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Rodger L Bick

Publications and source records attributed to Rodger L Bick.

29 records · Page 2Linked to original sources
PubMed2003

Heparin, low-molecular-weight heparins, and heparin pentasaccharide: basic and clinical differentiation.

As a result of advanced technology, dramatic developments in the area of new anticoagulant and antithrombotic drugs appear to have made a profound impact on the use of LMWHs. Furthermore, because porcine mucosal heparin is used for the preparation of these agents, it is likely that alternative drugs with comparable pharmacologic and clinical efficacy are sought. Antithrombin drugs such as argatroban and hirudin are already approved for alternative management of heparin-compromised patients. Their efficacy in other indications is less superior. The development of specific anti-Xa drugs is slow. Although these agents may inhibit factor Xa and thrombin generation, none of them are capable of mimicking the polytherapeutic effects of LMWHs and thus can only be given in drug combinations. Synthetic and recombinant protein-derived anti-tissue factor agents have also been developed. These drugs only inhibit the tissue factor-mediated process and are limited in their therapeutic spectrum. Plasma-derived and recombinant serine protease inhibitors (serpins) are also available for the management of thrombotic and inflammatory disorders, but these agents cannot be given subcutaneously. Furthermore, because they are proteins, antibodies to these agents are generated. Nucleic acid derivatives (natural and synthetic aptomers) are developed for intravenous administration, but they are relatively weak antithrombotic agents. Dermatans, heparans, and chondroitin sulfates represent nonheparin GAGs, and, in mono-compositional and polycompositional form, these drugs are mainly used for the intravenous management of DVT prophylaxis. They can be given to patients who are heparin compromised. Synthetic heparinomimetics include heparin consensus-binding oligosaccharides and synthetic oligosaccharides with non-serpin affinity. In addition, binding oligosaccharides are conjugated with antithrombin agents to mimic the anti-Xa/anti-IIa activities of heparin. Biotechnology using bacterial and yeast cultures, aqua cultures for marine products, and plant carbohydrates have been the focus of developing heparin analogues. Development of these agents is in the early phase; however, it is likely that this approach may provide a reasonable alternative to LMWHs. Despite these developments, it is unlikely that any of these drugs will have a profound impact on the use of LMWHs in the near future. Unfractionated heparin and LMWHs collectively represent an important group of polypharmacologic drugs without which the management of thrombosis and vascular disorders would not be possible. The continual development of LMWHs in expanded indications did not comprise the use of unfractionated heparin in surgical and interventional cardiovascular indications. Ever since their introduction in the 1980s, the use of LMWHs has continually increased. This is primarily because of expanded indications and growing awareness among the clinicians. It is likely that once an antidote is developed and additional information is available on the mechanism of action of LMWHs, these drugs may gradualty be used for surgery patients. Despite these developments, it is likely that unfractionated heparin will continue to be used for specific indications. Drug combinations with heparins may necessitate dose adjustments, but it is unclear whether unilateral reduction of heparins will be optimal. The coming years will provide useful clinical and applied data on the improved use of unfractionated heparin. LMWHs, and pentasaccharide in the management of thrombotic and cardiovascular disorders. In addition, use of these drugs will be extended to many conditions, including cancer, inflammation, sepsis, and autoimmune diseases. Polytherapeutic approaches emphasizing LMWHs as primary and secondary drugs will also have an impact on the management of thrombotic and nonthrombotic disorders. Ultra-LMWHs and synthetic heparinomimetics, such as fondaparinux, that exhibit a narrow pharmacologic spectrum will only be useful in specific indications and in combination with other drugs.

Fibrinolytic Agents↗
PubMed2003

Thromboprophylaxis and thrombosis in medical, surgical, trauma, and obstetric/gynecologic patients.

The International Consensus and the ACCP Sixth Consensus had a great impact on the clinical acceptance of LMWHs. These recommendations have been instrumental in initiating further clinical trial to answer key questions regarding thromboprophylaxis and in setting a new standard for patient care. Also, the key to cost containment in management of DVT/PE is to (1) define the etiology (blood coagulation protein or platelet defect), institute appropriate long-term therapy as indicated, and assess appropriate family members as indicated if a hereditary defect is found and (2) use LMWH as inpatient management. saving a minimum of 210,000.00 dollars per 1000 patients simply from cost savings of recurrence, saving 17 lives per 1000 patients, and saving exorbitant costs of care for patients with recurrence and development of chronic venous insufficiency. The use of outpatient LMWH will save 4,900,000.00 dollars per 1000 patients if applied to the 70% of patients with DVT who fit the criteria of no comorbid condition requiring hospitalization and who arrive early enough to allow a diagnosis to be sent home or hospitalized for 24 hours or less. The simple defining of defects leading to unexplained thrombosis will add another 3,000,000.00 dollars in savings per 1000 patients with DVT and approximately 350,000.00 dollars per 100 patients with thrombotic stroke. In those with transient ischemic attacks, defining the defect and instituting appropriate antithrombotic therapy, thereby potentially saving approximately 30% from developing a thrombotic stroke, amounts to approximately 350,500.00 dollars (= 30% of 1,168,500.00 dollars) in savings per 100 patients.

Anticoagulants↗
PubMed2003

Prothrombin G20210A mutation, antithrombin, heparin cofactor II, protein C, and protein S defects.

These defects are not as common as factor V Leiden, but they are more common than many other hereditary procoagulant defects. The incidence of the prothrombin gene (G20210A) mutation is not yet known with certainty, but it may approach or even exceed that of factor V Leiden. These defects also seem less common than hereditary sticky platelet syndrome; however, they are all common enough that they always should be considered in any individual with unexplained thrombosis and should be part of the work-up for patients with thrombotic disorders. Of the defects discussed herein, prothrombin G20210A mutation seems, thus far, to be more common than AT, protein C, protein S, or HC-II defects. Assessment of prothrombin gene mutation should be part of the primary evaluation of patients with unexplained thrombosis.

Antithrombins↗
PubMed2003

Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis, and treatment.

The pathophysiologic mechanisms and clinical and laboratory manifestations of DIC are complex, partly because of inter-relationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiologic inter-relationships 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 to be made are controversial and lack validation. Nevertheless, newer antithrombotic agents and agents that can block, blunt, or modify cytokine activity and the activity of vasoactive substances seem to be of value. The complexity and variable degree of clinical expression suggest that therapy should be individualized depending on the nature of DIC, the patient's age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamics and other appropriate clinical parameters.

Disseminated Intravascular Coagulation↗
PubMed2003

Antiphospholipid thrombosis syndromes.

Antiphospholipid antibodies are associated strongly with thrombosis and are the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanisms whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, numerous theories, as previously discussed, have been advanced. The most common thrombotic events associated with ACLAs are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Patients with type V disease are those with antiphospholipid antibodies and RMS. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLAs in association with arterial and venous thrombosis strongly suggests that they should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I-VI) should be defined, if possible, because this identification may dictate both the type and the duration of immediate and long-term anticoagulant therapy. Unlike those patients with ACLAs, patients with primary LA-thrombosis syndrome usually have venous thrombosis. Because the aPTT is unreliable in patients with LA (prolonged in only approximately 40%-50% of patients) and usually is not prolonged in patients with ACLAs, definitive tests, including ELISA for ACLA, the dilute Russell's viper venom time for LA, hexagonal phospholipid-neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be ordered immediately when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these test results are negative, subgroups also should be assessedin the appropriate clinical setting. Most patients with antiphospholipid thrombosis syndrome will fail to respond to warfarin therapy, and except for retinal vascular thrombosis, may fail some types of antiplatelet therapy, so it is of major importance to make this diagnosis so patients can be treated with the most effective therapy for secondary prevention-LMWH or unfractionated heparin in most instances and clopidogrel in some instances.

Antiphospholipid Syndrome↗
PubMed2003

Management of thrombotic and cardiovascular disorders in the new millenium.

Anticoagulants and antithrombotic drugs have played a key role in the prophylaxis, treatment and surgica/interventional management of thrombotic and cardiovascular disorders. There are several newer drugs which are currently developed for the anticoagulant management of cardiovascular diseases in both the medical and surgical indications. These include the low molecular weight heparins (LMWHs), antithrombin agents such as the Hirudin, Hirulog and Argatroban and indirect and direct anti-Xa drugs, represented by Pentasaccharide (Arixtra) and DX 9065a, respectively. Several other agents such as the natural and recombinant anti-Xa drugs and anti-tissue factor agents are also developed. The antiplatelet agents include Clopidogrel, Cilostazol, Anplag and GP IIb/IIIa inhibitors. For the subcutaneous indications, unfractionated heparin is gradually replaced by the low molecular weight heparins (LMWHs). LMWHs such as the Enoxaparin and Dalteparin are commonly used for the management of acute coronary syndrome. These drugs have been approved for the treatment of unstable angina and are currently undergoing rigorous trials for interventional indications. Arixtra is also developed for various subcutaneous indications. However, it exhibits lower anticoagulant effects and may not be optimal for intravenous and interventional purposes. At a higher dosage when administered intravenously the LMWHs produce varying degrees of anticoagulation at relatively lower activated clotting times (150-200). Several studies in vascular and cardiovascular interventions have shown that even at a relatively lower anticoagulant level the LMWHs are as effective as unfractionated heparin at the recommended dosages which produce a relatively higher level of anticoagulation (ACT > 200 secs.). Thus, these agents are currently developed for interventional and surgical indications. It should be emphasized that different LMWHs produce different degrees of anticoagulation and should therefore be individually optimized for a given interventional or surgical purposes. At a relatively high dosage the levels of LMWHs can be measured by using the ACT and APTT. When administered with such GP IIb/IIIa inhibitors as the Abciximab, Aggrastat or Eptifibratide, these drugs may require dosage adjustment However, since the introduction of the front loading of Clopidogrel, the unqualified use of GP IIb/IIIa is debated. LMWHs will find expanded indications in both the medical and surgical management of patients with cardiovascular disorders including atrial fibrillation and congestive heart failure. The only approved anti-Xa drug is represented by a synthetic heparinomimetic, namely, Arixtra. This drug is given for the prophylaxis of post orthopedic indications. This agent is undergoing additional clinical trials in the management of coronary artery diseases. Because of the dependence on antithrombin III (AT) and the sole anti-Xa effects, it has a narrow therapeutic index and its efficacy in this indication may be limited. Additional clinical trials are needed at this time to validate the clinical potential of this drug. The antithrombin agents (Hirudin, Hirulog and Argatroban) were initially developed for arterial indications. However, these agents are approved as a substitute anticoagulant in patients with heparin induced thrombocytopenia (HIT) and PCI. Currently an of these agents are being developed for surgical and interventional use. However, since there is no available antidote at this time, the development is somewhat limited. The antithrombin agents may be useful in patients with HIT which require further clinical validation. Many other anti-Xa agents are also developed. Most of these can be given parenterally. However, the clinical data is somewhat limited. Similarly, several of the new antiplatelet drugs can be administered parenterally and may be useful in CAD. Since most of these newer anticoagulant and antithrombotic drugs are mono-therapeutic their therapeutic index is rather limited. Only in combination these agents can mimic heparins. At this time it is safe to state that heparin and its LMW derivatives will remain the anticoagulant of choice for cardiovascular indications until these newer agents have been validated in extended clinical trials in polytherapeutic settings.

Anticoagulants↗
PubMed2002

Disseminated intravascular coagulation: a review of etiology, pathophysiology, diagnosis, and management: guidelines for care.

The pathophysiologic mechanisms, clinical, and laboratory manifestations of DIC are complex in part due to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiologic 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 to be made are controversial and lack validation. Nevertheless, newer antithrombotic agents, and agents that can block, blunt, or modify cytokine activity and the activity of vasoactive substances appear to be of value. The complexity and variable degree of clinical expression suggests that therapy should be individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamics and other appropriate clinical parameters. At present, treatment of the triggering event, low-dose heparin or antithrombin concentrate and wise choice of components when indicated appear to be the most effective modes of therapy.

Adult↗
PubMed2002

Fondaparinux: a synthetic heparin pentasaccharide as a new antithrombotic agent.

Fondaparinux (Arixtra, Sanofi-Synthélabo/Organon) is the first of a new class of antithrombotic agents distinct from low molecular weight heparins (LMWHs) and heparin. It is a chemically synthetic pentasaccharide mimicking the site of heparin that binds to antithrombin III (AT). It exhibits only factor (F) Xa (FXa) inhibitor activity via binding to AT, which in turn inhibits thrombin generation. In contrast to heparin and LMWH, plasma anti-Xa activity corresponds directly to levels of fondaparinux. It does not release tissue factor pathway inhibitor (TFPI). There is nearly complete bioavailability by the sc. route, rapid onset of action, a prolonged half-life in both iv. and sc. (14 - 20 h) dosing regimens and no metabolism preceding renal excretion. Phase IIb clinical studies have identified a dose of 2.5 mg once-daily for prophylaxis of venous thrombosis. Four Phase III studies (n > 7000) have demonstrated a combined 50% relative risk reduction of venous thromboembolic events in orthopaedic surgery patients in comparison to the LMWH, enoxaparin. Haemmorrhagic complications for fondaparinux were either comparable to or higher than those for LMWH. The activated partial thromboplastin time (aPTT) is not affected by fondaparinux. At present, laboratory monitoring is not recommended. Clinical trials for treatment of established thrombosis, coronary syndromes and adjunct to thrombolytic therapy are in progress.

Animals↗
PubMed2002

Management of venous thrombosis and thromboembolism: prevention and treatment.

Thrombosis is a common cause of death in the United States. More than two million people die each year from an arterial or venous thrombosis, or the consequences thereof. Approximately an equal number suffer non-fatal thrombosis; for example, deep venous thrombosis (DVT), non-fatal pulmonary embolus (PE), non-fatal cerebrovascular thrombosis (CVT), transient cerebral ischemic attacks (40% of these have a fatal or non-fatal CVT within one year), non-fatal coronary artery thrombosis, retinal vascular thrombosis (RVT), and other non-fatal thrombotic deaths. These numbers emphasize the scope of the problem. By contrast, approximately 550,000 people will die this year in the United States from cancer; thus, fatal thrombosis is approximately four times as prevalent as fatality from malignancy. Thrombosis, therefore, accounts for extraordinary morbidity, mortality, and cost of medical care.

Humans↗