Comparison of immunogenic potentials of bovine thrombin preparations.

Using a membrane filtration step, bovine crude thrombin was purified into thrombin 4A and 4B preparations. The purpose of this study was to determine whether the improved purity of a bovine thrombin preparation can reduce its overall immunogenic potential and lower the risk of development of factor V antibodies. Bovine crude thrombin and its purified versions, thrombin 4A and 4B, were administered to individual groups of rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic methods.

Reduced immunogenic potential of membrane filtered bovine thrombin preparations for hemostatic application.

There is concern that exposure to bovine thrombin can result in the development of antibodies, usually against factor V/Va, which can lead to hemostatic abnormalities. It is thought that purer preparations of bovine thrombin might be less immunogenic. Utilizing newer methods including a membrane filtration step, bovine crude thrombin is further purified into thrombin 4A and 4B preparations which exhibit a higher specific activity and are devoid of some of the protein contaminants.

Controversies and unresolved issues in antiphospholipid syndrome pathogenesis and management.

While much is understood concerning the clinical features of patients with antiphospholipid syndrome (APS), many issues remain. The proper designation of patients with "definite" APS and the correct categorization of patients by both laboratory and clinical features are matters of ongoing debate. Recent proposals have identified new subsets of patients who have many typical features of APS but either do not fit the criteria for a "definite" diagnosis or have initially negative laboratory tests for antiphospholipid antibodies.

Treatment options for patients who have antiphospholipid syndromes.

The antiphospholipid thrombosis syndrome, associated with anticardiolipin (aCL) or subgroup antibodies, can be divided into one of six subgroups (I-VI). There is little overlap (about 10% or less) between these subtypes, and patients usually conveniently fit into only one of these clinical types. Although there appears to be no correlation with the type, or titer, of aCL antibody and type of syndrome, the subclassification of thrombosis and aCL antibody patients into these groups is important from the therapy standpoint.

Antiphospholipid syndrome in pregnancy.

During the past 5 years the author and his colleagues have assessed carefully 351 women referred for evaluation of thrombosis and hemostasis after they had suffered recurrent miscarriages. This article describes the flow protocol the author and associates follow to maximize success and keep the costs of evaluation of recurrent miscarriage syndrome/infertility at a minimum while providing the best chances for defining a cause and thus providing optimal therapy for successful term pregnancy outcome. It presents the outcomes of the author's protocol and those of others in treating women who have antiphospholipid syndrome and who have suffered recurrent miscarriages.

The clinical spectrum of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a disorder characterized by a wide variety of clinical manifestations. Virtually any organ system or tissue may be affected by the consequences of large- or small-vessel thrombosis. There is a broad spectrum of disease among individuals with antiphospholipid antibodies (aPL).

Laboratory evaluation of the antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is among the most common acquired blood protein defects that have been identified as leading to thrombosis. This article describes the laboratory diagnosis of APLS, including the detection of lupus anticoagulants, anticardiolipin antibodies, and subtypes of antiphospholipid antibodies.

Product individuality of commercially available low-molecular-weight heparins and their generic versions: therapeutic implications.

The currently available brand-name low-molecular-weight heparins (LMWHs) in the United States include dalteparin (Pfizer), enoxaparin (Aventis), and tinzaparin (Pharmion). Other products available, in Europe, include certoparin (Novartis), reviparin (Abbott), nadroparin (GlaxoSmithkline), and parnaparin (Alpha-Wasserman). Each of these LMWHs has a characteristic molecular weight profile and biological activity in terms of an anti-FXa and anti-FIIa potency.

Cancer-associated thrombosis: focus on extended therapy with dalteparin.

The increased risk of thrombosis-related morbidity and mortality in patients with cancer remains, even in the face of anticoagulant therapy. Moreover, recurrent venous thromboembolism (VTE) complicates the management of cancer and adversely affects quality of life and survival. Until recently, initial therapy with unfractionated heparin or low-molecular-weight heparin (LMWH) followed by long-term therapy with an oral anticoagulant was the standard of care for the secondary prevention of acute thromboembolism in most patients.

Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update.

Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period.

Development of generic low molecular weight heparins: a perspective.

It is clear that the introduction of generic versions of low molecular weight heparins (LMWHs) is inevitable; however, it is important that the generic products are manufactured in strict compliance with the manufacturing specification of the branded product. Furthermore, regulatory agencies should require additional data on the chemical biologic, pharmacologic/toxicologic, and dose-response relationship in specific settings. Although there is strong opposition to stop the introduction of these drugs, their development will reduce cost and permit availability to all patients who need them.

Unfractionated heparin, low molecular weight heparins, and pentasaccharide: basic mechanism of actions, pharmacology, and clinical use.

During the past decade, a large number of new anticoagulant and antithrombotic drugs have been developed. These agents represent a wide variety of substances that are derived using natural sources, biotechnology-based methods, and synthetic approaches. Because of the structural and molecular characteristics, these agents exhibit physicochemical and functional diversities.

Generic low-molecular-weight heparins: some practical considerations.

It is now widely accepted that various low-molecular-weight heparins (LMWHs) exhibit specific molecular and structural attributes that are determined by the type of manufacturing process used. For example, enoxaparin, which is prepared by benzylation followed by alkaline hydrolysis of unfractionated heparin (UFH), exhibits a double bond at the nonreducing end and the presence of a unique bicyclic structure namely 1,6 anhydromanno glucose or mannose, or both, at the reducing end. Similarly, the other LMWHs, such as dalteparin, nadroparin, tinzaparin, and parnaparin, exhibit specific structural characteristics that may contribute to their own unique biochemical and pharmacological profiles.

Thromboprophylaxis in surgical patients.

This review has presented current information regarding thromboprophylaxis in surgery, including pregnancy. Where feasible, references have included current consensus conference recommendations and reliable review articles. Orthopedic surgical thromboprophylaxis has intentionally been deleted, as this topic is well covered in other articles in this issue (EurJ Med Res 9(3), March 2004).