic inflammatory diseases of genital organs among the pregnant with appendicitis, among 72,2% (n=26) and 71,4% (n=30) women correspondingly. Of somatic pathologies chronic gastritis prevailed in the main group and comparison group (55,6% and 54,8% correspondingly) as well as dyskinesia of large bowels (52,8% and 52,4%).

Regardless of non-typical nature of clinic expressions of appendicitis in combination with pregnancy, in all cases accurate diagnostics and surgical treatment were carried out during the 1st day of patient’s presence in hospital. The analysis of the results of morphologic study has shown a prevalence of destructive forms of appendicitis under pregnancy in both groups (82,1%): phlegmon of vermicular sprout has been revealed among 45 patients, phlegmon-ulcerous form – among 4 patients, gangrenous - among 6 patients, and gangrenous-perforate form – among 10 patients. Catarrhal appendicitis was revealed only among 13 women. According to literature, frequency of diagnostic mistakes under acute appendicitis of the pregnant remain within limits of 11,9 to 44,0%, providing for frequent non-profile hospitalization, late diagnostics, and delayed surgical treatment, thus increasing the frequency of destructive forms of appendicitis [8].

While studying parameters of hemostasiogramme, we have stated a development of chronic form of DIC-syndrome among all pregnant women with acute appendicitis (table 1). We have also discovered a reliable increase in fibrinogen concentration 1,5 times, compared to control data (3,31±0,26 g/l; P<0,05), a significant increase (3-4 times) in contents of soluble complexes of fibrin monomers (SCFM) with a further reliable increase in their concentration in during post-surgical period (P<0,05). According to coagulation tests that describe sum activity in factors of internal pro-coagulate link of the system of hemostasis, such as activated partial thrombo-palst time (APTT), we observed its shortening among patients with appendicitis before surgical involvement, compared to similar parameters of the control group (30,6±0,92 seconds) and reliable decrease in this value in dynamics after appendectomy (Pk<0,05). Prothrombin index (PI) in the main group and comparison group exceeded control data (Pk<0,05). While studying platelet link of the system of hemostasis, a number of platelets among patients with appendicitis was reliably higher than control indexes (Pk<0,05). During post-surgical period, on days 2-3, an insignificant increase in number of platelets was observed in all groups (Р<0,05). At the same time we have registered an increase in aggregation ability of platelets while stimulating APD 1х10-3 M Tma among women with appendicitis and after surgery (Pk<0,05). In all case of clinic observation combinations of appendicitis and pregnancy we have stated an initial weakening in fibrinolysis in comparison to the indexes of the control group (Pk<0,05). While studying one of specific markers of chronic DIC-syndrome – dimer, we have not revealed reliable differences between its average indexes before surgery in groups of studied women (Pk<0,05). Low concentrations of dimer, in our opinion, are linked to a decrease in fibrinolytic activity among patients with acute appendicitis. An increase in dimer has been revealed among patients on days 2-3 after appendectomy, besides, a reliable difference in comparison to the data of the control group has been received (Р<0,05).

Thus, complex study of hemostasis system has sown a development of hypercoagulation among the pregnant with appendicitis. As known, in obstetrics, DIC is an important link in pathogenesis of many pathologic conditions, including loss of pregnancy [4, 5, 6]. According to some authors, an increase in fibrinogenesis and platelets is studied as sub-compensated form of chronic DIC-syndrome that is linked to a formation of placental inconsistence and delay in fetus development [5, 7]. Aggravation in hemocoagulative disorders has been registered on days 2-3 after surgical interference, it can be explained by a potential impact of surgical injury over the system of hemostasis [3].

Comparative analysis of dynamic study of hemostasis on days 5-7 after appendectomy has shown that additional usage of discreet plasma exchange on days 3 and 5 after the surgery among patients of the main group provides for normalization of major parameters of hemostasigram, unlike the comparison group (picture 1, 2). The received data correspond to an opinion of many authors on a positive impact of plasma exchange during the development of chronic form of DIC-syndrome [6].

Observation over the pregnant took place during the whole term of gestation. Analysis of the process and results of pregnancies after appendectomy has shown a higher frequency in compications of gestation under a standard flow of post-surgical period. A risk of pregnancy loss during the first month after the surgery was observed in all observations of the comparison group. After carrying out appendectomy and treatment in surgical department, 15 pregnant women (35,7%) have been transferred for a further therapy to gynaecological and obstetrics divisions due to a preserving clinic of a threatening abortion (early delivery). Further observation over the pregnant allowed us to reveal the highest of pregnancy losses in the comparison group: under development of appendicitis during gestation terms under 12 weeks, frequency of spontaneous miscarriage equaled 23,8% (n=10), undeveloped pregnancy – 21,4% (n=9). In our opinion, instability of hormone background at small periods of gestation (under 12 weeks) and development of coagulation disturbances in this gravid period has an unfavourable impact upon the process of embryogenesis, formation of fetal placental complex and pregnancy development, thus increasing a frequency of reproductive losses [4, 6, 7].

A favourable result of pregnancy after appendectomy in the comparison group has been stated only among 54,8% of women (n=23), besides, in 35,7% of cases, pregnancy ended with early delivery with terms of gestation from 30 to 36 weeks. In the main group, carrying out plasma exchange within a complex of treating measures among the pregnant after appendectomy provided for a prolongation of pregnancy in all cases. We should underline that additional usage of plasma exchange within a complex of treating measures among the pregnant after appendectomy allowed us to decrease frequency of threatening break of pregnancy 4 times, and decrease a number of perinatal losses 2 times, and increase a percent of favourable outcomes.

Table 1

Main indexes of hemostasiogram among patients with acute appendicitis

Pic. 1. Contents of fibrinogen in blood of the studied women.

Pic. 2. Concentration of FMSC in blood of the studied women in dynamics.

Summary.

1. Complex study of the system of hemostasis in combination of pregnancy with an acute appendicitis has shown a development of gypercoagulation with a synchronous suppression of fibrinolysis and increase in products of paracoagulation.

2. Progressing of the revealed disorders in coagulation potential of blood of the pregnant during post-surgery period has an unfavourable impact on the flow of gestation process, thus increasing risk of thrombohemorrhagic complications and losses of pregnancy.

3. Additional usage of discreet plasma exchange on days 2 and 3 after surgical treatment of appendicitis allows us to stop and level the series of hemostasiological disorders in response to the development of inflammatory process and consequences of surgical injury, thus providing for an increase in a percent of favourable results of pregnancies after appendectomy.

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