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Biomedical subjects

B M Alving

Publications and source records attributed to B M Alving.

At least 19 recordsLinked to original sources
PubMed1995

Acquired von Willebrand's disease: a rare manifestation of postpartum thyroiditis.

This report describes the diagnosis of acquired type I von Willebrand disease in a 30-year-old woman (G5P5) who presented with complaints of excessive bleeding in the postpartum period. The patient's additional complaints of fatigue, depression, and inability to lose weight resulted in laboratory testing that indicated hypothyroidism due to thyroiditis. Clinical symptoms and laboratory tests for von Willebrand disease and hypothyroidism normalized with L-thyroxine replacement. Thyroiditis resulting in symptomatic hypothyroidism occurs in 2-4 per cent of postpartum women. The possibility of underlying hypothyroidism should be considered for those patients, especially if they are parous women, who appear to have an acquired bleeding disorder suggestive of von Willebrand disease.

Adolescent↗
PubMed1995

Inhibition of platelet deposition by combined hirulog and aspirin in a rat carotid endarterectomy model.

PURPOSE: Hirulog, a thrombin-specific inhibitor, has shown efficacy in reducing arterial thrombosis in patients treated with aspirin who require angioplasty or have unstable angina. In this study, the effect of hirulog on reducing deposition of indium 111-labeled platelets was assessed in a surgical model of aspirin-treated rats undergoing carotid endarterectomy. METHODS: Animals were randomly assigned to one of five groups: control (no aspirin or hirulog); aspirin alone (10 mg/kg); aspirin plus low-dose hirulog (0.2 mg/kg bolus followed by 0.5 mg/kg/hr); aspirin plus medium-dose hirulog (0.4 mg/kg bolus followed by 1.0 mg/kg/hr); or aspirin plus high-dose hirulog (0.6 mg/kg bolus followed by 1.5 mg/kg/hr). Hirulog was infused before surgery and continued until termination of the experiment 30 minutes after endarterectomy. RESULTS: Platelet deposition in rats receiving aspirin alone was reduced by 19% +/- 23% SE (p = 0.26) compared with controls. Deposition in aspirin-treated groups receiving low-, medium-, and high-dose hirulog decreased in a dose-dependent manner by 37% +/- 20% (p = 0.048), 44% +/- 19% (p = 0.061), and 56% +/- 13% (p = 0.022), respectively. As the dose of hirulog was increased, the plasma hirulog levels and activated partial thromboplastin time ratios (final:initial) also increased in a dose-dependent manner. The mean plasma hirulog levels ranged from 0.74 +/- 0.08 micrograms/ml in the low-dose hirulog group to 2.55 +/- 0.08 micrograms/ml in the high-dose hirulog group, and the corresponding activated partial thromboplastin time ratios were 1.5 +/- 0.12 (p = 0.001) and 3.3 +/- 0.63 (p = 0.001). Bleeding was easily controlled by local hemostatic measures for all experimental groups. CONCLUSION: Hirulog causes significant decrease in 111In-labeled platelet deposition in aspirin-treated rats subjected to microsurgical endarterectomy at doses that allow surgical hemostasis to be easily established.

Animals↗
PubMed1995

Fibrin sealant: summary of a conference on characteristics and clinical uses.

The 2-day conference clearly outlined the formulations of products that are being developed or are commercially available in Europe. The major difference between products in the United States and those in Europe is that US manufacturers are preparing fibrin sealant that does not contain aprotinin, epsilon amino caproic acid, or any other type of antifibrinolytic agent, whereas antifibrinolytic agents are included in all such preparations used in Europe. The conference provided no clear consensus that such agents are essential to the efficacy of the product. Although many investigators believe in the clinical benefit of fibrin sealant, most of the studies to demonstrate efficacy have not been performed in a well-controlled fashion. However, fibrin sealant, if found in a controlled trial to have clinical efficacy, could be approved by the FDA for a narrow indication. Opportunities remain for greater exploration of different forms of the product, not only as a hemostatic agent, but as an adjunct to wound healing and as a matrix for delivery of drugs and proteins with other biologic activities.

Animals↗
PubMed1995

Effect of fibrin structure on plasmin-mediated dissolution of plasma clots.

Previous studies in purified systems have demonstrated that fibrin structure influences the rate of conversion of plasminogen to plasmin by t-PA as well as the rate of plasmin-mediated clot digestion. The present study extended these observations to a plasma system in which fibrin structure was altered by varying the thrombin concentration, varying the plasma ionic strength, or by adding dextran 40. The effect of fibrin structure on the rate of fibrinolysis was assessed by adding plasminogen activators (t-PA or urokinase (UK)) either before or after clot formation. Gel formation and dissolution were monitored optically (turbidity) and isotopically (125I-fibrinogen). Clots formed under conditions of high ionic strength and/or high thrombin concentration were composed of thin fibrin fibres that dissolved slowly. Clots formed at lower ionic strengths, at lower thrombin concentrations or in the presence of dextran were composed of thicker fibres and dissolved more rapidly. The difference in fibrinolytic rate between thin and thick fibres was noted when t-PA or UK was added before or after clot formation. These data indicate that even in a plasma milieu fibre diameter is a factor in determining fibrinolytic rate induced by either UK or t-PA. The method by which fibre diameter is altered does not influence the conclusion that fibrinolytic rate is increased with increasing diameter.

Dextrans↗
PubMed1995

Increased anticardiolipin antibodies associated with the development of anetoderma in HIV-1 disease. Military Medical Consortium for the Advancement of Retroviral research (MMCARR).

BACKGROUND AND OBJECTIVE: Anetoderma has been reported in patients with HIV-1 disease. In patients with autoimmune disease, anetoderma has been associated with increased levels of antiphospholipid antibodies (APL) that include anticardiolipin antibodies (ACA) and lupus anticoagulant (LA). This has led to speculation that the autoimmune phenomena seen in HIV-1 disease and the immune dysregulation induced by HIV-1 disease may play a role in the development of these lesions. We have seen both primary and secondary lesions of anetoderma in patients followed for HIV-1 disease. In this study, we wanted to determine whether there was an association in the development of anetoderma and elevated anticardiolipin antibodies (ACA) in HIV-1 patients. METHODS: Quantitative ACA levels were measured in eight HIV-1-infected patients with anetoderma and four HIV-1-infected patients without anetoderma. RESULTS: Anticardiolipin antibodies were moderately elevated in seven of eight patients with lesions and were borderline in the four HIV-1-positive patients without lesions of anetoderma. CONCLUSIONS: There appears to be a correlation between increased ACA and the development of cutaneous lesions of anetoderma in HIV-1 disease. Patterns of immune dysregulation, including APL, may predispose to the development of lesions of anetoderma in HIV-1-positive patients. Although some of the lesions appear to represent primary anetoderma, the majority of our patients develop lesions in areas secondary to well characterized eruptions.

Adult↗
PubMed1994

Inhibitory effects of lysine analogues on t-PA induced whole blood clot lysis.

The lysine analogues epsilon-aminocaproic acid (EACA) and trans-4-amino-methyl cyclohexane carboxylic acid (AMCA) are used to prevent excessive bleeding in patients with coagulopathies, such as hemophilia and thrombocytopenia, or in those who have received tissue plasminogen activator (t-PA). However, their relative efficacy in inhibiting lysis of clots that have been formed in the presence of exogenous t-PA or that have been formed and then exposed to exogenous t-PA has not been well characterized. The present study utilized blood from normal volunteers and 125I-fibrinogen in a dilute whole blood clot assay to determine the relative concentrations of lysine analogues required for inhibition of clot lysis induced by exogenous t-PA. AMCA (0.06 mM) and EACA (0.6 mM) were effective in prolonging clot lysis if (1) whole blood clots were formed and then exposed to a lysine analogue and exogenous t-PA or if (2) whole blood clots were formed in the presence of exogenous t-PA and a lysine analogue. However, their inhibitory effect was markedly reduced if clots were formed in the presence of t-PA and then exposed to either of the lysine analogues. The analogues did not inhibit the initial binding of t-PA to fibrin. They did inhibit binding of plasminogen to fibrin as well as the activation of plasminogen by t-PA in the absence of fibrin. The data suggest that lysine analogues, even at low concentrations, reduce the rate of t-PA induced whole blood clot lysis by several mechanisms.

Aminocaproic Acid↗
PubMed1994

Hemostatic assessment of patients before tonsillectomy: a prospective study.

The purpose of this prospective study in patients undergoing tonsillectomy was to determine whether perioperative bleeding could be predicted by use of a standardized questionnaire concerning bleeding risk combined with measurement of the activated partial thromboplastin time and prothrombin time. Of the 96 patients enrolled in the study, none had a history of a severe bleeding disorder, but 6 (6%) had histories suggestive of a mild bleeding disorder. Further evaluation showed possible von Willebrand's disease in one of these patients. Of the 90 patients with negative questionnaires, 16% had prolongation of the activated partial thromboplastin time. One of these patients had possible von Willebrand's disease. However, none of the patients with positive questionnaires or a prolonged activated partial thromboplastin time bled after surgery. Bleeding that resulted in additional hospital use occurred in 2% of patients, and blood-tinged sputum was described by 4% after discharge; all of these patients had negative questionnaires and normal screening studies. The data provide further evidence that routine measurement of the activated partial thromboplastin time and prothrombin time in asymptomatic patients is not useful for predicting postoperative bleeding. In addition, histories suggestive of a mild bleeding disorder are also not accurate predictors of postoperative bleeding. Excessive bleeding associated with tonsillectomy is usually not a result of an identifiable coagulation disorder.

Adenoidectomy↗
PubMed1993

A quantitative thrombin time for determining levels of hirudin and Hirulog.

The anticoagulant effect of recombinant hirudin (rHir) and Hirulog has been monitored in patients with the activated partial thromboplastin time. Accurate monitoring with this test cannot be achieved if plasmas contain heparin, lupus anticoagulants, low concentrations of fibrinogen or other factors, or elevated fibrinogen-fibrin degradation products (FDP). We have therefore developed a simple, rapid, sensitive clot-based method, the quantitative thrombin time (QTT), to measure levels of rHir and Hirulog in patient plasma (or whole blood). The QTT is performed by mixing a 1:10 dilution of patient plasma (50 microliters) with human fibrinogen (50 microliters, 128 mg/dl) at 37 degrees C; the clotting time is initiated by adding human thrombin (50 microliters, 5-7.5 U/ml). The concentration of Hirulog or rHir in plasma can be determined by comparing the QTT in patient plasma with a standard curve that is generated by adding different concentrations of anticoagulant to pooled normal plasma. Studies with whole blood using the same procedure yield similar results. In the absence of Hirulog or rHir, the baseline QTT is the same in normal and abnormal plasmas (fibrinogen < 150 mg/dl and FDP as high as 1024 micrograms/ml, elevated FDP alone, lupus anticoagulant, or heparin < 0.9 U/ml). When known concentrations of either rHir or Hirulog are added to abnormal plasmas, the mean observed concentrations as determined by the QTT deviate from the expected values by less than 10% (range 0-19%). The data indicate that the QTT is a simple, rapid, and accurate test for the determination of levels of rHir and Hirulog in plasma or whole blood.

Heparin↗
PubMed1992

Comparison between a one-point dilute phospholipid APTT and the dilute Russell viper venom time for verification of lupus anticoagulants.

In the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RVVT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of greater than or equal to 1.3 for the PL-APTT with liposomes and greater than or equal to 1.2 for the PL-APTT with Thrombofax and the RVVT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RVVT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.

Adult↗
PubMed1992

Effect of plasminogen activator inhibitor-1 on tissue-type plasminogen activator-induced fibrinolysis.

The effect of fibrin on the interaction of human recombinant single-chain tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in normal rabbit plasma and in plasma with high levels of native PAI-1. t-PA was added to diluted plasma containing calcium (10 mM) and 125I-fibrinogen at 37 degrees C. Clotting was initiated with human thrombin, and lysis was monitored both turbidimetrically and by release of 125I-fibrin degradation products (fdp). The activity of t-PA (50 IU/ml) was rapidly reduced to 15% of the initial value in plasma containing PAI-1 (23 AU/ml). When thrombin and t-PA were added simultaneously to the plasma, more than 70% of the activity was retained through incorporation of t-PA into the fibrin clot. t-PA-induced fibrinolysis in PAI-1 enriched plasma was further delayed when the temperature was reduced from 37 to 25 degrees C. Turbidimetric and 125I-fdp release data provided complementary information. The former technique traced fiber dissolution, while the latter reflected network integrity. These results indicate that t-PA-induced fibrinolysis in PAI-1 enriched plasma is modulated by the presence of fibrin and by temperature.

Animals↗
PubMed1992

Recent advances in understanding clotting and evaluating patients with recurrent thrombosis.

Significant advances have been made in defining the regulatory mechanisms that control blood clotting. These are reviewed, with special attention to the functions of the natural inhibitors antithrombin III, protein C, and protein S. Congenital deficiencies of these inhibitors as well as acquired abnormalities, such as defective fibrinolysis, and their role in promoting thrombosis are also discussed, as are thrombotic complications of pregnancy. Pregnancy decreases levels of protein S to 40% to 50% of normal levels. The decrease occurs early in pregnancy and persists into the postpartum period; it appears to be a hormonal rather than a dilutional effect. It is not known whether the thrombotic risk associated with pregnancy is increased in women who are congenitally deficient in protein S. Oral contraceptives decrease levels of protein S by about 20%. Women with a personal or family history of thrombosis should be evaluated for predisposing conditions before they start an oral contraceptive, as should women taking oral contraceptives who develop deep venous thrombosis.

Antithrombin III↗
PubMed1992

Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis.

BACKGROUND: The efficacy of fibrinolytic therapy is limited by the small surface area of the clot that is available for the binding of the thrombolytic agent, such as tissue-type plasminogen activator (t-PA). We hypothesized that exposure of the clot to ultrasound during thrombolytic treatment could enhance lysis through perturbation of the thrombus, which would expose additional fibrin binding sites for t-PA. METHODS AND RESULTS: Whole human blood clots containing radiolabeled fibrinogen were incubated in vitro for 200 minutes with Tris-albumin buffer containing t-PA at concentrations ranging from 3 to 3,000 IU/ml. In paired experiments, one of the clots also was exposed to intermittent ultrasound (1 MHz, 1.75 W/cm2) throughout the experiment. The ultrasound was delivered as a 2-second exposure followed by a 2-second rest interval. The overall difference in mean clot lysis between thrombi receiving ultrasound and those receiving no ultrasound was significant (p less than 0.001) at all concentrations of t-PA. For clots incubated with t-PA at a concentration of 300 IU/ml, ultrasound increased the percent lysis at 200 minutes from 42 +/- 5% (mean +/- SEM) to 64 +/- 10%. In six paired experiments in a rabbit jugular vein thrombosis model, rabbits received 1 mg t-PA alone or t-PA and intermittent ultrasound (1 MHz, 1.75 W/cm2) for 200 minutes. For rabbits receiving ultrasound and t-PA, lysis was 55 +/- 11% at 100 minutes compared with 30 +/- 12% for rabbits receiving only t-PA. Lysis was 6 +/- 10% for rabbits (n = 4) receiving ultrasound alone. No evidence for tissue damage was noted in rabbits exposed to intermittent ultrasound. CONCLUSIONS: Exposure of whole blood clots in vitro to intermittent ultrasound combined with t-PA caused a significant enhancement of thrombolysis compared with t-PA alone. Intermittent ultrasound also showed a trend toward enhancement of t-PA-induced clot lysis in an animal thrombosis model. These data suggest that noninvasive intermittent ultrasound may be a useful adjunct to thrombolytic therapy.

Animals↗
PubMed1991

Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-treated rabbits.

Endotoxin-treated rabbits produce high levels of plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrinolysis by neutralizing endogenous tissue-type plasminogen activator (t-PA). These animals will develop renal fibrin deposition when infused with ancrod, an enzyme that acts directly on fibrinogen. In normal rabbits with an intact fibrinolytic system, ancrod induces hypofibrinogenemia without fibrin deposition. Rabbit PAI-1 activity can be neutralized by recombinant human t-PA or by bovine activated protein C. The present study determined the efficacy of these two agents used alone or in combination in neutralizing increased PAI-1 activity and in preventing renal fibrin deposition in a rabbit model. Male New Zealand rabbits first received intravenous endotoxin to increase PAI-1 activity. Ancrod was infused intravenously during hour 4 to 5, and the kidneys were examined at hour 5.5. Renal fibrin deposition occurred in 100% (6 out of 6) of the endotoxin-treated rabbits that received ancrod; this was reduced to 14% (1 out of 7) for rabbits receiving t-PA (170 micrograms/kg) before and during the ancrod infusion. Fibrin deposition occurred in only 12% (1 out of 8) of the rabbits that received a 10-fold lower dose of t-PA (17 micrograms/kg) combined with activated protein C (1 mg/kg) before and during the ancrod. Activated protein C at this dose completely neutralized plasma PAI-1 activity. However, low-dose t-PA and activated protein C did not prevent fibrin deposition when used as single agents, with fibrin deposition occurring in 75% and 100% of rabbits, respectively. The data indicate that activated protein C can neutralize plasma PAI-1 activity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod↗
PubMed1991

Recurrent venous thrombosis and hypercoagulable states.

Patients with recurrent venous thrombosis, or those with thrombosis at a young age (less than 45 years) and a family history of thrombotic disorders, may have an inherited hypercoagulable disorder. The most common disorders are deficiencies of protein S, protein C and antithrombin III, inhibitors of the coagulation cascade. These deficiencies may be found in approximately 10 percent of patients who are under age 45 and have venous thrombosis. Acquired disorders associated with recurrent venous thrombosis include carcinoma and antiphospholipid antibody syndrome. Appropriate anticoagulation can reduce the risk of recurrent thrombosis in patients with inherited and acquired abnormalities.

Adult↗
PubMed1990

Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

Adult↗
PubMed1990

Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times.

PURPOSE: An increased incidence of thrombosis has been reported in patients with a prolonged activated partial thromboplastin time (APTT) due to a lupus anticoagulant (LA), which is an antibody to negatively charged phospholipids. The antiphospholipid antibodies can be quantitated in an enzyme-linked immunoabsorbent assay (ELISA) that utilizes cardiolipin as the antigen. With the development of the ELISA, two major areas of controversy have arisen. First, the correlation between assay results for LA and for the ELISA has varied widely among laboratories. Second, some investigators have described a correlation between high levels of anticardiolipin antibodies (ACA) and thrombotic disorders, whereas others have found no association between ACA levels and thrombosis in a general population of medical patients. To explore these issues further, the present study determined the sensitivity and specificity of an LA assay for detecting ACA in medical patients with a prolonged APTT. The association between the isotype and titer of ACA and thrombosis was examined in those patients positive for LA. PATIENTS AND METHODS: Plasma samples from 70 medical patients with a prolonged APTT by routine screening studies were tested for the presence of LA by dilution of phospholipid in an APTT system and for IgM and IgG ACA according to a standardized ELISA. Clinical records were reviewed for a history of thrombotic events by an investigator who had no knowledge of the laboratory results. RESULTS: The ACA assay gave positive results in 47 patients, 44 of whom also tested positive for LA. Thus, the sensitivity for the LA assay for detecting ACA was 94% (confidence interval, 82% to 99%). The result of the LA assay was negative in 20 of 23 patients who were ACA-negative. The specificity of the LA assay was 87% (confidence interval, 67% to 98%). Twelve of the 47 patients (26%) had a history of venous or arterial thrombosis. Of these patients, 75% tested in the high-positive range for IgG or IgM ACA, or both. Of the 35 patients without thrombosis, only 14% were in this range. Patients with thrombosis had either underlying systemic lupus erythematosus, lymphoma, or no apparent etiology for LA. There was no history of thrombosis in patients with LA associated with infection or medication. CONCLUSION: A test for LA in medical patients with a prolonged APTT can be sensitive and specific for ACA. Determination of ACA levels in patients who have LA that is not induced by medication or infection may define those patients at increased risk for thrombosis.

Adult↗