A Novel Approach to the Assessment of Variations in the Human Platelet Count

2000 ◽  
Vol 83 (03) ◽  
pp. 480-484 ◽  
Author(s):  
John James ◽  
Dianne Brown ◽  
Gordon Whyte ◽  
Mark Dean ◽  
Colin Chesterman ◽  
...  
Keyword(s):  
Platelet Count ◽  
Seasonal Variation ◽  
Individual Variation ◽  
Human Platelet ◽  
First Report ◽  
Platelet Counts ◽  
Novel Approach ◽  
Platelet Number ◽  
Genetically Determined

SummaryThis is the first report of a method to assess the significance of numerical changes in the platelet count based upon a result exceeding the normal intra-individual variation in platelet numbers. Serial platelet counts from 3,789 subjects were analysed to determine the intra-individual variation in platelet numbers. A platelet count difference of 98 × 109/L in males was found to represent a change that would occur by chance in less than 1 in 1,000 platelet count determinations. Tables to determine the significance of platelet number variations, given N previous observations, are provided at two probability levels. The repeatability of the platelet count was calculated as 0.871 (males) and 0.849 (females) indicating that the heritability of platelet count is high and that the platelet count is predominantly genetically determined. A seasonal variation in platelet count was found with a ‘winter’ versus ‘summer’ difference of 5.10 × 109/L (males) and 5.82 × 109/L (females).

Activation of Human Platelets by Endotoxin

1975 ◽  
Author(s):  
John Das ◽  
Dianna Ausprunk ◽  
Judah Folkman
Keyword(s):  
Platelet Count ◽  
Human Platelet ◽  
Human Platelets ◽  
Gram Negative ◽  
Platelet Counts ◽  
Membrane Changes ◽  
The One ◽  
Limulus Test

Endotoxin-like activity (ELA) can be detected in platelets in human Gram-negative sepsis1. With our photometric version of the Limulus test, we quantified the ELA of platelets in 12 children with gastroenteritis of Gram-negative origin. 5 severe cases had thrombocytopenia (41 × 103/μl), and an ELA-equivalent of 10.4 ± 6.9 ng in platelets from 1 ml PRP; 4 died of DIC. 7 patients wore moderately ill, with platelets 138 × 103/μl, and an ELA of 5.3 ± 3.9 ng. In fi controls with a background platelet-ELA of 1.9 ng, incubation with endotoxin (50 ng/ml PRP) raised the ELA by 3 ng. In the one infant surviving severe enteritis, a similar incubation raised the platelet-ELA by 16 ng, the platelet count being 26 × 103/μl. In DIC, we routinely find platelet-ELA at 20 ng and platelet counts of 25 χ 103/μl. In in-vitro EM studies, endotoxin complexed with Cu2+ adhered to human platelet surfaces; pseudopods and degranulation were also seen along with fragmentation of endotoxin particles. The membrane changes suggested peroxidation.We postulate that endotoxin adheres to an activates human platelets to release materials with procoagulant properties in the Limulus test, and capable of precipitating DIC. As sensitized platelets are phagocytized by the RES, platelets may prove to be a system for clearing circulating endotoxin. 1 Das, Schwartz and Folkman: Surgery 74, 235, 1973.

Immune-dependent thrombocytopaenia in mice infected with Schistosoma mansoni

Parasitology ◽  
2003 ◽  
Vol 126 (3) ◽  
pp. 225-229 ◽  
Author(s):  
R. G. STANLEY ◽  
J. R. NGAIZA ◽  
E. ATIENO ◽  
G. JELL ◽  
K. FRANCKLOW ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Response ◽  
Schistosoma Mansoni ◽  
Adult Worm ◽  
Human Platelet ◽  
Human Origin ◽  
Igg Antibodies ◽  
Platelet Counts ◽  
Platelet Number ◽  
Egg Stages

As has been shown previously, immunologically intact mice with patent Schistosoma mansoni infections has a significantly lower mean platelet number than intact uninfected mice (P<0·0001). However, platelet numbers in T-cell deprived mice with patent infections were not significantly different from those in uninfected T-cell deprived mice. Also, platelet counts in both the infected and uninfected T-cell deprived groups were not significantly different from those in intact uninfected mice. The S. mansoni-induced thrombocytopaenia in mice is thus seemingly immune dependent. Immunologically intact mice with chronic 12-week-old S. mansoni infections has IgG antibodies that were reactive in an ELISA-type assay wit whole fixed platelets of both mouse and human origin. In Western immunoblots the IgG antibodies from chronically-infected mice reacted in particular against mouse and human platelet antigens of 90, 37 and 30 kDa. Antisera raised from 2 rabbits, immunized respectively with mouse and human platelet antigens, cross-reacted with antigens of the larval, adult worm and egg stages of S. mansoni. These results support the hypothesis that an anti-platelet antibody response may be the cause of the thrombocytopaenia observed in mice with patent schistosome infections.

Platelet Number and Function in Diamond-Blackfan Anemia

PEDIATRICS ◽  
1981 ◽  
Vol 68 (2) ◽  
pp. 238-241
Author(s):  
George R. Buchanan ◽  
Blanche P. Alter ◽  
Christine A. Holtkamp ◽  
Elaine G. Walsh
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Signs And Symptoms ◽  
Red Cell ◽  
Normal Range ◽  
Platelet Counts ◽  
Diamond Blackfan Anemia ◽  
Platelet Number ◽  
And Function

Congenital red cell aplasia (Diamond-Blackfan anemia) is occasionally associated with hematologic defects other than a deficiency of red blood cell progenitors, but such alterations have not been well studied. The frequency and magnitude of abnormalities in platelet count and platelet function were therefore examined in 38 patients. Thrombocytosis was seen in 21 patients, and 12 had mild thrombocytopenia on at least one occasion. Elevated platelet counts were demonstrated repeatedly in nine children. The three patients with the lowest platelet counts also had leukopenia. Platelet aggregation was normal in all 16 patients in whom it was studied, and bleeding times were within the normal range in 14 of them. Bleeding signs and symptoms were not observed. It is concluded that thrombocytosis or thrombocytopenia often occurs but that platelet function is normal in patients with Diamond-Blackfan anemia.

Platelet Factor 4 Levels Inversely Correlate with Platelet Transfusion Needs In Pediatric Patients Treated for Standard Risk Acute Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 725-725
Author(s):  
Michele Lambert ◽  
Alisa Reznikov ◽  
Yvonne Nguyen ◽  
Lubica Rauova ◽  
Mortimer Poncz
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Platelet Transfusion ◽  
Pediatric Patients ◽  
Human Platelet ◽  
Lymphoblastic Leukemia ◽  
Platelet Factor ◽  
Platelet Counts ◽  
Standard Risk ◽  
Count Recovery

Abstract Abstract 725 Platelet factor 4 (PF4) is a chemokine found almost exclusively in megakaryocytes and platelets. PF4 has been previously shown to be a negative paracrine inhibiting megakaryopoiesis in vitro in humans and mice. We confirmed this finding and also found an inverse correlation between PF4 and steady-state platelet counts in mice. In both chemotherapy- and radiation-induced thrombocytopenia, platelet PF4 levels inversely correlated with platelet count recovery after bone marrow injury, and blocking this effect ameliorated the thrombocytopenia. We now asked whether platelet PF4 levels are of clinical relevance on human platelet biology in patients undergoing chemotherapy. We selected pediatric patients who had completed treatment for standard risk acute lymphoblastic leukemia at the Children's Hospital of Philadelphia, as this was a fairly large population that have reached remission after relatively uniform therapy. Enrolled patients had completed therapy since January 1999. Blood samples were obtained and medical records were retrospectively reviewed for platelet counts, platelet transfusion requirements and duration of therapy during delayed intensification (DI). DI was chosen for investigation as a preliminary study showed that 35% of our patients require platelet transfusion during DI and need for transfusion at that point in therapy is unlikely to be related to primary underlying bone marrow disease. To date, 68 subjects have been enrolled. Sixty-two subjects had evaluable PF4 levels. PF4 levels were independent of age and sex. Leukemia survivors did not have significantly different PF4 levels when compared to a pediatric control population. There was a direct relationship between measured total PF4 level and platelet count (Pearson r 0.36, p<0.006) although contrary to animal studies, there was no correlation between PF4 per platelet and platelet count. Transfusion data from the first 22 patients have been evaluated. Patients who did not require platelet transfusion during DI had markedly lower PF4 per platelet (6.35 ± 1.85 SE) when compared to patients who required transfusion (13.26 ± 1.89 SE, p<0.02). In addition, duration of therapy (for girls) was inversely correlated with PF4 per platelet (r 0.689, p=0.04), consistent with animal data in which platelet count recovery was inversely correlated with PF4 per platelet. These data suggest that PF4 may be an important in vivo regulator of human platelet counts in the setting of bone marrow injury. Further clinical studies will confirm these findings and begin to explore potential interventions to allow for intensified chemotherapy regimens in subjects at risk for more severe chemotherapy-induced thrombocytopenia based on their level of this negative paracrine of megakaryopoiesis. Disclosures: No relevant conflicts of interest to declare.

Use of the Megathrombocyte to Demonstrate Thrombopoietin

1972 ◽  
Vol 28 (01) ◽  
pp. 024-030
Author(s):  
Weiner Marc ◽  
Karpatkin Simon
Keyword(s):  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Large Platelet ◽  
Platelet Number ◽  
Lag Period ◽  
Platelet Antibody

SummaryQuantitation of megathrombocyte (large platelet) number was used as an assay for the detection of a humorally-transmitted thrombopoietic stimulus, thrombopoietin. Donor guinea pigs were depleted of circulating platelets by the injection of rabbit anti-guinea pig platelet antibody. Plasma from these donor guinea pigs, when injected into recipient guinea pigs raised their platelet count 1.5 fold and their megathrombocyte number 2.7 fold when compared to plasma injected from donor guinea pigs with normal platelet counts. A lag period of 4 to 5 days preceded the rise in platelet count and megathrombocyte number.

scholarly journals miR-125a-5p regulates megakaryocyte proplatelet formation via the actin-bundling protein L-plastin

Blood ◽  
2020 ◽  
Vol 136 (15) ◽  
pp. 1760-1772 ◽  
Author(s):  
Seema Bhatlekar ◽  
Bhanu K. Manne ◽  
Indranil Basak ◽  
Leonard C. Edelstein ◽  
Emilia Tugolukova ◽  
...  
Keyword(s):  
Platelet Count ◽  
Human Platelet ◽  
Interindividual Variation ◽  
Strong Correlations ◽  
Protein L ◽  
Platelet Counts ◽  
Genome Wide ◽  
Health And Disease

Abstract There is heritability to interindividual variation in platelet count, and better understanding of the regulating genetic factors may provide insights for thrombopoiesis. MicroRNAs (miRs) regulate gene expression in health and disease, and megakaryocytes (MKs) deficient in miRs have lower platelet counts, but information about the role of miRs in normal human MK and platelet production is limited. Using genome-wide miR profiling, we observed strong correlations among human bone marrow MKs, platelets, and differentiating cord blood–derived MK cultures, and identified MK miR-125a-5p as associated with human platelet number but not leukocyte or hemoglobin levels. Overexpression and knockdown studies showed that miR-125a-5p positively regulated human MK proplatelet (PP) formation in vitro. Inhibition of miR-125a-5p in vivo lowered murine platelet counts. Analyses of MK and platelet transcriptomes identified LCP1 as a miR-125a-5p target. LCP1 encodes the actin-bundling protein, L-plastin, not previously studied in MKs. We show that miR-125a-5p directly targets and reduces expression of MK L-plastin. Overexpression and knockdown studies show that L-plastin promotes MK progenitor migration, but negatively correlates with human platelet count and inhibits MK PP formation (PPF). This work provides the first evidence for the actin-bundling protein, L-plastin, as a regulator of human MK PPF via inhibition of the late-stage MK invagination system, podosome and PPF, and PP branching. We also provide resources of primary and differentiating MK transcriptomes and miRs associated with platelet counts. miR-125a-5p and L-plastin may be relevant targets for increasing in vitro platelet manufacturing and for managing quantitative platelet disorders.

The significant relationship between platelet count and haemorrhagic complications on ECMO

Perfusion ◽  
1994 ◽  
Vol 9 (4) ◽  
pp. 265-269 ◽  
Author(s):  
Anthony Stallion ◽  
Barry R Cofer ◽  
Janice A Rafferty ◽  
Moritz M Ziegler ◽  
Frederick C Ryckman
Keyword(s):  
Platelet Count ◽  
Bleeding Complication ◽  
Bleeding Complications ◽  
Platelet Counts ◽  
Significant Difference ◽  
Platelet Number ◽  
Perfusion Time ◽  
Group 2 ◽  
And Function ◽  
Group 1

Haemorrhagic complications, which occur in up to 35% of infants during extracorporeal membrane oxygenation (ECMO), often produce devastating sequelae. Although many complex factors interact to control haemostasis, platelet number and function has significant impact on the development of primary haemostasis. The optimum platelet count on ECMO, however, has not been defined. At our institution prior to August 1987, platelet counts were maintained at greater than 100 000/mm3. After August 1987, however, platelet counts of greater than 200 000/mm 3 were maintained. In a retrospective study, patients were randomly chosen from these two treatment periods: group 1 - March 1986 to July 1987; and group 2 - June 1988 to June 1989. The average platelet count, platelets administered, hours on ECMO, and bleeding complications were compared to each other and to the July 1992 ELSO Registry. There was a significant difference in average platelet counts between group 1 and group 2. However, the amount of platelets administered per kg per day was similar. There was a significant difference in overall bleeding complications between Group 2 (12%) and the ELSO Registry (35%) (p < 0.01). There was a trend towards decreased complications in all subgroups, although sample size precluded significance. We conclude that increasing platelet counts to greater than 200 000/mm3 decreases the overall bleeding complication rate. This advantage is achieved without a continuous need for increased platelet administration once the desired level is reached and without an increase in perfusion time, mechanical complications, or mortality.

Platelet Mobilization Induced by PAF and Its Role in the Thrombocytosis Triggered by Adrenaline in Rats

1989 ◽  
Vol 62 (04) ◽  
pp. 1107-1111 ◽  
Author(s):  
Hugo C Castro-Faria-Neto ◽  
Patricia T Bozza ◽  
Marco A Martins ◽  
Paulo M F L Dias ◽  
Patricia M R Silva ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Blood Samples ◽  
Platelet Counts ◽  
Platelet Number ◽  
Edta Solution ◽  
Web 2086 ◽  
Dependent Mechanism

SummaryThe injection of PAP (6 μg/kg, i. v.) induced, in rats, haemoconcentration accompanied by an increase in the platelet number, as attested by the counts of platelets in blood samples diluted in formalin-free EDTA solution. This increase was significant at 15 min, peaked from 1 to 4 h and returned to basal levels 24 h after the lipid administration. The release of platelets induced by PAP was inhibited dose-dependently by specific PAP receptor antagonists such as WEB 2086 (0.5-2 mg/kg), BN 52021 and 48740 RP (5-25 mg/kg). Furthermore, platelet mobilization was clearly impaired in splenectomized animals stimulated by PAP, whereas thrombocytopenia and haemoconcentration by the same stimulus were intact. It was also noted that a second injection of PAP, 24 h after the initial stimulation with the lipid, failed to induce an increase in platelet counts, indicating autodesensitization. Desensitization to PAP or pretreatment with PAP antagonists clearly prevented the increase in the platelet counts after stimulation by adrenaline (15 μg/kg). These findings suggest that, in rats, PAP can induce release of platelets by a spleen-dependent mechanism and that this lipid may be relevant to the thrombocytosis triggered by adrenaline.

The Influence of Serotonin on Clot Retraction and the Thrombelastogram

1958 ◽  
Vol 02 (01/02) ◽  
pp. 111-124 ◽  
Author(s):  
E Deutsch ◽  
K Martiny
Keyword(s):  
Human Plasma ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Specific Effect ◽  
High Dose ◽  
Clot Retraction ◽  
Platelet Counts ◽  
Essential Value ◽  
High Doses ◽  
Free Plasma

Summary1. Normal platelets are necessary for induction of normal clot retraction.2. Serotonin does not induce retraction in human platelet-free plasma-clots or enhance clot firmness as measured in the coagulogram.3. Serotonin does not improve clot retraction or firmness in plasma clots with sub-optimal platelet counts.4. Methylserotonin inhibits clot retraction of platelet-rich plasma to a certain extent in moderate doses, whereas, high doses are ineffective. BOL 148 has a similar, but less significant action. There is a possibility that these effects are specific antiserotonin-effects.5. LSD 25 was ineffective in all concentrations used.6. Largactil and reserpin inhibit retraction in high doses. There seems to be a non specific effect caused by the high dose.7. Reserpine does not release a retraction-inducing agent from the platelets, which could be detected in the centrifuged platelet-free plasma used for the incubation.8. Serotonin does not replace the retraction-cofactor of Hartert, or the dialyzable factor of Lüscher in synthetic clotting substrates.9. Serotonin is of no essential value in inducing normal retraction of human plasma clots.

scholarly journals Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Andrew B. Kelly ◽  
Ellen Cheung ◽  
Aaron Tomer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Neutrophil Count ◽  
Growth And Development ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Colony Stimulating Factor ◽  
Platelet Counts ◽  
Development Factor ◽  
Trough Serum ◽  
Stimulating Factor

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.

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