Simple scoring system for early management of heparin-induced thrombocytopenia.

This study was performed to develop a simple scoring system to aid in the early clinical management of patients suspected of heparin-induced thrombocytopenia (HIT) with regard to decisions for continued heparin therapy. The system was designed to arrive at low (0) or possible (1) probability scores without knowledge of laboratory test results (except platelet counts) to avoid delays. As the safest clinical approach is to discontinue heparin, intermediate and high scores were combined. Critically ill VA hospital patients (n = 100) with a ≥30% fall in platelet count were assessed by platelet aggregation (PA), (14)C-serotonin release assay ((14)C-SRA), and GTI ELISA. In this population, 53% were scored 1 and of these 43% were positive by laboratory test. Emphasizing the decision to discontinue heparin, the clinical signs of HIT were paramount for the immediate determination of a diagnosis of HIT without dependence on a positive laboratory test.

Rivaroxaban--an oral, direct Factor Xa inhibitor--has potential for the management of patients with heparin-induced thrombocytopenia.

Rivaroxaban is an oral, direct activated Factor Xa (FXa) inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. Currently available anticoagulants include unfractionated heparin (UFH) and low molecular weight heparins (LMWHs); however, their use can be restricted by heparin-induced thrombocytopenia (HIT). HIT is usually caused by the production of antibodies to a complex of heparin and platelet factor-4 (PF4). This study was performed to evaluate, in vitro, the potential of rivaroxaban as an anticoagulant for the management of patients with HIT. UFH, the LMWH enoxaparin, fondaparinux and the direct thrombin inhibitor argatroban were tested to enable comparative analyses. Rivaroxaban did not cause platelet activation or aggregation in the presence of HIT antibodies, unlike UFH and enoxaparin, suggesting that rivaroxaban does not cross-react with HIT antibodies. Furthermore, rivaroxaban did not cause the release of PF4 from platelets and did not interact with PF4, unlike UFH and enoxaparin. These findings suggest that rivaroxaban may be a suitable anticoagulant for the management of patients with HIT.

Human sexual intercourse.

The comprehensive therapist needs to view human sexual intercourse comprehensively to avoid its hazards and to promote its benefits for all patients.

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.

Alcohol consumption: benefit versus peril.

Like medication, alcohol has benefits in appropriate small doses and has perils in greater doses. Comprehensive therapists need to understand both!

Wine, beer, and spirits metabolism.

Comprehensive therapists regularly encounter patients consuming alcoholic beverages. It remains important that they understand how the body deals with its consumption, whether temperate and intemperate.

Thromboembolism in cancer patients: pathogenesis and treatment.

In this review we summarize the causes of cancer related thrombosis as well as modern treatment approaches. Malignancy as a risk factor for thromboembolism is becoming increasingly recognized by clinicians caring for these patients. The probability of thrombosis occurring in an individual patient is dependent on several factors, including accompanying medical problems, the type of cancer, the clinical stage, performance status, and the treatment modalities employed. Thrombophilia with a history of thromboembolism is important as well. The overall risk of thrombosis is sevenfold that of noncancer patients. Though much has been learned about the pathogenesis of cancer-related thrombosis, we are in fact just beginning to understand the cross-talk between cancer cells and their related microenvironment, and such investigations are likely to increase our knowledge of cancer-related thrombosis mechanisms. Research in these areas may also suggest new strategies for cancer prevention, metastasis suppression, and new treatments. Drugs used in cancer therapy are increasingly recognized to directly contribute to the thrombotic tendency. Few studies provide data on the optimal management of cancer patients with thrombosis. It has been learned that retreating with the same drug can be very hazardous. In general the approach to prevention of thrombosis is the same as for noncancer patients, recognizing that specific cancer types and stage can place a patient in a high-risk category. Initial coumadin therapy fails in a significant number of patients with cancer. Recognition of the cancer patients at highest risk for coumadin failure is challenging. Low-molecular-weight heparins appear to be more effective in such situations where coumadin is likely to fail or has failed, but these drugs are thought to be costlier. Newer agents such as Factor Xa inhibitors and TF inhibitors are currently under investigation and may be found useful in the management of cancer-related thrombosis.

Pain, analgesics, and the cardiovascular system.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most used medications in the world. Ordinarily considered to be safe and effective when used according to labeling instructions, their safety for patients with cardiovascular disease is now being reassessed.

The classical vs nonclassical NSAIDs: can the reduction in pain overcome the thrombotic risk?

The advent of cyclooxygenase-2 inhibitors has been both a blessing and a curse for pain management. An in-depth understanding of the biological molecules in the arachidonic acid metabolism may alleviate pain without risk.

Antiplatelet agents: current drugs and future trends.

Antiplatelet drugs in clinical use are discussed in terms of their mechanisms of action and the relevancy of that to the physiology of platelets and the pathophysiology of arterial thrombosis. Current clinical usage is outlined in detail for each drug. Experimental antiplatelet drugs also are discussed.

Anti-Xa and anti-IIa drugs alter international normalized ratio measurements: potential problems in the monitoring of oral anticoagulants.

Several of the newly developed anti-Xa and anti-IIa agents have been shown to influence the International Normalized Ratio (INR) values. During phase I trials with normal healthy volunteers and phase II study patients who were given warfarin and concomitant anti-IIa or anti-Xa agents, it has been reported that INR values were falsely elevated. It is of critical importance to know of the effects of these agents on INR to avoid dosage errors. To study the influence of these agents on INR, we used several anti-IIa agents (argatroban, recombinant hirudin, efegatran, and PEG-hirudin) and anti-Xa drugs (pentasaccharides such as fondaparinux and idraparinux, DX-9065a and JTV-803). The anti-IIa drugs were supplemented in citrated plasma at a concentration of 0 to 1 microg/mL level and anti-Xa drugs in the range of 0 to 25 microg/mL. The IC(50) values for each of these agents were calculated. Four different commercially available prothrombin time (PT) reagents were used to perform the PT assays and to calculate the relative INR values. Direct synthetic factor IIa and Xa inhibitors exhibited a concentration-dependent increase in the INR values. Hirudin, efegatran, and PEG-hirudin showed a weaker effect, whereas argatroban showed a much higher elevation of the INR values. Synthetic indirect anti-Xa agents such as the pentasaccharide did not show any effect on the INR values. Furthermore, prothrombin time reagents with high ISI values exhibited disproportionally higher INR values for both the direct anti-Xa and anti-IIa agents. Elevation of INR values has therapeutic implications when non-oral anticoagulant drugs are used in combination with drugs such as warfarin. Because of the false elevation of INR values with some of the non-oral anticoagulant drugs, patients who are on concomitant warfarin therapy should be carefully evaluated for their corresponding INR values for proper dosing. To avoid dosing errors it is best not to use the INR values in the therapeutic monitoring of anti-Xa and anti-IIa agents either in the monotherapeutic or polytherapeutic modalities. These data also warrant the development clinically relevant methods for the monitoring of the concomitant use of newly developed anti-Xa and anti-IIa drugs with oral anticoagulants.