RESUMO
Mobilization and collection of stem cells is difficult in a proportion of patients intended for autologous stem cell transplantation (ASCT). We have evaluated mobilization kinetics of blood CD34(+) cells (B-CD34(+)) to form basis for algorithm to facilitate rational pre-emptive plerixafor use. Altogether 390 chemomobilized patients were included.Forty-three patients (11%) did not reach BCD34+count ≥10×10(6)/l. Mobilization kinetics differed according to the mobilization capacity observed. Among those who were very poor or inadequate mobilizers (peak BCD34(+)count ≤5×10(6)/l and 610×10(6)/l, respectively), BCD34+counts rarely rose after white blood cells (WBC) >510×10(9)/l, whereas in many standard mobilizers a later rise in CD34(+) counts could be observed. Four algorithms based on WBC and CD34(+) counts were constructed. According to this patient series, algorithm II (WBC >5×109/l and BCD34+≤10×10(6)/l) and algorithm IV (WBC >10×10(9)/l andB-CD34(+) ≤10×10(9)/l) were the most applicable. For algorithm II the sensitivity was 0.97 and specificity 1.00, respectively, to identify patients for plerixafor use provided that all patients with B-CD34+ maximum ≤10×10(6)/l would have needed plerixafor.This simple model needs a prospective validation.
Assuntos
Antígenos CD34/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Mieloma Múltiplo/terapia , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Antígenos CD34/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzilaminas , Quimioprevenção/métodos , Ciclamos , Esquema de Medicação , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Cinética , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Prognóstico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Falha de TratamentoRESUMO
Limited information is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients >65 years of age. In 1995-2005, 22 myeloma patients >or=65 years (median 68, eight >or=70) and 79 patients <65 years (median 57) were included in an identical treatment protocol. The first progenitor cell mobilization with cyclophosphamide plus granulocyte-colony stimulating factor (G-CSF) was successful in 95 and 96% of the patients, respectively. To date, 92 patients have received MEL (melphalan) 200 mg/m2 supported by ASCT. No early treatment-related deaths were observed among 22 elderly patients, whereas one younger patient died early. Engraftment and the need for supportive care were comparable between groups. The elderly patients tended to have more WHO grade 3-4 oral or gastrointestinal toxicity when compared to the younger patients (45 vs 23%, P=0.06). After ASCT, a complete response was observed in 44% of the elderly patients and 36% of the younger patients, respectively. No difference was observed between these age groups in progression-free survival (23 vs 21 months) or overall survival (57 vs 66 months) after ASCT. We conclude that MEL200 is a safe and efficacious treatment in selected elderly myeloma patients.
Assuntos
Melfalan/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Agonistas Mieloablativos/farmacologia , Transplante de Células-Tronco/métodos , Adulto , Fatores Etários , Idoso , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Células-Tronco/metabolismoRESUMO
BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , DNA Complementar/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Animais , DNA Complementar/análise , DNA de Neoplasias/análise , Proteínas de Choque Térmico/análise , Proteínas de Choque Térmico/genética , Humanos , Imuno-Histoquímica , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Masculino , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia , Hiperplasia Prostática/genética , Neoplasias da Próstata/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo , Falha de TratamentoRESUMO
Gastrinomas are rare gastrin-secreting endocrine tumors that usually arise in the duodenum or pancreas and, if untreated, can cause severe peptic ulcers or metastatic disease. Although most tumors are sporadic they are especially common in patients with multiple endocrine neoplasia type 1 (MEN1), and most studies of these tumors have focused on the role of the MEN1 gene. Although the gene is commonly altered in sporadic tumors, this finding is not universal, and it is highly likely that other genetic defects play a significant role. In the present study, an in-depth analysis of the DNA of eight tumors was carried out in an effort to localize these areas. The experiments consisted of an analysis of 400 microsatellite marker loci distributed evenly throughout the human genome, and the results were confirmed with comparative genomic hybridization. Whereas deletions encompassing the MEN1 gene were seen in two tumors, the most striking result was multiple large rearrangements on chromosome 1 in two of the tumors with hepatic metastases. In several instances, an individual tumor had abnormalities of every informative maker on a given chromosome, presumably as a result of aneuploidy affecting that chromosome. Such defects were only seen in the four large or aggressive tumors, and the total number of chromosomes affected in a tumor ranged from 1 to a high of 13 in a patient who had an unusually aggressive tumor This tumor also showed microsatellite instability, and this is the first report of such a defect in gastrinomas. This study implicates chromosome 1 defects, aneuploidy, and perhaps mismatch repair defects as importan features of gastrinomas; deletions involving the MEN1 gene were con firmed, but the rest of the genome was free of large deletions or amplifications.
Assuntos
Neoplasias Duodenais/genética , Gastrinoma/genética , Neoplasias Pancreáticas/genética , Desequilíbrio Alélico , Aneuploidia , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 5 , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Neoplasias Duodenais/patologia , Genoma Humano , Humanos , Metástase Linfática , Repetições de Microssatélites , Hibridização de Ácido Nucleico , Neoplasias Pancreáticas/patologia , Reação em Cadeia da PolimeraseRESUMO
Breast cancer cell lines provide a useful starting point for the discovery and functional analysis of genes involved in breast cancer. Here, we studied 38 established breast cancer cell lines by comparative genomic hybridization (CGH) to determine recurrent genetic alterations and the extent to which these cell lines resemble uncultured tumors. The following chromosomal gains were observed: 8q (75%), 1q (61%), 20q (55%), 7p (44%), 3q (39%), 5p (39%), 7q (39%), 17q (33%), 1p (30%), and 20p (30%), and the most common losses were: 8p (58%), 18q (58%), 1p (42%), Xp (42%), Xq (42%), 4p (36%), 11q (36%), 18p (33%), 10q (30%), and 19p (28%). Furthermore, 35 recurrent high-level amplification sites were identified, most often involving 8q23 (37%), 20q13 (29%), 3q25-q26 (24%), 17q22-q23 (16%), 17q23-q24 (16%), 1p13 (11%), 1q32 (11%), 5p13 (11%), 5p14 (11%), 11q13 (11%), 17q12-q21 (11%), and 7q21-q22 (11%). A comparison of DNA copy number changes found in the cell lines with those reported in 17 published studies (698 tumors) of uncultured tumors revealed a substantial degree of overlap. CGH copy number profiles may facilitate identification of important new genes located at the hotspots of such chromosomal alterations. This was illustrated by analyzing expression levels of 1236 genes using cDNA microarrays in four of the cell lines. Several highly overexpressed genes (such as RCH1 at 17q23, TOPO II at 17q21-q22, as well as CAS and MYBL2 at 20q13) were involved in these recurrent DNA amplifications. In conclusion, DNA copy number profiles were generated by CGH for most of the publicly available breast cancer cell lines and were made available on a web site (http://www.nhgri.nih.gov/DIR/CGB/++ +CR2000). This should facilitate the correlative analysis of gene expression and copy number as illustrated here by the finding by cDNA microarrays of several overexpressed genes that were amplified.
Assuntos
Neoplasias da Mama/genética , DNA Complementar/genética , DNA de Neoplasias/genética , Perfilação da Expressão Gênica/métodos , Hibridização de Ácido Nucleico/métodos , Neoplasias da Mama/metabolismo , Deleção Cromossômica , Feminino , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Células Tumorais CultivadasRESUMO
Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/normas , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carmustina/administração & dosagem , Carmustina/toxicidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/toxicidade , Citarabina/administração & dosagem , Citarabina/toxicidade , Progressão da Doença , Etoposídeo/administração & dosagem , Etoposídeo/toxicidade , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Mobilização de Células-Tronco Hematopoéticas , Humanos , Infecções/induzido quimicamente , Masculino , Melfalan/administração & dosagem , Melfalan/toxicidade , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Podofilotoxina/toxicidade , Taxa de Sobrevida , Fatores de Tempo , Condicionamento Pré-TransplanteRESUMO
Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.
Assuntos
Mobilização de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Antígenos CD34/química , Medula Óssea/patologia , Estudos de Coortes , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Análise Multivariada , Curva ROC , Risco , Sensibilidade e Especificidade , Células-Tronco/metabolismo , Resultado do TratamentoRESUMO
Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD+/-local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m(2)) (n=25) or intermediate-dose CY (ID-CY, 4 g/m(2)) (n=32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 x 10(6)/kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, P<0.001), lower frequency of fever (20 vs 73%, P<0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P=0.004) and days on parenteral antibiotics (0 vs 4 days, P<0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile.
Assuntos
Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Fluorescence in situ hybridization (FISH) was performed on interphase bone marrow cells to study numerical chromosome abnormalities in childhood acute lymphoblastic leukemia (ALL). Ten patients were selected for this study on the basis of having an extra chromosome 6 in the abnormal clone of the bone marrow at diagnosis. The numerical changes that were detected by FISH with a chromosome 6 specific alpha-satellite DNA probe correlated well with the cytogenetic and clinical data in all patients. Three hybridization signals were seen in 43.8--83.0% of interphase cells in the specimens with a hyperdiploid karyotype. The diagnostic bone marrow sample of the patient with a tetraploid karyotype revealed four signals in 67.0% of cells. Two signals were detected in the majority of the cells in the three nonleukemic control bone marrow samples (97.0--97.7%), assessing the cut-off value of about 1% for trisomy 6. This study demonstrates that FISH analysis is a useful and sensitive tool to screen for the presence of extra chromosomes in interphase cells and is important clinically for evaluating the achievement and maintenance of remission in hyperdiploid childhood ALL. However, to detect structural chromosome aberrations which carry important diagnostic and prognostic information, as seen in our patient with the translocation t(1;19) at diagnosis but not at relapse, conventional cytogenetic analysis should be performed both at diagnosis and at relapse.
Assuntos
Aberrações Cromossômicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Cytogenetic, clinical, and laboratory findings of three patients with a small cell variant of T-cell prolymphocytic leukemia (T-PLL) are presented. Immunophenotypic studies of the morphologically typical small cell variant prolymphocytes showed a mature helper T-cell phenotype (CD4+CD8-) in one patient and a common thymocyte phenotype (CD4+ CD8+) in two other patients. The cytogenetic analysis revealed complex karyotypes with several structural aberrations in the peripheral blood lymphocytes of all three patients. In all cases chromosome 14 was affected with the breakpoint at 14q11. Inversion (14) and isochromosome 8q, often reported as an additional aberration in T-PLL, were detected in two of the patients. In two patients a translocation of the short arm of chromosome 12 was also seen. The T-cell receptor beta-chain gene showed a clonal rearrangement in all three patients, whereas no rearrangements were detected in the immunoglobulin genes. The survival of the patients ranged from 10 weeks to 48 months. The association between cytogenetic, clinical, and laboratory data is discussed.
Assuntos
Aberrações Cromossômicas , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica/genética , Adulto , Idoso , Feminino , Humanos , Cariotipagem , Leucemia Prolinfocítica/patologia , Leucemia Prolinfocítica de Células T/patologia , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
The authors describe a combination technique enabling detection of in situ hybridization (ISH) signals from chromosome-specific probes in interphase or mitotic cells that still retain the alkaline phosphatase antialkaline phosphatase (APAAP) or Sudan black B (SBB) staining reactions (simultaneous detection) or have been first classified morphologically and then by APAAP or SBB. The technique can be used on cell suspensions, in situ cultures and tissue sections. Examples from leukemias (chronic lymphocytic, myeloid, and acute myeloid leukemia) and solid tumors (chondromyxoid fibroma and glioblastoma) illustrate the potential of the technique in investigation of cancer tissue heterogeneity. In leukemias, it can be used to study cell lineage involvement, stem cells, and minimal residual disease, as well as to monitor therapy. In solid tumors, it can be used to identify neoplastic areas of tissue and to track the site of origin of neoplastic cells. Finally, it can be used to study the significance of chromosome abnormalities in carcinogenesis.
Assuntos
Neoplasias/genética , Adulto , Idoso , Fosfatase Alcalina , Compostos Azo , Condroma/genética , Bandeamento Cromossômico , Feminino , Seguimentos , Genótipo , Glioma/genética , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ/métodos , Hibridização in Situ Fluorescente , Leucemia/genética , Masculino , Pessoa de Meia-Idade , Naftalenos , Fenótipo , Coloração e Rotulagem/métodosRESUMO
A 54-year-old female with acute myeloid leukemia (AML) (FAB M4eo) was treated at second relapse with a combination of low-dose cytosine arabinoside (LDAraC) (20 mg b.i.d. subcutaneously) and all-trans retinoic acid (ATRA) (45 mg/m2/d orally) on days 1-10. The patient achieved a complete hematological remission after the first cycle and was consolidated with three similar cycles at four-week intervals. Subsequently, the patient relapsed several times. Altogether seven complete hematological remissions including some cytogenetic remissions were induced with the same regimen. The patient survived 81 months after the start with LDAraC-ATRA regimen. This low-toxicity regimen may be useful in some patients with poor-risk AML.
Assuntos
Citarabina/administração & dosagem , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Tretinoína/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Análise Citogenética , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Indução de Remissão/métodosRESUMO
Comparative genomic hybridization (CGH) analysis was performed on bone marrow specimens from 19 children with acute myeloid leukemia (AML) at diagnosis. The results of CGH were compared to those of conventional cytogenetic analysis. The most common CGH aberrations were gains of whole chromosomes 6 and 8, both of which appeared three times. Two losses were seen twice; losses of whole chromosomes 7 and X. The CGH findings were concordant with the results of conventional karyotyping. CGH did not add new information to the karyotypes. Since no high-level amplification was found among the samples and standard karyotyping was highly successful, we do not advocate routine use of CGH in the diagnostic evaluation of childhood AML.
Assuntos
Análise Citogenética , DNA de Neoplasias/genética , Leucemia Mieloide/genética , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Hibridização de Ácido NucleicoRESUMO
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.