McDonald K. Horne

Individualized treatment for iron deficiency anemia in adults

Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia.

The effect of red blood cells on thrombin generation

We have developed an assay of thrombin generation in clotting whole blood. Because our goal was to study patients with red blood cell diseases that are associated with thrombosis, the initial evaluation of this assay analysed the effect of the haematocrit and haemolysate on the total amount of thrombin activity generated and the maximal concentration of thrombin achieved. Both of these parameters were proportional to the haematocrit throughout a wide range of clinically relevant cell concentrations. Red cell lysate also augmented thrombin generation. Because this effect was removed by filtration of the lysate, we propose that it was related to red cell microparticles.

Controlled study of citrate effects and response to IV calcium administration during allogeneic peripheral blood progenitor cell donation

BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors.

The effect of molecular weight on heparin binding to platelets

Low molecular weight heparin is reported to be less reactive with platelets than larger heparins. We probed the molecular basis for this pattern of reactivity by characterizing the saturable platelet binding of [3H]heparin in plasma using heparins of different molecular weights (Mr˜ 3000, ˜ 5000, ˜ 10 000, ˜ 15000). Binding affinity increased with increasing molecular weight, as expressed by decreasing apparent dissociation constants (Kdapp˜ 1.3 μM for Mr˜ 3000, to Kdapp˜ 0.31 μM for Mr˜ 15000). After adjusting for the effect of antithrombin III in the plasma, true dissociation constants (Kd) could be calculated and these showed the same trend with molecular weight (Kd˜ 1.1 μM for Mr ˜ 3000 to Kd˜ 0.096 μM for Mr˜ 15 000). Platelet binding capacity for the different heparin fractions also increased with molecular weight, although this correlation appeared to lessen with the largest species. Heparin antithrombin III affinity was shown not to affect heparin binding to platelets. We propose a model in which heparin binding to platelets is mediated by charge interaction. Larger molecules with more charge bind with greater affinity and to sites with a broader range of electronegativity than do smaller, less

Simultaneous Binding of Heparin and Platelet Factor-4 to Platelets: Further Insights Into the Mechanism of Heparin-Induced Thrombocytopenia

Heparin‐induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor‐4 (PF4) and heparin. Although it has been assumed that these complexes bind to platelets and provide a target for the antibody, this has never been demonstrated. Furthermore, there is evidence suggesting that heparin‐PF4 complexes do not bind to platelets. We have analyzed the effect of each ligand on the platelet binding of the other. We particularly focused on the result when heparin and PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT‐IgG increased on the platelet surface. We found that when the molar concentration of PF4 approximates or exceeds that of heparin, the ligands bind simultaneously to the cells and HIT‐IgG binds also. However, when heparin is in molar excess, both PF4 binding and HIT‐IgG binding are diminished. Our data are consistent with the hypothesis that heparin‐PF4 complexes bind via their heparin component to heparin binding sites on the platelet membrane rather than by their PF4 component to PF4 sites. The conditions promoting the binding of the complexes also lead to binding of HIT‐IgG. Am. J. Hematol. 58:24–30, 1998.

Sickle cell anemia as a rheologic disease

Sickle cell anemia represents an aberration of blood rheology due to a loss of normal red cell deformability. The characteristically low hematocrit compensates for the stiffness of the sickle cells, leaving the patient with approximately normal whole blood viscosity. However, the microvascular flow of sickle cell blood is constantly jeopardized by hemoglobin gellation due to hypoxemia. The cells containing the highest concentration of hemoglobin S are the most viscous and are at the greatest risk for abrupt sickling. Successful treatment of this disease will require interruption of the basic pathogenetic mechanisms and preservation of normal blood rheology.

Increased Frequency of Venous Thromboembolism with the Combination of Docetaxel and Thalidomide in Patients with Metastatic Androgen‐Independent Prostate Cancer

Study Objective. To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen‐independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide.

Relation of fibrinolytic potentiation by estrogen to coagulation pathway activation in postmenopausal women.

To determine whether enhanced fibrinolysis is a primary effect of estrogen or is secondary to activation of coagulation, we measured hemostatic factors before and after conjugated equine estrogen 0.625 mg/day for 1 month in 9 postmenopausal women. We found that potentiation of fibrinolysis is a primary effect of conjugated equine estrogens at this commonly used dosage in healthy postmenopausal women.

Pulse-Spray Treatment of Subclavian and Jugular Venous Thrombi with Recombinant Tissue Plasminogen Activator☆

PURPOSE To evaluate the efficacy of recombinant tissue plasminogen activator (rtPA) injected by pulse-spray in lysing subclavian and jugular venous thrombi. MATERIALS AND METHODS Twelve patients with symptomatic, venogram-confirmed, occlusive thrombi of the subclavian-axillary or jugular veins were treated with one or two daily 15-minute injections of rtPA delivered directly into the clots with pulse-spray catheters. Twenty-four hours after each treatment, repeated venograms were obtained to assess venous patency. Successful thrombolysis was defined as antegrade flow through the previously occluded segments with minimal collateral venous flow. Continued patency was assessed with repeated venograms obtained after 1 and 2 months of oral anticoagulation. RESULTS The 15-minute rtPA injections successfully lysed thrombi in eight of the 12 patients. Hypofibrinogenemia developed in only one patient. The technique had a high success rate with thrombi less than 2 weeks old (seven of eight) regardless of the length of the clot, but had limited success with thrombi more than 2 weeks old (one of four). Continued patency over a 2-month interval was documented in four of the eight patients whose thrombi were successfully lysed. However, patency could be maintained in only one of the four patients who retained a venous access device in the treated vein. CONCLUSION Pulse spray rtPA is an effective, safe, and practical alternative to continuous infusions of thrombolytic agents to treat upper extremity venous thrombi.

Serologic evidence of heparin sensitization in cancer patients receiving heparin flushes of venous access devices.

Abstract Cancer patients with venous access devices (VADs) often receive daily flushes of heparin. Even this relatively small heparin exposure has been reported to induce immune-mediated thrombocytopenia. To estimate how frequently this occurs we tested for heparin-related antibodies in 49 patients receiving daily heparin flushes of their VADs. Although one-third of the patients showed evidence of heparin sensitization on at least one occasion during their surveillance, their antibody titers were generally low and typical of those found in other cohorts of patients who become sensitized to heparin but do not develop secondary thrombocytopenia. However, one patient developed a positive serotonin release assay indicative of a more significant sensitization, but without thrombocytopenia. Therefore, our observations suggest that heparin-induced thrombocytopenia (HIT) related to heparin flushes of VADs is uncommon but still an important diagnosis to entertain.