CC BY
33
Prevention of postoperative thombotic complications at women with uterine myoma with low molecular weight heparin...
Mamadjanova Nodira Nosirjonovna, Republican specialized scientific-practice medical center of obstetrics and gynecology, Tashkent, Uzbekistan,
scientific researcher E-mail: nodira762901@mail.ru
Prevention of postoperative thombotic complications at women with uterine myoma with low molecular weight heparin in complex system enzyme therapy
Abstract: This study aimed to study of evaluate an administering of low-molecular weight heparin (LMWH) in complex with system enzyme therapy (Wobenzym) efficiency on prevention of postoperative thrombotic complications at 60 women with uterine myoma concerning to the high risk. All operated women were concerned to the high risk degree of development a postoperative thromboembolic complications (POTC). And they have been administered LMWH Clexan in a daily dosage of 0.4 ml. once a day subcutaneously up till 10 days after operation. Primary early thromboprofilaxys and its postoperative continuously specific prevention was spent with a preparation — Wobenzym in a daily dosage for 3-5 tabs a 3 times a day up till 4 weaks.
Keywords: uterine myoma, a haemostasis, deep veins thrombosis, low-molecular weight heparin.
Introduction
The problem a prevention of thromboembolic complications for operative gynecology is rather actual. Frequency of deep veins thrombosis after various gynecologic operations varies within 11-37 %, and pulmonary thromboembolism (PTE) developed due to deep veins thrombosis (DVT) is one of the reasons of postoperative lethal outcomes in 18-22 % cases [3]. Venous thromboembolism (VTE) is an important and potentially preventable complication of major gynecologic surgery, and the common frequency postoperative thromboembolic complications with rates of DVT, PTE, and fatal PTE (19-20 %) are comparable to those seen after general surgical procedures [3; 4].
Despite the quality which has increased during last two decades period of the operative gynecologic care, deep veins thrombosis of lower limbs and generated by it PTE take a leading place among postoperative complications in gynecologic patients and it's still recognized as a important problem of operative gynecology.
All gynecologic patients who are especially undergoing to the operative treatment, to some extent, are thrombotic dangerous, as in majority of them there are can be observed a hypercoagulation alterations in haemostasis system and venous circulation failure in the lower limbs and a pelvic can be observed (L. A. Ozolini, 1999, Russia)
Purpose
To evaluate of administering of low-molecular weight heparin (LMWH) in complex with system enzyme therapy efficiency on prevention of postoperative thrombotic complications at women with uterine myoma concerning to the high risk.
Materials and methods
Our study has been carried out in department of operative gynecology, consultative polyclinic and haemostasiology laboratory of Republican specialized scientific-practice medical center of obstetrician and gynecology, Tashkent.
Criteria of inclusion ofpatients to the study: patients with uterine myoma which recommended operative treatment, and those patients, which distances the written informed consent.
Criteria of exclusion of patients: patients with a uterine myoma which administered a conservative treatment with blood diseases, blood diseases characterizing with the hypocoagulation; intolerance to preparation components ofWobenzym or Clexan; patients who have not given the consent to participation in study. Further, in purpose of an estimation of efficiency of an offered thrombopro-phylaxys technique all patients from prospective study have received
medicamentous thromboprophylaxys by a technique offered by us: LMWH (Clexan) + SET (Wobenzym).
For comparison of LMWH efficiency there were conducted a retrospective studying of 158 case histories of patients (II group) at the similar age with investigated group, which undergone to the abdominal hysterectomy due to uterine myoma at Department of operative gynecology of RSSPMC of O&G of Uzbekistan during the period from 2005 up to 2008 years.
All patients from the retrospective analysis on purpose preventing of postoperative thrombotic complications had been administered unfractionated heparin (UFH) subcutaneously in dosage on 5000 IE 3 times a day. The results of analyzing a reproductive function, the structure of accompanied extragenital and gynecological diseases, clinical-anamnesis dates in both investigated group were almost similar. For the comparison of haemostasiological results there was studied haemostasis system of 20 rather somatically healthy women (control group) at the reproductive age without any accompanied gynecologic diseases.
The estimation of haemostasis state was conducted in dynamics prior to and on 1st, 3rd, 7th days on the postoperative period at haemostasiological laboratory of RSSPMC O&G. And there were used a reactants of firm Barnaul (Russia) which included in itself definition of: activated partial thromplastine time (APTT), prothrombin time (PT), prothrombin ratio (PR), the International normalized ratio (INR), amount of soluble fibrin — monomer complexes (SFMC), and fibrinogen, platelets count (PLC).
Results
Due to all patients from prospective study aged above 40 years and concerned to the high risk (aa of them undergone to the total hysterectomy) they are included to the high risk. By our developed technique, medicamentous thomboprophylaxys (MTP) was spent on 2 stage:
• 1st stage of MTP was spent in out-patient conditions in case a revealing of pre thrombotic conditions at laboratory research. The purpose of the given stage was to define degrees of risk of development of postoperative thrombotic complications (POTC), hence preparation of patients for the operative performance, carrying out an early preventive maintenance of intra — and early POTC in accordance of risk degree. Risk degrees of POTC was defined by using of the special criteria, developed by French anaesthesiologists Samama M, Samama N, and modified by us. Preoperative thromboprophylaxys with LMWH Clexan was spent in those patients who had deeply
Section 6. Medical science
changes in coagulation system characterized with pre thrombotic condition which established laboratorically (table 3). Daily dosage and duration of administering of medicaments was determined taking into account of risk degree. In other cases patients as a primary prevention were administered SET — Wobenzym in a daily dosage for 3-5 tablets a 3 times a day before meal till up 2 weaks.
• 2nd stage thromboprophylaxys was spent in the conditions of hospital for the purpose of prevention of development of early and late POTC by following scheme:
A. Nonspecific thromboprophylaxys: elastic bandaging prior to operative performance which continued until discharging from hospital; early activation after surgery, adequate hydratation.
B. Specific thromboprophylaxis:
- Clexan (LMWH, enoxaparin) 0.4 ml. 1 time injection in the field of umbilicus till up 10 days;
- in a high risk degree III C daily dosage of Clexan was increased till up 0.6 ml.
^ Medicamentous thromboprofylaxis with Wobenzym: (In existing of thrombotic anamnesis or thrombophilia, daily dosage of Wobenzym is consisted a 5 tabl 3 times a day on 1st weak, gradually increasing in 1 tabl a weak: on the 2nd weak on 4 tabl a 3 times a day, on the 3rd weak on 3 tabl 3 times a day) administering Wobenzym was began just after stopping to injection a latest dosage of Clexan.
Nonspecific not medicamentous preventive maintenance was spent in all patients. Postoperative medicamentose thromboprofyp-axys was spent with Clexan, and its Efficiency and duration of postoperative application were defined on haemostasiologically and by objective, subjective criteria of the patients, which developed by us.
The proximate results have been estimated on the early postoperative period by laboratory parametres and by postoperative condition of the patient (objective and subjective dates).
The distant results estimated in 6 months after operation by questioning by use of the special questionnaire (the General questionnaire of health (MOS SF - 36)) estimations of quality of the life of postoperative patients.
All patients have been undergone to the total hysterectomy. The average size of both uterus and fibroid were 12 weeks (min. 8 week; max. 24 week). At 7 (37 %) of surveyed women there is revealed a fast-growing uterine myoma. Prominent features of reproductive function of women of the given contingent of patients has shown, that 7 (35 %) among of them were multiparas, and 11 (55 %) were multigravidas, hence, recurrent artificial abortions are revealed at 6 (30 %), spontaneous abortions at 7 (35 %) women. In the structure of extragenital diseases there are most often observed pathologies had appeared cardiovascular disease in 12 (60 %), obesity in 4 (20 %), anemia in 6 (30 %), varicose veins of the lower limbs at in (15 %), a gastrointestinal tract disease in 3 (15 %) patients with uterine myoma.
In majority patients there are most often revealed some concurrent diseases such as obesity, hypertension, anemia and varicose veins of lower limbs. Most often occurring accompanied gynecologic pathologies at investigated patients with uterine myoma were ovarian cysts and cystomas, cervical erosion, endocervicitis, endoservicosis, ovuli naboti which because of all patients were exposed to the operative intervention in volume of extirpation of uterus with its appendages and without of them.
All patients admitted to the department of operative gynecology of RSSPMC of O&G with the diagnosis of symptomatic uterine myoma for the operative treatment, further confirmed histologically. All patients were exposed to the abdominal hysterectomy
by indications, as a preference method of anesthesia in majority cases we have administered of spinal anesthesia (SA). Duration of operation performance in investigated group averaged about 65 minutes, average volume of interoperation hemorrhage was 200 ml.; and at IInd group (comparison group) these rates were 95 minutes and 350 ml. accordingly.
To all investigated patients were carried out nonspecific preventive maintenance, including to Pharmacological prophylaxis was conducted with LMWH Clexan (Enoxaparin, Sanofi Aventis, France) taking in account of risk factors degrees, thus because all patients from both investigated groups were aged above 40 years, and all of them were exposed to hysterectomy with appendages or without of them, we have included all women to high degrees of risk of development a postoperative thromboembolic complications. In this connection, they have been administered LMWH Clexan in a daily dosage of 0.4 ml. once a day subcutaneously in the field of abdomen till 10 days. On administration of spinal anesthesia preoperative dose of Clexan injected 12 hours and on administrating general anesthesia and 2 hours prior to operation. The subsequent doses began at once after 8 hours of the surgical intervention. In addition of to pharmacological prevention we have prescribed as a system enzyme therapy — Wobenzim (Mucous farm, Germany), which contains in its composition an enzyme bromealin, in a daily dosage by 3 dragee three times a day a 30 minutes before meal till four weeks.
Results of the analysis a coagulogram which had being carried in dynamics at IInd group of patients were distinctly differed from Ist, and comparison results with I and control groups were statistically significant (p < 0.05). At patients, which pharmacologic method of thromboprophylaxis were carried out with UFH on the 3rd and 7th days at the postoperative period a fibrinogen concentration had statistically significant increased, results of SFMC analysis was characterized by progressing reliable increase its amount of the last on 1st, 3rd, 7th days (Table 3). In contrast, comparing to Ind I group, at patients from Ist group against the carried complex preventive maintenances with administration LMWH depending on degree of thrombotic complications development risk on the 3rd, 7th days on the postoperative period there are any significant hyperco-agulation alterations changes have not revealed (Table 2).
As a shown the dates from Table 3 the analysis of conducted haemostasiological studying results was at women from IInd group receiving thromboprophylaxis with UFH characterized with increasing of the concentration of SFMC in comparison with control group and with its initial level which was revealed before operation. At these patients on admission to the hospital initial average level of SFMC (N up to 3.5 mg %) was 4.0 ± 1.0 mg %, in comparison with control group (2.8 ± 1.3 mg %) was to 42.8 % more (on the reliability p < 0.05); on the1st, 3rd, 7th days ofpostoperative period there was detected increase of its quantity (5.3 ± 1.3 mg. of %, 6.3 ± 1.6 mg %, 7.3 ± 0.8 mg % accordingly), the highest average curve occurred on 7-day (7.5 ± 0.6 mg %) and in comparison with its initial level was authentically increased to 82.5 % (p < 0.05), and against the control group it was on 2.7 times more. Fibrinogen concentration has begun to increase about on 3rd day (3.7 ± 0.7 g/l) and the highest average curve were observed on 7th day (4.3 ± 0.7 g/l) after hysterectomy. As increase SFMC at these patients confirmed about thrombinemia, joining increased amount of fibrinogen (N 2-4 g/l) in the 7-day confirms intensifying coagulation of investigated patients in the postoperative period (Table 3).
The analysis of results APTT which conducted in dynamics has demonstrated, that as distinctly from patients administered LMWH,
Prevention of postoperative thombotic complications at women with uterine myoma with low molecular weight heparin.
in patients from II nd group on 7th day was detected shortening of its meaning (on the average 33.8 ± 6.3 sec.) which testified to alteration of blood coagulation towards hypercoagulation. Despite on conducting thromboprofylaxion with UFH on the 7th day of postoperative period there were observed an activation of initial mechanisms of the internal cascade of haemostasis in these patients.
The analysis of dynamics oflaboratory parameters on the 7th day of postoperative period at patients of IInd group concerning to the high risk has shown, at these patients in comparison with patients concerning to the high risk of thromboembolic complications development under exposing abdominal hysterectomy against carrying out thromboprophylaxis with UFH haemostasiological pattern characterized of prethrombotic state which demands carrying out an optimal complex thromboprophylaxis. This is accompanied with synchronic increasing of SFMC and fibrinogen concentration with simultaneously shortening a time of APTT.
On the contrary, at carrying out thromboprophylaxis with LMWH there was demonstrated another haemostasiological pattern at control laboratory analysis which conducted in dynamics (Table 2). In comparison from patients of the retrospective analysis (II group), increasing amount of SFMC was insignificant, and it's the highest average curve in patients of I group was detected on 3-day (3.4 ± 2.9 mg %) in the postoperative period, in comparison with initial level was reduced on 10.5 % (prior to operation 3.8 ± 0.6 mg %). Significant increase of SFMC in the postoperative period during the studying of haemostasiogram analyses in patients from retrospective studying have detected especially in those patients who had accompanying extragenital pathologies, such as arterial hypertension, obesity, moderate anemia, varicose veins disease. Have especially been expressed at what had some accompanying pathologies.
Table 2. - Haemostasis state indices in after hysterectomy received
Table 1. - Haemostasis state indices in women from control group (n = 20)
Parameters Meanings Parameters Meanings
Fibrinogen (2-4 g/l) 2.3 ± 0.5 PR 1.02 ± 0.3
APT T (32-42 sec.) 37.7 ± 3.1 INR 1.2
PT (14-17 sec.) 15.3 ± 0.7 SFMC (up to 3.5 mg %) 2.8 ± 1.3
Postoperative decrease of PLC was detected in patients from II group in the 3rd day of postoperative period (229.0 ± 66.7 x 10 9/l), which explaining by heparin induced thrombocytopenia causing with administering of UFH, however LMWH does not influence of amount of platelets. Other parameters were within the limits of norm at all patients from I and II investigated groups (Table 1).
Conclusion
1. Received dates from studying have demonstrated, that traditional preventive maintenance of thromboembolic complications with administering UFH does not allow to result coagulation potential of patients with uterine myoma concerning to the high risk of development of thromboembolic complication at carrying out of abdominal hysterectomy even in an initial level which at them was before operative treatment.
2. Receiving LMWH simultaneously with complex measures for preventive maintenance postoperative thromboembolic complications with the account of degree of risk allows to decrease a little of thrombotic complications in women with uterine leyomyoma. Thus, administrating of Wobenzim as a desagregate therapy simultaneously with LMWH leads to the improvement ofhaemostasiological conditions, also, prevents and reduces not only developing of post operative thromboembolic complications, but reduces haemorragic complications caused by administering of antithrombotic therapy.
women with uterine myoma before and LMWH Clexan (I group n = 60)
Parameters Prior to 1st day 3rd day 7th day
Fibrinogen, g/l 2.5 ± 0.5 2.6 ± 0.6 2.7 ± 0.6 2.8 ± 0.7
APTT, sec. 35.3 ± 2.1 36.5 ± 2.4 37.5 ± 2.8 37.2 ± 3.1
PT, sec. 15.4 ± 0.9 16.2 ± 0.8 16.8 ± 1.4 16.6 ±1.4
PR, IU 1.03 ± 0.07 1.07 ± 0.06 1.05 ± 0.05 1.05 ± 0.05
INR 1.0 ± 0.1 1.1 ± 0.2 1.1 ± 0.2 1.1 ± 0.2
SFMC, mg % 3.8 ± 0.6 2.6 ± 2.1 3.4 ± 2.9 3.3 ± 2.8
T, 10 9/l 218.2 ± 33.6 217.2 ± 32.7 227.2 ± 33.8 220 ± 30.5
Table 3. - Haemostasis state indices in women with uterine myoma before and after hysterectomy received UFH (II group n = 158)
Parameters Prior to 1st day 3rd day 7th day
Fibrinogen, g/l 2.8 ± 0.6 3.0 ± 0.6 3.7 ± 0.7 4.3 ± 0.7*
APTT, sec. 37.7 ± 5.2 37.4 ± 5.2 35.3 ± 4.4 31.8 ± 6.3*
PT, sec. 15.6 ± 1.2 15.9 ± 1.2 15.9 ± 0.9 15.9 ±1.0
PR, IU 1.0 ± 0.1 1.1 ± 0.1 1.1 ± 0.1 1.1 ± 0.1
INR 1.0 ± 0.1 1.1 ± 0.1 1.1 ± 0.1 1.1 ± 0.1
SFMC, mg % 4.1 ± 1.1 5.3 ± 1.4 6.5 ± 1.6 7.5±0.6*
T, 10 9/l 210.7 ± 44.5 202.3 ± 27.4 229.7 ± 76.7 215.0 ± 35.4
References:
1. Antropova H. Yu., Korobov V. V., Kurtasanova E. S. Improvement of treatment-prophylactic maintenance for predict of developing thrombotic complications in patients with uterine myoma after uterine artery embolization//Med. Almanah. - Sep. 2010. - № 3 (12) - P. 86-89.
2. Dobrohotova Y. E., Allahverdiev S. A. Deep vein thrombosis and pulmonary thromboembolism problem in gynecological pa-tients//Zdorov'e. - Baku, 2007. - № 10. - P. 21-27.
3. Tihomirov A. L., Oleynik C. G. Preventive maintenance of thrombotic complications in the postoperative period in gynecology//Gy-necology. - Moscow, 2006. - № 1. - P. 41-44.
4. Geerts William H., Pineo Graham F., Heit John A. Prevention of venous thromboembolism//Chest. - 2004. - V. 126. - P. 338-400.
