Survey on the threshold for platelet transfusions

We carried out a survey on platelet transfusions performed in nine general hospitals. We evaluated 303 adults who received a total of 24455 units over 1864 platelet transfusions. The underlying diseases were hematologic disorders with chemotherapy (59.7%), hematologic disorders without chemotherapy (15.5%), hematopoietic stem cell transplantation (18.5%), and others (2.0%). The patient platelet count before transfusion (platelet trigger value) was measured in only 77.1%. The platelet trigger value differed greatly between the hospitals, with an average of 2.2 x 10(4)/microl, a minimum of 1.3 x 10(4)/microl, and maximum of 3.2 x 10(4)/microl. Only 55.3% of the platelet transfusions carried out complied with the Platelet Transfusion Guideline published by the Ministry of Health, Labour and Welfare. The hospitals surveyed could be divided into those who gave mainly around 10 units and those who gave over 10 units. The total dose of platelets transfused was more in the hospitals that used mainly 15 or more unit-PCs than in the hospitals that used mainly 10 unit-PCs. These results indicate that platelet transfusion may be greatly reduced by complying with the 2 x 10(4)/microl of platelet transfusion threshold and by selecting less than 10 units of PC per transfusion.     

Four cases of pseudothrombocytopenia due to platelet cold agglutinins

We report 4 cases of pseudothrombocytopenia due to platelet cold agglutinins. Case 1 was a 57 y.o. female whose platelet count was 97 x 10(3)/microl. Case 2 was a 37 y.o. male with a platelet count of 96 x 10(3)/microl. Case 3 was a 74 y.o. male with a platelet count of 28 x 10(3)/microl. Case 4 was a 62 y.o. female whose platelet count was 34 x 10(3)/microl. The platelet counts in these 4 cases were decreased and blood smears showed platelet clumping in blood drawn in a tube without anticoagulant just after withdrawal, as well as in blood drawn in a tube with anticoagulant. The platelets from these patients agglutinated at a temperature below 10 degrees C (case 1 and 4) and 24 degrees C (case 2). The immunoglobulin class of the platelet cold agglutinins in cases 1, 2 and 4 was IgM. Agglutinated platelets showed no activation marker, such as CD62P, CD63 or CD40L, on the surface of the platelets. The target antigen of cold agglutinins was GPIIb-IIIa in cases 1 and 2. We considered that the detection of platelet agglutination in blood without anticoagulant is important to diagnose pseudothrombocytopenia due to platelet cold agglutinins. Although this disease is considered to be very rare, we suspect that this disease may be misdiagnosed as pseudothrombocytopenia due to the presence of an anticoagulant, and overlooked.     

Recovery of hematopoiesis after high-dose chemotherapy and peripheral blood stem cell autografts in children]

Hematopoietic recovery kinetics were evaluated in 34 children with therapy-refractory malignant tumors who underwent a total of 35 peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy without total body irradiation. A negative correlation was found between the numbers of colony-forming units of granulocyte-macrophage (CFU-GM) infused per kilogram of the patients' body weight and the time of achieving an absolute granulocyte count (AGC) of 0.5 x 10(9)/l or a platelet count of 50 x 10(9)/l (granulocyte: r = -0.631, p less than 0.001, platelet: r = -0.590, p less than 0.001). The patients were classified into three groups; 14 patients who received less than 1 x 10(5) CFU-GM/kg (group A), 7 patients who received 1-3 x 10(5) CFU-GM/kg (group B), and 14 patients who received greater than or equal to 3 x 10(5) CFU-GM/kg (group C). The AGC recovered to 0.5 x 10(9)/l by 21 day in group A, 14 day in group B, and 10 day in group C. The platelet count recovered to 50 x 10(9)/l 102 in group A, 23 in group B, and 16 day in group C patients. The final platelet infusion was on day 60 in group A, day 12 in group B, and day 12 in group C. Transient decrease in the blood cell count developed in all patients 3 to 7 weeks after transplantation, and two cases developed reversible ITP. In the remaining patients, the recovered hematopoietic function was sustained for 1-48 months after transplant action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effective treatment with rituximab in a patient with refractory idiopathic thrombocytopenic purpura

A 75-year-old woman had an episode of sudden nasal and oral bleeding. After that, petechiae appeared on her entire body. She received a platelet transfusion, and was referred to our hospital. On admission, the platelet count was as low as 1.2 X 10(4)/microl, and the PAIgG level was slightly elevated. Bone marrow cellularity was low, with a normal count of megakaryocytes. Anti-glycoprotein IIb/IIIa antibody-secreting B cells in the peripheral blood and platelet-associated anti-glycoprotein IIb/ IIIa antibodies were significantly high, and the patient was diagnosed as having idiopathic thrombocytopenic purpura (ITP). She failed to respond to corticosteroids, splenectomy and other therapies, so we administered rituximab, anti-CD20 monoclonal antibody, 375 mg/m2 weekly for four weeks. After the second infusion of rituximab, the platelet count began to increase. The platelet count continued to rise until a peak count (15.0 x 10(4)/microl) observed after 2 weeks from the fourth infusion, and the response was maintained for 8 more weeks. The levels of anti-glycoprotein IIb/IIIa antibody-secreting B cells and platelet-associated anti-glycoprotein IIb/IIIa antibodies decreased after the administration of rituximab. Rituximab was effective in this case of refractory ITP.     

Three cases of idiopathic thrombocytopenic purpura showing an increase in the platelet count following clarithromycin treatment

Macrolides have immuno-modulatory effects as well as anti-bacterial effects. We successfully treated three idiopathic thrombocytopenic purpura (ITP) patients with clarithromycin (CAM). Case 1: A 69-year-old male ITP patient was treated with CAM at a dose of 400 mg/day. His platelet count increased from 5.6 x 10(4)/microliter to 10.1 x 10(4)/microliter. Case 2: A 72-year-old male ITP patient was treated with CAM at the same dose. The platelet count increased from 1.3 x 10(4)/microliter to 12.3 x 10(4)/microliter. Case 3: A 68-year-old female ITP patient was treated with CAM at the same dose. The platelet count increased from 2.3 x 10(4)/microliter to 13 x 10(4)/microliter. These facts suggest that CAM is useful in the treatment of ITP.     

Evaluation of the Use of a Platelet-Counting Tool in Plateletpheresis

OBJECTIVE: For years, blood transfusion centers in Taiwan have used the Quantitative Buffy Coat (QBC(R)) Hematology System for platelet counts on capillary blood samples in the laboratory screening of apheresis donors. The system has not been evaluated for the prediction of yields in plateletpheresis. Methods : The QBC instrument was evaluated for reproducibility of platelet counts and compared with five electronic cell counters. We also collected both capillary and venous blood from voluntary donors before donation and counted platelets, comparing the QBC system and an electronic blood cell counter (Sysmex K1000). The correlation between donors' predonation platelet counts and plateletpheresis yields was analyzed. RESULTS: The R values for platelet counts between the QBC Hematology System and other electronic counters are lower (0.759-0. 890) than among the electronic counters (0.929-0.973). The mean capillary platelet count and the mean venous platelet count were 241. 9+/-50.3x10(3)/microl and 233.2 +/-47.9x10(3)/microl by the QBC system, and 244.9+/-54.1x10(3)/microl and 218.9+/-46.5x10(3)/microl by the Sysmex K1000, respectively. Linear regression analysis showed that platelet yields correlated well with donors' predonation platelet counts using the Sysmex K1000 counter (R = 0.777- 0.890, p<0.001), but not with the QBC system (R = 0.326 approximately 0.755, p<0.05). CONCLUSION: The QBC Hematology System is not accurate enough to determine predonation platelet counts that are to be used for calculating the number of processing cycles for plateletpheresis.     

Association of platelet counts on presentation and clinical outcomes in ST-elevation myocardial infarction (from the TIMI Trials)

Platelet activation and aggregation play pivotal roles in the thrombotic process of acute coronary syndromes. However, data regarding platelet count and its association with clinical outcomes in the setting of ST-elevation myocardial infarction (STEMI) are limited. We hypothesized that higher platelet counts on presentation would be associated with poorer clinical outcomes. Data from 10,793 patients with STEMI in the Thrombolysis In Myocardial Infarction (TIMI) trials database were analyzed. Mean platelet count on presentation was 254.8 x 10(3)/microl. Higher platelet counts were associated with higher rates of adverse clinical outcomes at 30 days. In a multivariable analysis that adjusted for confounders of platelet counts (age, gender, weight, diabetes, and smoking), higher platelet counts remained associated with an increased risk of the combined end point of death, reinfarction, and congestive heart failure. With a reference group of platelet counts <200 x 10(3)/microl, the multivariable odds ratios were 1.22 (95% confidence interval 1.05 to 1.42, p = 0.009) for platelet counts of 201 to 300 x 10(3)/microl, 1.37 (95% confidence interval 1.11 to 1.68, p = 0.002) for counts of 301 to 400 x 10(3)/microl, and 1.71 (95% confidence interval 1.16 to 2.51, p = 0.005) for counts >400 x 10(3)/microl. Further, a greater decrease in follow-up platelet counts (compared with baseline values) was independently associated with an increased risk of reinfarction at 30 days (odds ratio 1.44 for every decrease of 100 x 10(3)/microl unit of platelets, 95% confidence interval 1.13 to 1.82, p = 0.03). In conclusion, in STEMI, a higher platelet count on presentation was independently associated with adverse clinical outcomes, whereas a greater subsequent platelet count decrease was associated with an increased risk of reinfarction.     

Platelet transfusion prophylaxis for patients with haematological malignancies: where to now?

National guidelines for platelet transfusion in many countries recommend that the general platelet transfusion trigger for prophylaxis is 10x10(9)/l. This annotation reviews the evidence for this threshold level and discusses other current unresolved issues relevant to platelet transfusion practice such as the optimal dose and the clinical benefit of a strategy for the prophylactic use of platelet transfusions when the platelet count falls below a given threshold.     

The frequency of bleeding complications in patients with haematological malignancy following the introduction of a stringent prophylactic platelet transfusion policy

Indications for platelet transfusion remain controversial and are frequently based on arbitrary numerical criteria. In October 2000, we introduced a stringent prophylactic-platelet transfusion policy < 10 x 109/l for stable patients and < 20 x 10(9)/l in the presence of major bleeding or additional risk factors. A trigger of < 50 x 10(9)/l was introduced for patients undergoing invasive procedures. A prospective analysis was performed measuring the frequency of minor and major bleeding events, morbidity, mortality and duration of pancytopenia. Blood product usage was assessed and health care savings measured. A total of 98 patients were evaluated on 2147 patient study days and 271 bleeding episodes were recorded. Major bleeding occurred on 1.39% (30/2147) of the study days when platelet counts were < 10 x 10(9)/l and 2.3% (50/2147) of the study days when platelet counts were 10-20 x 10(9)/l. In patients with platelets > 20 x 10(9)/l, there were 117 major bleeding episodes observed on 5.4% of the study days. In patients with no identified additional risk factors present, major haemorrhages were recorded in 0.51% (11/2147) of the study days in patients with platelet counts > or = 10 x 10(9)/l . There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 x 10(9)/l was in place (P = < 0.02). Of note, a 16% reduction in red cell transfusions was recorded. These data confirm that the introduction of a transfusion trigger of < 10 x 10(9)/l in the absence of fresh bleeding and sepsis (> 38 degrees C) is safe and has a significant impact on overall hospital transfusion costs.     

The efficiency of transfusing high doses of platelets in hematologic patients with thrombocytopenia: results of a prospective, randomized, open, blinded end point (PROBE) study

We performed a prospective, randomized, open, blinded end point (PROBE) study to assess the efficiency of transfusing high doses of platelets in patients with thrombocytopenia, either acute leukemia (AL) or those undergoing autologous hematopoietic stem cell transplantation (AT). Patients were randomly assigned to receive transfusions with a target dose of 0.5 x 10(11)/10 kg (arm A) or 1 x 10(11)/10 kg (arm B). A total of 101 patients were included, of whom 96 were given at least one transfusion. The median time between the first transfusion and when the platelet count reached at least 20 x 10(9)/L increased from 63 hours to 95 hours in the arm B group (P = .001), and the median number of transfusions was lower in this group (2; P = .037). The total number of transfused platelets did not differ between groups (14.9 x 10(11) for arm A versus 18.5 x 10(11) for arm B; P = .156). In such patients, a prophylactic strategy of high doses of platelets could improve platelet transfusion efficiency.     

Pretransfusion trigger platelet counts and dose for prophylactic platelet transfusions

PURPOSE OF REVIEW: To assess critically both the blood platelet counts that prompt a platelet transfusion (i.e. trigger) in various clinical settings in patients with thrombocytopenia caused by marrow failure and the dose of platelets infused (i.e. number per each transfusion) for optimal hemostasis, feasibility, and safety. RECENT FINDINGS: Definitive studies (e.g. well-designed, prospective, randomized clinical trials) are not available either historically or at present to support evidence-based decisions. Instead, retrospective reviews and anecdotal reports provide observational data to assist in best guess clinical practices. SUMMARY: Reasonable clinical practice, until more definitive data become available, is to transfuse enough platelets per each transfusion to maintain the blood platelet count >10 x 10/L in stable nonbleeding patients, >20 x 10(9)/L in unstable nonbleeding patients, and >50 x 10(9)/L in bleeding patients or in those undergoing invasive procedures.     

Cyclic thrombocytopenia complicated with Sjögren syndrome and the mechanism of periodic platelet count fluctuation

Cyclic thrombocytopenia is a rare disorder with periodic changes of the platelet count. We experienced a patient with cyclic thrombocytopenia and Sj?gren syndrome (SS), and studied the mechanism of the cyclic changes of the platelet count. The patient, a 75-year-old woman, was referred to our hospital because of dry mouth, dry eyes, and severe thrombocytopenia. Her platelet count varied from 0.2 x 10(4)/microl to 22.7 x 10(4)/microl in 14-28-day cycles. Anti-SS-A/Ro antibody and Schirmer's test were positive. Histological examination of the salivary glands revealed infiltration of inflammatory cells, leading to the diagnosis of SS. There was an inverse relation between the platelet count and serum levels of PA-IgG. When the platelet count was low, the number of bone marrow megakaryocytes and the colony counts of CFU-Meg decreased. The serum thrombopoietin level increased at the nadir of the platelet count and decreased as platelets increased. After prednisolone therapy, her platelet count increased along with the improvement of sicca symptoms. These findings suggest that platelet fluctuation is due to the periodic increase of platelet destruction, as well as periodic failure of platelet production.     

Spontaneous omental bleeding presenting as acute abdomen during treatment for polycythemia vera

A 54-year-old woman with polycythemia vera (PV) presented as an emergency patient with acute abdomen. Her platelet count was 119 x 10(4)/microl. Computed tomography scan revealed fluid accumulation in the omentum and peritoneal space. An emergency laparotomy was undertaken because of severe abdominal pain and omental bleeding was diagnosed. Peritoneal hemorrhage and hematoma weighing in total 1040 g was drained. Although a part of the omentum and stomach was excised, we could not find any orifice from which bleeding could have occurred despite a thorough pathological examination. Massive hemorrhage should be considered in cases with PV presenting as acute abdomen, especially when the platelet count is extremely high (over 100 x 10(4)/microl).     

Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome.

This study reports that thrombocytopenia is a universal phenomenon post hepatic transplantation. In 53 consecutive adult patients undergoing liver transplantation the platelet count fell by a mean of 63% (157 x 10(9)/l to 50 x 10(9)/l). The platelet count reached a nadir at Day 5 post-transplant but returned to pre-operative levels by Day 14. Non-parametric regression analysis found that pre-operative platelet count, blood transfusion requirements and maximum post-operative ALT values were independent predictors of the percentage fall in platelet count. No correlation was seen with length of graft cold ischaemic time or the use of University of Wisconsin (UW) solution. The nadir day correlated with maximum post-operative bilirubin and ALT, graft ischaemic time and use of UW solution. Maximum post-operative ALT was also an independent predictor of nadir platelet count. It was observed that patients who did not survive the hospital admission had lower post-operative platelet counts and these did not return to pre-operative levels by Day 14. The percentage fall in platelet count was an independent predictor of survival. Severe thrombocytopenia was associated with cerebral haemorrhage in 3 patients. This report provides evidence that allograft dysfunction (maximum post-operative bilirubin and/or AST/ALT) was the most consistent independent predictor of the nadir platelet count, nadir day and percentage fall in platelet count post liver transplantation although the exact mechanism(s) of the platelet changes remain uncertain.     

γ干扰素质粒基因转染对支气管哮喘小鼠气道炎症的影响

目的观察气道内γ干扰素(IFNγ)基因转染对支气管哮喘(简称哮喘)小鼠气道炎症的影响。方法健康6周龄SPF级C57BL/6小鼠40只,按随机数字表法分为4组。正常对照组(A组)、哮喘模型组(B组)、模型空质粒干预组(C组)、模型IFNγ质粒干预组(D组),每组10只。B组、C组及D组以0.1%卵白蛋白(OVA)0.1ml腹腔注射致敏,以1%的OVA50μl滴鼻激发建立哮喘模型;A组用等量生理盐水分别代替0.1%的OVA0.1ml和1%OVA50μl;C组和D组分别经鼻滴入空质粒pcDNA3.1()和Lipofentamine2000混合液50μl或重组IFNγ质粒和Lipofentamine2000混合液50μl。观察各组小鼠支气管肺泡灌洗液(BALF)中的细胞成分、白细胞介素4(IL4)、IL5、IFNγ和肺组织病理学变化。结果B组小鼠BALF中炎性细胞总数、嗜酸粒细胞(EOS)、中性粒细胞和淋巴细胞计数分别为(0.102±0.020)×109/L、(0.0193±0.0047)×109/L、(0.0107±0.0039)×109/L、(0.0255±0.0042)×109/L,A组分别为(0.082±0.012)×109/L、(0.0041±0.0009)×109/L、(0.0051±0.0016)×109/L、(0.0201±0.0019)×109/L,A、B两组比较差异有统计学意义(P<0.05);D组小鼠BALF中炎性细胞总数、EOS、中性粒细胞和淋巴细胞计数分别为(0.086±0.016)×109/L、(0.0116±0.0031)×109/L、(0.0062±0.0018)×109/L、(0.0182±0.0041)×109/L,与B组比较差异有统计学意义(P<0.05)。B组小鼠BALF中IL4、IL5、IFNγ水平分别为[(39.2±5.1)pg/ml、(83.7±4.7)pg/ml、(15.7±2.7)pg/ml],A组小鼠分别为[(13.3±1.9)pg/ml、(12.1±2.3)pg/ml、(31.8±7.9)pg/ml],A、B两组比较差异有统计学意义(P<0.05);D组小鼠BALF中IL4、IL5、IFNγ水平分别为[(16.4±3.2)pg/ml、(26.3±3.4)pg/ml、(65.4±10.4)pg/ml],与B组比较差异有统计学意义(P<0.05)。A组小鼠气道无明显炎症变化,B和C组小鼠小支气管、血管黏膜下和周围肺组织有明显的炎症细胞浸润,血管壁明显水肿;D组小鼠气道炎症明显减轻。结论气道内转染干扰素质粒能有效改善哮喘小鼠细胞因子IL4、IL5和IFNγ异常,同时对EOS、中性粒细胞数和淋巴细胞肺内募集、肺组织炎症改变有一定抑制作用。     

Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin.

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.     

A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia

To determine the safety, biologic, and clinical benefits of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF; Amgen, Thousand Oaks, CA) after myelosuppressive chemotherapy in acute myeloid leukemia (AML), 108 adult patients with de novo AML were randomized to receive either PEG-rHuMGDF (2.5 microg/kg/d or 5 microg/kg/d) for up to 21 doses (group A), a single dose of 2.5 microg/kg PEG-rHuMGDF, 7 daily doses of 2.5 microg/kg PEG-rHuMGDF (group B), or placebo. The greatest biologic activity was seen in group A with a median peak platelet count of 1,084 x 10(9)/L, occurring at a median 9 days after the last dose of study drug, compared with 517 x 10(9)/L and 390 x 10(9)/L in group B and placebo group, respectively. Thrombocytosis (platelets >1,000 x 10(9)/L) was seen at rates of 52%, 8%, and 9% in groups A, B, and placebo, respectively, but were not associated with any adverse event. There was no effect on median time to transfusion independent platelet recovery (> or = 20 x 10(9)/L). The median time to neutrophil recovery (> or = 500/microL) and red blood cell transfusion requirements were similar in all groups, and there was no apparent stimulation of leukemia. PEG-rHuMGDF was biologically active and well tolerated. Further investigation of dose and scheduling is required, specifically earlier dosing before and during chemotherapy.     

Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.     

早期接种减毒活菌卡介苗对支气管哮喘小鼠气道炎症及黏液形成的预防作用

目的　探讨早期小剂量多次接种减毒活菌卡介苗 (BCG)对支气管哮喘 (简称哮喘 )小鼠气道炎症及黏液形成的影响。方法　选择出生 2 4h内C5 7BL/6幼鼠 2 5只 ,按随机数字表法分为 3组 ,生理盐水对照组 (A组 ,8只 ) ;鸡卵白蛋白 (OVA)致敏 /激发组 (B组 ,9只 ) ;BCG皮下接种组 (C组 ,8只 )。C组小鼠分别于第 0周、1周、2周、3周连续 4次皮下接种 2 5 μl的BCG(含 10 3 CFU/只 ) ,而A、B组小鼠皮下注射 2 5 μl的生理盐水进行对照 ;于第 4 2天和第 5 6天 ,A组以生理盐水致敏 ,B、C组以OVA致敏 ,而从第 6 6天开始雾化吸入生理盐水 (A组 )或 1%的OVA(B、C组 )进行激发 ,连续 3d ,于最后 1次激发后 4 8h收集支气管肺泡灌洗液 (BALF) ,计数白细胞总数及嗜酸粒细胞 (EOS)数 ;肺组织过碘酸 雪呋 (PAS)染色鉴定黏液形成 ,测定杯状细胞化生指数和上皮黏液储备指数 ,以及用逆转录 聚合酶链反应 (RT PCR)方法检测肺组织黏液素基因MUC5ACmRNA的表达。结果　BALF中白细胞总数A组为 (15 0± 1 4 )× 10 4/ml ,B组为 (12 3 8± 14 5 )× 10 4/ml,C组为 (77 4±14 1)× 10 4/ml,B、C组分别与A组比较差异有统计学意义 (P均 <0 0 1) ;但B组与C组比较差异无统计学意义 (P >0 0 5 ) ;EOS计数A组为 (0 0 90± 0 0 2 0 )×     

The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.