Plasma exchange-A useful adjunct therapy to red cell exchange in patients with sickle cell disease and multiorgan dysfunction.

BACKGROUND: Urgent red cell exchange (RBCx) is indicated for many complications of sickle cell disease (SCD), including acute chest syndrome, stroke, and hepatic/splenic sequestration. Many who receive RBCx remain hospitalized and develop further complications, including multiple organ dysfunction syndrome (MODS), a leading cause of death in intensive care units. Therapeutic plasma exchange (TPE) has been advocated as an effective treatment of MODS, but its role in SCD compared with RBCx alone is not well studied. METHODS: We identified all ICU encounters from 2013 to 2019 involving RBCx procedures for MODS or SCD crisis that progressed to MODS, a total of 12 encounters. Data regarding hospital length of stay (LOS), survival, number of TPE procedures following RBCx, and procedure characteristics were collected. Surrogate laboratory markers of end-organ damage and disease severity scores were recorded at the time of admission, post-RBCx, post-TPE, and at discharge. RESULTS: Eight encounters involved RBCx followed by TPE (TPE group) while four involved RBCx alone (RBCx group). The TPE group had a higher SOFA score at ICU admission (9.5 vs. 7.0), greater predicted mortality, and a statistical trend toward higher disease severity scores following RBCx relative to the RBCx group (p = 0.10). The TPE group showed a significantly greater decrease in SOFA score between RBCx and discharge (p = 0.04). No significant difference in mortality or hospital LOS was observed between the groups. CONCLUSION: The findings suggest TPE may be considered as an adjunct treatment for patients with acute complications of SCD that progress to MODS, especially in cases where there is no significant improvement following RBCx.

New strategies for effective treatment of vitamin K antagonist-associated bleeding.

Vitamin K antagonists have been used as oral anticoagulants in the treatment and prevention of thromboembolic events for over half a century. Although vitamin K antagonists are effective in the management of thromboembolic events, the need for routine monitoring and the associated risk of bleeding has resulted in the development and licensing of direct oral anticoagulants for specific clinical indications. Despite these developments, vitamin K antagonists remain the oral anticoagulants of choice in many clinical conditions. Severe bleeding associated with oral anticoagulation requires urgent reversal. Several options for the reversal of vitamin K antagonist exist, including vitamin K, prothrombin complex concentrates and plasma. In this manuscript, we review current evidence and provide physicians with treatment strategies for more effective management of vitamin K antagonist-associated bleeding.

Physiological responses in rats fed extracts of endophyte-free and endophyte-infected tall fescue seed relative to some known ergot alkaloids.

Ethanol and ethanol-water extracts of endophyte-infected tall fescue seed were effective for extracting toxin(s) responsible for feed intake and average daily weight gain (ADG) depression in Sprague Dawley rats. Although the ethanol extract of endophyte-infected seed depressed serum prolactin (Prl) concentrations, the data were less reflective of overall toxicity than feed intake and weight gain. Inclusion of commercially available ergonovine maleate, ergocryptine and ergotamine tartrate had no effect on rat feed intake, ADG or serum Prl at the levels tested. Dietary addition of a recombination of hexane, ethanol and ethanol-water extracts caused a toxicity response (depressed feed intake, ADG, and serum Prl) equivalent to that of the whole seed. The toxic factor(s) were extracted primarily in more polar solvents such as ethanol and ethanol-water. Rat assays can be used successfully in lieu of cattle assays as a routine evaluation of toxic components in endophyte-infected tall fescue. However, species differences dictate that eventually all suspected toxins be evaluated in the bovine.

Videothermometry for assay of fescue foot in cattle.

Surface temperatures of hoofs of calves given toxic anion fractions of tall fescue were measured with an infrared sensitive camera. These changes expressed in terms of a weighted average coronary band temperature relate to clinical signs of fescue foot. The weighted average coronary band temperature values for control calves given saline solution were 27 to 31 C; those values of test calves given anion fractions of tall fescue were as low as 22 +/- 1 C. Videothermometry provides an independent, permanent, objective measure that is useful in assessing fescue-foot potential of tall fescue fractions by intraperitoneal injection. Videothermometry may also serve as a clinical means for determining progression of the total fescue foot syndrome.

Current arterial prostheses. Experimental evaluation by implantation in the carotid and circumflex coronary arteries of the dog.

Five types of 4-mm diameter arterial prostheses (three Dacron, one expanded Teflon, one preserved umbilical vein) were studied in the dog to assess graft thrombogenicity. Separate experiments involving six hours of controlled blood flow, one-week carotid implantation, and aortocoronary implantation were performed. In general, graft thrombogenicity derived from controlled flow study was more predictive of a graft's long-term implantation success than were one-week implantation results. In order of increasing thrombogenicity, we ranked grafts studied as follows: noncrimped Dacron, expanded Teflon, crimped Dacron, umbilical vein. Results of 19 experimental left coronary artery implantations using Dacron or Teflon prostheses are reported that indicate grafts with low measured thrombogenicity are most likely to succeed in this site. Data presented in this report suggest there is reason to evaluate noncrimped, kink-resistant, porous Dacron grafts for use both in the left coronary artery and below the knee when there is compelling clinical indication and no autogenous vessels are available.

The preclotting of porous arterial prostheses.

A four-step preclotting method is presented for use with porous filamentous Dacron prostheses in the fully-heparinized patient. The method employs controlled fibrin formation within graft interstices, heparin neutralization of all thrombin remaining in the graft wall, and delay of systemic heparin neutralization until 15--20 minutes after clamp release. The resulting flow surface is impervious, smooth and hypothrombogenic. Experimental data are presented which support the rationale of this four-step preclotting method. Four years of clinical experience with the method are summarized, involving 300 prosthesis limbs used in aortic bifurcation, aortofemoral, femorofemoral, axillary-femoral and femoropopliteal positions in 192 patients. A clinical perspective of preclotting techniques is presented in which the proper use of this new method is suggested.

A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S.

Human prothrombin, factor IX, and factor X have been idolated in high yield and characterized as the their amino-terminal sequence, molecular weight, amino acid composition, and migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An additional human plasma protein, called protein S, has also been purified and its properties have been compared with those of prothrombin, factor IX, and factor X. Prothrombin (mol wt 72 000), factor IX (mol wt 57 000), and protein S (mol wt 69 000) are single-chain glycoproteins, while factor X (mol wt 59 000) is a glycoprotein composed of two polypeptide chains held together by a disulfide bond(s). The amino-terminal sequence of the light chain of human factor X is homologous with prothrombin, factor IX, and protein S. The heavy chain of human factor X is slightly larger than the heavy chain of bovine factor X and differs from bovine factor X in its amino-terminal sequence.

Geometric comparison of aortic bifurcation prostheses to the normal and atherosclerotic human aorta, and clinical trial of a vertical seamed bifurcation prosthesis.

The 12 bifurcation prostheses generally available in the United States were compared. One was woven Teflon, two woven Dacron, and nine knitted Dacron. Ten were "seamless" in construction, and two were "seamed," but close examination revealed that all prostheses actually were seamed at the bifurication point. The grafts varied considerably in construction, porosity, and geometry. To compare the geometries, each prosthesis was preclotted in plasma, inflated to 120 mm. Hg, and quick frozen in alcohol and dry ice. Transverse and frontal bisections of the frozen specimens were photographed with a millimeter scale for sizing. For comparison, eight human aortofemoral bifurcations were distended and frozen similarly. The prostheses had far wider bifurcation shelves than did the normal aortas. The five normal human aortofemoral bifurcations had an average ratio of limb: body diameter of 0.61; the three atherosclerotic specimens averaged 0.49. The prostheses had an average limb:body diameter ratio of 0.48. or the "seamless" grafts, 0.48 for the circular transverse limb-seamed grafts, and 0.58 for the vertical-seamed grafts. Vertical-seamed aortic bifurcation grafts implanted in 102 patients between 1970 and 1976 (average follow-up, 29.5 months) have developed only a single limb closure, at 53 months.

Induction of fescue foot syndrome in cattle by fractionated extracts of toxic fescue hay.

Tall fescue (Festuca arundinacea Shreb) hay from a source known to cause "fescue foot" in grazing cattle was extracted with 80% ethanol. The ethanolic extract was further refined and fractionated into cation,nion, and neutral f fractions by ion-exchange chromatography. The cation fraction was partitioned with alkaline-chloroform to give chloroform-extractable cation and residual cation fractions. All fractions plus the crude ethanolic extract were assayed for toxic activity by intraperitoneal injection into 12 calves (weighting 152.4 to 241.3 kg each) over a 14-day period. Clinical signs of fescue foot were observed on the 5th day in calves given the anion and crude ethanolic extracts. Lameness, swelling, and reddening of the rear coronary bands, discoloration of the tip of the tail, and other signs of fescue foot were seen. Microscopically, coronary bands and tail tips of affected calves had blood vessels with thick walls and small lumens.

Correlation of biological to chromatographic data for two mycotoxins elaborated by Fusarium.

Thirty-seven identified strains of Fusarium, most of them isolated from fescue grass, were tested for their ability to elaborate mycotoxins in laboratory culture. The presence of the toxins was determined by infrared light, thin-layer chromatography, mouse toxicity, fungistatic effects, and phytotoxic properties. A good correlation was demonstrated between T-2 toxin detection by thin-layer chromatography and inhibition of Rhodotorula rubra by culture extracts. All of the strains producing either butenolide or T-2 toxin were toxic to mice with but one exception; those producing T-2 toxin inhibited growth of the yeast.

Survey of tall-fescue pasture: correlation of toxicity of Fusarium isolates to known toxins.

Several aspects of fescue foot in cattle suggest that this disease is caused by fungi growing on fescue grass. Certain fungi isolated from winter pasture yield toxins when grown on synthetic medium. Most of these toxin producers belong to the genus Fusarium. All but 1 of the 21 toxic and 7 questionably toxic Fusarium isolates produce either 4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone, or 4beta, 15-diacetoxy-8alpha-(3-methylbutyryloxy)-12, 13-epoxytrichothec-9-en-3alpha-ol, or both.