[Significance of the determination of B2-glycoprotein-1 antibodies in recognizing the thrombogenicity in antiphospholipid syndrome].

According to the recent data, the determination of the higher titer of antibodies to beta2-glycoprotein-I (beta2-GP-I) that is included in a complex compound with negative phospholipid membranes determinates the thrombogenicity in antiphospholipid syndrome (APS). To specify this regularity, the authors examined 86 patients with primary APS and 20 patients with venous and arterial thrombosis without APS. With increased beta2-GP-I antibody levels, the incidence of thrombotic events was established to w significantly higher than in APS without the increased titer of beta2-GP-I antibodies. In primary APS-associated persistent miscarriage, the increased titer of beta2-GP-I is much more infrequently encountered.

[Laboratory monitoring of recombinant factor VIIA effects].

Recombinant activated factor Vll originally proposed to prevent and arrest bleedings in patients with the inhibitory form of hemophilia has been shown to be a universal hemostatic agent that is effective in arresting and preventing a broad spectrum of spontaneous and postoperative hemorrhages. Procedures for monitoring the action of this agent on the hemostatic system have not been studied so far. The paper presents the results of a study of various parameters of the hemostatic system in patients with profuse hemorrhages before and after the use of recombinant activated factor VII. It has been ascertained that monitoring of the pharmacokinetics of the agent can be achieved when the prothrombin test with bovine thromboplastin is carried out.

[Diagnostic procedure for thrombophilia due to factor VIII hyperproduction].

The range of factor Vlll (FVlll) is known to be very wide and its elevated concentration is a risk factor of thromboses. This paper describes a simple and available laboratory method for determining the high level of coagulation FVlll. Moreover, the results of determination of FVlll levels in 102 patients were used to study the incidence of thrombophilia due to FVlll hyperproduction in a region of Western Siberia.

[Phlebothrombosis and pulmonary thromboembolism in patients with thrombophilia].

A study was made of the course of phlebothrombosis ana pulmonary thromboembolism in 54 patients with thrombophilia. Of these, 23 patients had factor la resistance to protein C, 15 presented with antiphospholipid syndrome, four with protein C deficit, one with protein S deficit, three with antithrombin III deficiency, and three patients with hyperhomocysteinemia. Five patients presented with the following combined forms of thrombophilia: thrombophilia due to protein C deficit and antiphospholipid syndrome; protein C deficit and hyperhomocysteinemia; protein C and antithrombin III deficit; factor Va resistance to protein C and hyperhomocysteinemia; antiphospholipid syndrome and hyperhomocysteinemia. Thrombosis of the inferior vena cava (IVC) was present in 52 and PTE in 27 patients, The recurrence of phlebothrombosis was recorded in 40 (76.9%), that of PTE in 12 (44.4%) patients. The time elapsed between disease exacerbations accounted for one month to nine years, the number of recurrences constituted two to 6. Initially, thrombosis in three patients was located in lower limb saphenous veins, in 18 in the tibial and femoral veins, in 29 in the femoral and iliac veins; two patients presented with femoroiliocaval phlebothrombosis. The recent control examination revealed thrombosis of the saphenous veins in two patients. In ten patients, thrombosis was located in the tibiofemoral segment, in 19 patients, it was discovered in the femoroiliac and in two cases, in the femoroiliocaval segment. During observation period, venous thrombosis in the previously intact lower limb developed in nine (16.7%) patients. Thrombosis of other vessels inclusive of the organ ones was present in 14 (25.9%) patients. Of these, seven patients had thrombosis of the arteries of the upper and lower limbs: in four cases, it was located in the system of the IVC and in two cases, in the mesenterial arteries; ischemic stroke was recorded in two cases, thrombosis of the portal vein in one, and myocardial infarction was also marked in one case. In view of different hemostatic changes underlying the development of venous thromboses and PTE, we carried out differentiated therapy applying anticoagulants, platelet inhibitors, and transfusions of quickfrozed plasma. In acute femoroiliac and caval thromboses and PTE, 40 patients were provided implantation into the IVC of the cava filter <>. After cava filter implantation 16 patients developed tnrombosis of the IVC. Embolism to the cava filter occurred in seven patients. In three cases, it terminated in occlusion of the IVC and in the remaining cases, in its recanalization. Over the period one to six years, occlusive thrombi of the IVC underwent recanalization in 11 patients. Analysis of the course of phiebothrombosis and PTE in patients with thrombophilia made it possible to define situations that require its goal-oriented search. It is demonstrated that it is advisable to implant the cava filter <> to the permanent position in thromboses of the femoral, iliac veins and of the IVC as well as in PTE.

[Changes of platelet aggregation in cancer patients].

Aggregation function of platelets was investigated in 119 patients with breast cancer, 17--gastric cancer and 11--cancer of large bowel. Levels of spontaneous and induced aggregation were abnormally high thus contributing to thrombophilic potential. Also, they were a factor of tumor progression and metastatic spread. Risk of thrombotic complication can be reduced and survival improved by administration of antiaggregants.

[A new method for determination of antithrombin III and its diagnostic significance]. / Novyi metod opredeleniia antitrombina III i ego diagnosticheskoe znachenie.

A new assay based on using an original chromogenic substrate (z-Ala-Ala-Arg-pNa) and designed for the determination of antithrombin III is described in the paper. It was used in examinations of patients with malignancy after surgery. The content of antithrombin III was detected to be lower in 12% of cases in 2 days after surgery. Additionally, patients with DIC, as complications after surgery, were examined to find out that the antithrombin III content was decreasing in them.

[A method for determining plasminogen with a Russian chromogenic substrate and its diagnostic significance]. / Metod opredeleniia plazminogena s otechestvennym khromogennym substratom i ego diagnosticheskoe znachenie.

Measurement of plasminogen, the key component of fibrinolysis system, is one of the basic methods for estimation of fibrinolysis. Methods based on the use of chromogenic substrates are often used in diagnosis. Plasminogen measurements are important for laboratory diagnosis of thrombophilia caused by deficiency or abnormalities of this fiber, for detection and evaluation of the DIC syndrome, and for monitoring the treatment by fibrinolytic preparations (streptokinase, t-PA, urokinase, etc.). An original chromogenic substrate having no foreign analogs has been created at Institute of Genetics and Selection of Industrial Microorganisms and Research Center of Hematology (Moscow). Unlike previously described plasmin substrates, pNa has been obtained by microbiological methods with Russian commercial enzymes subtilisine 72 and megaterine. This paper presents the results of plasminogen measurements in patients with DIC with the use of the original chromogenic substrate. The results were compared with those of tests with Berihrom-Plasminogen diagnostic kit (Behringwerke AG).

[Biochemical characteristics of liver involvement in patients with antiphospholipid syndrome]. / Biokhimicheskie osobennosti porazheniia pecheni u bol'nykh s antifosfolipidnym sindromom.

The incidence of hepatitis B and C virus and cytomegalovirus infection is high in patients with the antiphospholipid syndrome (APS). The specific features of virus infection in APS patients are determined by the activity of APS. During clinically manifest stage, the activities of aminotransferases, lactate dehydrogenase (LDH), and alkaline phosphatase increase, while during remission only aspartate aminotransferase and LDH levels remain high, for this latter enzyme high activities of isoenzymes LDH5 and LDH4 being recorded. These data indicate that the pathological process in APS involves not only the liver, but the sinusoidal endothelium as well. This seems to account for some other clinical and laboratory manifestations of APS, such as increased level of circulating immune complexes, dysfunction of physiological anticoagulants, etc.

Safety of low-molecular-weight heparin in pregnancy: a systematic review.

Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical reports concerning the use of LMWH during pregnancy. In addition, participants of an international interest group contributed a cohort of pregnant women treated with LMWH. Pregnancies were divided into two groups; those with and those without maternal comorbid conditions. The number of adverse fetal outcomes and the occurrence of maternal complications were evaluated in the two groups. In the group of women with comorbid conditions (n = 290), 13.4% of the pregnancies were associated with an adverse fetal outcome. In contrast, in the group of women without comorbid conditions (n = 196), 3.1% were associated with an adverse outcome, which is comparable to that seen in the normal population. We conclude that LMWH appear to be a safe alternative to unfractionated heparin as an anticoagulant during pregnancy.

[Comparative data on the use of a cryosupernatant and fresh-frozen plasma in the therapy of a protracted infectious-septic syndrome of disseminated intravascular coagulation]. / Sravnitel'nye dannye ob ispol'zovanii kriosupernatanta i svezhezamorozhennoi plazmy v terapii zatiazhnogo infektsionno-septicheskogo sindroma disseminirovannogo vnutrisosudistogo svertyvaniia krovi.

AIM: To compare therapeutic effectiveness of cryosupernatant plasma fraction (CSP) and fresh-frozen plasma (FFP) in long-term infectious-septic DIC syndrome arising in acute abscess and gangrene of the lung. MATERIALS AND METHODS: 106 and 131 patients with infectious-septic DIC syndrome were treated with CSP and FFP, respectively. The results of the treatment were compared clinically and hemotopogically. RESULTS: Clinical response to both treatments was evident from positive changes in XIIa-dependent fibrinolysis, lowering of fibrinogen level and enhanced activity of antithrombin III. CSP treatment brought about a decrease in the number of thromboses, lethal cases, unfavorable outcomes. CONCLUSION: The cryosupernatant can be used instead of fresh-frozen plasma in combined treatment of long-standing infectious-septic DIC syndrome.

[Use of elimination of plasma phospholipid membranes for detection of "lupus anticoagulant" effects]. / Ispol'zovanie eliminatsii fosfolipidnykh membran plazmy dlia vyiavleniia effektov "volchanochnogo anticoagulianta".

The coagulation activity of plasma phospholipid membranes (PM) was measured in plasma depleted for platelets (PDP) in 50 normal subjects and 33 patients with the antiphospholipid syndrome (APS) and the "lupus anticoagulant" in the plasma. The normal value for phospholipid activation of clotting was 99.8 +/- 3.5% (from 75 to 125%), whereas in patients with APS and lupus anticoagulant it was 42.1 +/- 8.2% (p < 0.001). Addition of PM from patients' PDP to normal plasma free from PM did not normalize clotting. Addition of PM from normal plasma to patients' PDP normalized the clotting time. Therapy with discrete plasmapheresis increased the phospholipid activation value in the patients from 42.1 to 73.3% (p < 0.01), which was due to removal of the PM-antiphospholipid antibody complex from PDP. The proposed microfiltration method can be used in the complex of tests for detecting the lupus anticoagulant in patient's plasma.

[Comparative analysis of various methods of determination of fibrinogen in the plasma]. / Sravnitel'nyi analiz razlichnykh metodov opredeleniia fibrinogena v plazme krovi.

Fibrinogen was measured in the plasma of normal subjects and patients with various hemostasis disorders by gravimetric methods with thromboplastin coagulation and coagulation with Echis multisquamatus snake venom. Coagulation was assessed using optic Coag-Mate HM (Netherlands) and roll Amelung KC4A (Germany) coagulometers during coagulation with thrombin after Klauss and with the above venom. The results were compared with those of fibrinogen measurements by radial immunodiffusion using Behring antifibrinogen serum. The data of all methods coincided if the initial levels of fibrinogen were normal, whereas in manifest hypo- or hyperfibrinogenemia Klauss' method was the most accurate and informative.

[Initial experience in the diagnosis of thrombophilia due to activated protein C resistance]. / Pervyi opyt diagnostiki trombofilii, obuslovlennoi rezistentnost'iu k aktivirovannomu proteinu C.

The authors describe the first in Russia cases of thrombophilia caused by factor Va resistance to activated protein C. This abnormality was diagnosed in 6 of 25 patients (24%) with recurrent early thrombosis. The diagnosis was conducted according to a modified method implying the addition of protac (activator of protein C) to normal platelet poor plasma (PPP) free of factor V containing 100% of protein C. Protac dose was adjusted to increase the activated partial thromboplastin time (APTT) 2.4-2.8-fold in mixing PPP of the examinee with plasma containing activated protein C. The indices were estimated indicative of insufficient prolongation of APTT in response to activated protein C. Of 6 patients, 2 had apparent and 4 strong resistance to activated protein C. Treatment policy in this variant of thrombophilia is discussed.

[Prevalence, diagnosis and clinical significance of thrombophilia caused by Va factor resistance to activated C protein]. / Rasprostranennost', diagnostika i klinicheskoe znachenie trombofilii, obuslovlennoi rezistentnost'iu faktora Va k aktivirovannomu proteinu C.

Examining 26 patients with early recurrent venous thrombophilias and ischemic attacks revealed that 6 cases had Va factor resistance to activated C protein. The latter suggests that thrombophilia associated with hereditary C- protein resistance is recorded in the Russian population, among the residents of West Siberia in particular.