A. Myron Johnson

Clinical indications for plasma protein assays: transthyretin (prealbumin) in inflammation and malnutrition: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC): IFCC Scientific Division Committee on Plasma Proteins (C-PP)

Abstract A large number of circumstances are associated with reduced serum concentrations of transthyretin (TTR), or prealbumin. The most common of these is the acute phase response, which may be due to inflammation, malignancy, trauma, or many other disorders. Some studies have shown a decrease in hospital stay with nutritional therapy based on TTR concentrations, but many recent studies have shown that concentrations of albumin, transferrin, and transthyretin correlate with severity of the underlying disease rather than with anthropometric indicators of hypo- or malnutrition. There are few if any conditions in which the concentration of this protein by itself is more helpful in diagnosis, prognosis, or follow up than are other clinical findings. In the majority of cases, the serum concentration of C-reactive protein is adequate for detection and monitoring of acute phase responses and for prognosis. Although over diagnosis and treatment of presumed protein energy malnutrition is probably not detrimental to most patients, the failure to detect other causes of decreased concentrations (such as serious bacterial infections or malignancy) of the so-called visceral or hepatic proteins could possibly result in increased morbidity or even mortality. In addition to these caveats, assays for TTR have a relatively high level of uncertainty (“imprecision”). Clinical evaluation – history and physical examination – should remain the mainstay of nutritional assessment. Clin Chem Lab Med 2007;45:419–26.

Amniotic fluid proteins: maternal and fetal contributions.

No fetal contribution to amniotic fluid orosomucoid or Gc-globulin is detectable by sensitive methods of phenotyping. These proteins have relatively low molecular weights and are readily cleared into urine and other body fluids. It would appear from this and from the close similarity of amniotic fluid to a passive filtrate of maternal serum that the adult-type plasma proteins found in amniotic fluid are almost entirely of matermal origin. α 1 -Fetoprotein probably enters the amniotic fluid predominately by a route other than renal excretion by the fetus. It appears highly unlikely that genetically determined abnormalities of most fetal plasma proteins can be detected by analysis of amniotic fluid.

Serum proteinase inhibitors in infants with hyaline membrane disease

Concentrations of the two predominant plasma proteinase inhibitors (α 1 -AT and α 2 -M), albumin, and total protein in newborn infants with hyaline membrane disease or other disorders were compared with those in normal preterm and full-term infants. During the first day, infants with hyaline membrane disease had significantly reduced levels of both inhibitors, both absolute and relative to total protein. α 2 -M levels were also low in infants with other forms of respiratory distress. On the second day, no significant differences were found. The relative lack of inhibition of proteinases and possibly of the vasoconstrictor effects of catecholamines and serotonin, whether primary or secondary, may play a role in the evolution of hyaline membrane disease.

Standardizing Plasma Protein Measurements Worldwide: A Challenging Enterprise

Abstract The need for harmonizing laboratory results is particularly intense in the field of quantitative protein assays in consideration of the clinical impact of specific protein measurements and their relevance in monitoring disease. We report the efforts made by the Committee on Plasma Proteins of the IFCC Scientific Division to achieve worldwide comparability in plasma protein results. We focus on the production of reference materials and the methods applied throughout their production process. Particularly, the recent characterization of ERM-DA470k/IFCC and ERM-DA472/IFCC has demonstrated that it is possible to reproduce the earlier established procedures and thereby maintain standardization. Plasma protein reference materials have had a substantial impact in improving the harmonization of patient protein results that should translate into better patient care. Clin Chem Lab Med 2010;48:1567–75.

Defibrination syndrome after intra-amniotic infusion of hypertonic saline

n To determine the role of changes in coagulation factors in hermorrhagic complications after intraamniotic infusion of hypertonic saline for therapeutic abortion, 21 women undergoing this operation, ranging 15-38 years in age with an average gestation of 18 weeks, were studied for coagulation factors, fibrinogen survival, and plasma volume. Blood tests were taken before, immediately after, and at 3-hour intervals after infusion of hypertonic saline. Significant changes were found in the following factors: Thrombin clotting time was consistently prolonged from the third hour after infusion. The platelet count dropped significantly from 310,000/cu. mm before infusion to 223,000/cu. mm 18 hours later. Fibrinogen levels dropped significantly from a mean preinfusion level of 393 mg/100 ml to 297 mg/100 ml at 18 hours. Factor VIII levels also fell significantly from 131% of normal at preinfusion to 85% of normal at 6 hours. Factor V levels declined significantly from a preinfusion mean of 104% of normal to 91% at 6 hours, though the rate of decrease varied widely among the patients. Fibrinogan/fibrin, degradation products, negative at preinfusion, appeared in all patients serums. Euglobulin lysis time was not accelerated. Fibrinogen survival studies were conducted in only 5 patients, 4 of whom showed a significant decrease, notably immediately preceding abortion, with a highly significant correlation to the time from infusion. Plasma volume increased significantly with a corresponding decrease in hematocrit. It is concluded that a mild form of diffuse intravascular coagulation develops after the intraamniotic infusion of hypertonic saline, but further research is necessary to pinpoint the cause of serious coagulopathy and hemorrhage.n

Acquired Coagulation Disorders in Children

Acquired coagulation disorders are complications of some other primary pathologic process, so that their treatment cannot be definitive without control of the underlying disease. Moreover, the hemostatic defects encountered are usually multiple and changing.