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Biomedical subjects

H L Messmore

Publications and source records attributed to H L Messmore.

At least 19 recordsLinked to original sources
PubMed1999

Selectins in the HIT syndrome: pathophysiologic role and therapeutic modulation.

The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be at increased levels during acute phases of the HIT syndromes, the circulating levels of soluble P-, E-, and L- selectins have not been reported. Since the pathophysiology of HIT involves the activation of platelets, endothelium, and leukocytes, it is expected that activation products related to these hemostatic systems, including soluble selectins, will also be increased in circulating blood. These alterations may provide an index of the pathophysiologic process. With the availability of highly sensitive ELISAs for soluble P-, E-, and L-selectins, it is now possible to measure these adhesion molecules in biological fluids. This study reports on the circulating levels of P-, E-, and L-selectins in HIT patients and their modulation after therapeutic intervention. With the availability of recombinant hirudin, it is now possible to provide alternate anticoagulants to HIT patients. However, the immunoactivation of platelets and other cells may require additional adjunct therapeutic approaches.

Anticoagulants↗
PubMed1995

Molecular markers of hemostatic activation. Implications in the diagnosis of thrombosis, vascular, and cardiovascular disorders.

Until recently, the diagnosis of thromboembolic disorders remained difficult to establish before the occurrence of a pathologic event. Clearly, thrombosis is the result of a progressive alteration of the blood and vasculature. Various molecular markers of hemostatic alteration are found in increased or decreased amounts predisposing to thrombosis or in increased circulating amounts during the activation process.

Biomarkers↗
PubMed1994

Medical assessment of bleeding in the surgical patient.

The key to avoidance of hemostatic failure during surgery is to be able to identify the high-risk patient and make a diagnosis and treat the defect before surgery. A thorough history and physical examination are mandatory in this regard. A screening coagulation profile is not a substitute for the history and physical examination. Selected presurgical tests are useful in major surgical cases and in certain high-risk cases. Otolaryngologists have advised presurgical testing for patients undergoing tonsillectomy, but the subject of presurgical testing is still a matter for investigation in view of the necessity for cost containment. Knowledge of the hemostatic system combined with a knowledge of the tests available to diagnose coagulation defects permits a rational approach to therapy of the bleeding surgical patient.

Blood Coagulation Disorders↗
PubMed1993

Evaluation of a low molecular weight heparin as an anticoagulant in a model of cardiopulmonary bypass surgery.

Heparin, the classically used anticoagulant in cardiopulmonary bypass surgery, has several disadvantages such that alternate anticoagulants are being sought. Previous reports have described questionable safety with the clinical use of low molecular weight (LMW) heparin in cardiac surgery. The dog cardiopulmonary bypass model described herein may provide a useful means to study the pharmacology of new drugs prior to clinical use. Dogs were given a single loading dose of 250 USP units/kg (1.66 mg/kg) of unfractionated heparin (control) or 250 anti-factor Xa units/kg (2.3 mg/kg) LMW heparin and placed on bypass for 60 minutes. Prior to, during, and following bypass blood samples were taken to measure coagulation and hematological parameters. The dogs remained anesthetized for 150 minutes post-bypass. Post-operative blood loss and fibrin deposition in the arterial line filters were measured. Our findings showed there was no significant blood loss (heparin 452 +/- 67 gms; LMW heparin 289 +/- 82 gms) and no significant fibrin deposition (heparin 22 +/- 3 gms; LMW heparin 28 +/- 7 gms) with the LMW heparin. These findings suggest that this LMW heparin should be safe and effective at the studied bolus dose as an anticoagulant for use in cardiopulmonary bypass surgery, and that protamine should be used to reverse the anticoagulant response after surgery.

Animals↗
PubMed1992

Tracheal and bronchial cartilaginous rings: warfarin sodium-induced calcification.

Progressive calcification of the cartilaginous rings (CCR) of the trachea and bronchi has been observed in patients undergoing prolonged prophylactic anticoagulant therapy with warfarin sodium. The purpose of this study was to validate the relationship of warfarin sodium and CCR, as well as to present the appearance and sex and age distribution of the normal degenerative CCR seen in the elderly. Chest radiographs were scrutinized for evidence of CCR in 92 patients who underwent warfarin sodium therapy and in 105 patients used as a control group. CCR was classified as not present (scored as 0), subtle (scored as 1), and extensive (scored as 2). In the warfarin sodium study group, 47% of patients (43 of 92) exhibited level 1 or level 2 CCR. This proportion was 19% (20 of 105) in the control group. The difference was statistically significant (P less than .001). A significant positive correlation (P less than .001) was also present between the duration of warfarin sodium therapy and increased levels of CCR.

Aged↗
PubMed1991

Acute venous thrombosis. Therapeutic choices for superficial and deep veins.

Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence.

Acute Disease↗
PubMed1991

Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model.

Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Animals↗
PubMed1991

Comparison of recombinant hirudin and heparin as an anticoagulant in a cardiopulmonary bypass model.

Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Animals↗
PubMed1991

Interaction of heparinoids with platelets: comparison with heparin and low molecular weight heparins.

Heparin interacts with platelets to impair collagen-induced aggregation and adhesion to collagen. Low molecular weight heparin and heparinoids have little or no inhibitory activity in these platelet-collagen interactions. Thrombin-induced aggregation of platelets is inhibited by any of the glycosaminoglycans that will block the action of thrombin on fibrinogen. However, heparin is a much more potent inhibitor than low molecular weight heparins or heparinoids at equigravimetric concentrations in these reactions. The inhibition of ristocetin or asialo-von Willebrand factor aggregation of platelets is partially blocked by high dose heparin but not by low molecular weight heparin or heparinoids. The heparin-induced IgG antibody, produced to a heparin-platelet complex, aggregates platelets strongly in the presence of heparin, less strongly in the presence of low molecular weight heparins and pentosan polysulfate and not at all with dermatan sulfate or the pentasaccharide. Heparan sulfate does interact with platelets and this antibody, which is of interest because of the heparan sulfate on endothelial cells. Clinical information to date suggests a low incidence of heparin antibodies in patients receiving only low molecular weight heparin of the depolymerized type. Whether long-term clinical use of low molecular weight heparins, heparan sulfate, and dermatan sulfate will give rise to specific antibodies that would cause a similar problem as heparin remains to be seen.

Autoantibodies↗
PubMed1990

Risk of thromboembolism during diagnostic and interventional cardiac procedures with nonionic contrast media.

To investigate the relationship between clot formation and thromboembolism, canine blood was withdrawn into catheter-syringe or catheter-steerable wire systems containing either contrast medium or normal saline as used in debubbling techniques. The contrast media used were iohexol, iopamidol, ioxaglate, and diatrizoate. Without the use of heparin, after a 30-minute incubation, blood clots were harvested from all catheter-syringe systems except those with diatrizoate and from all catheter-steerable wire systems. Significantly more blood clot was harvested from the catheter-steerable wire system. With use of heparinized blood, no clot was found in any system. Twelve dogs that underwent coronary angiography were divided into two groups; one received heparin (5,000 IU) and the other did not. Thromboembolism occurred in all nonheparinized dogs that underwent angiography with iohexol or iopamidol but not in any other group. The authors found that in a dog model nonionic contrast media are more thrombogenic than ionic contrast media, especially in the catheter-steerable wire system. The blood clot in the catheters is associated with thromboembolism during angiography. The authors maintain that in this setting, blood clotting and thromboembolism with nonionic agents can be eliminated with heparin.

Animals↗
PubMed1990

Thromboembolic disease during pregnancy: problems with anticoagulant therapy.

Thromboembolic complications of pregnancy and the puerperium deserve renewed attention not only because they are the most frequent nonobstetrical complications encountered in these circumstances, but also because of current litigious attitudes, the greater survival of women with prosthetic heart valves, and the inadequacy of current treatment regimens that put the physician, as well as the patient, in special peril. New techniques are available to the clinical laboratory for studying the coagulation and hypocoagulant proteins, coagulation inhibitors, and the fibrinolytic system. They provide fresh insight into this perplexing medical problem. Attention to the details of current investigations, efforts to control the risk factors, and the perspicacious use and suitable monitoring of pharmacological agents can be expected to reduce the risks for both the pregnant patient and her attending physicians.

Anticoagulants↗
PubMed1989

In vitro studies of the interaction of heparin, low molecular weight heparin and heparinoids with platelets.

Heparin, low molecular weight heparins, and heparinoids were studied for their ability to inhibit the aggregation of platelets by various agonists and for their ability to adhere to collagen. Heparin was a very effective inhibitor of aggregation with collagen and with ristocetin as it was with adhesion to collagen. The heparinoids showed little effect on aggregation or adhesion. Heparan sulfate and pentosan polysulfate did show slight inhibitory activity against collagen aggregation and adhesion and both interacted with the antibody induced by heparin therapy. It is of interest that dermatan sulfate and the pentasaccharide were almost inert in these experiments, and are unlikely to induce bleeding by inhibition of platelet function. It is highly probable that interference with the interaction of von Willebrand factor with platelets and collagen is a major mechanism for bleeding in the heparinized patient.

Adenosine Diphosphate↗
PubMed1988

Validity of the newly established low-molecular-weight heparin standard in cross-referencing low-molecular-weight heparins.

Four low-molecular-weight-heparin (LMWH) preparations have recently become available for clinical usage. Some ten preparations are currently under preclinical development. The safety/efficacy profile of each of these LMWHs is now known to be quite distinct from one and other. In order to minimize the variations in the pharmacologic responses and to cross-reference different products on a common scale, the WHO has recently introduced a LMWH standard. This standard is a nitrous-acid-depolymerized product provided by KabiVitrum (Stockholm, Sweden) with a specific physiochemical and biological profile. Although the in vitro characteristics of this standard are comparable to other LMWH, the in vivo behavior of this reference and the parent product, Fragmin, are quite different in comparison to other products. In a well-defined uniform biochemical and pharmacologic screening, seven LMWH were compared at WHO reference-adjusted potency using pharmacologically valid dose-response curves. Cross-referencing of various LMWHs against the WHO standard in terms of anti-Xa activity resulted in a marked elevation of the anti-IIa component of some of the LMWHs. Establishment of this WHO standard stipulated that the clinical performance of cross-referenced LMWHs would be equivalent to one another and variation in potency could be minimized. Our data suggest that utilizing the WHO, standard individual potency (anti-Xa)-adjusted LMWHs exhibit distinct safety/efficacy profiles which were not related in their observed in vitro potency. Each LMWH has distinct multiparametric molecular and biochemical characteristics which determine the pharmacologic activities of individual agents. Thus cross-referencing of LMWHs by one in vitro assay is of questionable value as it may result in serious dosimetric errors, resulting in serious thrombotic and bleeding complications.

Animals↗