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Samuel J Machin

Publications and source records attributed to Samuel J Machin.

25 records · Page 2Linked to original sources
PubMed2003

Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura.

Venous thromboembolism (VTE) is not a feature of thrombotic thrombocytopenic purpura (TTP), but there has been a recent report of VTE in association with plasma exchange (PEX) treatment for TTP using the solvent detergent (SD) plasma, PLAS+SD. We reviewed the occurrence of VTE in 68 consecutive patients with TTP (25 men, 43 women). Eight documented VTE events [six deep venous thromboses (DVTs), three pulmonary emboli] were identified in seven patients (all female) during PEX therapy. All six DVTs were associated with central lines at the site of thrombosis. Other known precipitating factors included pregnancy, immobility, obesity and factor V Leiden heterozygosity. VTE occurred at a mean of 53 d following the first PEX. The European SD plasma, Octaplas was the last plasma to be used in PEX prior to the VTE in 7/8 events. This is the first report of VTE following Octaplas infusion. VTE is a multifactorial disease and, although several known precipitating factors were present in all patients in this study, the use of large volumes of SD plasma in PEX may be an additional risk factor. We recommend prevention of VTE with graduated elastic compression stockings (class I) at diagnosis and prophylactic low-molecular-weight heparin once the platelet count rises above 50 x 10(9)/l.

Adult↗
PubMed2003

Activation of platelets in whole blood by recombinant factor VIIa by a thrombin-dependent mechanism.

Using a diluted whole blood method of flow cytometric analysis, we have shown that platelets could be activated in vitro in the presence of high concentrations (100 nmol/l) of recombinant factor (F) VIIa (rFVIIa; NovoSeven(R)) and 2.5 mmol/l calcium chloride. This was demonstrated by a significant increase in the mean percentage of platelets expressing CD62P and their mean fluorescent intensity (MFI) after 30 min versus platelets incubated with calcium or rFVIIa alone or diluted blood alone. The presence of rFVIIa and calcium increased the exposure of the PAC-1 activation epitope of glycoprotein (Gp) IIb/IIIa. This effect was equally influenced by the presence of calcium alone but not by rFVIIa. The effect of rFVIIa was time and concentration dependent. Thrombin generation was also necessary, as the effect of rFVIIa was completely abrogated by the additional presence of hirudin. Furthermore, soy bean trypsin inhibitor (SBTI) but not corn trypsin inhibitor (CTI) abrogated CD62P exposure, suggesting that thrombin was derived via FX but not FXII activation. Exposure of CD62P demonstrated a significant lag phase, sometimes of the order of > 30 min, as well as large intersubject variation. Significant platelet activation was observed at a concentration as low as 25 nmol/l rFVIIa. Platelet-leucocyte aggregation was also increased in the presence of 25 nmol/l rFVIIa and calcium. No significant difference was observed between levels of CD62P in diluted whole blood and platelet-rich plasma adjusted to an identical platelet count after their exposure to rFVIIa and calcium for 30 min.

Blood Platelets↗
PubMed2003

An update on the pathogenesis and management of acquired thrombotic thrombocytopenic purpura.

PURPOSE OF REVIEW: Thrombotic thrombocytopenic purpura, a clinical syndrome characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange therapy in the 1970s. Current outcomes have improved dramatically with the initiation of prompt plasma exchange, a treatment routinely used without any real understanding of why it is effective. RECENT FINDINGS: Recent advances suggest that a deficiency of a specific plasma metalloprotease, responsible for the physiological processing of von Willebrand factor multimers, plays a substantial role in the pathogenesis of congenital and acquired idiopathic thrombotic thrombocytopenic purpura. The von Willebrand factor-cleaving protease has now been identified as a new member of the ADAMTS family of metalloproteases, designated ADAMTS13. The acquired form of thrombotic thrombocytopenic purpura is associated with inhibitory autoantibodies against ADAMTS13, and the congenital chronic relapsing form is caused by mutations in the ADAMTS13 gene, resulting in a constitutional deficiency. Plasma exchange has been proved to be the most important therapy in thrombotic thrombocytopenic purpura, but clinical data for adjunctive therapies, such as corticosteroids, antiplatelet drugs and other immunosuppressive agents often used in combination with plasma exchange, are less well defined. SUMMARY: Recent advances in our understanding of the pathological mechanisms of thrombotic thrombocytopenic purpura not only provide a rationale for the previously empirical plasma exchange therapy (removal of the inhibitory antibodies and replacement of the deficient protease from the plasma infused), but may also help in developing more rational and targeted treatment strategies. This review discusses the clinical presentation, pathophysiology and current management of thrombotic thrombocytopenic purpura.

Humans↗
PubMed2003

Evaluation of immature granulocyte counts by the XE-IG master: upgraded software for the XE-2100 automated hematology analyzer.

We evaluated an automated immature granulocyte (IG) count in the peripheral blood with the XE-IG Master (Sysmex Corporation). The XE-IG Master is the upgraded software package for the XE-2100 automated hematology analyzer. Reproducibility tests demonstrated a mean coefficient of variation of 7.02% for the IG percentage (IG%) and 6.93% for the absolute IG count. Correlations of the IG counts were assessed in two ways. A flow cytometric IG count using CD11b, CD16, and CD45 monoclonal antibodies and a manual differential count were used as reference methods. The regression equation and the correlation coefficient of the IG% for the flow cytometric reference count versus results with the XE-IG Master were: y = 0.91x + 0.10; r = 0.96. For the comparison with the manual differential count of promyelocytes, myelocytes, and metamyelocytes, the regression equation and correlation coefficient were: y = 0.81x + 1.27; r = 0.78. Samples were found to be stable up to 48 hours both at room temperature and when refrigerated. We investigated the clinical significance of the IG count as a new marker of acute inflammation. In this preliminary study, most samples with a high IG count had positive values for C-reactive protein and the erythrocyte sedimentation rate (positive sample rates were 84.0% and 95.0%, respectively) despite neutrophil counts within the normal range. Elevated IG counts correlated most closely with CD64 expression on polymorphonuclear cells and less so with the concentration of interleukin 6. Compared with other available inflammation markers, the IG count is rapidly generated with each full blood count at no extra cost and with no delay in sample analysis.

Acute Disease↗
PubMed2002

Successful treatment of congenital thrombotic thrombocytopenic purpura using the intermediate purity factor VIII concentrate BPL 8Y.

There is increasing evidence that congenital thrombotic thrombocytopenic purpura (TTP) is caused by an absolute deficiency of von Willebrand factor-cleaving protease. The recent identification of this protease and the development of assays for its detection have enabled its quantification in a number of plasma products, including some commercial intermediate-purity plasma-derived factor VIII preparations. We report the successful, weekly prophylactic use of a commercial intermediate-purity plasma-derived factor VIII concentrate in the treatment of a 14-year-old girl with severe congenital TTP who had previously required transfusions of fresh-frozen plasma every 2 weeks from the age of 4 months.

Adolescent↗
PubMed2002

Tissue factor pathway inhibitor antigen and activity in 96 patients receiving heparin for cardiopulmonary bypass.

OBJECTIVE: To identify patients with poor tissue factor pathway inhibitor (TFPI) response to heparin and observe any association with increased risk of excessive coagulation activation, morbidity, or mortality. DESIGN: Prospective, observational cohort study. SETTING: University hospital. PARTICIPANTS: Patients (n = 96) undergoing cardiopulmonary bypass for various types of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: TFPI antigen and activity were determined in patients before and after heparin administration, before cardiopulmonary bypass for cardiac surgery. The clinical progress of each patient was recorded. Median levels of TFPI activity were 0.98 U/mL (interquartile range, 0.83 to 1.14 U/mL) preheparin and 2.34 U/mL (2.18 to 2.54 U/mL) postheparin (p < 0.0001), representing a median 2.3-(2.1- to 2.8-) fold increase. Median TFPI antigen levels were 92.4 ng/mL (73.0 to 119.5 ng/mL) preheparin and 422.9 ng/mL (398.7 to 501.6 ng/mL) postheparin (p < 0.0001), representing a median 4.6-fold (3.6- to 6.2-fold) increase. Two patients had low (<300 ng/mL) postheparin levels of TFPI antigen that were not associated with low functional TFPI or adverse clinical outcome. Fourteen patients showed a low ratio of increased functional TFPI postheparin; all had a ratio of TFPI antigen increase of at least 3-fold. CONCLUSION: The TFPI response to heparin is heterogenous. Two nonresponders were identified, with low postheparin levels of TFPI antigen, who did not suffer adverse clinical outcomes.

Adolescent↗