Thrombosis Prediction Based on Reference Ranges of Coagulation-Related Markers in Different Stages of Pregnancy.

INTRODUCTION: Careful monitoring of the hypercoagulable state is required during pregnancy. However, coagulation and fibrinolysis markers are not fully utilized because there are no reference values reflective of coagulation and fibrinolysis dynamics during pregnancy, which differ from the nonpregnant state. METHODS: Changes in antithrombin (AT), fibrinogen (Fbg), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), soluble fibrin (SF), D-dimer (DD), and protein S (PS) were investigated in healthy pregnant women, and reference ranges in the early, mid, late, and end stages of pregnancy were established. RESULTS: The AT was essentially constant throughout pregnancy. The Fbg, F1+2, TAT, and DD increased significantly as pregnancy progressed. In contrast, SF did not show a significant increase throughout the entire pregnancy period. Total PS antigen and total PS activity showed a corresponding decrease from early gestation. When test data in 3 cases in which deep vein thrombosis or intrauterine fetal death occurred during pregnancy were compared to the established reference ranges, all of the cases had multiple markers with values that exceeded the reference ranges. CONCLUSION: Establishing reference ranges for each week could potentially make it possible to evaluate abnormalities of the coagulation and fibrinolysis systems during pregnancy. Of note, SF might be a useful marker that reflects thrombus formation during pregnancy. Larger-scale studies will be required to establish reference ranges for every gestational week.

[Usefulness of reticulocyte hemoglobin equivalent for the safety of pre-operative autologous blood donation].

Pre-operative autologous blood donation (PABD) provides safe blood for patients at the expense of the risk of iron deficiency anemia that may compromise the patients. The reticulocyte hemoglobin equivalent (RET-He) is an indirect measure of the functional iron available for the erythropoiesis over the previous 2-3 days. The aim of this study was to evaluate the clinical usefulness of RET-He quickly measured by the automated hematology analyzer Sysmex XE-2100 in patients undergoing PABD at our hospital. Receiver-operating characteristic curve analysis revealed that RET-He was reliable in the diagnosis of iron deficiency anemia. Two of 14 patients in the absence of post-PABD iron replacement developed marked anemia with low RET-He levels after PABD, suggesting that this anemia was due to iron deficiency. Of 26 patients receiving post-PABD iron replacement, 8 who had already showed low RET-He levels at PABD developed statistically significant reduction in hemoglobin levels after PABD despite adequate iron replacement, indicating that the 8 patients had iron deficiency prior to PABD. These findings suggest that automated measurement of RET-He may contribute to improve the safety of PABD.

Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosis.

OBJECTIVES: Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. METHOD: Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. RESULTS: IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 x 10(9)/L (median, 71 x 10(9)/L), respectively. Twelve patients showed platelet counts more than 50 x 10(9)/L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. CONCLUSIONS: These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities.

Changes in molecular markers of hemostatic and fibrinolytic activation under various sampling conditions using vacuum tube samples from healthy volunteers.

Molecular makers such as thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), and D-dimer, are useful markers in the diagnosis and assessment of various thrombotic conditions. These markers are measured in plasma after blood sampling. Difficult blood sampling is known to falsely elevate plasma TAT levels. However, it is not known exactly why this occurs. In the present study, we examined how levels of molecular markers of haemostatic and fibrinolytic activation change under various sampling conditions using vacuum tube samples from healthy volunteers. When blood was sampled continuously by taking 10 consecutive vacuum tube samples following application of a tourniquet, blood sampling resulted in an accurate assessment of these molecular makers. When blood was sampled continuously by taking vacuum tube samples every one minute over a total of 9 minutes to investigate possible changes in the levels of the molecular markers over time, plasma levels of TAT, SF, and F1+2 gradually increased with time. Plasma levels of TAT, F1+2, and SF increased beyond the normal range over the course of nine minutes. When blood was sampled using three alternative methods, which varied in terms of the duration of needle puncture (sampling B), duration of tourniquet use (sampling C), or both (sampling A), plasma TAT and SF levels were significantly increased with all three methods, compared to control samples. Plasma F1+2 levels were significantly increased with sampling methods A and B, compared to control samples, but not with sampling method C. On the other hand, plasma D-dimer levels were not significantly altered by any of the sampling methods. In conclusion, the results suggest that molecular markers of haemostatic and fibrinolytic activation, except for D-dimer, may be affected by sampling method, particularly the duration of needle puncturing. Therefore, care needs to be taken when using TAT, F1+2, and SF levels to diagnose and estimate activation of the coagulation system.

Successful treatment of minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia with imatinib followed by reduced-intensity unrelated cord blood transplantation after allogeneic peripheral blood stem cell transplantation.

We describe a 35-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic sibling donor peripheral blood stem cell transplantation (PBSCT) and entered a second complete remission. Upon detection of BCR-ABL transcripts after PBSCT, the patient received imatinib, leading to molecular remission. Following the failure of donor leukocyte infusions, she underwent reduced-intensity unrelated cord blood transplantation (RI-UCBT), and has continued durable molecular remission for more than 30 months without substantial graft-versus-host disease. Because of a lack of adverse effects of imatinib on transplantation outcome, a treatment strategy consisting of molecular monitoring-guided initiation of imatinib followed by RI-UCBT may be promising in the management of Ph+ ALL after allogeneic SCT.

[Reliability of low platelet counts--comparison of microscopic counts with automated hematology analyzer XE-2100].

Sysmex XE-2100 is an automated hematological analyzer with excellent features that can count platelets by both impedance and optical fluorescent method. Particularly, it is notable that platelet counts by optical fluorescent method (PLT-O) are automatically adopted when platelet counts by impedance method (PLT-I) are less than 50 x 10(3)/microl or platelets have abnormal distribution. We compared PLT-I with PLT-O, and also with microscopic counts, using the samples with thrombocytopenia. Regarding reproducibility, mean coefficient of variation values were 5.3% in both PLT-I and PLT-O, when no flags of "PLT Abn Distribution" appeared in the samples with thrombocytopenia. Coefficient of variation values was 10.4% in PLT-I and 5.9% in PLT-O, when flags of "PLT Abn Distribution" appeared in the sample with thrombocytopenia. Correlation among the data obtained by PLT-I, PLT-O and microscopic counts were excellent. When a large difference was observed between PLT-I and PLT-O, PLT-O was more closely consistent with microscopic counts. PLT-O was useful compared with PLT-I, and this system was considered to measure platelet counts more correctly in the samples with thrombocytopenia. Thus, it was suggested that reliable platelet counts could be reported even in the samples with thrombocytopenia by switching system in XE-2100.

Isolated hyperkalemia associated with cyclosporine administration in allogeneic stem cell transplantation for renal cell carcinoma.

Two patients with advanced renal cell carcinoma underwent allogeneic hematopoietic stem cell transplantation and received cyclosporine (CSP) as part of their immunosuppressive therapy. Despite adequate renal function, both patients developed hyperkalemia. CSP was the only pharmaceutical agent to which this electrolyte abnormality could be attributed. Evaluation of renal tubule function suggested that CSP-associated isolated hyperkalemia resulted from tubular resistance to aldosterone. We propose that the presence of a single functional kidney may be a risk factor for isolated hyperkalemia due to CSP.