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In a trial evaluating two daily-dose levels of voxelotor, which binds to sickle hemoglobin and prevents polymerization under hypoxic conditions, hemoglobin levels increased by more than 1 g per deciliter in approximately half the patients who received the drug, and markers of hemolysis decreased. Toxic effects were mainly low grade and not different from those with placebo.

For decades, if a patient required a parenteral anticoagulant agent, the choice was simple: unfractionated heparin was the only such agent available. Unfractionated heparin has a long track record of effectiveness in both the treatment of and prophylaxis against arterial and venous thromboembolic disease. However, because of differences among batches of heparin and problems related to the bioavailability of the drug, monitoring of the anticoagulant effect of heparin has been not only necessary but also problematic. In addition, heparin-induced bleeding and thrombocytopenia can threaten life and limb. Moreover, there have always been problems with the use of unfractionated heparin to . . .

Patients with venous thromboembolic disease require treatment to stop the thrombotic process. The importance of immediate therapy with parenteral anticoagulants or thrombolytic agents (or both) is unquestioned. 1 , 2 Furthermore, several well-designed clinical trials have demonstrated that oral anticoagulant therapy with warfarin derivatives prevents the development of recurrent thromboembolic disease, 3 – 6 whereas inadequate anticoagulant therapy carries a risk of recurrent thromboembolism that can be as high as 25 percent. 5 These studies also show that prolonged anticoagulant therapy is associated with an increased risk of bleeding. 3 – 6 This risk can be lessened, but not eliminated, by appropriate monitoring of warfarin therapy. 7 , . . .

To the Editor: Eriksson et al. (Nov. 1 issue) 1 report that fondaparinux was more effective than enoxaparin and equally safe in preventing venous thromboembolism after hip-fracture surgery. In their study, the first dose of enoxaparin was to be administered 12±2 hours preoperatively and the second dose 12 to 24 hours postoperatively, according to the recommendation of the manufacturer. However, enoxaparin was first given postoperatively in as many as 74.4 percent of the patients in the enoxaparin group. The delay in the initiation of enoxaparin may have resulted in an underestimation of its preventive effects against thromboembolism and its hemorrhagic risks, . . .

In that group, it is clear that fixed-dose prophylaxis is inadequate, yet treatment with adjusted-dose heparin or adjusted-dose warfarin poses the additional problem of monitoring therapy. Since 1987, when the first low-molecular-weight heparin was approved for use in the United States, there has been an explosion in the number of available parenteral anticoagulant drugs.

Most investigators view these patients as making up a special category in which treatment should be continued for a long period. [...]recently, the various groups of patients had not been clearly delineated, a fact that makes it difficult to interpret most of the early studies.3 ,11 Moreover, many studies on this topic simply lack a sufficient number of patients to have the statistical power to come to any firm conclusions.9 ,10 Consequently, they have generated an enormous amount of heat but have shed very little light on the subject.

A mutant factor IX, designated factor IXCambridge, was isolated from a patient with hemophilia B. This protein includes an 18-residue propeptide attached to the NH2 terminus of factor IX. A point mutation at residue -- 1, from an arginine to a serine, precludes cleavage of the propeptide by a processing protease and interferes with γ -carboxylation of the factor IX, indicating the importance of the leader sequence in substrate recognition by the vitamin K-dependent carboxylase. This represents an example of an enzyme defect due to the presence of a point mutation in a precursor protein (preproenzyme) that is the cause of a human hereditary disease. This defect will serve as a prototype for understanding the molecular basis of some forms of hemophilia and other hereditary enzyme deficiencies.

To the Editor: Schulman et al. (Feb. 6 issue) 1 reported that long-term anticoagulant therapy may benefit patients with recurrent venous thromboembolism. Their conclusions will be difficult to interpret in a clinical setting, however, because of the heterogeneity of their study population. Twenty percent of their patients were identified as having temporary risk factors for thromboembolism. For them, removing or resolving the risk factor may substantially reduce the risk of recurrent thrombosis, independently of the anticoagulant therapy; moreover, intuitively, those patients would be expected to be the best candidates for a short course of such therapy. The failure either to exclude . . .

Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH). We conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH. There were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin–platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69×109/L (22-126×109/L) vs 87.5×109/L (63-149×109/L); P = .04. The lowest platelet count on the day of HIT testing was 43 × 109/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT. The evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin–platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure.