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McDonald K Horne

Publications and source records attributed to McDonald K Horne.

16 recordsLinked to original sources
PubMed2006

Venlafaxine-induced ecchymoses and impaired platelet aggregation.

OBJECTIVE: To describe a case of venlafaxine-induced ecchymoses. METHODS: A patient with a history of ecchymoses coincident with venlafaxine therapy was rechallenged with the drug. Her platelet function was assessed with aggregation and ATP release studies before the rechallenge and after she developed ecchymoses. In addition, the effect of venlafaxine on platelet aggregation and ATP release was studied in vitro by adding the drug to platelet-rich plasma from normal donors. RESULTS: After 4 wk of treatment with venlafaxine our patient developed extensive ecchymoses. At that time her platelet aggregation and release responses to epinephrine, ADP, collagen, and arachidonic acid were markedly suppressed. Adding venlafaxine to normal platelet-rich plasma also dramatically reduced the aggregation and release responses to the same agonists as well as to serotonin, but the concentrations of venlafaxine required were 1000-fold greater than those normally achieved clinically. CONCLUSIONS: Our patient demonstrated an idiosyncratic hypersensitivity to the platelet inhibitory effects of venlafaxine. Because venlafaxine is an inhibitor of serotonin uptake by platelets and neurons, this mechanism may contribute to the impact of this drug on platelet function. However, our in vitro studies suggest that this hypothesis is inadequate to explain the observations completely.

Adenosine Triphosphate↗
PubMed2006

The effect of red blood cells on thrombin generation.

We have developed an assay of thrombin generation in clotting whole blood. Because our goal was to study patients with red blood cell diseases that are associated with thrombosis, the initial evaluation of this assay analysed the effect of the haematocrit and haemolysate on the total amount of thrombin activity generated and the maximal concentration of thrombin achieved. Both of these parameters were proportional to the haematocrit throughout a wide range of clinically relevant cell concentrations. Red cell lysate also augmented thrombin generation. Because this effect was removed by filtration of the lysate, we propose that it was related to red cell microparticles.

Blood Coagulation↗
PubMed2006

Factor V Leiden as a common genetic risk factor for venous thromboembolism.

PURPOSE: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait for venous thromboembolism. ORGANIZING FRAMEWORK: An overview of the history, prevalence, and predisposition of the FVL genetic mutation, including who should be tested and how and in what circumstances people with FVL should be treated. FINDINGS: FVL is the most commonly recognized genetic trait associated with venous thrombosis. It is found predominantly in Caucasian populations. Biochemically it causes "activated protein C resistance (APCR)." The decision to test for FVL depends on whether the information gained will potentially improve the health care of the person or family. For people who have had deep venous thrombosis, testing for FVL will likely not alter treatment approaches. Currently the advantage for testing is primarily limited to asymptomatic family members who carry FVL and who have had deep vein thrombosis. Close relatives who also carry the mutated gene might benefit from prophylactic anticoagulation when their risk of thrombosis is increased by temporary factors such as surgery. CONCLUSIONS: Nurses are in a unique position to provide accurate information and counseling when patients and their family members are presented with the results of thrombophilia testing.

Activated Protein C Resistance↗
PubMed2006

Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes.

BACKGROUND: High serum vitamin B12 concentrations have been reported in patients with hepatic disease, disseminated neoplasia, myeloproliferative disorders, and hypereosinophilic syndromes. We recently discovered an extraordinarily increased vitamin B12 concentration in a patient without these underlying conditions. METHODS: Affinity and size-exclusion chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and ELISA methods were used to determine the cause of the increased vitamin B12 concentrations in this patient's serum. RESULTS: The protein G column eluates from 2 apparently healthy volunteers and 2 patients with recent vitamin B12 treatment for anemia had vitamin B12 concentrations of <74 pmol/L, whereas the vitamin B12 concentration in the protein G column eluate from the patient was 7380 pmol/L. The elution profile from size-exclusion chromatography of vitamin B12-binding proteins in the patient's serum revealed an abnormal vitamin-B12-binding protein. SDS-PAGE analysis of the concentrated eluates from the protein G column, under reducing conditions, revealed an additional band with an apparent molecular mass of 76 kDa, which was not present in control column eluates. MALDI-TOF MS identified this band as an IgM heavy chain. By use of a modified ELISA, we determined that the IgM present in the patient's eluates was associated with the IgG to form IgG-IgM immune complexes. CONCLUSIONS: This case demonstrates the unusual circumstance of a patient with markedly increased vitamin B12 concentrations attributed to immune complexes composed of IgG, IgM, and vitamin B12 and illustrates techniques that can be used to identify this occurrence.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Use of heparin versus lepirudin flushes to prevent withdrawal occlusion of central venous access devices.

STUDY OBJECTIVE: To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices. DESIGN: Randomized, double-blind clinical trial. SETTING: Research institution-tertiary referral center. PATIENTS: Forty-nine adults undergoing bone marrow transplantation for hematologic malignancies or metastatic solid tumors. INTERVENTION: Twenty-four patients received heparin and 25 received lepirudin flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100 microg/ml (300 microg) per catheter lumen at least once/day. After 3-4 weeks, all 49 patients received the heparin flushes. MEASUREMENTS AND MAIN RESULTS: Efficacy was assessed by the frequency with which the patients were treated with alteplase instillations for withdrawal occlusion of their central venous access devices during the first 4 months of catheterization. Three (12.5%) patients treated with heparin alone and five (20%) treated initially with lepirudin required alteplase instillations for an estimated relative risk with lepirudin versus heparin of 1.6 (95% confidence interval [CI] 0.40-13.86, p=0.70). CONCLUSION: Lepirudin was not more effective than heparin, which may have been related to the conservative dose of lepirudin administered. However, higher lepirudin doses are likely to incur an unacceptable risk of systemic anticoagulation.

Anticoagulants↗
PubMed2005

Disseminated intravascular coagulation in an ambulatory young woman.

We are reporting the case of an ambulatory young woman with a 10-year history of recurrent venous thrombosis who presented to us with diffuse intravascular coagulation (DIC). After excluding the recognized causes of DIC, we examined the possibility that her clinically quiescent ulcerative colitis might be the underlying stimulus. We documented sepsis-range endotoxemia in this patient at a time when she was afebrile and had a normal C-reactive protein level. In vitro her serum upregulated tissue factor in cultured endothelial cells. We postulate that she had become tolerant to the systemic effects of endotoxin leaking from her inflamed colon but that the endotoxin stimulated her endothelium and/or monocytes to produce tissue factor that made her intensely hypercoagulable. Her prothrombotic state may have been compounded by the fact that she was heterozygous for prothrombin G20210A and that her plasma clotting time demonstrated resistance to activated protein C.

Adult↗
PubMed2005

Plasminogen interaction with platelets: the importance of carboxyterminal lysines.

INTRODUCTION: Thrombin stimulation enhances plasminogen binding to platelets and promotes platelet-dependent plasmin generation. The objective of this study was to determine whether carboxyterminal lysines (C-lysines) are important for these processes, as they are in other cell types. MATERIALS AND METHODS: 125I-plasminogen and varying concentrations of unlabeled plasminogen were added to washed platelets that were either resting or stimulated with thrombin, thrombin receptor activating peptide, or ADP. In some experiments the platelets were digested with carboxypeptidase B to remove C-lysines. Platelet-dependent plasmin generation was also studied by adding plasminogen and tissue plasminogen activator to platelet suspensions and monitoring the conversion of a plasmin specific chromogenic substrate. The cells were either resting or stimulated with thrombin, thrombin receptor activating peptide, or ADP. The effect of the thrombin inhibitor lepirudin and the plasmin inhibitor aprotinin on plasminogen binding and the appearance of C-lysines was also investigated. RESULTS: Thrombin, but not thrombin receptor activating peptide or ADP, stimulated high-affinity binding of plasminogen and greatly promoted platelet-dependent plasmin generation. Digestion with carboxypeptidase B eliminated thrombin-induced high-affinity binding and reduced thrombin-induced plasmin generation by increasing the Michaelis constant. Lepirudin, but not aprotinin, inhibited thrombin-stimulated plasminogen binding to platelets. CONCLUSION: C-terminal lysines are necessary for high-affinity binding of plasminogen to platelets and for platelet-supported plasmin generation. The origin of the C-lysines is not clear, but they may result from a direct effect of thrombin, rather than an intermediate enzyme such as plasmin.

Blood Platelets↗
PubMed2004

Retention of lepirudin at the tip of a silicone catheter: a better catheter flush solution?

Because central venous catheters often become blocked by clot at their tip despite heparin flushes, a more effective anticoagulant is needed. We hypothesize that lepirudin, a recently introduced protein anticoagulant, might be more effective than heparin because of its tendency to adsorb to silicone, a commonly used catheter material. We preliminarily tested this hypothesis in vitro by measuring residual lepirudin and heparin activity at the tip of a catheter that had been submerged in a flowing stream of water for various periods of time. We observed that lepirudin is less readily removed than heparin from the catheter by fluid washing over it. This "slow-release" property of lepirudin might provide prolonged protection against clot formation at the catheter tip. A clinical trial will be necessary, however, to determine whether this property translates into significant improvement in catheter function.

Adsorption↗
PubMed2004

Is thyroid hormone suppression therapy prothrombotic?

The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1 + 2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P < 0.05) higher in the hyper- than in the hypothyroid state, whereas protein C and plasmin-antiplasmin complexes were significantly lower during the hyperthyroid period. When the 10 female patients were hyperthyroid, their levels of prothrombin fragment 1 + 2, fibrinogen, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher (P </= 0.05) than in healthy female controls, whereas when the female patients were hypothyroid, their antithrombin and plasmin-antiplasmin were lower and their protein S was higher than in controls. Factor II, plasminogen, and D-dimer were not significantly affected by the thyroid status in either assessment. In conclusion, we found evidence that the majority of patients treated with THST have a prothrombotic profile.

Adult↗
PubMed2003

Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.

STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.

Aged↗
PubMed2002

Parameters of coagulant and fibrinolytic capacity and activity in postmenopausal women: within-subject variability.

We have analyzed the within-subject variability of a battery of parameters of coagulant and fibrinolytic capacity and activity in postmenopausal women. We observed large differences in within-subject variability among the tests and have demonstrated how such data can be used to estimate the number of times a parameter must be measured to produce a statistically adequate sample.

Biomarkers↗