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PubMed1997

Radioreceptor assay for sirolimus in patients with decreased platelet counts.

OBJECTIVE: Sirolimus (RAPA) is a new immunosuppressive drug currently in Phase III clinical trials in combination with cyclosporine A (CsA). The toxicity profiles for CsA and RAPA are only partially overlapping, with RAPA toxicity consisting primarily of hyperlipidemia and myelodepression but without the nephrotoxicity, neurotoxicity, and hepatotoxicity, which are seen with CsA. Patients in the clinical trial are being monitored using HPLC or LC/MS/MS assays; there is no immunoassay for RAPA reported to date. We have previously reported a radioreceptor assay (RRA) for RAPA, which has an excellent correlation with the HPLC assay (r = 0.997). The RRA has several advantages including excellent precision, sensitivity, rapid turnaround time, and a one-step extraction procedure. We report the evaluation of blood samples from patients who were exhibiting RAPA toxicity and comparison of the RRA results with the HPLC results. METHODS: EDTA whole blood specimens (n = 42) were obtained from six renal transplant recipients taking RAPA and CsA and exhibiting decreased platelet counts. Thirty-two samples from patients without decreased platelet counts were also received. The samples were analyzed with the RRA and the results were compared to those obtained with the HPLC assay. RESULTS: By HPLC, the results ranged from 3.2-72.6 micrograms/L RAPA with 43% of the results > or = 30 micrograms/L. With the RRA, the range was 7.7-83.0 micrograms/L RAPA equivalents, with 60% of the results > or = 30 micrograms/L. The RRA results are distinctly higher than the HPLC results all along the range. The correlation between the two assays was 0.861, with a slope of 0.966 and a Y-intercept of 11.1. CONCLUSION: Since the RRA is consistently higher than HPLC concentration in patients with decreased platelet counts, but correlates well in patients with no signs of toxicity, the RRA may be useful for monitoring patients for toxicity, by giving a better indication of increasing degree of immunosuppression than the HPLC assay.

Chromatography, High Pressure Liquid↗

PubMed2001

Outcome measures and treatment endpoints other than platelet count in childhood idiopathic thrombocytopenic purpura.

Therapy for children with acute idiopathic thrombocytopenic purpura (ITP) has been controversial, in great part because it is not evidence based. Some physicians are activists, treaters, or interventionists with regard to therapy of ITP whereas others have been described as nontreaters or noninterventionists. Platelet count (which is often extremely low in ITP) has generally been employed as a surrogate measure of hemorrhagic risk even though life-threatening or fatal bleeding is rare. Virtually all of the randomized clinical trials conducted in childhood ITP have focused on platelet counts as the sole outcome measure. However, other determinants should influence clinical decision making, including assessment of bleeding tendency. Laboratory testing has not been helpful in this regard, but clinical assessment by means of semiquantitative bleeding scores may prove more useful than simply designating a patient as having a "dry" or "wet" purpura. The side effects as well as costs (direct and indirect) of therapy must also be considered when attempting to weigh the merits of drug therapy against their risks. Finally, the effect of ITP and its treatment on health-related quality of life should be determined. Measurement tools to assess each of these alternative outcome measures are in early stages of development. Employing them in addition to platelet counts in future clinical trials will allow treatment to be based more on scientific data than treatment philosophy.

Adolescent↗

PubMed1977

Assay of ristocetin co-factor using fixed platelets and a platelet counting technique.

A new assay of ristocetin co-factor has been developed which is based on platelet counting using a Coulter Counter. A modified method of washing and fixing platelets has also been devised to provide a suitable platelet preparation which can be used in this assay. These fixed platelets have consistently proved to be satisfactory and have given high levels of maximum percentage aggregation. They have been stored for periods up to 6 months without significant deterioration. The method of platelet counting is simple in operation and sensitive to relatively low levels of platelet aggregation. It is precise and seems to offer distinct advantages over existing methods.

Blood Cell Count↗

PubMed2004

Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies.

Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet antibodies. Many of the current immunomodulatory therapies act by reducing platelet destruction and usually do not have a lasting effect. This prospective, exploratory study characterized patients with ITP by identifying their demographic and comorbid clinical factors, use of treatments, serologic markers of autoimmunity, and possible relationships between platelet counts, concentrations of endogenous thrombopoietin (eTPO), and the presence of circulating anti-TPO antibodies. Data including medical history and laboratory evaluations were collected at a single patient visit on 205 patients (19 children, 186 adults). Reported histories revealed a 5% rate of thrombotic/ischemic events. Autoimmune markers including direct antiglobulin test and antinuclear antibodies were found more frequently than in the normal population; antiplatelet antibody testing was not done. eTPO concentrations were comparable to concentrations found in healthy volunteers. Our study confirmed that no significant inverse correlation occurred between circulating concentrations of eTPO and platelet counts in patients with ITP (Spearman r = -0.15). Two of the 205 patients tested (1%) had neutralizing activity of recombinant human TPO in a biological assay; however, this activity was confirmed to be anti-TPO antibody in only 1 patient.

Abortion, Spontaneous↗

PubMed1994

Increases in leucocyte and platelet counts induced by the alkyl phospholipid hexadecylphosphocholine.

Hexadecylphosphocholine (HePC) is a new alkyl phospholipid that has been shown to have antitumour activity in vitro and in vivo. In vivo studies have shown absence of bone marrow toxicity at therapeutic doses. In addition, at the highest dosage group in rats, an increase in white blood cell counts (WBC) was observed. To study the presence of a similar phenomenon in man, frequent measurements of haematological parameters were performed in a series of phase II studies. 70 patients were treated with daily doses of 100-200 mg of the oral formulation of HePC. WBC and platelet counts were performed weekly. In a subgroup of 23 patients serum levels of haemopoietic growth factors were measured before and during treatment. A significant increase in WBC and platelet counts was seen in 74 and 73% of the patients, respectively. In 4 patients, bone marrow showed normal cellularity, and in 1 patient, bone marrow culture showed normal numbers and sizes of colony forming units. No abnormal levels or trends over time of cytokines were observed. We conclude that oral HePC induces an increase in WBC and platelet counts in the majority of those treated.

Administration, Oral↗

PubMed1980

Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura.

The optimal method of infant delivery for gravida women with immunologic thrombocytopenic purpura (ITP) is controversial because of the unpredictability of the fetus developing thrombocytopenia and the uncertainty of the relation between vaginal birth and intracranial hemorrhage in thrombocytopenic infants. We have employed the technique of platelet counts on fetal scalp blood obtained prior to or early in the course of labor in 12 patients with ITP. A count of 50,000/cu mm, selected on the basis of literature review and retrospective analysis of our own experience, was used to define fetal thrombocytopenia. Three thrombocytopenic fetuses were delivered by cesarean section. Trial labor was permitted in the other nine cases in which fetal scalp platelet count exceeded 50,000/cu mm. The outcome was good in all instances. If cesarean section is to be employed in ITP patients to obviate the potential danger of fetal hemorrhage with vaginal delivery, the use of platelet counts of fetal scalp blood seems to provide the most rational basis for management at present.

Blood Platelets↗

PubMed1984

Clinical significance of beta-thromboglobulin in patients with high platelet count.

The aim of the study was to investigate the relevance of beta-thromboglobulin (beta tg) measurement in patients with thrombocytosis. We have, therefore, studied the level of plasma and platelet beta tg in 74 patients with high platelet count in addition to the evaluation of platelet aggregation and platelet serotonin (5-HT) content. The determinations of platelet serotonin content and aggregation are confirmed to be useful in the differentiation between primary and secondary forms of thrombocytosis. The mean plasma level of beta tg in patients with myeloproliferative disease was significantly raised, but the amount observed in subjects with secondary thrombocytosis is increased too. Considering the amount of beta tg in relation to whole blood platelet count (beta tg ratio), no difference was observed between all patients and controls. The beta tg ratio allowed the identification of a group of patients with an increased ratio and a decreased beta tg platelet content who showed the highest occurrence of thrombosis (66%).

Adult↗

PubMed2003

Platelet count is independently associated with insulin resistance in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the relationship between platelet count and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 163 non-obese Japanese type 2 diabetic patients (112 men and 51 women, aged 36 to 84 years, body mass index [BMI] 16.2 to 26.9 kg/m(2)) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose and serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), and hematological parameters (platelets, white blood cell count, red blood cell count, hematocrit, hemoglobin) were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that HOMA-IR was positively correlated to BMI (r = 0.465, P <.0001), HbA(1c) (r = 0.423, P <.0001), platelet count (r = 0.310, P <.0001), triglycerides (r = 0.277, P <.0005), white blood cell count (r =.222, P =.005), red blood cell count (r = 0.210, P =.008), hematocrit (r = 0.156, P =.047), total cholesterol (r = 0.178, P =.023), and systolic (r = 0.216, P =.011) and diastolic (r = 0.263, P =.002) blood pressure, and inversely correlated to HDL cholesterol (r = -0.312, P <.0001) level in our diabetic patients. Multiple regression analysis showed that HOMA-IR was independently predicted by BMI (P <.0001, F = 22.45), HbA(1c) (P <.0001, F = 16.15), platelet count (P <.0001, F = 10.75), and serum triglycerides (P <.0001, F = 10.47) levels, which explained 34% of the variability of HOMA-IR in non-obese Japanese type 2 diabetic patients. These results indicate that not only BMI, HbA(1c), and triglycerides levels but also platelet counts are independent predictor of insulin resistance in non-obese Japanese type 2 diabetic patients.

Adult↗

PubMed1997

Severe thrombocytopenia after cytomegalovirus infection in an immunocompetent host--correlation between CMV infection and platelet count in immunocompetent host.

We report a case of severe thrombocytopenia after cytomegalovirus mononucleosis and the changes of the platelet count in 13 cases (including documented case) with CMV mononucleosis (4 cases) or Epstein-Barr virus mononucleosis (9 cases), who were admitted to our hospital from 1991 to 1995. A decrease of the platelet count was observed in some patients at diagnosis compared to the following days, suggesting that thrombocytopenia may be induced by CMV as well as EBV, and mild thrombocytopenia may be more frequent than expected after CMV infection in immunocompetent adults, although severe thrombocytopenia is rare.

Adult↗

PubMed1993

Hemogram in normal newborn babies with special reference to platelet count.

A prospective study was performed to verify the hemogram of 318 healthy fullterm newborn babies aged one hour to thirty days. The mean hemoglobin, hematocrit and reticulocyte count were between 17.6-17.9 g/dl, 52.2-53.4% and 5.7-6.7% in the first 72 hours of life. After that, they were decreased gradually approaching adult level at the later half of one month old. The white blood count at 12 to 24 hours was 18,482 +/- 6,600/microliters, gradually decreased to 9,817 +/- 2,496/microliters during 14 to 30 days. The ratio of immature to total neutrophils between 1-12 hours was 0.07 and 12 hour to 30 day was 0.04-0.05. The mean platelet counts in the first 72 hours was between (280 +/- 69) x 10(3)-(285 +/- 93) x 10(3)/microliters, it increased thereafter until 30 days old with a peak of 402 x 10(3)/microliters during 7-14 days. The platelet counts below 150 x 10(3)/microliters in the newborn period should be considered as thrombocytopenia.

Age Factors↗

PubMed1979

Platelet counting with a laser nephelometer.

A method for platelet counting is described, based on the Laser nephelometric principle. Experimental results are reported, together with the practical considerations for the standardisation and correlation of the method, and for application of the method in the routine biochemical laboratory. Venous blood, taken with EDTA-NaCL solution according to Schulz et al (1071, Z. Klin. Chem. Klin. Biochem. 9, 329-333) is used. The blood is centrifuged at 100 g for 10 min and 10 microliter of the supernatant is added to 3000 microliter of a suspending medium (dilution 1:80); 300 microliter platelet suspension are read in a nephelometer cuvet or tube against blank. The number of platelets per liter blood are determined with the aid of a standard curve. The sensitivity and reproducibility of the method, and the correlation with the "electronic coulter counting" method are satisfactory.

Humans↗

PubMed2005

The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography.

Clot retraction and fibrinolysis may present as a decrease in amplitude on thrombelastography (TEG). The former represents normal or hyperactive platelet function, and the latter represents a fibrinolytic state. It is important to distinguish clot retraction from fibrinolysis because the treatment of each condition is different. To distinguish between these phenomena, we performed TEG with platelet-poor plasma (PPP) and platelet-rich plasma (PRP) with an increasing platelet count (range, 50-1200 x 10(9)/L) with or without abciximab. Maximum amplitude (MA) and the percentage decrease of amplitude at 30 and 60 min after MA were examined for each sample. Blood samples to which tissue plasminogen activator (tPA) was added served as positive controls for fibrinolysis. Morphological changes of clots and D-dimer levels were also examined. With higher platelet counts, the percentage decrease of amplitude after MA increased significantly at 30 and 60 min, but not in the abciximab samples. Morphological changes of clots have shown clot retraction in PRP, but not in PPP or PRP pretreated with abciximab. D-dimer levels increased only in samples to which tPA was added, but not in native PPP or PRP samples. In conclusion, we have shown that the decrease in amplitude at 30 and 60 min can be due to platelet-mediated clot retraction and can be attenuated by sample pretreatment with abciximab, which interrupts platelet-fibrin(ogen) binding.

Abciximab↗

PubMed1985

The HELLP (haemolysis, elevated liver enzymes, low platelet count) syndrome in severe hypertensive crises of pregnancy--does it exist?

The HELLP syndrome, comprising haemolysis, elevated liver enzyme values and a low platelet count, was studied in 26 women with hypertensive crises of pregnancy and in matched controls. Platelet counts and bilirubin, lactate dehydrogenase, aspartate transaminase and haematocrit levels together with peripheral blood smears were studied on the day of admission and on the 7th day after delivery. Only 1 woman with pre-eclampsia was found to have had the HELLP syndrome; the case report is presented and the laboratory investigations are discussed.

Adolescent↗

PubMedDate not supplied

Hydroxyurea-associated platelet count oscillations in polycythemia vera: a report of four new cases and a review.

Cyclic oscillations in the peripheral blood platelet count were recently described in two patients with polycythemia vera (PV) receiving therapy with hydroxyurea (HU). This phenomenon can make proper HU dosing very challenging and may be especially problematic in PV patients who are at risk for thrombohemorrhagic complications. In this report, we describe four new cases of HU-associated platelet oscillations in patients with PV and extend our observations on one of the two previously reported cases. We also review cyclic thrombocytosis within the broader context of periodic hematopoiesis. A thrombopoietin-mediated negative feedback loop is central to most models of periodic thrombopoiesis, but this is probably an oversimplification. It is possible that HU destabilizes the delicate balance of thrombopoietin/c-Mpl signaling in megakaryocytic lineage hematopoiesis that is already markedly altered in PV; this hypothesis remains speculative. For patients who develop oscillatory variation in their platelet counts associated with HU use, keeping the HU dose constant may result in damping or termination of the cycles. However, this strategy is not always successful.

Adult↗

PubMed1977

Depression of the platelet count after inoculation of mice with L1210 or L5178Y cells.

The inoculation of L1210 or L5178Y leukaemia cells decreased the platelet count of the recipient mouse before extensive infiltration of marrow was expected by either tumour line. The decrease was more pronounced after intravenous inoculation of L1210 leukaemia than after intraperitoneal inoculation. Inoculation of L5178Y cells by both routes caused an initial decrease but the count recovered to 80% of normal before becoming markedly depressed prior to death of the host. Implantation of diffusion chambers containing L1210 cells also decreased the platelet count, which later returned to normal.

Animals↗

PubMed2004

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

Adult↗

PubMed1988

Evaluation of bone marrow megakaryocyte ploidy distributions in persons with normal and abnormal platelet counts.

Using bone marrow smears of the type prepared routinely in clinical practice, we determined megakaryocyte ploidy distributions in five normal persons, eight patients with both normal platelet counts and normal bone marrow morphology, and 18 patients with quantitative platelet disorders. To include 2N and 4N megakaryocytes in the ploidy distribution histograms, all megakaryocytes were identified by serial immunologic labelling with rabbit antiserum to human platelet glycoproteins and rhodamine-conjugated goat anti-rabbit igG. Cell nuclei were concurrently Feulgen stained with bis-aminophenyl-oxdiazole, and the nuclear fluorescent signals were quantified photometrically. A modal megakaryocyte ploidy value of 32N was seen in 10 of the 13 persons with normal platelet counts, and geometric mean megakaryocyte ploidy values averaged 24.9N +/- 7.0N (arithmetic mean +/- SD). In these normal control individuals, 2N and 4N megakaryocytes accounted for 11.1% of all megakaryocytes, and 2.6% of the megakaryocytes were 128N. Shifts to a higher mean ploidy were observed in five of seven patients with idiopathic thrombocytopenic purpura, resulting from increased percentages of 64N and 128N megakaryocytes at the expense of 4N, 8N, and 16N cells. Shifts to lower ploidy were demonstrated in two patients with acute myelogenous leukemia and one patient each with thrombotic thrombocytopenic purpura and isoimmune thrombocytopenia. Four of five patients with essential thrombocythemia had strikingly abnormal megakaryocyte ploidy histograms characterized by the presence of unusually high ploidy 256N and 512N megakaryocytes. These 256N and 512N cells were virtually unique to the patients with essential thrombocythemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗

PubMedDate not supplied

[Analysis of Bcr-abl type transcript and its relationship with platelet count in Mexican patients with chronic myeloid leukemia].

PROBLEM: It has been suggested that type of chimeric mRNA is associated with differences in the clinical and hematologic characteristics of chronic myeloid leukemia (CML). However, prognostic value of type of chimeric mRNA bcr-xabl (b3a2 or b2a2) is still controversial. METHODS: We analyzed 97 cases of Philadelphia-positive CML to determine mRNA type by reverse-polymerase chain reaction (RT-PCR) and its relationship with clinical features. RESULTS: We detected b3a2 bcr-abl transcripts in 27 (28%) cases, b2a2 in 57 (59%) cases, and 13 (13%) with both mRNA transcripts b3a2/b2a2. These frequencies were the total reverse of other reports. Age, sex, hemoglobin, and white-cell counts showed no significant difference for those with either b3a2 or b2a2 bcr-abl transcripts. However, platelet counts of b3a2 patients were significantly higher than those of b2a2 patients (743.3 vs 477.3 x 109/L; p = 0.01). In addition, in the subgroup of patients whose white-cell count at diagnosis was < 100 x 10(9)/L, those with b3a2 transcript had a significantly higher platelet count (679.1 vs. 352.2 x 10(9)/L; p = 0.001). CONCLUSIONS: We observed reversed frequency of bcr-abl transcripts in this population, but agreement with other Latin-American reports. In addition, our data suggested that there is different CML biological behavior in our population and that there is a subpopulation of CML patients in whom b3a2 is associated witH higher thrombopoietic activity.

Adolescent↗