Supportive transfusion therapy in cancer patients with acquired defects of hemostasis.

Bleeding occurs in approximately 10% of patients with cancer: supportive transfusion therapy with Platelets Concentrates (PC), Fresh Frozen Plasma (FFP) and plasma-derived or recombinant concentrates is often required for the cessation and prevention of the bleeding episodes. The most frequent causes of bleeding in cancer is thrombocytopenia followed by liver insufficiency with or without vitamin K deficiency, disseminated intravascular coagulation (DIC) and the inappropriate or excessive use of anticoagulants. Other acquired hemostatic defects such as acquired hemophilia (AHA) and acquired von Willebrand syndrome (AVWS) are rare but they can be life-threatening. Thrombocytopenia in cancer patients may be the consequence of marrow invasion, chemotherapy or platelet auto-antibodies; patients with severe hypoproliferative thrombocytopenia, must be treated with PC and carefully followed to assess refractoriness to PC. The management of the other acquired defects of hemostasis usually requires the use of FFP and specific plasma-derived or recombinant concentrates. PC, FFP and plasma-derived concentrates can induce complications and/or adverse events in cancer patients: these include mainly allergic (ALR) or anaphylactic reactions (ANR), Transfusion-Associated Graft-Versus-Host Disease (TA-GVHD), Trasfusion-transmitted bacteriemia (TTB), Transfusion-Related Acute Lung Injury (TRALI), Acute Hemolytic Transfusion Reactions (AHTR), Febrile Non Hemolytic Transfusion Reactions (FNHTR). Therefore, modifications such as leukocyte-reduction and irradiation of the blood components to be transfused in cancer patients are recommended to reduce the risk of these complications.

Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: results from a randomized controlled trial.

OBJECTIVE: Large acute ST-elevation myocardial infarction (STEMI) sometimes leaves extensive ischemic damage despite timely and successful primary angioplasty. This clinical picture of good recanalization with incomplete reperfusion represents a good model to assess the reparative potential of locally administered cell therapy. Thus, we conducted a randomized controlled trial aimed at evaluating the effect of intracoronary administration of CD133 stem cells on myocardial blood flow and function in this setting. METHODS: Fifteen patients with large anterior STEMI, myocardial blush grade 0-1 and more than 50% ST-elevation recovery after optimal coronary recanalization (TIMI 3 flow) with stenting were randomly assigned to receive CD133 cells from either bone marrow (group A) or peripheral blood (group B), or to stay on drug therapy alone (group C). The cells were intracoronary injected within 10-14 days of STEMI. Infarct-related myocardial blood flow (MBF) was evaluated by NH positron emission tomography 2-5 days before cell administration and after 1 year. RESULTS: MBF increased in the infarct area from 0.419 (0.390-0.623) to 0.544 (0.371-0.729) ml/min per g in group A, decreased from 0.547 (0.505-0.683) to 0.295 (0.237-0.472) ml/min per g in group B and only slightly changed from 0.554 (0.413-0.662) to 0.491 (0.453-0.717) ml/min per g in group C (A vs. C: P = 0.023; B vs. C: P = 0.066). Left ventricular volume tended to increase more in groups B and C than in group A, ejection fraction and wall motion score index remained stable in the three groups. CONCLUSION: These findings support the hypothesis that intracoronary administration of bone marrow-derived, but not peripheral blood-derived CD133 cells 10-14 days after STEMI may improve long-term perfusion.

A rapid assay for ristocetin cofactor activity using an automated coagulometer (ACL 9000).

We have set up a rapid assay for measuring the activity of the von Willebrand factor ristocetin cofactor (VWF : RCo) using an automated coagulometer (ACL 9000; Instrumentation Laboratory, Lexington, Massachusetts, USA) and commercially available lyophilized platelet reagents (Dade-Behring, Marburg, Germany). Since VWF : RCo tested with the coagulometer (ACL-VWF : RCo) did not require loading, calculation of von Willebrand factor (VWF) activity or pretreatment of samples (calibration standard and tested plasmas), we thought it might be useful for rapid, automatic screening of VWF activity. To assess the precision and the potency of this ACL-VWF : RCo, we tested the assay in this laboratory's internal normal and abnormal controls, in a group of 67 healthy individuals and in 28 patients with different types of von Willebrand disease (VWD). We compared the ACL-VWF : RCo findings with those of the standard agglutination test (Agg-VWF : RCo), normalizing both assays against VWF antigen (VWF : Ag) measured by 'automatic' and standard enzyme-linked immunosorbent assay 'in-house' methods, to calculate the VWF : RCo/VWF Ag ratios. The within-assay and between-assay repeatability of the automatic ACL-VWF : RCo gave coefficients of variation < 5%, and reproducibility in normal and abnormal laboratory controls gave coefficients of variation of 7.9 and 9.3%, respectively. In VWD patients the results were equivalent to those of the standard Agg-VWF : RCo assay but, because of the good sensitivity, the ACL-VWF : RCo was more accurate in evaluating the VWF : RCo and establishing the VWF : RCo/VWF : Ag ratios in VWD patients with low VWF levels. Moreover, this ACL-VWF : RCo is faster than Agg-VWF : RCo, providing results of calibration curves and of 10 patient samples within 15 min. We can conclude that this automatic ACL-VWF : RCo gives a reliable and useful measure of VWF activity and can be proposed as a screening test for rapid diagnosis of VWD even in patients with low VWF levels in plasma.