Hemostasis activation in patients undergoing brain tumor surgery.

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk (nine patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastasis). The level of D-dimer was elevated at baseline in patients with metastasis, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastasis (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower than preoperative levels (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml, respectively). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.

Disturbed latex immunoassays for C-reactive protein and ferritin in a renal transplant patient due to polyclonal IgM hypergammaglobulinaemia.

BACKGROUND: C-reactive protein (CRP) and ferritin serum levels represent routine laboratory parameters in the monitoring of renal failure patients. Analysis of CRP, ferritin and other serum proteins can be performed using latex-enhanced or non-latex-enhanced immunoassays. We report on a renal transplant patient with polyclonal IgM hypergammaglobulinaemia having markedly elevated serum CRP and ferritin levels (as detected by latex-enhanced immunoassays) in the absence of clinical signs of an infectious or malignant disorder. METHODS: CRP and ferritin serum levels were determined with various immunoassays with and without latex enhancement. To characterize the causative agent for the elevated CRP and ferritin values, the patient's and a control serum were fractionated by gel filtration on a Sephacryl S-300 column. Serum fractions were subjected to further analysis for reactivity in CRP and ferritin assays. In addition, patient's serum samples were investigated for reactivity with various other latex-based immunoassays (rheumatoid factor, antistreptolysin O, antistreptococcal DNase B). RESULTS: Using latex-enhanced CRP and ferritin immunoassays, markedly elevated serum levels were obtained (CRP 726 mg/l determined by turbidimetry, 398 mg/l determined by nephelometry; ferritin, 20,000 micrograms/l determined by turbidimetry). In contrast, assays without latex enhancement revealed levels within the normal range for both serum proteins (CRP < 5 mg/l, ferritin 52 micrograms/l). The analysis of the patient's serum by gel filtration revealed an interference of the patient's IgM with latex particles used in the CRP and ferritin assays. CONCLUSION: Our study demonstrates that even polyclonal IgM hypergammaglobulinaemia can disturb a large array of latex-enhanced immunoassays used for routine diagnostic procedures. This is of particular interest for the management of allograft recipients in whom monoclonal and polyclonal gammaglobulinaemia are frequently observed. We therefore recommend reanalysis of the respective plasma proteins by latex-free assays in patients with hypergammaglobinaemia showing no clinical signs of an acute infectious disease or malignant disorder.

Hemostasis activation in patients undergoing brain tumor surgery.

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk ( 9 patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastases). The level of D-dimer was elevated at baseline in patients with metastases, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastases (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower levels than preoperatively (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.

The effect of near-normoglycemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients.

Diabetic patients have elevated plasma levels of factor VIII/von Willebrand factor (F VIII/vWF), and such elevations have been linked to vascular endothelial injury. In a prospective study we investigated the effect of metabolic regulation on the plasma levels of F VIII/vWF and cross-linked fibrin degradation products (XL-FDP), an indicator of intravascular coagulation, in 15 insulin-dependent diabetic patients who had no demonstrable vascular abnormalities. Eight patients had newly diagnosed diabetes, and 7 had been diabetic for an average of 12 yr. The patients were tested before and 1, 2, 4, and 8 weeks after the start of a structured diabetes education and care program, including introduction of a basal-bolus form of insulin treatment. Treatment for 8 weeks resulted in a highly significant improvement of metabolic control [hemoglobin Aic, 11.1 +/- 1.3% (+/- SD) vs. 6.8 +/- 1.0%; plasma fructosamine, 4.8 +/- 1.0 vs. 2.9 +/- 0.7 mmol/L; plasma glucose, 13.5 +/- 4.2 vs. 6.3 +/- 2.2 mmol/L; P less than 0.0001, respectively]. Compared to age- and sex-matched normal subjects, plasma activity of factor VIII (F VIII:C) was significantly elevated in the diabetic patients initially (1.5 +/- 0.6 vs. 1.0 +/- 0.1 x 10(3) U/L; P less than 0.01). After 2 weeks of intensified therapy it was 1.1 +/- 0.4 x 10(3) U/L. The mean plasma vWF value also was significantly elevated initially [vWF antigen, 1.8 +/- 0.7; normal group, 0.9 +/- 0.1 x 10(3) U/L (P less than 0.01); vWF ristocetin cofactor activity, 1.9 +/- 0.9; normal group, 1.0 +/- 0.3 x 10(3) U/L (P less than 0.001)] and decreased significantly after only 1 week of therapy. In the following 7-week period plasma vWF remained near normal. Plasma XL-FDP levels were elevated in all patients initially (190 +/- 150; normal group, 35 +/- 30 micrograms/L): the value was most abnormal in the patients with newly diagnosed disease (300 +/- 150 micrograms/L), indicating intravascular fibrin formation. The mean XL-FDP level declined significantly in the patients with newly diagnosed diabetes after 1 week of therapy; in the other patients, however, XL-FDP levels remained slightly elevated. In all 15 patients the plasma F VIII:C and XL-FDP levels were correlated significantly at all times. The plasma vWF and XL-FDP levels were correlated after 1, 2, 4, and 8 weeks of treatment as were the plasma vWF levels and glucose concentrations before and 1 and 2 weeks after the start of treatment program.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative determination of human protein C. Evaluation of a "fast" functional assay in comparison to a "traditional" functional and an immunological assay.

A fast functional assay for protein C was evaluated and compared with a traditional functional and an enzyme linked immunosorbent assay in parallel for the same plasma samples derived from 43 healthy subjects, 12 patients with severe hepatic dysfunction, and 23 patients under stable oral anticoagulation. By all three test systems significantly lower levels of protein C were obtained in both groups of patients compared with normal subjects (p less than 0.0001). No significant between - assay differences were found in normal subjects and in patients with hepatic dysfunction; by correlation analysis coefficients higher than 0.8 were calculated between the measurements of the three tests. In patients under stable oral anticoagulation, however, the immunologic test yielded higher values than the traditional (p less than 0.05) and, more pronounced, the fast functional assay (p less than 0.0001); no or only borderline significant correlations between the results were found. In these patients protein C levels measured with the traditional functional assay were in the same range as the activity levels of factors II, VII, IX, and X, whereas the fast functional test yielded significantly lower levels. The presented results indicate that very similar protein C levels were obtained with both functional and the immunologic assay except in patients under oral anticoagulation.

The protein C system in patients undergoing cardiopulmonary bypass.

Fifteen men undergoing extracorporeal circulation for aorta-coronary bypass grafting were investigated for alterations of the plasma levels of cross-linked fibrin degradation products, protein C, free protein S, coagulation factor II, immunoglobulin G, and albumin. Although all patients were given heparin, a progressive increase of cross-linked fibrin degradation products was recorded during extracorporeal circulation, which indicates an activation of the plasmatic coagulation system. This increase was most pronounced in the late phase of extracorporeal circulation after reperfusion of the lung and in the early postoperative period. The levels of all other investigated plasma proteins decreased drastically after the patient was connected to the bypass circuit, which was primed with saline solution. These levels increased after termination of extracorporeal circulation and administration of fresh-frozen plasma. To study the consumption of protein C, protein S, and factor II during extracorporeal circulation, we formed ratios of the values of these parameters to the value of immunoglobulin G. After this volume correction, protein C was found to decrease significantly in the late phase of extracorporeal circulation, remaining low in the early postoperative period; protein S increased significantly soon after the onset of extracorporeal circulation and decreased after termination of extracorporeal circulation; factor II was unaffected by extracorporeal circulation, showing only a slight, insignificant increase in the postoperative phase. These results suggest a disturbance of the protein C system by extracorporeal circulation, which is possibly linked to the reported high bleeding tendency in patients undergoing operations with extracorporeal circulation.

Decreased protein C levels in patients with insulin-dependent type I diabetes mellitus.

The plasma levels of protein C were investigated in 54 type I diabetic patients without retinopathy and in 14 diabetic patients with diabetic retinopathy and compared with the findings in 35 sex- and age-matched healthy control subjects. In the total group of type I diabetic patients, protein C was significantly less than in the controls. The lowest levels of protein C were found in diabetic patients with the poorest metabolic control. Protein C levels showed a significant negative correlation with the blood glucose levels, but they were not correlated with hemoglobin A1c (HbA1c). Although patients with retinopathy showed the least decrease of the plasma level of protein C among the diabetic subjects, the ratio of protein C to factor II was significantly decreased compared with the control subjects. Because the levels of coagulation factor II were not reduced in diabetic patients, the reduction of protein C seems to be caused, not by reduced synthesis in the liver, but more likely by an increased clearance from the blood plasma. The decrease of protein C in the plasma of type I diabetic patients indicates an abnormal, probably hypercoagulable, hemostatic situation in this disorder.

Multimers of von Willebrand antigen in therapeutic factor VIII concentrates.

By crossed immunoelectrophoresis (XIEP), the pattern of von Willebrand factor antigen (vWF:Ag) was investigated in six commercially available factor VIII (F VIII) concentrates and in normal human plasma. At least 5 subpopulations of vWF:Ag were recognized by XIEP in the therapeutic F VIII concentrates and in normal plasma. F VIII preparations high in ristocetin cofactor activity (vWF:RICof) and low in the ratio of vWF:Ag to vWF:RiCof were found to be similar in the multimeric structure of vWF:Ag to normal plasma. However, F VIII concentrates low in activity of vWF:RiCof and high in the ratio of vWF:Ag to vWF:RiCof were found to be deficient in the slowly migrating, high molecular weight multimers of vWF:Ag present in normal plasma.

Homo- and heterogeneous forms of human factor VIII.

In order to determine the molecular size of human F VIII as found in fresh plasma and as found in fresh-frozen plasma and in cryoprecipitate and to study the relationship of the factor-related properties, namely F VIII:C, F VIIR:Rcof and F VIIIR:Ag to F VIII, the factor's elution pattern on Sephacryl 1000 was investigated. When fresh plasma was chromatographed on this gel, F VIII eluted in a single sharp peak with all three F VIII-related activities appearing in the separation range of the gel column. The molecular weight of F VIII was calculated to be higher than 8 X 10(5). When fresh-frozen plasma was chromatographed on this gel, the elution pattern was identical to that of fresh plasma with the single exception that in several samples F VIII eluted in a broader peak tailing to higher molecular forms. When cryoglobulin fraction of fresh-frozen plasma was chromatographed, F VIII showed distinct heterogenicity in the elution pattern with respect to molecular size and relationship to the F VIII-related properties. Chelation of the endogenous plasma Ca-ions by citrate was found to have no influence on the factor's elution pattern.