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R Kekomäki

Publications and source records attributed to R Kekomäki.

At least 19 recordsLinked to original sources
PubMed2006

Multi-laboratory evaluation of procedures for reducing the volume of cord blood: influence on cell recoveries.

BACKGROUND: Various procedures can be used to isolate stem and progenitor cells from cord blood. This study evaluated the hydroxyethyl starch sedimentation (HES) with two centrifugation steps, and the top and bottom (T&B) isolation of buffy coat following a single centrifugation, and two filter systems for processing cord blood, one developed by Asahi Kasei Medical (filter A) and the second by Terumo (filter B). METHODS: Each of seven laboratories was randomly assigned the evaluation of either the HES or T&B method and one of the filter methods (n=8 cord blood units, per laboratory, for each method). The leukocyte-containing fraction with the stem/progenitor cells was recovered from the filters by reverse flushing. Utilizing the routine traditional processing and testing procedures of each laboratory, in vitro parameters were determined, with samples obtained after collection, after processing and after freezing/thawing. The results were expressed as the percentage recovery of viable cells in processed vs. collected samples (performance 1; PF1) and in thawed vs. processed samples (performance 2; PF2). The composite results obtained by the seven laboratories were summarized. RESULTS: The median PF1 percentage recovery of total nucleated cells (TNC) was comparable with both traditional methods (HES 79%, T&B 86%) and statistically reduced with both filtration procedures (filter A 58%, filter B 61%). Mononuclear cell (MNC) PF1 recovery was highest statistically with the T&B method (91%) and reduced on using filter A (77%) and filter B (70%) and the HES method (72%). CD34+ cell recovery was judged to be essentially comparable with the four methods, although the range of unit recoveries differed. The percentage recovery of TNC and MNC in PF1 was influenced by the volume of the collected cord blood, especially with use of the filtration procedures. This correlated with TNC content. A greater percentage of red cells and platelets was removed during processing with both filter methods. The time to process cord blood preparations with filter A was significantly shorter than the other methods. Processing with the HES method took the longest time. The recoveries for TNC, MNC and CD34+ cells in PF2 did not appear to be influenced by the specific processing procedure. DISCUSSION: These data indicate that filters that capture stem and progenitor cells may be an appropriate methodology for processing cord blood collected for banking.

Antigens, CD34↗
PubMed2004

Birthweight of full-term infants is associated with cord blood CD34+ cell concentration.

AIM: CD34+ cell counts are used to define the haematopoietic stem cell potential of a given cord blood transplant. The aim was to test the hypothesis that high concentration of cord blood haematopoietic progenitor and stem cells could be a reflection of intrauterine growth, of which birthweight is an indicator. METHODS: Simple and multiple regression analyses were applied to test cord blood bank data on 1368 infants for associations of selected obstetric factors and cellular contents of cord blood. RESULTS: When groups were formed based on the extreme values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the term infants having the highest birthweights were found to have statistically significantly higher median cord blood CD34+ cell concentrations. Also, infants in the top 50th percentile of relative birthweight had higher median CD34+ cell concentration than infants in the low 50th percentile. In multiple regression analysis, the correlation between birthweight and CD34+ cell concentration was statistically clearly significant. Notably, while an expected correlation between gestational age and nucleated cell concentration was found, there was no association between infant gestational age and CD34+ cell concentration. CONCLUSION: Haematopoietic progenitor and stem cells may reflect intrauterine growth and have a more central role in foetal development than has been reported earlier.

Antigens, CD34↗
PubMed2004

High birth weight is associated with human leukocyte antigen (HLA) DRB1*13 in full-term infants.

In cord blood banking, substantial amounts of data on infants and cord blood are gathered at high cost, including birth weights and human leukocyte antigen (HLA) genotypes. As certain HLA alleles have been associated with protective host responses, it is possible that an HLA allele, or another factor linked to it, might even affect normal intrauterine growth. We explored cord blood bank data (n = 1381 infants) to elucidate whether there is an association between birth weight and HLA class II (DRB1) alleles. HLA DRB1 data were available from 1263 infants. We observed an association between birth weight and HLA DRB1*13, which was over-represented among full-term infants with the highest birth weights. The association remained when the birth weight was corrected for varying gestational age (relative birth weight) according to gender (P = 0.015). After correction of the P-value for multiple comparisons, the association was not statistically significant. However, when the birth weights of all infants were analysed for the effect of DRB1*13, infants positive for HLA DRB1*13 (n = 319) were found to have higher birth weights than infants negative for this allele (n = 944; median 3690 g vs. 3650 g, respectively; P = 0.044). Although the difference in median birth weight was only 40 g, it may be considered significant because it appeared after segregation of the infants into two groups according to the single HLA class II allele group earlier associated with protection against, for example, childhood type 1 diabetes and certain infectious diseases. The present finding may thus suggest identification of a new factor affecting normal intrauterine growth.

Alleles↗
PubMed2004

Chronic thrombocytopenia of childhood: use of non-invasive methods in clinical evaluation.

OBJECTIVES: An unselected group of 21 children with chronic thrombocytopenia was investigated to understand the patients' platelet abnormality better. METHODS: Platelet counts, mean platelet volumes (MPV), membrane glycoproteins and Fcgamma receptor type IIA (FcgammaRIIA) polymorphism H131R, reticulated platelets (% RP), antiplatelet antibodies and plasma thrombopoietin (TPO) were measured. RESULTS: Sixteen patients had idiopathic thrombocytopenic purpura (ITP) (group 1: platelets < 50 x 10(9)/L, n = 6; group 2: 50-99 x 10(9)/L, n = 4; group 3: 100-149 x 10(9)/L, n = 4; group 4: splenectomised patients with normal platelet counts, n = 2). Five patients had familial thrombocytopenia. Six healthy children were studied as a reference. In the 19 thrombocytopenic patients, the platelets were significantly larger and % RP and TPO levels were significantly higher than those in the controls. Increased megakaryocytosis at diagnosis was associated with larger MPV and higher % RP but not with platelet level or TPO. The % RP was remarkably high in all ITP patients of group 1 indicating a brisk production of platelets despite low peripheral count. In all patients with familial thrombocytopenia, TPO was increased suggesting that the syndrome was not because of defective TPO production. The distribution of FcgammaRIIA alleles in the patients was similar to that in the controls. CONCLUSIONS: A combined application of % RP and TPO could be helpful in classifying patients with chronic thrombocytopenia into different categories. The observations may be of value in the clinical evaluation of ITP patients and lead to avoidance of invasive examinations at least in some patients.

Adolescent↗
PubMed2003

Associations among nucleated cell, CD34+ cell and colony-forming cell contents in cord blood units obtained through a standardized banking process.

BACKGROUND AND OBJECTIVES: Nucleated cell content is one of the main components used when evaluating cord blood (CB) units for clinical use. However, other indicators of the haematopoietic potential of a CB unit, such as CD34+ cell and colony-forming cell (CFU-TOT) content, have also been investigated. The aim of this study was to determine whether the CD34+ cell content could be used in selecting CB collections for banking. MATERIALS AND METHODS: The collection data, as well as cellular contents of 588 CB collections obtained using a standardized CB banking process, were analysed. RESULTS: Altogether, 526 CB units from the 588 collections accepted for processing were included in international search registries. The volume collected was, as expected, 69 ml (range 28-116 ml). The correlation between total CD34+ cell and CFU-TOT (n = 88) content in the CB collection was higher (r = 0.87) than the correlation between the total nucleated cell and CFU-TOT content (r = 0.69, both P < 0.0001). The correlations of pre- and postvolume reduction values of the total nucleated cell and CD34+ cell numbers were highly significant (r = 0.96, P < 0.0001, both). The total CFU-TOT content of the CB collection correlated significantly with the total CD34+ cell content of the CB unit before cryopreservation (but after volume reduction) (r = 0.89, P < 0.0001). CONCLUSIONS: CD34+ cell content predicts the haematopoietic potential of a CB unit better than nucleated cell content. Accordingly, the CD34+ cell content of CB could be used to select CB for banking purposes and for transplantation.

Antigens, CD34↗
PubMed2003

Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants.

OBJECTIVE: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. PATIENTS AND MAIN OUTCOME MEASURES: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. RESULTS: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12-100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24-27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. CONCLUSIONS: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.

Asphyxia Neonatorum↗
PubMed2001

Platelet-specific alloantigens in cadaveric renal transplantation. A prospective study. Effect of HPA-5b mismatch in acute vascular rejection of renal allografts.

This prospective study comprised 166 renal allograft-recipient pairs that were studied for human platelet alloantigens (HPA) 1-3 and 5, which have been shown to be expressed by adhesion molecules of the vascular endothelium. Four of the five (80%) HPA-5a5a regraft recipients developing acute vascular rejection (AVR) had received an HPA-5b-incompatible graft in contrast to one of the 32 (3%) regraft recipients without rejection. The occurrence of AVR was not explained by the degree of HLA mismatches. All four regraft recipients of an HPA-5b-mismatched graft with AVR were HLA-A3,B7, and the combination of HLA-A3 and/or B7 match and an HPA-5b-mismatched graft was associated with AVR. No antibodies against HPA-5b were detected in the patients with AVR of an HPA-5b-mismatched graft. These preliminary findings suggest that HPA-5b is a minor histocompatibility antigen involved in the development of AVR.

Acute Disease↗
PubMed2001

On-site coagulation monitoring does not affect hemostatic outcome after cardiac surgery.

BACKGROUND: Rapid coagulation tests are now available for monitoring of bleeding patients after cardiac surgery. As inappropriate blood use in these patients may be due to lack of timely coagulation data, we studied the effect of an algorithm with on-line coagulation monitoring on transfusions in these patients. METHODS: Prospectively, patients bleeding (>1.5 ml kg(-1) 15 min(-1)) after cardiac surgery were randomly assigned to two groups: in group A (n=28), hemostatic treatment during the immediate recovery period (1 h after surgery) was based on an algorithm with on-site hemostasis monitoring, whereas during the same period group B patients (n=30) were managed solely according to the clinician's judgement; laboratory tests other than activated clotting time after heparin neutralization were prohibited. RESULTS: Cumulative chest tube drainage up to 16 h and total transfusion requirements did not differ between the groups. Using a platelet transfusion trigger of 100x10(9)/l, significantly more patients received platelets during the immediate recovery period in the algorithm group than in the control group (14 vs. 3 patients, P=0.001). Desmopressin acetate was administered more often in group A than in group B (8 vs. 2 patients, P=0.04). CONCLUSIONS: Algorithm-based therapy increased utilization of hemostatic interventions during the immediate recovery period without any obvious benefit to the hemostatic outcome. Re-evaluation of the platelet transfusion trigger seems warranted.

Aged↗
PubMed2001

Glycoprotein V-specific platelet-associated antibodies in thrombocytopenic patients.

In autoimmune thrombocytopenia, platelet-associated IgG (PA-IgG) frequently displays specificity against glycoprotein (GP) IIbIIIa and/or GP IbIX. Because in a high proportion of patients positive PA-IgG may not be explained by these GP specificities, studies on other target proteins are needed. We studied the presence of GP V-specific PA-IgG by direct monoclonal antibody-specific immobilization of platelet antigens (MAIPA) with the monoclonal antibody SW16. We focused on 69 consecutive random patients with histories of thrombocytopenia who were strongly positive for PA-IgG detected by the direct platelet immunofluorescence test (PIFT). PA-IgG against GP V (ratio > or = 1.5) was noted in 15 (22%) patients. The degree of PA-IgG measured by PIFT, and of GP IIbIIIa-and/or GP IbIX-specific PA-IgG measured by direct MAIPA, correlated directly with the GP V-specific PA-IgG (P < 0.001). In one patient, GP V-specific antibodies were associated with quinidine-induced thrombocytopenia. Although this patient had strongly positive GP V-specific PA-IgG, she remained negative in GP IIbIIIa- and GP IbIX-specific direct MAIPA. Two patients studied because of thrombocytopenia associated with gold therapy had strongly positive GP V-specific PA-IgG. In one patient with rheumatoid arthritis and severe gold-induced thrombocytopenia, the amount of GP V-specific PA-IgG decreased during the recovery phase. Thus, GP V may represent an important target antigen in autoimmune-mediated thrombocytopenia, especially in drug-induced thrombocytopenia.

Adult↗
PubMed2000

Thrombocytopenia in term infants: a population-based study.

OBJECTIVE: To assess the prevalence and causes of thrombocytopenia among full-term infants. METHODS: We conducted a 1-year, population-based surveillance study involving all full-term infants (at least 37 weeks' gestation) born to native Finnish women in Helsinki. In cases of thrombocytopenia (cord platelet count less than 150 x 10(9)/L) clinical risk factors were evaluated and immunologic studies were performed on both parents and on the infant; 95% confidence intervals (CIs) were calculated on the basis of binomial distribution. RESULTS: Platelet counts were done in cord blood from 4,489 infants, 84.9% of the study population. Eighty-nine infants had platelet counts below 150 x 10(9)/L (2.0%; 95% CI 1.5, 2.3) in cord blood and 11 were less than 50 x 10(9)/L (0.24%; 95% CI 0.10, 0.38). All causes of clinically important thrombocytopenia, those presenting with bleeding and requiring treatment, were related to fetomaternal alloimmune thrombocytopenia. The incidence of severe alloimmune thrombocytopenia was one in 1500 live births and one in 900 of all thrombocytopenia. An immunologic mechanism was involved in ten of 65 (15.4%; 95% CI 6.6, 24.2) infants studied and in four of 15 (26.7%; 95% CI 4.3, 49.1) cases of severe thrombocytopenia. CONCLUSION: Immunologic studies should be considered in all cases of severe neonatal thrombocytopenia for careful monitoring and prevention of potentially severe complications in subsequent pregnancies.

Female↗
PubMed2000

Detection of reticulated platelets: estimating the degree of fluorescence of platelets stained with thiazole orange.

The primary problem in the measurement of reticulated platelets (RP) stained with thiazole orange (TO) by flow cytometry is the definition of a threshold limit for fluorescence positivity. We evaluated settings for the threshold gate for TO positivity based on two principles: a fluorescence histogram (median FL1, Relative FL1) or a plot of forward light scatter (FSC; reflecting the distribution of the platelet size) versus fluorescence intensity (% RP). These methods were applied prospectively in examination of 54 healthy blood donors (16 females) and a total of 50 blinded patient samples: pregnant women with thrombocytopenia (Group 1A, n = 11), thrombocytopenic women after delivery (Group 1B, n = 9) and healthy women with a thrombocytopenic newborn (Group 2, n = 30). Group 1A displayed higher median FL1 (mean 306, CI 279-332) as compared to that of Group 2 (mean 266, CI 255-277; p = 0.0038) or to that of the female controls (mean 249, CI 231-268; p < 0.001). Relative FL1 was also higher in the patients of Group 1A than those of Group 2 (p = 0.037). When analysing the % RP, the difference between these groups was not significant. In the patients (n = 50), the median FSC (mean 407, SD 40, CI 395-418) was also higher than that of the controls (n = 54; mean 383, SD 25, CI 376-390; Mann-Whitney U-test, p = 0.0015). In Group 1A, a significant correlation was observed between the Patient median FL1 and Patient median FSC (r = 0.62, p = 0.043). When developing methods for the measurement of RP, it seems to be useful to analyse the data with more than one principle to define the threshold limit for TO positivity.

Adult↗
PubMed2000

Thrombopoietin levels in cord blood plasma and amniotic fluid in fetuses with alloimmune thrombocytopenia and healthy controls.

To extend our knowledge of the kinetics of fetal thrombopoietin (TPO), we studied TPO levels in cord blood plasma and amniotic fluid collected from 15 fetuses considered to be at risk of fetomaternal alloimmune thrombocytopenia and also from 10 healthy controls at caesarean delivery. In the plasma of all 25 fetuses and newborn infants studied, TPO was detected above the lower limit of detection (7 pg/ml) and correlated inversely with platelet counts (r = -0.53, P = 0.006). At term, TPO detected in amniotic fluid was at significantly lower levels (7 pg/ml; range 0-22 pg/ml) than simultaneously obtained cord plasma TPO (114 pg/ml; range 43-201 pg/ml; P < 0.001). There was no correlation between levels of TPO in amniotic fluid and cord plasma or platelet counts. In the serial samples collected from the five fetuses with HPA-1a alloimmunization before 37 weeks' gestation, the TPO levels in amniotic fluid were significantly higher than at term (P = 0.013): from 22 to 28 weeks' gestation, 42 pg/ml (30-78 pg/ml); from 32 weeks', 24 pg/ml (17-33 pg/ml); at term, 8 pg/ml (4-13 pg/ml), correlating inversely with gestational age (r = -0.81, P = 0.003). Thus, TPO is present in amniotic fluid at levels apparently inversely related to gestational age. Whether these high levels seen early in pregnancy are normal or are associated with the HPA-1 alloimmunization remains to be shown.

Amniotic Fluid↗
PubMed2000

Neonatal thrombocytopenia in two of six human platelet alloantigen (HPA) 5a-positive children of an HPA-5a-immunized mother.

We describe a human platelet alloantigen (HPA) 5a-alloimmunized HPA-5b5b mother. The children were obligatory heterozygotes for HPA-5a but despite IgG class maternal anti-HPA-5a antibodies only two (second and fifth) of the six children developed neonatal thrombocytopenia. Throughout the 4-year follow-up the mother had anti-HPA-5a antibodies (confirmed in the 8th Platelet serology workshop of International Society of Blood Transfusion in 1996). Antibodies against glycoproteins (GP) IIbIIIa or IbIX were not detected. Differences in the children's HPA type (HPA-1, -2, -3, -5) did not correlate with thrombocytopenia. We hypothesized that different expression of GPIaIIa recently associated with two silent polymorphisms (C807T and G873A) of GPIa could explain the unpredictable recurrence pattern of neonatal alloimmune thrombocytopenia (NAIT). Both parents were homozygous for the silent polymorphisms (C807 and G873) associated with the low expression of GP Ia. Thus, the inheritance pattern of the silent polymorphisms (C807T and G873A) did not help in predicting the recurrence risk of thrombocytopenia in the offspring. More detailed comprehension of the natural history of NAIT would be necessary to enable directing fetal blood sampling to the cases at the highest risk of thrombocytopenia.

Adult↗
PubMed2000

Altered platelet shape change in hereditary gelsolin Asp187Asn-related amyloidosis.

Hereditary gelsolin-related amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T mutation in the gene coding for gelsolin, an actin-modulating protein. Altered platelet shape change has been demonstrated in gelsolin-deficient knock-out mice, but this has not been studied in humans with gelsolin deficiency. We measured platelet shape change, characterized by maximal decrease in light transmission (D) and reaction time (T), and aggregation, associated with stimulation of platelets with different agonists in platelet rich plasma, as well as coagulation factor VIII and ristocetin cofactor activities in 20 patients, 10 healthy sibs and 20 healthy control subjects. Statistically significant alterations of parameters describing platelet shape change (D, T) were observed after stimulation with adenosine diphosphate and collagen in patients when compared to healthy subjects, but not in maximal aggregation responses, platelet counts, coagulation factor VIII or ristocetin cofactor activity levels. Patients had more haemostatic derangements. Our results suggest that, in addition to amyloid deposition, the G654A gelsolin gene defect causes altered gelsolin-mediated cellular mechanisms, which may contribute, e.g., to bleeding tendency in AGel amyloidosis patients.

Adult↗
PubMed2000

Maternal thrombocytopenia at term: a population-based study.

BACKGROUND: Thrombocytopenia is a common problem during pregnancy and often inappropriately managed. This study aimed to assess the prevalence and causes of maternal thrombocytopenia at term with special attention to immune mechanisms of thrombocytopenia and the need for assessing fetal risks. METHODS: We conducted a 1-year population-based surveillance study involving 4,382 fullterm (at least 37 weeks' gestation) women (83.8% of the study population) and their infants from the city of Helsinki. Maternal and cord platelet counts were performed at delivery. Immune studies were performed if maternal platelet counts were less than 100 x 10(9)/l; 95% confidence intervals (CIs) were calculated from the binomial distribution. RESULTS: A total of 317 women (7.3%; 95% CI 6.5, 8.1) had platelet counts of less than 150 x 10(9)/l. Most cases (81%) of maternal thrombocytopenia at term were due to gestational thrombocytopenia, which had no impact on either the mother or the fetus unless associated with some other medical or obstetric disorder. Other causes of thrombocytopenia were preeclampsia (16%) and idiopathic thrombocytopenic purpura (ITP) (3%). There was no association between maternal and fetal platelet counts: of the infants born to thrombocytopenic mothers, 2.1%, had thrombocytopenia in the cord blood, which did not differ significantly from the 2.0% of thrombocytopenic infants born to non-thrombocytopenic mothers. CONCLUSION: Women with gestational thrombocytopenia do not require alteration of their treatment. Fetal blood sampling is not considered necessary when thrombocytopenia is discovered unexpectedly at term.

Adult↗