Protein C, protein S and von Willebrand factor levels correlate with bleeding symptoms: a population-based study.

Although natural anticoagulant deficiencies are the established causes of thrombosis, their roles in bleeding are not fully studied. The objective is to correlate haemostatic factors with haemorrhagic symptoms quantified by a standardized questionnaire. Adult subjects were recruited from Bangkok and nearby provinces as part of routine health surveys/checkups. The validated MCMDM-1VWD form was used to assess their bleeding symptoms. At the same time, von Willebrand factor (VWF) activity, free protein S levels and protein C activity were measured. There were 5196 individuals. The mean age was 44.3 years (range 15-99) and 41% were male subjects. The mean bleeding score was -0.28 and 95% of subjects had scores between -2 and +2. The scores were lower in female subjects than in male subjects (-0.35 vs. -0.16, P < 0.001). Bleeding scores correlated negatively with age, VWF and protein C activities (Spearman's ρ-0.258, -0.091 and -0.098, respectively, all P < 0.001), but did not significantly correlate with protein S levels. Using multivariate analysis, female gender, VWF below 100 IU dL(-1), protein C below 100 IU dL(-1) and protein S over 150 IU dL(-1) significantly related to high (≥3) bleeding scores (adjusted odds ratio 1.95, 1.83, 1.56 and 2.84, P = 0.001, 0.001, 0.039 and 0.017, respectively). These findings may suggest interacting roles of VWF and natural anticoagulants in modifying bleeding symptoms.

Iron deficiency: effect on plasma luteinizing hormone and testosterone levels in the adult male rat.

We studied four groups of animals, all of which received an iron-deficient diet for 6 wk followed by a 4-wk recovery period during which all groups received Fe supplements. Group 1 (n = 12) and group 2 (n = 10) were intact male rats; group 1 received a dietary Fe supplement whereas group 2 received no Fe supplement. Group 3 (n = 12) and group 4 (n = 12) were castrated male rats; group 3 received a dietary Fe supplement whereas group 4 received no supplement. Analysis of circulating hormone values revealed that after 6 wk of dietary treatment, neither LH nor testosterone levels were affected by the Fe-deficient diet in either the castrated or intact groups. These observations suggest that neither testosterone secretion per se nor its feedback control by LH is affected by short-term Fe deficiency.

Guillain-Barré syndrome and optic neuropathy in acute leukemia.

We report the unique case of an 18-year-old man with acute myelomonoblastic leukemia in whom Guillain-Barré syndrome and optic neuropathy developed as a part of a clinical presentation.

Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases.

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.

CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL.

Anemias in Thai patients with cirrhosis.

Anemia is a frequent complication in patients with cirrhosis. Only one study has been previously reported regarding the etiology of anemias in Thai cirrhotic patients. The diagnosis of iron deficiency in the study however was not based on standard criteria. Herein we report the frequency and hematological manifestations of various causes of anemias diagnosed by using gold standard criteria in 72 consecutive Thai cirrhotic patients. The diagnosis of cirrhosis was based on the characteristic clinical features and the ultrasonographic findings. The median age of the patients was 49 years; male:female was 1:1.3. The mean hemoglobin value was 8.3 g/dl and the mean MCV was 96.6 fl. Most patients revealed macrocytosis, normal WBC count and mild thrombocytopenia. Iron deficiency, defined as absent bone marrow iron stores, was the most common anemia found in 40% of the patients while folate deficiency, diagnosed when red cell folate was < 160 ng/ml packed RBC, was documented in 10% of the patients. Megaloblastosis, hemolysis and anemia of chronic disease was found in 4%, 28% and 13% of the patients, respectively. Folate deficiency was significantly more common in the alcoholic patients (P = 0.01). Iron deficiency was thus the most common anemia in Thai patients with cirrhosis. The frequency of folate deficiency was not rare and the rate was comparable to data reported from western countries in spite of the Thai diet being relatively rich in folates.

Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy.

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.

Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study.

The objective of this study was to determine the hematopoietic effects and toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF (Lenograstim) was administered by daily subcutaneous injection with an initial dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2 weeks. Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions. Thirty-two MDS patients were recruited from 6 university hospitals. Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L. Three of 6 patients who did not respond to the initial dosage responded to the escalated dosage of 1 microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded compared with 8 (80%) of 10 patients with RAEB. The response rates in patients with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were 80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant changes in hemoglobin levels or platelet counts were observed. In conclusion, low-dose G-CSF administered by subcutaneous injection is well tolerated and effective in improving neutropenia in MDS patients.

A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma.

The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC < or = 0.5 x 10(9)/l) and febrile neutropenia (FN, an ANC < 0.5x10(9)/l in association with a body temperature of > or = 38.3 degrees C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged > or = 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibility included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of > or = 38.3 degrees C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had > or = 2 extranodal diseases, 59% had serum LDH > 1 x normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of < or = 3.5 g/dl, serum LDH > 1 x normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5-90.7) (high risk), 23.9% (95% CI, 12.6-38.8) (intermediate risk) and 4.4% (95% CI, 0.5-15.1) (low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4-83.5), 17.4% (95% CI, 7.8-31.4) and 2.2% (95% CI, 0.05-11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (> or = 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated.