Hemoglobin titration

The response to erythropoietin products must be monitored closely to prevent adverse effects associated with these agents. The common adverse effects experienced include hypertension and thrombosis. Concomitant drugs with the same adverse-effect profile may increase a patient s risk for these complications. Also, the patient s overall survival may be decreased if the hemoglobin level is titrated to above the recommended 11 to 12 g/dL (110-120 g/L or 6.82-7.44 mmol/L) value. Therefore, it is important to follow the dosing and titration scheme recommended by the NCCN and summarized in... 

Closely monitor patients for efficacy and toxicity while they are receiving hydroxyurea. Monitor mean corpuscular volume (MCV) because it increases as the level of HbF increases. If the MCV does not increase with hydroxyurea use, the marrow may be unable to respond, the dose may not be adequate, or the patient may be noncompliant.27 HbF levels also can be monitored to assess response. Assess blood counts every 2 weeks during dose titration and then every 4 to 6 weeks once the dose is stabilized. Temporary discontinuation of therapy is warranted if the hemoglobin level is less than 5 g/dL (50 g/L or 3.1 mmol/L), the absolute neutrophil count is less than 2000/mm3 (2 x 109/L), platelets are less than 80,000/mm3 (80 x 109/L), or reticulocytes are less than 80,000/mm3 (80 x 109/L) if the hemoglobin is less than 9 g/dL (90 g/L or 5.6 mmol/L). Monitor for increases in serum creatinine and transaminases. Once the patient has recovered, hydroxyurea may be restarted with a dose that is 2.5 to 5 mg/kg less than the dose associated with the patient s toxicity. Doses then may be increased by 2.5 to 5 mg/kg daily after 12 weeks with no toxicity. 

Maintenance dose - When the desired response is attained, titrate the dose to maintain the response based on factors such as variations in zidovudine dose and the presence of intercurrent infectious or inflammatory episodes. If hemoglobin exceeds 13 g/dL, stop the dose until hemoglobin drops to 12 g/dL. 

When resuming treatment, reduce the dose by 25%, then titrate to maintain desired hemoglobin. 

Correction of anemia The recommended starting dose of darbepoetin for the correction of anemia in chronic renal failure (CRF) patients is 0.45 mcg/kg body weight, administered as a single IV or subcutaneous injection once weekly. Titrate doses to not exceed a target hemoglobin concentration of 12 g/dL. Some patients have been treated successfully with subcutaneous darbepoetin administered once every 2 weeks. 

Conversion from epoetin alfa to darbepoetin Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Due to the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if... 

During treatment initiation and dose titration, use 1 hour postprandial plasma glucose to determine the therapeutic response to acarbose and identify the minimum effective dose for the patient. Thereafter, measure glycosylated hemoglobin at intervals of about 3 months. 

Titration studies of hemoglobin have made important contributions to our knowledge of this protein. The three outstanding features are ... 

The titration curve in the acid region is time-dependent and irreversible, as was first clearly demonstrated by Steinhardt and Zaiser (1951). This aspect of the titration of hemoglobin has also been reviewed previously (Steinhardt and Zaiser, 1955), but there was some ambiguity about the meaning of this phenomenon at the time of the review, which has been removed by more recent work, as will be briefly described here. 

It should be noted that four of the anomalous imidazole groups are the four groups by which the heme iron atoms are attached to the protein. These cannot be titrated as long as the hemes remain attached. The other groups must be simply buried in the interior. Such groups occur in myoglobin (see below), as well as in hemoglobin. 

A titration curve for sperm whale myoglobin has been reported by Bres-low and Gurd (1962). The most striking feature is that it exhibits a time-dependent acid denaturation, which resembles that observed for the similar protein hemoglobin. To elucidate the physical nature of this reaction, emphasis was placed on the back titration to neutral pH of denatured protein. As in the case of hemoglobin (mentioned earlier), there are two major differences between the titration curves of native and denatured myoglobin, as shown by the data of Table XV. 

B. German, and J. Wyman, The titration curves for oxygenated and reduced hemoglobin, J. Biol. Chem. 117, 533-550 (1937). 

A low pretreatment platelet count, the dose of interferon alfa, and the haptoglobin phenotype are risk factors for ribavirin-induced anemia, and the fall in hemoglobin is independent of dose in the therapeutic range (16). In five patients with chronic hepatitis C on hemodialysis who received subcutaneous interferon alfa-2b and oral ribavirin for 40 weeks, the dose of ribavirin was titrated based on hemoglobin, with bone marrow support by erythropoietin (17). There was significant bone marrow toxicity in all five. A dose of 200 mg/day produced a steady-state AUC comparable to that obtained with 1000-1200 mg/ day in historical controls with normal renal fnnction. More severe anemia was possibly due to chronic renal insufficiency in addition to the prolonged effects of ribavirin. 

This composite satellite image displays areas on the surface of the Earth where chlorophyll-bearing plants are located. Chlorophyll, which is one of nature s most important biomolecules, is a member of a class of compounds called porphyrins. This Glass also includes hemoglobin and cytochrome c, which is discussed in Feature 19-1. Many analytical techniques have been used to measure the chemical and physical properties of chlorophyll to explore Its role in photosynthesis. The redox titration of chlorophyll with other standard redox couples reveals the oxidation/ reduction properties of the molecule that help explain the photophysics of the complex process that green plants use to oxidize water to molecular oxygen. 

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