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PubMed1999

Association of a decrease in antithrombin III activity with a perinatal elevation in aspartate aminotransferase in women with twin pregnancies: relevance to the HELLP syndrome.

BACKGROUND/AIMS: Decreased antithrombin III (AT-III) activity and/or thrombocytopenia associated with an elevated serum level of aspartate aminotransferase in late pregnancy can threaten the lives of both the mother and the fetus. We investigated whether antenatal declines in AT-III activity and the platelet count occur in late twin pregnancy and whether reduced AT-III activity and/or thrombocytopenia precedes an increase in the serum level of aspartate aminotransferase. METHODS: The platelet count, AT-III activity, and the serum level of aspartate aminotransferase were determined weekly or biweekly in 237 women with twin pregnancies in a longitudinal and partly prospective study. RESULTS: Both AT-III activity and the platelet count decreased gradually in the last month of pregnancy, irrespective of the presence or absence of clinical signs of pre-eclampsia. A perinatal elevation in aspartate aminotransferase occurred in 36 (15%) of 237 women. The risk of a perinatal elevation in aspartate amino-transferase increased as the antenatal AT-III activity and/or the platelet count decreased. Pre-eclampsia developed in 60 women (25%). The relative risk of a perinatal aspartate aminotransferase elevation (95% confidence interval) for the 60 women with pre-eclampsia, the 60 women with a platelet count < or = the 25th percentile (164 x 10(9)/1), and the 60 women with AT-III activity < or = the 25th percentile (76% of normal) was 1.9 (1.0 to 3.4), 4.1 (2.3 to 7.5), and 5.9 (3.2 to 11.1), respectively, compared with the remaining 177 women. CONCLUSIONS: AT-III activity and platelet count gradually decreased in the last month of twin pregnancies. A perinatal aspartate aminotransferase elevation was preceded by marked decreases in these parameters in women with twin pregnancies. The monitoring of AT-III activity and platelet count in women who exhibit a gradual decline in these parameters may help to avoid the development of severe HELLP syndrome.

Adult↗
PubMed2003

Novel approach for preparation of heparins specific to factor Xa using affinity chromatography coupled with synthetic antithrombin III-related peptides.

In the blood coagulation cascade, heparin activates human plasma antithrombin III (hAT III), resulting in the inhibition of factor Xa. This polysaccharide also exhibits hemorrhagic tendency mediated by the inhibition of thrombin in heparinotherapy. Therefore, attention has focused on the development of low molecular weight heparins (LMW-heparins) that inhibit factor Xa but not thrombin. In this investigation, we examined the biochemical and physicochemical properties of hAT III-derived heparin-binding peptides (HBPs). Of all the tested HBPs, hAT III (123-139) exhibited the highest affinity with heparin and showed an inhibitory effect on the heparin-induced enhancement of hAT III activity toward factor Xa, indicating that hAT III (123-139) specifically interacts with the active region in heparin. We prepared a synthetic hAT III (123-139)-coupled affinity chromatography system, and demonstrated that this novel affinity chromatography is useful for fractionation of highly active moieties in LMW-heparins.

Anticoagulants↗
PubMedDate not supplied

[Treatment of deep venous thrombosis in congenital antithrombin III deficiency with low molecular weight heparin].

A 19-year old male patient with hereditary antithrombin III type I deficiency was admitted for thrombosis of the right iliac, femoral and popliteal veins. Treatment with a low molecular weight heparin resulted in recanalization of the veins confirmed by phlebography. After two weeks of treatment, the drug was replaced by another low molecular weight heparin and this was followed, 3 weeks later, by a documented relapse of thrombosis.

Adult↗
PubMed1991

Effect of hemodialysis on protein C, protein S, and antithrombin III levels.

We studied the effect of hemodialysis on natural coagulation inhibitors including protein C (PC), protein S (PS), and antithrombin III (AT III), as well as the correlations between the antigen level (immunological activity) and functional activity of individual coagulation inhibitor. Plasma AT III, PS, and PC were measured in 20 uremic patients on maintenance hemodialysis immediately before, during, and after dialysis treatment. These values were compared with those obtained from 20 matched healthy controls. Plasma PC and total PS antigen levels were measured by enzyme immunoassay. The plasma AT III antigen level was determined by Laurell rocket immunoelectrophoresis. Functional activities of PC and AT III were determined by the amidolytic method. Free PS antigen level was quantitated by measuring the free PS-related antigen after the sample was treated with polyethylene glycol to remove the C4b-binding protein. Uremic patients on maintenance hemodialysis had a higher total PS antigen level, but a lower free PS antigen level compared with the controls. Both the antigen level and functional activity of AT III in uremic patients were significantly lower than those of controls. Their predialysis plasma PC antigen level and functional activity were not different from those of normal controls. A significant correlation between the antigen level and functional activity of PC, PS, and AT III was demonstrated in healthy controls, but not in hemodialysis patients. No significant change in the level of AT III or PS was observed with hemodialysis, but a progressive increase of functional activity of PC was documented with hemodialysis. Furthermore, the coefficient of correlation between the antigen level and functional activity of PC improved significantly with dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1980

Anticoagulant activity of artificial biomedical materials with co-immobilized antithrombin III and heparin.

An approach to providing anticoagulant activity to biomedical materials was presented, applying an immobilization technique. Antithrombin III (AT III) inactivates the activated coagulation factors including Factor Xa and thrombin. Heparin stimulates the inactivation of Factor Xa and thrombin by AT III. Thus AT III and heparin were co-immobilized on Sepharose 4B, polyvinyl alcohol, polyhydroxy-ethyl methacrylate and silicone-coated nylon by the cyanogen bromide procedure. Those co-immobilized preparations, abbreviated as I-AT III . Hep, actively neutralized both Factor Xa and thrombin. The activity of I-AT III . Hep was much higher than immobilized heparin and/or immobilized AT III. I-AT III . Hep, like soluble AT III and heparin, instantaneously neutralized both thrombin and Factor Xa. When two enzymes, thrombin and Factor Xa, were present, I-AT III . Hep neutralized Factor Xa in preference to thrombin : The neutralization of thrombin was inhibited by the presence of Factor Xa, but neutralization of Factor Xa was independent of the presence of thrombin. The amount of Factor Xa neutralized was higher than that of thrombin.

Animals↗
PubMed1996

Fibronectin and antithrombin as markers of pre-eclampsia in pregnancy.

INTRODUCTION: The differential diagnosis between pre-eclampsia and chronic hypertension is not easy, but is essential to proper management of a pregnancy. Patients presenting pre-pregnancy hypertension can be treated conservatively, if not a superimposed pre-eclampsia occurs, controlling pressure pharmacologically and completing the pregnancy with a natural delivery. In pre-eclampsia, hypertension is merely the visible sign of a process of endothelial damage and coagulation cascade activation which is often destined to emerge clinically on a dramatic scale. MATERIALS AND METHODS: The study involved 18 women with physiological pregnancies, 19 with pre-eclampsia and 13 with chronic hypertension since superimposed pre-eclampsia. The following laboratory tests were performed: PT, PTT, AT-III, proteins C and S, platelet count, D-dimer, fibrinogen and plasma fibronectin. The three groups were compared using the Kruskall Wallis test, the median test and, for multiple comparisons, the Mann-Whitney test. A 'P' value of < 0.01 was considered as statistically significant. RESULTS: The values for plasma fibronectin were higher in the pre-eclampsia group (410 mg/l (253-727)) than in controls (262 mg/l (183-385)) (P < 0.01) and values for AT-III were lower in the pre-eclampsia group (73% (40-100)) than in controls (93% (80-126) (P < 0.01) (Table 2). The groups with chronic hypertension revealed no such significant differences, however, in relation to the control group (fibronectin = 296 mg/l (198-530), AT-III = 86% (75-103)). CONCLUSIONS: Measuring antithrombin and fibronectin to monitor any onset of pre-eclampsia can help the obstetrician to avoid important diagnostic and therapeutic errors.

Adult↗
PubMed1997

Generation of thrombin in blood plasma of non-pregnant and pregnant women studied through concentration of thrombin-antithrombin III complexes.

OBJECTIVE: The main question in this study is how much more thrombin is generated in blood plasma of pregnant women than in non-pregnant women. STUDY DESIGN: Thrombin-antithrombin III complexes (TAT) were used as markers of thrombin generation in vivo. They were measured by the ELISA method in blood plasma of 15 non-pregnant and 43 pregnant, as well as 30 parturient women and 10 women after delivery. RESULTS: With normal menstrual cycles, TAT levels did not change significantly throughout the cyclic phases, and the mean +/- S.D. calculated for all cyclic phases was 1.9 +/- 0.3 micrograms/l. In the 2nd trimester the level of TAT was 16.0 +/- 2.8 micrograms/l and at term 21.5 +/- 11.9 micrograms/l. Throughout the 1st and 2nd stage of labour the level of TAT increased insignificantly, but after placenta separation it was significantly higher than before labour (30.8 +/- 20.4 micrograms/l). In the 3rd and 7th days after delivery the level of TAT was still higher than in non-pregnant women. CONCLUSION: It was found that the level of TAT in normal menstrual cycles is stable, whereas it increases in pregnancy. Relating the values of the cycle to those of pregnancy it was calculated, that at the end of pregnancy there is a ten-fold increase of TAT level and after placenta separation and expulsion--temporarily even fifteen-fold--increase. In the 3rd to 7th day after delivery, the TAT level was still higher than in non-pregnant women.

Adult↗
PubMed2001

Probing the molecular basis of factor Xa specificity by mutagenesis of the serpin, antithrombin.

The molecular basis of the substrate and inhibitor specificity of factor Xa, the serine proteinase of the prothrombinase complex, was investigated by constructing two mutants of human antithrombin (HAT) in which the reactive site loop of the serpin from the P4-P4' site was replaced with the corresponding residues of the two factor Xa cleavage sites in prothrombin (HAT/Proth-1 and HAT/Proth-2). These mutants together with prethrombin-2, the smallest zymogen form of thrombin containing only the second factor Xa cleavage site, were expressed in mammalian cells, purified to homogeneity and characterized in kinetic reactions with factor Xa in both the absence and presence of cofactors; factor Va, high affinity heparin and pentasaccharide fragment of heparin. HAT/Proth-1 inactivated factor Xa approximately 3-4-fold better than HAT/Proth-2 in either the absence or presence of heparin cofactors. In the absence of a cofactor, factor Xa reacted with the HAT/Proth-2 and prethrombin-2 with similar second-order rate constants (approximately 2-3x10(2) M(-1)s(-1)). Pentasaccharide catalyzed the inactivation rate of factor Xa by the HAT mutants 300-500-fold. A similar 10(4)-10(5)-fold enhancement in the reactivity of factor Xa with prethrombin-2 and the HAT mutants was observed in the presence of the cofactors Va and heparin, respectively. Factor Va did not influence the reactivity of factor Xa with either one of the HAT mutants. These results suggest that (1) in the absence of a cofactor, the P4-P4' residues of HAT and prethrombin-2 primarily determine the specificity reactions with factor Xa, (2) factor Va binding to factor Xa is not associated with allosteric changes in the catalytic pocket of enzyme that would involve interactions with the P4-P4' binding sites, and (3) similar to allosteric activation of HAT by heparin, a role for factor Va in the prothrombinase complex may involve rearrangement of the residues surrounding the scissile bond of the substrate to facilitate its optimal docking into the catalytic pocket of factor Xa.

Antithrombins↗
PubMed2001

The impact of antithrombin (H) concentrate infusions on pulmonary function in the acute phase of thermal injury.

BACKGROUND: Pulmonary complications occur frequently after thermal injury. OBJECTIVE: This open pilot study was performed as an initial assessment of the safety and efficacy of antithrombin H [AT(H)] concentrate in ameliorating the respiratory morbidity during the acute phase of injury. MATERIALS & METHODS: Thirty-two patients were eligible for the study; of these, nine opted for treatment with q8 h [AT(H)]. The mean daily peak values of pulmonary parameters such as PaO(2)/FiO(2) ratio, and RAW scores were computed for days 1-8. RESULTS: Control and AT(H)-treated patients were similar in age, % total burn surface area, inhalation injury, and mortality. Forty-three percent of the burn controls, and 23% of the AT(H)-treated patients had pneumonia, p<0.01. The median hospital stay for both groups was 42 days; however, the median number of ventilatory days for burn controls was 23 days vs 10 days for AT(H)-treated patients. The AT(H)-treated patients had admission AT plasma levels of 46+/-14% vs 49+/-18% in burn controls, (normal=100+/-20%). The AT plasma level was maintained at 120+/-24% in the AT(H)-treated patients vs 50+/-15% in the burn control group for the first four days following the acute injury, p<0.002. Thrombate(R) concentrate infusions were, in general, well tolerated by patients. The median dose was 97 u/kg/dose q8 h. Compared to burn controls, AT(H)-treated patients had higher PaO(2)/FiO(2) ratios between days 4-6, p<0.01. In comparing these two groups with and without inhalation, airway resistance (assessed by the RAW score) was significantly lower in the AT(H)-treated group with inhalation compared to the burn controls with inhalation on days 2 and 6, p<0.02. CONCLUSIONS: With a trend toward decreased airway resistance during AT(H) concentrate infusions, and increased oxygenation, AT(H)-treated patients had significantly fewer episodes of pneumonia compared to controls. AT(H) concentrates may modify the impact of thrombin on acute inflammation, and improve respiratory function in the acute phase of thermal injury.

Adult↗
PubMed2003

Antithrombin (human) concentrate infusion in pediatric patients with >50% TBSA burns.

BACKGROUND: Antithrombin (human) [AT(H)] concentrate infusions have been safely utilized in adult burn patients to counteract subclinical disseminated intravascular coagulopathy and pulmonary complications. OBJECTIVE: AT(H) concentrate was given to two thermally injured pediatric patients to evaluate safety and dosage requirements. DESIGN: The first patient was a 2-year-old with 83% total burn surface area (TBSA) full thickness flame burn and severe inhalation injury. The second patient was a 14-month-old who sustained 56% TBSA deep partial and full thickness scald injury. Each child received 10 infusions of AT(H) concentrate (106 units/kg) in the first 4 days post-injury. RESULT: For these two patients, the plasma AT level (normal range: 100+/-20%) increased, respectively, from 25 and 66% on admission to 224 and 217% on day 1, 114 and 116% on day 2, and 193 and 171% on day 3. Both patients tolerated the infusions well. In one patient, the eschar on all four extremities easily peeled off the subcutaneous tissues along a natural demarcation between viable and non-viable tissue with only a 40cc estimated blood loss (EBL). CONCLUSIONS: AT(H) concentrate is tolerated in the pediatric population in the acute phase of injury. Lack of bleeding during eschar removal may be of benefit to burn excision and grafting.

Antithrombins↗
PubMed1997

Is there a need for antithrombin III substitution early after burn injury?

The changes in antithrombin III (AT-III) levels in the blood and restitution in coagulation parameters between patients receiving and not receiving AT-III substitution were examined early after burn injury. The study was divided into two parts with a total of 14 consecutive patients (per cent total body surface area (TBSA) > or = 20 per cent). The first six patients were given AT-III substitution when AT-III levels fell below 50 per cent. The second part examined the restitution of the coagulation parameters when the patients (n = 8) obtained AT-III substitution only at extremely low values of AT-III. The decline in AT-III observed occurred in parallel to the permeability changes and the haemodilution normally seen secondarily to the initial fluid rescucitation. The observed changes in the coagulation parameters were modest and no hepatic dysfunction was noted. In addition, no differences of the restitution in these coagulation parameters were noted between the substituted and non-substituted groups. These results suggest that changes in AT-III early after burn injury depend mainly on factors other than an ongoing disseminated coagulation process. Probable causes are increased capillary leak and haemodilution. Our results suggest that substitution of AT-III in the early postburn period, on the assumption that low levels alone indicate ongoing coagulation, is not warranted.

Adolescent↗
PubMed2000

Antithrombin III concentrate in the acute phase of thermal injury.

BACKGROUND: Thermal injury disrupts homeostasis by inducing subclinical disseminated intravascular coagulation, fibrinolysis. and an acquired deficiency of Antithrombin III (ATIII), a natural anticoagulant. As a result, thermally injured patients have a high incidence of hypercoagulability and thrombosis. OBJECTIVE: ATIII (Human) concentrate was given to a thermally injured patient to evaluate safety, and dosage requirements in this setting. DESIGN: The patient was a 40 yr old male with a 68% total burn surface area, right femoral comminuted fracture, and C5-C6 subluxation sustained in a vehicular crash. He received nine infusions of AT III (H) concentrate (100-50 u/kg) within the first four days of injury. RESULT: The ATIII plasma level increased from 45% on admission (normal = 100+/-20%) to 120+/-25% in the next four days. During the 64 day hospitalization, there were 11 grafting procedures with an estimated blood loss (EBL)/procedure: 1140 cc; and EBL/grafted surface area ratio: 0.6 cc cm2. The average time to healing of the meshed autograft was 6.4 days. CONCLUSION: ATIII (H) concentrate can be safely utilized in the acute phase of thermal injury: no excessive bleeding or prolongation of wound healing was documented.

Acute Disease↗
PubMed1989

Chromatography of human plasma on aminohexyl Sepharose: separation of factor VIII/vWf and behaviour of factors II, VII, IX and X and antithrombin III.

Human plasma was chromatographed under different experimental conditions on aminohexyl Sepharose. A strong retention of factor VIII/vWf and of factors VII, II, IX and X was observed. A satisfactory stabilization of eluted factor VIII clotting activity was obtained after addition of albumin and sucrose to the buffers used during chromatography. Albumin and antithrombin III were found apparently intact in the column effluent.

Albumins↗
PubMed1997

Acquired protein S and antithrombin III deficiency caused by nephrotic syndrome: an unusual cause of graft thrombosis.

Thrombotic phenomena are well-recognized complications of nephrotic syndrome attributable to loss of intermediate-sized antithrombotic proteins in the urine, resulting in a hypercoaguable state. As such, nephrotic syndrome may be associated with a reduction in circulating antithrombin III and free protein S levels. Associated spontaneous thrombotic complications are generally venous in nature, with arterial thrombosis occurring less frequently. Hypercoagulability caused by acquired nephrotic syndrome has not generally been recognized as a cause of acute thrombosis of arterial bypass grafts. We report two patients who after having nephrotic syndrome sustained acute thrombosis of their arterial bypass grafts. Pathogenesis and management are discussed.

Antithrombin III Deficiency↗
PubMed1983

[Prevention of the thromboembolic risk during the operative period in a patient with a congenital antithrombin III deficiency].

The case of a woman with congenital antithrombin III (AT III) deficiency undergoing elective hysterectomy is reported. AT III deficient patients have high risks of thromboembolic disease, especially developing during and after surgery. It is usual practice to discontinue oral anticoagulants with antivitamin K activity and to obtain effective AT III activity by the transfusion of freeze-dried concentrates of AT III and/or fresh frozen plasma (FFP). Heparin is prescribed as soon as AT III activity reaches 70%. The oral anticoagulant regimen is reinstituted in the late postoperative period. In our case, transfusion of FFP, in the pre- and postoperative periods, results in an AT III activity of 63%. Heparin was not used because oral anticoagulants were readministered early, 12 h after operation. No clinical thrombo-embolic complication was observed.

Adult↗
PubMed1998

The effect of cell surface glycosaminoglycans (GAGs) on the inactivation of factor VIIa--tissue factor activity by antithrombin III.

We investigated the effect of cell surface glycosaminoglycans (GAGs) on the inactivation of factor VIIa-tissue factor activity by antithrombin III (ATIII) on a human bladder carcinoma (J82) cell line and an ovarian carcinoma (OC-2008) cell line, two tumor cell lines which constitutively synthesize and express high levels of cell surface tissue factor. We observed that ATIII inactivated factor VIIa-tissue factor more readily on OC-2008 cells than on J82 cells in the absence of added heparin. Likewise, factor Xa was more effectively inactivated on OC-2008 cells than on J82 cells. The ability of ATIII to inactivate factor VIIa-tissue factor activity on the OC-2008 cell was reduced following treatment of the cells with heparinase. This indicated that heparin-like GAGs were expressed on the OC-2008 cell surface, and that these GAGs were important for the inhibition of factor VIIa-tissue factor activity by ATIII. In addition, we demonstrated that the ability of ATIII to inactivate factor VIIa-tissue factor activity was markedly reduced following treatment of cells with calcium ionophore (A23187). However, the effect of cell surface GAGs on the inhibition of factor Xa by ATIII remained even after treatment of OC-2008 cells with A23187. In contrast to the manner of inhibition by ATIII/heparin, TFPI effectively inactivated factor VIIa-tissue factor activity on the cell surfaces even after induced physical damage or disruption of the cell by treatment with A23187. Our collective findings suggest that GAGs on cell surfaces play an important role in regulating factor VIIa-tissue factor activity by ATIII under normal conditions, or in the early phases of physical damage or destruction of the cell. However, TFPI may play a more important role than ATIII in regulating the activity of factor VIIa-tissue factor in a vascular trauma site following extensive cell injury.

Antithrombin III↗
PubMed2001

Antithrombin III inhibits lymphocyte proliferation, immunoglobulin production and mRNA expression of lymphocyte growth factors (IL-2, gamma-IFN and IL-4) in vitro.

BACKGROUND: Antithrombin III (AT-III) is a physiological inhibitor of thrombin and other serine proteases, and has antiinflammatory properties. Thrombin is known to enhance T lymphocyte activation in vitro and serine proteases can act as costimulators for lymphocyte proliferation and cytokine production. We have previously shown that AT-III significantly inhibited allograft rejection in a highly histoincompatible model of rat lung transplantation and in vitro cell proliferation in ConA-stimulated rat spleen cells. In this study, we examined the involvement of cytokine gene expression in the above inhibitory effect of AT-III. We also examined the effect of AT-III on several in vitro immune reactions in human peripheral blood mononuclear cells (PBMCs). METHODS: mRNA expression of cytokines/cytokine receptor important in lymphocyte activation was examined. Rat spleen cells were stimulated with Con-A with/without AT-III and submitted for reverse transcriptase-polymerase chain reaction (RT-PCR). To assess the effect of AT-III on human PBMCs, we examined the effects of AT-III on cell proliferation of human PBMCs stimulated in mixed lymphocyte reaction (MLR) (allogeneic stimulation), with OKT3 (T cell receptor activation) and with PHA (mitogenic stimulation). The effect of AT-III on PWM-stimulated immunoglobulin (Ig) production by human PBMCs was also examined. All experiments for cell proliferation were performed in 10% serum and in serum-free (SF) media to determine whether AT-III exerted its effects through its interaction with thrombin in serum. RESULTS: mRNA expression of IL-2, gamma-IFN and IL-4 in ConA-stimulated rat spleen cells was nearly completely inhibited by AT-III at 15 IU/ml. mRNA levels for IL-6, IL-2R and TGF-beta1 were not significantly affected by AT-III. AT-III showed a dose-dependent inhibition of cell proliferation in human PBMCs. At 15 IU/ml, cell proliferation was inhibited by approximately 86%, approximately 81% and approximately 56% in the MLR-, OKT3- and PHA-stimulated PBMCs, respectively in both serum and SF media. AT-III inhibited PWM-stimulated Ig production in a dose-dependent manner. IgG, IgM and IgA production was reduced by approximately 60%, 80% and 70%, respectively in cultures incubated with 15 IU/ml AT-III. CONCLUSIONS: (1) Inhibition of IL-2, gamma-IFN and IL-4 mRNA expression might be responsible for inhibition of cell proliferation by AT-III in ConA-stimulated rat spleen cells, (2) AT-III inhibits cell proliferation in the MLR-, OKT3- and PHA-stimulated human PBMCs, and Ig production in PWM-stimulated human PBMCs, (3) The immune regulatory effects of AT-III are independent of its interaction with thrombin since similar levels of suppression were seen in SF media, and (4) These results suggest that AT-III has potent inhibitory effects on lymphocyte activation and cytokine production and may have potential applications as an immunomodulatory agent.

Animals↗
PubMed1994

Feasible synthesis and biological properties of six 'non-glycosamino' glycan analogues of the antithrombin III binding heparin pentasaccharide.

In this paper, we report the synthesis of 'non-glycosamino' glycan analogues 5-10 of the antithrombin III binding pentasaccharide 1. Pentasaccharides 5-10 feature a pseudo-alternating EFGH tetrasaccharide sequence, that is, the disaccharide fragments EF and GH have the same substitution pattern. In the synthetic strategy applied for the synthesis of pentasaccharides 5-10, the properly protected EF disaccharide fragments 19 and 20 are obtained from their GH counterparts 17 and 18 by base-catalyzed epimerization. Series I, comprising pentasaccharides 5-7, has an invariable EFGH tetrasaccharide containing 2-O-sulfate 3-O-methyl uronic acid moieties. Series II, on the other hand, contains pentasaccharides 8-10 and has an invariable EFGH tetrasaccharide containing 2,3-di-O-methyl uronic acid moieties. Coupling disaccharides 17 with 25 and 18 with 26 exclusively afforded the alpha-coupled tetrasaccharides 27 and 28, respectively. Glycosylation of acceptor tetrasaccharides 29 and 30 with glucosyl donors 35, 36 and 39 provided, after deprotection and sulfation, the title-compounds 5-10. Biological data obtained with series I and II indicate that the in vivo half-life but not the intrinsic anti-Xa activity depends on the substitution pattern of the D-unit. In addition, the applicability of reversed UV capillary electrophoresis as an analytical tool to determine the purity of these 'non-glycosamino' glycans is demonstrated.

Amino Acid Sequence↗