Method of selecting heparin application for prevention of thrombotic complications

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used for determination of selection of heparin application for prevention of thrombotic complications. For this purpose level of soluble fibrin-monomer complexes is determined in blood plasma by means of ortho-phenantroline test. If its value is lower than 15.0 mg/100 ml transdermal way of heparin introduction is used. If the value is higher than 15.0 mg/100 ml parenteral way of heparin introduction is used.

EFFECT: method ensures efficient prevention of thrombotic complications due to selection of way of heparin introduction depending on degree of intravascular thrombus-formation.

4 tbl

 

The invention relates to medicine, in particular to laboratory diagnosis, and can be used to determine the choice of anticoagulant prophylaxis and therapy in patients with an increased risk of blood clots.

One of the important problems of medicine in many countries of the world, including in Russia, is the occurrence of venous thrombosis and thromboembolic complications, leading to high mortality and disablement. According to epidemiological data, the frequency of deep vein thrombosis in the General population in Russia annually is about 160 cases per 100,000 population. This danger is often underestimated by clinicians because these complications are usually latent, asymptomatic and develop in the nearest or the remote period after discharge from hospital for medical, surgical, rheumatic, gynecological and other categories of patients, including women with varicose disease of lower extremities during pregnancy and in the postpartum period, as well as with gestosis. High risk of thromboembolic complications requires hearingprotection. Currently available literature is not described laboratory criteria differentiated use of various forms of heparin, including, depending on the level of soluble Phi is Rin-monomer complexes (; fibrin monomer complex) - markers trombini.

There is a method of treatment and prophylaxis of thrombosis and thromboembolic complications by applying nefrackzionirovannam heparin and low molecular weight heparin in the form of a parenteral injection, intravenous or subcutaneous. The purpose of an injectable heparins substantiated the clinical picture of the disease and the increase in blood levels of markers of trombini - soluble fibrin-monomer complexes (; fibrin monomer complex), thrombin-antithrombin complex (TAT) and fragments 1+2 prothrombin (PT 1+2) (Barkagan SS, Momot A.P. Diagnostics and controlled therapy of disorders of hemostasis. - M.: Novamed, issue 3-E. - 292 S.).

The disadvantage of this method is the high invasiveness, risk of infection, the development of heparin-induced thrombocytopenia and osteoporosis.

The known method of prevention of thrombotic complications of percutaneous or transdermal route of administration of heparin based on the appropriate application of heparin ointment or gel (Gepatrombin, Lioton, Trembles and others). The known method of prevention of thrombotic complications has a systemic effect and can reduce the likelihood of thrombosis by reducing markers of trombini (Momot A.P., Roytman E.V., Serdyuk, GV, Agarkova T.A., Fadeeva NI Effectiveness of transdermal thrombosis prophylaxis drug "HepB is the thrombin pregnant risk for thrombosis and thromboembolic disease. // Thrombosis, hemostasis and rheology, 2008. No. 4. - P.39-42).

However, it is not clear at what level of trombini and, accordingly, the degree of thrombogenic risk shows the use of parenteral and in a transdermal routes of administration of heparin.

The authors propose a selection method, use of heparin for the prevention of thrombotic complications, transdermal or parenteral injection in patients with hypercoagulation syndrome and thrombogenic risk level of soluble fibrin-monomer complexes in plasma, determined by orthophenanthroline test, consisting in the application of the transdermal method of heparin in patients with a value of soluble fibrin-monomer complexes in plasma to 15.0 mg/100 ml, inclusive, and in the use of the parenteral forms of administration of heparin in the level of soluble fibrin-monomer complexes in plasma over 15,0 mg/100 ml

The technical result of the proposed method is differentiated approach to the choice of the use of heparin for the prevention of thrombotic complications due to the choice of route of administration: parenteral or transdermal.

The technical result is achieved in that the method is carried out taking into account the level of soluble fibrin-monomer complexes in plasma by orthophenanthroline test and p and the values less than 15,0 mg/100 ml apply the transdermal route of administration, but values over 15,0 mg/100 ml parenteral heparinization.

The method is as follows.

Determine soluble fibrin-monomer complexes in plasma by orthophenanthroline test.

Blood taken in the morning on an empty stomach from the cubital vein with a needle without syringe (by gravity) and immediately mixed with a 3.8% solution of sodium citrate. Stable blood before centrifugation (including during transportation) store at room temperature (+18...+25°C) not more than 1 hour a Study of blood with clots or hemolysis is not allowed. Stable blood is centrifuged at 1000 rpm (140-160 g) for 5-7 min, while the precise number of rpm in accordance with the radius of the centrifuge rotor. Platelet-rich plasma with a pipette and transferred to another test tube, in which it further centrifuged at 3000-4000 rpm (1200-1400 g) for 15 minutes, the result is poor platelet plasma (BTP).

Material for the study. BTP.

BTP exploring not later than 1 h after receiving blood, freezing is not recommended.

The reagents. 1. Orthophenanthroline hydrochloride, 70 mg vial (the production company "Technology Standard", Barnaul, catalogue No. 081). Bred by introducing into the vial 10.0 ml of distilled water.

The course definition. At room temperature (+18...+25°C) to 0.1 ml of ASC is adhemas plasma add 0.1 ml orthophenanthroline, immediately include stopwatch. With continuous rocking of the tube in transmitted light against a dark background, record the time from the moment of addition of the reagent prior to the occurrence of the first cereals (grains) of fibrin. Accounting is carried out for 150 C.

An assessment of the results. In transmitted light is recorded, the time of appearance of the first visible flakes or grains of paracomplete.

Table 1 shows the evaluation results of orthophenanthroline test (in seconds) and the quantitative content of soluble fibrin-monomer complexes in plasma. Note the time of their appearance in seconds and table 1 define the number; fibrin monomer complex in the plasma. The average normal level; fibrin monomer complex plasma is 3,38±0.02 mg/100 ml with limits of normal variability (±1,5σ) from 2,72 up to 4.03 mg/100 ml

The test is a quantitative indicator of the presence; fibrin monomer complex in plasma and is used to assess the effectiveness and adequacy of anticoagulation prophylaxis and therapy for the ultimate result is the elimination of trombini.

Approbation of the proposed selection method, use of heparin for the prevention of thrombotic complications

Testing of the proposed method were studied in 40 patients with hypercoagulation syndrome and high thrombogenic risk in the plasma which was identified elevated levels of soluble fibrin-monomer is of kompleksow: 15 pregnant women with preeclampsia (mild or moderate severity (the average age of 26.8±1,5), 10 pregnant women with varicose disease of lower extremities (the average age is 27.4±1,50) and 15 patients with hematogenous thrombophilia and postthrombotic syndrome without exacerbation (mean age of 36.7±2,2), of which the increase of orthophenanthroline test less 15,0 mg/100 ml was observed in 21 (53%) patients and more than 15,0 mg/100 ml - 19 (47%) of the surveyed.

Methods of transdermal application of gel heparin "Lioton 1000": the gel is applied on the inner surface of the leg by 5 cm (about 2500 units), not massaging fabric on both legs in the morning and evening for 7 to 14 days. The duration of use of the gel was motivated by the dynamics of indicators of trombini concentration of soluble fibrin-monomer complexes in the plasma of venous blood 7-10 and 11-14 days. From the beginning of reception of a preparation in 34 (85%) of 40 patients thrombinase the level of soluble fibrin-monomer complexes decreased and the patients continued to take heparin in gel form. In 6 patients (15%) were received positive level of soluble fibrin-monomer complexes, and these patients were transferred to an injectable form of heparin, the purpose of which was decreased soluble fibrin-monomer complexes in plasma (table 2-4). In table 2 are given the dynamics of soluble fibrin-monomer complexes when using transdermal (in the form of a gel and parenteral administration of heparin in pregnant women with preeclampsia mild and moderate. In table 3 are given the dynamics of soluble fibrin-monomer complexes when using transdermal (in the form of a gel) and parenteral administration of heparin in pregnant women with varicose disease of lower limbs. Table 4 presents the dynamics of soluble fibrin-monomer complexes when using transdermal (in the form of a gel) and intravenous heparin in patients with hematogenous thrombophilia and postthrombotic syndrome.

The results obtained indicate that the proposed selection method, use of heparin for the prevention of thrombotic complications in the level of soluble fibrin-monomer complexes, defined orthophenanthroline test showed that the application of ointment (gel)containing nefrackzionirovannam heparin having anticoagulant activity, can be used for the prevention of intravascular thrombus formation when hypercoagulation syndrome and in patients with low-to-moderate thrombogenic risk in the concentration of soluble fibrin-monomer complexes in plasma to 15.0 mg/100 ml on orthophenanthroline test. In patients with Terminalia by the presence of soluble fibrin-monomer complexes in plasma over 15,0 mg/100 ml to prevent further intravascular thrombus formation and occurrence of thrombosis is neobhodimy injectable form of heparins.

Thus, the inventive method of choice use of heparin for the prevention of thrombotic complications in determining trombini depending on the level of soluble fibrin-monomer complexes orthophenanthroline method allows for a degree of intravascular thrombosis conduct differentiated hearingprotection in the form of transdermal or parenteral administration of heparin.

10
Table 1
The selection method of the use of heparin for the prevention of thrombotic complications
TimeConcentration; fibrin monomer complex, mg/100 mlTimeConcentration; fibrin monomer complex, mg/100 ml
5-628,021-2310,0
726,024-259,0
824,0268,5
922,027-288,0
21,029-317,5
1119,032-337,0
12of 17.034-366,5
1316,037-406,0
1415,041-455,5
1514,046-545,0
1613,055-694,5
17-18to 12.070-874,0
19-2011,088-1203,5
Over 1203,0

-
Table 2
The selection method of the use of heparin for the prevention of thrombotic complications
The group surveyedLevel; fibrin monomer complex in plasma, mg/100 ml
Before the treatmentWhen heparin (day)
The transdermal route of administrationParenteral route of administration
7-1011-147-1011-14
1. D.N.of 17.015,06,0--
2. I.E.of 17.0to 12.09,0--
3. CU21,019,0-9,0-
4. GA16,014,0 8,5--
5. P.E.24,021,0-10,0-
6. SN.22,018,015,0--
7. V.O.of 17.013,011,0--
8. VEof 17.0to 12.09,0--
9. E.E.16,0to 12.08,0-
10. P.A.16,013,011,0-
11. SURDS19,016,014,0-
12. GU16,010,07,5--
13. O.T.of 17.0to 12.06,5--
14. MV18,011,09,0--
15. A.L.22,019,0-11,0-
X±m18,3±0,714,5±0,98,8±0,610,3±0,9-

Table 3
The selection method of the use of heparin for the prevention of thrombotic complications
The group surveyedLevel; fibrin monomer complex in plasma, mg/100 ml
Before the treatmentWhen heparin (day)
The transdermal route of administrationParenteral route of administration
7-1011-147-1011-14
1. M.A.14,09,06,5--
2. BO15,010,07,5--
3. M.I.16,011,05,5--
4. O.Y18,0to 12.010,0--
5. M.E. Ter-Minassian13,06,55,5--
6. RU 15,011,08,0--
7. NSof 17.013,010,0--
8. P.A.16,09,57,5--
9. G.14,010,06,0--
10. K.L.15,09,06,5--
X±m15,3±0,511,0±1,18,2±1,2--

Table 4
The selection method of the use of heparin for the prevention of thrombotic complications
Grumpyoldman Level; fibrin monomer complex in plasma, mg/100 ml
Before the treatmentWhen heparin (day)
The transdermal route of administrationParenteral route of administration
7-1011-147-1011-14
1. A.T.15,0to 12.09,5--
2. L.M.14,010,07,5--
3. LI18,013,06,0--
4. T.A.19,0of 17.0-7,0-
5. C.Oof 17.014,0 11,0--
6. G.19,018,0-11,0-
7. V.O.18,0to 12.09,0--
8. K.A.15,09,58,0--
9. II18,015,011,0--
10. L.A.14,011,08,0--
11. B.A.13,010,07,0--
12. HL14,010,07,0- -
13. GV15,09,04,5--
14. K.L.13,06,54,0--
15. GT19,0of 17.0-10-
X±m16,1±0,612,3±0,97,7±0,69,3±1,2

The selection method of applying heparin to prevent thromboembolic complications, which is carried out taking into account the level of soluble hybridmonolith complexes in plasma by orthophenanthroline test and at values less than 15,0 mg/100 ml apply the transdermal route of administration, but values over 15,0 mg/100 ml parenteral heparinization.



 

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