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The coagulation and fibrinolysis profile was evaluated in 40 patiens with newly diagnosed untreated colorectal carcinoma (24 males, 16 females; 29 patients without and 11 patients with metastases). Fibrinogen, von Willebrand factor antigen, FVIILC, thrombin-antithrombin III complex (TAT III), fibrin monomers (FM), plasminogen activator inhibitor-1 (PAI-1) and I-dimers were tested. None of the patients had clinical or laboratory evidence of serious hemorrhage or thrombosis. The results of global routine coagulation tests (aPTT, PT) were not significantly changed. Significant elevations were found for median fibrinogen, von Willebrand factor antigen, FVIILC, TAT III and D-dimers, compared with a healthy reference group. These results confirm earlier reports of an enhanced level of both coagulation and fibrinolysis markers in carcinoma patients and might be helpful in trying to understand the impact of several relatively new sensitive coagulation and fibrinolysis parameters in colorectal cancer. Moreover the position of the coagulation/fibrinolysis balance might be an explanation for the elevated incidence of thrombotic events in patiens with cancer.

13 patients suspected of intra-uterine growth retardation (IUGR) were treated with a combination of heparin and dipyridamole. The effect of this anticoagulant therapy on platelet count, clot retraction, fibrinogen degradation products, antithrombin III (AT-III), plasminogen, fibrinogen and platelet aggregation induced by epinephrine, ADP, collagen and ristocetin has been examined. All parameters were measured both before and after treatment with heparin-dipyridamole. The results were compared with the results from a control group consisting of pregnant women of the same gestational age using no medication and not suspected of IUGR (n = 17). A significant decrease in the clot retraction was observed in patients with IUGR as compared to pregnant controls (p < 0.05). A significant decrease in the AT-III level (p < 0.01) and a significant increase (p < 0.01) in the fibrinogen level were observed after heparin-dipyridamole treatment of patients suspected of IUGR. We conclude that the combination of a high fibrinogen and a low AT-III level will cause an increased risk for the development of thrombosis upon termination of treatment. We also observed that heparin clearance is increased during pregnancy.

The slide test method of Velaskar and Chitre for determining platelet aggregation in whole blood after induction of aggregation was modified for spontaneous platelet aggregation and evaluated. The reproducibility was satisfactory (CV 1-3%). The results obtained with this method and the method of Velaskar were not significantly different. The Spearman rank correlation was 0.75 (p < 0.0001). We established reference values for the particle counter method and Velaskar’s method in pregnant and non-pregnant women; no significant change in spontaneous platelet aggregation was seen throughout pregnancy. In order to estimate the clinical value of the test in pregnancy, we followed up a number of pregnant patients with primary enhanced spontaneous whole-blood platelet aggregation before and after treatment with low-dose acetylsalicylic acid. The test was found to be suited for the detection of spontaneous whole-blood platelet aggregation and for the follow-up after treatment with acetylsalicylic acid. Further studies are necessary, however, to assess the predictive value of an aberrant test result during pregnancy.

Forty-eight patients with freshly diagnosed carcinoma of the lung (40 males, 8 females) were evaluated for a coagulation profile including activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, F VIII R:Ag, fibrin monomers (FM), thrombin-antithrombin-III complex (TAT-III), D-dimers and the platelet count. Thirty-eight patients had a normal aPTT and 37 patients a normal PT. None of the patients had clinical or laboratory indications of serious hemorrhage or thrombosis. On the other hand, high percentages of increased values were found for fibrinogen and F VIII R:Ag, which can be seen as prethrombotic factors. The very high percentages of elevated results for the FM, TAT-III and .D-dimer are strongly indicative for low-grade coagulation activation with reactive fibrinolysis. Nevertheless, most lung cancer patients are able to maintain a normal or near normal hemostatic function. The results shown here are indicative of a coagulation and fibrinolysis equilibrium at an enhanced level and demonstrate why an unbalance between the two systems can result in thrombotic complications in (lung) cancer patients as earlier reported.

Thirty-two patients suspected of deep venous thrombosis (DVT) of the leg were evaluated after simple plasma tests (latex D-dimer and Elisa D-dimer) against echography and phlebography as the gold standard of DVT. Seven patients showed negative results in the latter test. The classification conformity between the D-dimer methods amounted 84.4%. With regard to the diagnostic classification a high specificity of 100% was found for the latex D-dimer test at the cut-off level of 450 ng/ml, whereas for sensitivity, 96% was reached. The Elisa D-dimer test was striking by its high sensitivity of 100%, but its low specificity of 28.5 %. In summary, these results demonstrate that when there is a suspicion of DVT according to the clinical symptoms, a negative latex test may reject the diagnosis, whereas the latex test is less useful to establish the diagnosis. On the contrary, the Elisa .D-dimer test has a too high false-positive rate. The latex D-dimer test seems to be a reliable tool to exclude the diagnosis after which an ascending contrast venography can be omitted.

We investigated 148 diabetic patients with regard to their relationship between fibrinolysis (D-dimer and plasminogen activator inhibitor; PAI) and glycometabolic control (HbA1c, HbA1 and fructosamine). The percentage of moderately controlled patients as indicated by HbA1c, HbA1 and fructosamine is relatively high (29.7, 41.7 and 30.4%, respectively). Simultaneously, the D-dimer and PAI levels turned out to be enhanced in 30.8 and 22.4% of the patients. There was a positive nonsignificant correlation between D-dimer and HbA1c, a highly significant negative correlation between D-dimer and HbA1 and a nonsignificant negative correlation between D-dimer and fructosamine. According to the upper limits of the distinct reference ranges for HbA1c, HbA1 and fructosamine, we splitted up the .D-dimer results and calculated the mean D-dimer values belonging to each category. Comparing the D-dimer means for each parameter, we separately obtained significant differences of the D-dimer means between the lower and higher HbA1 and fructosamine groups, whereas in the case of HbA1c the mean D-dimer values of the categories under and over 9% showed no significant difference. For PAI, we found only weak nonsignificant positive correlations to D-dimer and fructosamine and weak but highly significant correlations to HbA1c. These results are indicative for an increase of PAI with diminished glycometabolic control as measured with the HbA1c and fructosamine level. Both D-dimer and PAI showed positive, highly significant correlations to the age of the diabetic patients, whereas HbA1c and fructosamine were age independent. The results described in this report demonstrate that the fibrin degradation to D-dimer fragments by the specific fibrinolytic enzyme plasmin is dependent on the glycometabolic control state as measured with HbA1 and fructosamine and thus on the nonenzymatic glycosylation, which reduces the susceptibility of fibrin to degradation by plasmin.

One hundred and fourty-eight insulin-dependent diabetic patients were available for this study; 56 males and 92 females. For the investigation of coagulation activation we determined activated partial thromboplastin time, thrombin time, and fibrinogen besides fibrin monomers and thrombin-antithrombin III complexes (TAT-III). We assessed large percentages of increased fibrinogen levels but non-significant increases of the mean values in comparison with the reference group. The values for thrombin time were significantly prolonged, although relatively small percentages were exceeding the reference range. For the activated partial thromboplastin time, the values exceeded the upper reference limit, and the mean values were significantly higher than those of the reference group. Also for the fibrin monomers we obtained often enhanced values, and, moreover, the values were significantly higher as compared with the reference subjects. The amount of TAT-III concentrations above the reference range was much smaller than for the fibrin monomers and the TAT-III levels were not significantly enhanced. The results presented here are indicative of coagulation activation in diabetics, as indicated by the fibrin monomers and more or less by the TAT-III levels. Moreover, there could be demonstrated a positive correlation between fibrin monomer levels and HbA1 concentrations.

A Cobas Bio® centrifugal analyzer was used in a clinical laboratory for the performance of chromogenic clotting assays. Three commercially available photometric clotting tests – prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen – were compared with the traditional clotting assays during 3 months. No great discrepancies were found between the traditional assays and the new photometric assays. The chromogenic PT could replace the traditional thrombotest®, PT and Normotest®, because it was sensitive and accurate over a broad range of clotting factor activity. Furthermore the chromogenic PT could be used to discriminate between a decreased clotting activity due to vitamin K deficiency or to a decreased protein synthesis by the liver. A decreased protein synthesis was confirmed by measuring a decrease in the serum cholinesterase activity. The chromogenic aPTT could be used for the assay of heparin concentrations in the therapeutic range and turned out to be more sensitive for deficiencies of factor VIII and factor IX than a traditional clotting aPTT. We conclude that the accuracy and practicability of clotting assays are improved by the new assays without diminishing the clinical value of the results.