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Biomedical subjects

R L Bick

Publications and source records attributed to R L Bick.

At least 37 records · Page 2Linked to original sources
PubMed1999

Low molecular weight heparins: differences and similarities in approved preparations in the United States.

There is adequate preclinical data to support the differential biochemical and pharmacological behavior of the currently approved low molecular weight heparins (LMWHs) in the United States. Initial studies on the anti-Xa, anti-IIa, and U.S. Pharmacopoeial (USP) potencies have clearly demonstrated differences among these products. Furthermore, the ratios between the anti-X and anti-IIa activities vary from one product to another. This is primarily due to the composition of each product manufactured by using different patented methods. Studies in pharmacologic animal models, using gravimetric dosages or adjusted anti-Xa dosages of the LMWHs, produce product-specific results. The pharmacokinetics and pharmacodynamics of each product also vary markedly and are not predictable on the basis of any pharmacopoeial potency designation. These agents are capable of releasing tissue factor pathway inhibitor (TFPI), an inhibitor of the coagulation process. Its release is also dependent on the type of LMWH. In the United States enoxaprin, dalteparin, and ardeparin have been approved for DVT prophylaxis. Only enoxaparin and dalteparin have been approved for the acute coronary syndrome. Recently the clinical differentiation among these LMWHs has been demonstrated in the treatment of acute coronary syndrome. Similarly, when these drugs are used at high dosages, they are expected to produce product-specific pharmacodynamic effects. It must be noted that while these drugs may be interchangeable at clinically optimized/approved dosages, these drugs are not interchangeable at equivalent anti-Xa dosages. Even at optimized dosages, the clinical provile of each drug may be different. Thus, each of the LMWHs should be considered a distinct entity and their use in a given clinical situation should be validated in proper clinical trials.

Anticoagulants↗
PubMed1999

Long-term outpatient dalteparin (fragmin) therapy for arterial and venous thrombosis: efficacy and safety--a preliminary report.

The availability of low molecular weight heparin (LMWH), with associated ease of home delivery and enhanced efficacy and safety, has rendered the long-term outpatient use of LMWH feasible. Although warfarin is usually used for long-term secondary prevention, it is not the drug of choice for a variety of conditions such as antiphospholipid thrombosis syndrome, sticky platelet syndrome, and patients with malignancy and other medical conditions who have failed adequate warfarin doses. We assessed the long-term efficacy and safety of outpatient dalteparin in a series of patients with conditions associated with prior warfarin failure or potential to warfarin therapy (antiphospholipid syndrome). The results of this study, detailed herein, demonstrate that long-term dalteparin is highly effective and safe when used as long-term therapy for secondary prevention in selected prothrombotic disorders.

Adult↗
PubMed1999

Low molecular weight heparins in the outpatient management of venous thromboembolism.

Low molecular weight heparin (LMWH) has challenged the position of unfractionated heparin (UFH) as the treatment of choice in preventing progression, recurrence, and complications of venous thromboembolism (VTE). A meta-analysis of 13 randomized trials has shown that subcutaneous LMWH is associated with lower rates of recurrence, bleeding, and mortality than is intravenous UFH. The use of subcutaneous LMWH yields substantial savings in pharmacy and nursing costs. Recent trials have demonstrated that home treatment with enoxaparin and dalteparin is at least as safe and effective as inpatient treatment with UFH, is feasible in more than 70% of patients with VTE, and is associated with improved quality of life. Home treatment saves as much as $6000 per patient relative to inpatient treatment with UFH and nearly $3000 per patient relative to inpatient treatment with LMWH. Of the three LMWH preparations available in the United States, enoxaparin, dalteparin, and ardeparin, only enoxaparin is approved for the treatment of deep-vein thrombosis. These LMWHs differ substantially in molecular weight and molecular size distribution, bleeding indices in animal models, anti-Xa activity, anti-Xa/anti-IIa ratio, and release of tissue factor pathway inhibitor. Although the clinical relevance of these differences remains uncertain, the United States Food and Drug Administration recognizes LMWHs as distinct noninterchangeable drugs.

Ambulatory Care↗
PubMed1999

Vascular damage correlates between heparin-induced thrombocytopenia and the antiphospholipid syndrome.

Antibody-mediated disorders of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome have remarkably similar clinical presentations, both of which can progressively result in severe vascular and thrombotic disorders. We hypothesized that the mechanism of platelet activation as occurs in heparin-induced thrombocytopenia may also occur in antiphospholipid antibody syndrome particularly at the vascular wall, that endothelial injury may be similar in heparin-induced thrombocytopenia and antiphospholipid antibody syndrome, and that these alterations may be caused by related antibodies. Antibody titers and vascular endothelial damage in patients with heparin-induced thrombocytopenia and antiphospholipid antibody syndrome were studied in plasma samples collected from normals (n = 17), heparin-induced thrombocytopenia patients (n = 15), antiphospholipid antibody syndrome patients (n = 30), and patients clinically diagnosed with antiphospholipid antibody syndrome and heparin-induced thrombocytopenia (n = 8). Diagnosis of heparin-induced thrombocytopenia was confirmed by 14C-serotonin release assay or positive antiheparin-platelet factor 4 antibody titer, and antiphospholipid antibody syndrome was confirmed by positive anti-beta 2-glycoprotein (GP) 1/cardiolipin (IgG or IgM) antibody titer. The antiheparin-platelet factor 4 antibody was not detected in any patient with antiphospholipid antibody syndrome. Patients with heparin-induced thrombocytopenia did not have elevated IgG anti-beta 2-GP1 titers, but three (20%) patients had low-positive IgM anti-beta 2-GP1 titers. The endothelial damage markers of soluble thrombomodulin, soluble P-selectin (p < 0.05 vs. normal), plasminogen activator inhibitor-1 and tissue factor were elevated in heparin-induced thrombocytopenia and antiphospholipid antibody syndrome patients. The soluble E-selectin was elevated only in the patients with both heparin-induced thrombocytopenia and antiphospholipid antibody syndrome (p < 0.05 vs. normal). Levels of soluble L-selectin and von Willebrand factor were not different from normals. The pathogenesis of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome appears to be due to two distinct antibodies but associated with similar damage to the vascular endothelium in both diseases.

Antiphospholipid Syndrome↗
PubMed1999

Antithrombin agents as anticoagulants and antithrombotics: implications in drug development.

The development of direct thrombin inhibitors goes back nearly four decades. Organic synthetic benzamidine derivatives were initially developed as direct antithrombin agents. Later, the structural analysis of fibrinogen, leading to the identification of thrombin cleavage sites, resulted in the recognition of specific peptide sequences where thrombin cleaved fibrinogen. These observations led to the development of synthetic peptide derivatives as inhibitors of thrombin. The leech salivary extract contained natural hirudin, the structural elucidation of which led to the development of a recombinant equivalent protein (r-hirudin). Understanding the biochemical actions of thrombin and the structure of various inhibitors prompted the development of hirulogs, a class of hybrid molecules with two sites of action. Currently, several of these thrombin inhibitors are being developed for various indications in both intravenous and subcutaneous protocols. The increased interest in thrombin inhibitors is also prompted by reports of heparin-induced thrombocytopenia (HIT) with heparin and the need to anticoagulate patients with alternate drugs. These agents produce a direct anticoagulant response by targeting thrombin. In addition, the amplification of the coagulation cascade by thrombin activation of factors V and VIII, stabilization of fibrin by activated factor XHI, and platelet activation is also inhibited by these thrombin inhibitors. Some of the synthetic thrombin inhibitors are also capable of inhibiting other enzymes in the coagulation cascade. Thrombin inhibitors therefore exert a complex effect on the coagulation network and should be carefully evaluated in clinical trials. These drugs can be used for prophylactic and therapeutic and surgical indications. However, the different thrombin inhibitors have shown distinct pharmacologic differences. There is now an interest in developing oral antithrombin inhibitors. Such issues as antagonism, laboratory monitoring, drug interactions, and long-term safety remain unresolved. Current research is focused on addressing these issues.

Amino Acid Sequence↗
PubMed1998

Syndromes of thrombosis and hypercoagulability. Congenital and acquired causes of thrombosis.

Blood coagulation protein and platelet defects are now known to account for up to ninety percent of unexplained venous thrombosis and up to seventy percent of unexplained arterial thrombotic or ischemic events. This article summarizes the common and uncommon blood protein and platelet defects which should be suspected, and searched for, in patients with such events. Defining such defects will have major impact on secondary prevention and duration of antithrombotic therapy in the afflicted patient and impact on primary prevention for identified family members in those harboring hereditary defects.

Antiphospholipid Syndrome↗
PubMed1998

Antithrombin agents as anticoagulants and antithrombotics. Implications in drug development.

Synthetic and recombinant thrombin inhibitors have undergone several clinical evaluations for thrombotic and cardiovascular indications. While the initial trials were focused in coronary indications, more recently, these agents are also developed for the prophylaxis and therapeutic management of thromboembolic disorders. Hirudin, PEG-hirudin and argatroban are in advanced clinical development. Recombinant hirudin has been approved in Europe as a substitute anticoagulant for the management of HIT patients. Several additional clinical trials are currently carried out to demonstrate the usefulness of these agents in thrombotic and cardiovascular indications. Despite these developments such issues as dosage optimization, laboratory monitoring, neutralization and drug interactions require additional studies for the optimal development of these drugs.

Animals↗
PubMed1998

International consensus recommendations. Summary statement and additional suggested guidelines. European Consensus Conference, November 1991. American College of Chest Physicians consensus statement of 1995. International Consensus Statement, 1997.

Since the NIH Consensus Conference in 1986, the developments in the field of prevention and treatment of venous thromboembolism were mainly characterized by a more specific and extended use of new prophylactic agents such as low-molecular-weight heparins as well as the perception that out-patients may be at risk for thromboembolic complications, too. Therefore, in 1991 and 1995, consensus conferences were held in Europe and North America in order to analyze the risk constellation of various patient populations and to give recommendations for primary prophylaxis and treatment of thromboembolic complications. The most recent, the 1997 International Consensus Recommendations are also discussed.

Anticoagulants↗
PubMed1998

Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy.

Although several new anticoagulant drugs are in development, heparin remains the drug of choice for most anticoagulation needs. The clinical effects of heparin are meritorious, but side effects do exist. Important untoward effects of heparin therapy including heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia and alopecia will be discussed in this article.

Animals↗
PubMed1998

Disseminated intravascular coagulation: pathophysiological mechanisms and manifestations.

Current concepts of the many complex pathophysiological mechanisms and clinical and laboratory manifestations of disseminated intravascular coagulation (DIC) are presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. The future holds promise for not only newer antithrombotic agents, but also agents which will block, blunt or modify cytokine activity and the activity of vasoactive substances. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamic and other clinical parameters.

Animals↗
PubMed1998

Recurrent miscarriage: causes, evaluation, and treatment.

Recurrent miscarriage or fetal loss syndrome (also known as fetal wastage syndrome) is characterized by recurrent spontaneous abortion. There are many syndromes associated with recurrent fetal loss, including anatomic anomalies, endocrine/hormonal abnormalities, genetic/chromosomal abnormalities, and blood coagulation protein/platelet defects. Many of these syndromes are treatable, leading to normal term pregnancy, if the clinician is astute and vigorously pursues a thorough evaluation of why the patient has suffered unexplained, spontaneous miscarriages. There is no uniform agreement on how many spontaneous, unexplained miscarriages are needed to diagnose recurrent fetal loss; we generally pursue an evaluation for causation if a women has had 2 or more such events. In this article, we discuss the common reasons for recurrent fetal loss, plus diagnostic procedures to consider in pinpointing the problem, such as cytogenetic studies, blood coagulation protein/platelet tests, hysterosalpingography, sonography, and magnetic resonance imaging. We also describe management strategies that often lead to successful pregnancy outcome when the underlying problem is addressed. For example, in the case of thrombotic defects, a common cause of recurrent fetal loss, we report a 100% success rate in achieving a normal-term delivery among women who took low-dose (81 mg/day) aspirin preconception followed by postconception low-dose (5000 units q 12 h) heparin.

Abortion, Habitual↗
PubMed1997

Antiphospholipid thrombosis syndromes: etiology, pathophysiology, diagnosis and management.

Antiphospholipid antibodies are increasingly being identified as a cause of both arterial and venous thrombosis as well as fetal wastage syndrome via placental vascular thrombosis. The antiphospholipid thrombosis syndromes should be considered and searched for when suggestive clinical findings are present or when unexplained arterial or venous thrombosis occurs. Noting the presence and type of antiphospholipid antibody thrombosis syndrome assumes major importance with respect to not only making an accurate diagnosis of cause of thrombosis but also in selecting effective antithrombotic therapy.

Animals↗
PubMed1996

Hodgkin's disease in association with hexavalent chromium exposure.

During an epidemiological study assessing cancer risk in a small isolated population exposed to excessive amounts of hexavalent chromium, we noted two patients with Hodgkin's disease after exposure for many years and after a long latency period. The study population demonstrated an observed risk between 65 and 92 times that of reported risks for non-exposed US populations. Although malignant lymphoma, as well as many other malignancies, has clearly been associated with hexavalent chromium exposure, no reports have yet specifically mentioned Hodgkin's disease. We herein report Hodgkin's disease specifically in two individuals so exposed. Although this may be a chance occurrence, clinicians should be aware of the potential association between hexavalent chromium exposure and Hodgkin's lymphoma.

Adult↗
PubMed1996

Anemia of malignancy.

Anemia is a common association of malignant disease. It may be the first diagnostic clue to an underlying malignant disease, it may contribute to the patient's symptoms from the disease, and it may affect treatment decisions. It is important to recognize that a number of underlying mechanisms may contribute to the anemia, and to exclude those that are treatable. The recognition that tumor-associated cytokine production is a major factor in the anemia of malignancy, and that recombinant EPO can overcome this suppression, are major steps forward.

Anemia↗
PubMed1996

Thrombosis and hemorrhage in oncology patients.

As outlined in this review, patients with cancer may harbor many alterations of hemostasis. These are multifaceted and must be considered when trying to control hemorrhage or thrombosis in cancer patients. Also, hemorrhage or thrombosis is often the final fatal event in many patients with metastatic solid tumor or hematologic malignancies. Patients with malignancy present a major clinical challenge in this new era of oncologic awareness and more aggressive care, which has led to prolonged survival for patients and a longer time frame during which these complications may develop. Therefore, these complications are occurring more commonly. It is important to realize that these alterations of hemostasis exist and must be approached in a sequential and logical manner with respect to diagnosis; only in this way can responsible, efficacious, and rational therapy be delivered to patients. By far the most common alteration of hemostasis in malignancy is that of hemorrhage associated with thrombocytopenia, either drug-induced, or radiation-induced, or from bone marrow invasion. Hemorrhage resulting from DIC, however, is also quite common and may present as hemorrhage, thrombosis, thromboembolus, or any combination thereof. Many antineoplastic drugs and radiation therapy may lead to or significantly enhance hemorrhage in patients with malignancy. Thrombosis, also commonly seen in patients with malignancy, is often a manifestation of low-grade DIC. When approaching the patient with malignancy and either hemorrhage or thrombosis, all the potential defects in hemostasis must be considered, defined from the laboratory standpoint, and treated in as precise and logical manner as possible.

Hemorrhage↗
PubMed1996

Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response.

Current concepts of the etiology, pathophysiology, clinical and laboratory diagnosis and management of fulminant and low-grade disseminated intravascular coagulation (DIC) have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding the pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Objective clinical and laboratory criteria for diagnosis of DIC have been delineated, thus avoiding needless confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for severity of DIC and objective criteria for defining a response to therapy. Also, since it is often difficult for the individual physician to decide when to stop expensive therapy, objective criteria by which therapy may be stopped when continuation is likely fruitless are presented as a guideline.

Biomarkers↗
PubMed1995

Laboratory evaluation of platelet dysfunction.

Platelet dysfunction, especially acquired forms, is a common cause of hemorrhage, especially when associated with trauma or surgery. Although the hereditary platelet function defects are generally rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients with easy and spontaneous bruising, mild-to-moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the face of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable, and platelet aggregation or lumi-aggregation should be done in applicable clinical situations. Prolongation of the template bleeding time is an unreliable predictor of clinical bleeding propensity. The mainstay of therapy for all of these defects, if bleeding is important, is the liberal infusion of suitable numbers of platelet concentrates. The acquired platelet function defects should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should immediately be stopped.

Blood Platelet Disorders↗