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PubMed1998

Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina.

BACKGROUND: In unstable angina, the clinical efficacy of heparin is limited in time, and recurrence of adverse events has been reported after discontinuation of the anticoagulant. METHODS: In 21 episodes of unstable angina, we used the plasma level of fibrinopeptide A (FPA) and of thrombin-antithrombin complex (TAT) to evaluate the pattern of thrombin inhibition by heparin and the effect of stopping heparin and initiating aspirin. RESULTS: At admission, the plasma level of FPA was increased: median value 3.7 ng/mL compared with 5.5 ng/mL in a control group of 20 patients with early myocardial infarction (not significant). The following findings were observed during a 4-day course of intravenous heparin infusion: (1) FPA decreased significantly 6 hours after the start of therapy; (2) FPA was lower when activated partial thromboplastic time (aPTT) was >1.5 times baseline; (3) there was a significant negative correlation between aPTT and FPA. Twenty-four hours after heparin was discontinued and aspirin initiated, a significant increase in TAT and FPA in plasma was observed. CONCLUSIONS: The results confirm ongoing fibrin formation in the active phase of unstable angina, indicate incomplete and variable inhibition of thrombin by heparin during continuous infusion, and suggest a risk of re-emergence of thrombosis (in spite of initiating aspirin) 24 hours after withdrawal of heparin. Data demonstrate a better control of thrombin activity when heparin is infused at rates that maintain aPTT at >1.5 times baseline, as currently recommended in unstable angina.

Aged↗

PubMed2000

In vivo demonstration of an antithrombin effect of abciximab.

Abciximab prolonged the activated clotting time (ACT) in a post hoc analysis from the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications trial and an in vitro study has suggested an antithrombin effect of platelet glycoprotein IIb/IIIa inhibition. The purpose of this study was to evaluate the in vivo effects of abciximab on ACT and thrombin generation. In 46 patients undergoing coronary intervention, 24 received heparin and abciximab (group I), whereas 22 received heparin alone (group II). All received the same dose (70 U/kg) of heparin. Heparin was given after a baseline ACT, and in group I, abciximab was administered after the 5-minute ACT. Serial ACTs were recorded at baseline, 5, 10, 20, and every 30 minutes thereafter and at the procedure's end. No intervention including balloon angioplasty was performed until after the 20-minute ACT. The prothrombin fragment F1.2 (Nm/L) was measured at baseline, 20 minutes, and at the end of the procedure. Before (baseline) heparin and at 5 minutes, ACTs were similar. Abciximab prolonged ACT by a mean of 34 to 64 seconds starting with the 10-minute ACT and extending to the 50-minute ACT (all p <0.01 vs heparin alone). There was a progressive decrease in the F1.2 with abciximab, and baseline minus end F1.2 was 0.12 +/- 0.02 in group I versus 0.05 +/- 0.04 in group II, p <0.05. These data indicate a significant in vivo effect of abciximab plus heparin in increasing ACT and decreasing F1.2, results that are consistent with an effect on reducing thrombin generation.

Abciximab↗

PubMed2000

A randomized trial of antithrombin concentrate for treatment of heparin resistance.

BACKGROUND: Heparin resistance is an important clinical problem traditionally treated with additional heparin or fresh frozen plasma. We undertook a randomized clinical trial to determine if treatment with antithrombin (AT) concentrate is effective for treating this condition. METHODS: Patients requiring cardiopulmonary bypass who were considered to be heparin resistant (activated clotting time < 480 seconds after > 450 IU/kg heparin) were randomized to receive either 1000 U AT or additional heparin. RESULTS: AT concentrate was effective in 42 of 44 patients (96%) for immediately obtaining a therapeutic activated clotting time. This compared favorably to 28 of 41 patients (68%) treated with additional heparin (p = 0.001). All patients who failed heparin therapy were successfully treated with AT. The patients receiving AT required less time to obtain an adequate ACT but there was no difference in clinical outcomes among the groups. Study patients had deficient AT activity at baseline (56%+/-25%), which improved in those given AT concentrate (75%+/-31% versus 50%+/-23%, p < 0.0005). CONCLUSIONS: Heparin resistance is frequently associated with AT deficiency. Treating this deficiency with AT concentrate is more effective and faster for obtaining adequate anticoagulation than using additional heparin.

Antithrombins↗

PubMed1986

Synthesis of heparin fragments. A chemical synthesis of the pentasaccharide O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1-4 )-O-(beta-D-glucopyranosyluronic acid)-(1-4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-glu copyranosyl)-(1-4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1-4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose decasodium salt, a heparin fragment having high affinity for antithrombin III.

Known allyl 4,6-O-benzylidene-alpha-D-glucopyranoside was first converted into methyl (prop-1-enyl 2,3-di-O-benzyl-4-O-chloroacetyl-alpha-D-glucopyranosid)-uronate. Acid hydrolysis, followed by treatment with (bromomethylene)dimethyl-ammonium bromide, gave methyl (2,3-di-O-benzyl-4-O-chloroacetyl-alpha-D-glucopyranosyl bromide)uronate. Condensation of this bromide with 3-O-acetyl-1,6-anhydro-2-azido-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-bet a-D-glucopyranose. Acetolysis, followed by treatment with titanium tetrabromide, then gave 3,6-di-O-acetyl-2-azido-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-alp ha-D-glucopyranosyl bromide. Condensation of this bromide with benzyl 6-O-acetyl-3-O-benzyl-2-benzyloxy- carbonylamino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L- idopyranosyluronate)-alpha-D-glucopyranoside provided benzyl O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-(1- ---4)-O-(3,6-di-O-acetyl- -2-azido-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-ac etyl-3-O- acetyl-3-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-alpha-D-gluc opyranoside. O-Dechloroacetylation followed by condensation with 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide provided benzyl O-(6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-beta-D-glucopyranosyl)- (1----4)-O-(methyl 2,3-di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)- O-(3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(m ethyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-ac etyl-3-O- benzyl-2-benzyloxycarbonylamino-2-deoxy-alpha-D-glucopyranoside in 70% yield. O-Deacetylation followed by re-esterification, O-sulfation, saponification, catalytic hydrogenolysis, and N-sulfation gave the decasodium salt of O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)-(1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gl ucopyranosyl)-(1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic+ ++ acid)-(1----4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose. This synthetic pentasaccharide binds to antithrombin III with an association constant similar to that of high-affinity heparin and elicits a potent anti-factor Xa activity in plasma.

Antithrombin III↗

PubMed1988

Synthesis of methyl glycoside derivatives of tri- and penta-saccharides related to the antithrombin III-binding sequence of heparin, employing cellobiose as a key starting-material.

Two key synthons for the title pentasaccharide derivative, methyl O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-acetyl- 2-azido - 3-O- benzyl-2-deoxy-beta-D-glucopyranoside and O-(methyl 2,3-di-O-benzyl-4-O- chloroacetyl-beta-D-glucopyranosyluronate)-(1----4)-3,6-di-O-acetyl-2-az ido-2- deoxy-alpha-D- glucopyranosyl bromide, were prepared from a common starting material, cellobiose. They were coupled to give a tetrasaccharide derivative that underwent O-dechloroacetylation to the corresponding glycosyl acceptor. Its condensation with the known 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide afforded a 77% yield of suitably protected pentasaccharide, methyl O-(6-O- acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)- O- (methyl 2,3- di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-O-(3,6-di-O-acetyl-2- azido-2 - deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L- idopyranosyluronate)- (1----4)-6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside. Sequential deprotection and sulfation gave the decasodium salt of methyl O-(2- deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)-O-(be ta-D- glucopyranosyl-uronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gluco pyranosyl)- (1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1----4)-2-deoxy-2- sulfamido-6-O- sulfo-beta-D-glucopyranoside (3). In a similar way, the trisaccharide derivative, the hexasodium salt of methyl O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)- (1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-2-deoxy-2-sulfamido-3,6- di-O- sulfo-alpha-D-glucopyranoside (4) was synthesized from methyl O-(6-O-acetyl-2- azido- 3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di-O- benzyl-beta- D-glucopyranosyluronate)-3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D- glucopyranoside. The pentasaccharide 3 binds strongly to antithrombin III with an association constant almost equivalent to that of high-affinity heparin, but the trisaccharide 4 appears not to bind.

Antithrombin III↗

PubMed2002

Further evidence that periodate cleavage of heparin occurs primarily through the antithrombin binding site.

Porcine mucosal heparin was fragmented into low-molecular-weight (LMW) heparin by treatment of periodate-oxidized heparin with sodium hydroxide, followed by reduction with sodium borohydride and acid hydrolysis. Gradient polyacrylamide gel electrophoresis analysis showed a mixture of heparin fragments with an average size of eight disaccharide units. 1D 1H NMR showed two-thirds of the N-acetyl groups were lost on periodate cleavage, suggesting cleavage had occurred at the glucopyranosyluronic acid (GlcpA) and idopyranosyluronic acid (IdopA) residues located within and adjacent to the antithrombin III (ATIII) binding site. The N-acetyl glucopyranose (GlcpNAc) residue was lost on workup. The GlcpA residue, within the ATIII binding site, is on the non-reducing side of the N-sulfo, 3, 6-O-sulfo glycopyranosylamine (GlcpNS3S6S) residue. Thus, periodate cleaved heparin should be enriched in GlcpNS3S6S residues. Two-dimensional correlation spectroscopy (2D COSY) confirmed that LMW heparin prepared through periodate cleavage contained GlcpNS3S6S at its non-reducing end. As expected, this LMW heparin also showed reduced ATIII mediated anti-factor IIa and anti-factor Xa activities.

Animals↗

PubMed2000

Effect of oligodeoxynucleotide thrombin aptamer on thrombin inhibition by heparin cofactor II and antithrombin.

'Thrombin aptamers' are based on the 15-nucleotide consensus sequence of d(GGTTGGTGTGGTTGG) that binds specifically to thrombin's anion-binding exosite-I. The effect of aptamer-thrombin interactions during inhibition by the serine protease inhibitor (serpin) heparin cofactor II (HCII) and antithrombin (AT) has not been described. Thrombin inhibition by HCII without glycosaminoglycan was decreased approximately two-fold by the aptamer. In contrast, the aptamer dramatically reduced thrombin inhibition by >200-fold and 30-fold for HCII-heparin and HCII-dermatan sulfate, respectively. The aptamer had essentially no effect on thrombin inhibition by AT with or without heparin. These results add to our understanding of thrombin aptamer activity for potential clinical application, and they further demonstrate the importance of thrombin exosite-I during inhibition by HCII-glycosaminoglycans.

Antithrombins↗

PubMed2001

The serine protease inhibitor antithrombin III inhibits LPS-mediated NF-kappaB activation by TLR-4.

In Drosophila, the Toll family of proteins mediates the innate immune response. Toll is activated by Spaetzle, which is generated in response to pathogens via a serine protease cascade. We wished to investigate if lipopolysaccharides (LPS) might activate Toll-like receptor (TLR) 4 via a serine protease in humans. The serpin antithrombin III (ATIII) and the thrombin inhibitor hirudin both inhibited nuclear factor (NF)-kappaB activation by LPS and Lipid A. ATIII and hirudin were also able to inhibit LPS-induced NF-kappaB activation in cells stably transfected with TLR4. These results suggest that LPS may activate a mammalian serine protease, which generates a product required for TLR4 signalling.

Antithrombin III↗

PubMed2001

Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage.

OBJECTIVE: To investigate whether a decrease in the values of protein C (PC), protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII (FXIII) has predictive value for subsequent miscarriages. DESIGN: Prospective study. SETTING: Nagoya City University Medical School. PATIENT(S): A total of 536 patients with a history of two or more first-trimester miscarriages. INTERVENTION(S): One hundred and twelve patients treated with low-dose aspirin were excluded from the analysis. MAIN OUTCOME MEASURE(S): The subsequent pregnancy outcome of 424 patients was compared for abnormal and normal levels of each parameter. RESULT(S): There were no differences in the subsequent miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII. However, the rate with abnormal FXII is significantly higher than that with normal FXII. CONCLUSION(S): A decrease in FXII (but not in PC, PS, ATIII, or FXIII) predicts subsequent miscarriage in patients with a history of first-trimester recurrent miscarriages.

Abortion, Habitual↗

PubMed2001

Separation of antithrombin III variants by micellar electrokinetic chromatography.

The characterisation of proteins is still one of the most challenging analytical tasks in modern bioanalysis. Due to the complex structure of proteins, several analytical techniques are often required to get sufficient information. Antithrombin III (AT III), a high-molecular-mass plasma glycoprotein which is an important protease inhibitor and the main modulator of thrombin activity, circulates in plasma in two isoforms, the so-called AT III-alpha (90-95%) and -beta (5-10%). Micellar electrokinetic chromatography was used to analytically separate these AT III variants, which differ in their affinity to the polysaccharide heparin.

Antithrombin III↗

PubMed1998

High-performance capillary electrophoresis for in-process control in the production of antithrombin III and human clotting factor IX.

Antithrombin III (ATIII) and factor IX (FIX), two proteins from the clotting cascade, were investigated in parallel experiments, using capillary gel electrophoresis and capillary isoelectric focusing. The results from these experiments were compared with the results obtained from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and slab gel isoelectric focusing. In the case of ATIII, capillary gel sieving showed comparable results to SDS-PAGE with the added advantage of the shorter time required for analysis. By optimizing capillary isoelectric focusing (cIEF), a separation of the ATIII isoforms was achieved. In the case of FIX, capillary gel electrophoresis (SDS-CE) of a FIX preparation gave similar results to those obtained by size-exclusion high-performance liquid chromatography and SDS-PAGE, but turned out to be less sensitive in detecting protein impurities at low concentrations. The microheterogeneity of this protein was shown by using cIEF.

Antithrombin III↗

PubMed1999

Antithrombin prevents stress-induced gastric mucosal injury by increasing the gastric prostacyclin level in rats.

The interaction of antithrombin (AT) with cell surface glycosaminoglycans has been shown to promote the endothelial release of prostacyclin (PGI2). Because PGI2 plays an important role in gastric cytoprotection, we examined whether AT prevents water-immersion restraint stress (WIR)-induced gastric mucosal injury in rats by promoting the endothelial release of PGI2. Intravenous administration of AT (250 U/kg) prevented WIR-induced gastric mucosal injury in rats. Gastric levels of 6-keto-prostaglandin F1alpha, a stable metabolite of PGI2, were significantly increased 0.5 and 1 hour after WIR in animals administered AT compared with control animals. The effects induced by AT in animals subjected to WIR were not observed in animals that were administered DEGR-Xa, a selective inhibitor of thrombin generation, or Trp49-modified AT, which lacks affinity for heparin. In animals subjected to WIR gastric mucosal blood flow was significantly reduced with a simultaneous increase in gastric mucosal microvascular permeability. Activated neutrophils have been implicated in the WIR-induced reduction of gastric mucosal blood flow by increasing microvascular permeability. Although AT prevented the reduction of gastric mucosal blood flow and the increase in gastric mucosal microvascular permeability in animals subjected to WIR, neither DEGR-Xa nor Trp49-modified AT had any effect. Pretreatment of animals with indomethacin completely inhibited the protective effects of AT against WIR-induced gastric mucosal injury and the AT-induced increase in post-WIR gastric 6-keto-prostaglandin F1alpha levels. These results strongly suggest that AT prevents stress-induced gastric mucosal injury by increasing the gastric levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing gastric mucosal blood flow both by vasodilation and by inhibiting neutrophil activation.

6-Ketoprostaglandin F1 alpha↗

PubMed1982

The effect of L-asparaginase on antithrombin, plasminogen, and plasma coagulation during therapy for acute lymphoblastic leukemia.

Hemostatic function was studied sequentially in 12 children receiving L-asparaginase, vincristine, and prednisone as remission induction chemotherapy for acute lymphoblastic leukemia. The three-week period of L-asparaginase therapy was characterized by progressive decreases in plasma antithrombin, plasminogen, and fibrinogen concentrations, and by progressive increases in plasma clotting times (prothrombin time, partial thromboplastin time, thrombin time). Platelet counts rose rapidly during the third and fourth weeks of therapy as bone marrow remission was achieved. Factor V levels increased steadily during a five-week period, perhaps related to vincristine or prednisone therapy. Recent reports of thrombosis and hemorrhage in children and adults receiving L-asparaginase may be explained by this complex set of abnormalities in coagulation and coagulation control.

Adolescent↗

PubMed1984

Persistent antithrombin III deficiency: risk factor for thromboembolic complications in neonates small for gestational age.

Coagulation and fibrinolytic factors were investigated daily in 24 SGA and 26 AGA neonates. The results were correlated with placental form and structure and with hematologic values. In the SGA infants, a higher incidence of placental infarction (P less than 0.01), polycythemia (P less than 0.005), and thrombocytopenia (P less than 0.001) was present. During the first 9 days, the mean antithrombin III level in the AGA group increased from 0.36 to 0.53 U/ml, whereas in SGA neonates this value was initially significantly lower (0.27 U/ml) and remained at that level for the entire observation period. The same pattern was found for alpha 2-antiplasmin. The persistent AT-III deficiency and reduced blood flow associated with polycythemia may explain the increased risk of thromboembolic complications in SGA infants described by others.

Antithrombin III Deficiency↗

PubMed2001

Plasma thrombin-antithrombin III complex is associated with the severity of experimental autoimmune encephalomyelitis.

Previous studies have shown that activation of blood coagulation and fibrin depositions around CNS vessels are observed in animals with experimental autoimmune encephalomyelitis (EAE), which provides an animal model for human autoimmune demyelinating disorders. We examined the values of peripheral blood fibrinogen, thrombin-antithrombin III complex (TAT), fibrinolytic activity, and fibrin degradation products in Lewis rats with EAE to elucidate the role of the blood coagulation-fibrinolysis system in EAE. Plasma TAT values increased immediately prior to development of symptoms, and decreased according to the improvement of symptoms. There was significant correlation between TAT values and clinical scores of EAE; other markers were not correlated with the symptoms of EAE. These results suggest that plasma TAT levels are sensitive markers of the severity of EAE, and may be useful clinical indicators for the severity of human autoimmune demyelinating disorders.

Animals↗

PubMed2002

The botanical extracts of Achyrocline satureoides and Ilex paraguariensis prevent methylglyoxal-induced inhibition of plasminogen and antithrombin III.

Endogenously produced dicarbonyls, such as methylglyoxal (MG), are involved in advanced glycation end-product formation and thus linked to the pathophysiology of diabetic chronic complications. While the search for synthetic new antiglycation agents continues, little attention has been paid to putative antiglycation agents in natural compounds. Given the link between glycation and oxidation, in this work, we study the effects of methylglyoxal on two model systems; plasminogen and antithrombin III (AT III), then we set out to unravel a possible antiglycation effect for extracts of the flavonoid-rich common herbal species Achyrocline satureoides (AS) and Ilex paraguariensis (IP). Using SAR-PRO-ARG-pNA as a specific thrombin substrate, we show that incubation of plasma with MG decreases heparin activation of AT III by up to a 70%, in a dose-dependent manner. A parallel dose-dependent decrease in plasminogen activity reaching more than 50% was shown using D-BUT-CHT-lys-pNA as a plasmin-specific substrate. Extracts of AS and IP display a dose dependent inhibition of the action of the dicarbonyl, already significant at a 1/100 dilution of the herbal infusions. The inhibition was comparable to that obtained by using millimolar concentrations of known AGE inhibitors such as aminoguanidine and carnosine as well as micromolar concentrations of the antioxidant ascorbic acid. We believe our system of whole plasma glycation over 16 h with micromolar concentrations of MG, coupled with the measurement of activities of plasminogen and AT III by specific substrates provides a straightforward, practical method for monitoring the action of putative antiglycation agents. If predictably milder glycated forms of AT III and plasminogen were to be secreted in vivo, the loss of activities shown here could act synergistically to generate hyperthrombicity.

Achyrocline↗

PubMed2003

Human antithrombin III-derived heparin-binding peptide, a novel heparin antagonist.

In the blood coagulation cascade, human antithrombin III (hAT III) acts as an inhibitor of serine proteases such as thrombin and factor Xa, and this anticoagulatory glycoprotein requires the binding of heparin for its activation. In this study, we synthesized the polypeptides corresponding to the proposed heparin-binding sites including the (41-49), (286-301) and (123-139) regions of hAT III, and examined their interactions with heparin by means of physicochemical and biochemical methods. All the synthetic peptides had a high affinity toward heparin, evidenced by the fact that they were eluted from a heparin-agarose column at the high salt concentration range of 520-700 mM. In addition, hAT III (123-139) attenuated the effect of heparin on the activation of hAT III, whereas other HBPs did not, suggesting that only hAT III (123-139) could interact with the active site of heparin. On the basis of these results, we prepared novel hAT III (123-139)-related derivatives as potent heparin antagonist candidates, and examined the influence of several modifications on their activity in vitro. The results provided new findings about the structure-activity relationship of hAT III (123-139), and led us to the successful development of a potent antagonist for heparin.

Anticoagulants↗

PubMed1996

Evaluation of thrombin-antithrombin complexes and fibrin fragment D in carbohydrate-induced acute laminitis.

Carbohydrate-induced laminitis has been associated with decreased platelet survival, decreased blood flow to the hoof wall and with the deposition of platelets and microthrombi within venules in the dermal laminae. To evaluate further the systemic prothrombotic events occurring in the prodromal stages of laminitis, plasma samples from control and laminitis-affected ponies and horses were tested for the presence of thrombin-antithrombin (TAT) complexes and fibrin fragment D (D-dimer). No statistically significant differences between the control and laminitis-affected animals were observed for either the D-dimer or the TAT complexes. Few of the values for individual animals exceeded the reference ranges for control animals. These data indicate that the prothrombotic events observed in carbohydrate-induced laminitis may not be associated with systemic activation of the coagulation or fibrinolytic systems.

Acute Disease↗