Clinical observations in thrombocytopenia:

We investigated clinical and laboratory aspects in three different situations of thrombocytopenia in which an immune mechanism is active, i.e. thrombocytopenia caused by autoantibodies (thrombocytopenia induced by the anticoagulant drug heparin (HITT) and immune thrombocytopenic purpura (ITP), thrombocytopenia and platelet alloimmunization and a platelet consumption type of thrombocytopenia (thrombotic thrombocytopenic purpura (TTP). First, we prospectively studied the incidence of HITT using new, will- defined criteria of a proportional fall in the platelet count in combination with the presence of HITT antibodies, in 358 patients with cardiac or neurological complaints. The observed incidence was 0.3%. Secondly, in an evaluation of the predictive value of HLA-antibody testing for the outcome of the first HLA-matched platelet transfusion in thrombocytopenic patients who were refractory to random donor platelet transfusions and who always had received non-leukodepleted blood products in case of transfusion, we found that almost 90% of the patients with a positive HLA test can be treated with HLA matched platelets. Third, in studying ITP patients we found a strong indication that intensive immunosuppressive treatment cannot prevent but only postpone splenectomy as the standard second-line therapy. In addition, the study of serum thrombopoietin levels and platelet kinetics, pointed to an impaired regulation of thrombo- and megakaryopoiesis in ITP. Finally, it was found that splenectomy could be effective in inducing durable remissions and in the prevention of relapse in patients with TTP

Trombotische trombocytopenische purpura in 13 Nederlandse centra: behandeling en beloop

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Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension

Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown. Methods: Consecutive SCD patients were screened for PHT (defined as a tricuspid regurgitant jet flow velocity ≥ 2.5 m/s) employing echocardiography and were evaluated for pulmonary artery obstruction with ventilation-perfusion (VQ) scintigraphy. Results: Fifty-three HbSS, 6 HbSβ0-thalassemia, 20 HbSC, and 6 HbSβ+-thalassemia patients were included. The overall prevalence of PHT was 41% in HbSS/HbSβ0-thalassemia patients and 13% in HbSC/HbSβ+-thalassemia patients. High-probability VQ defects (Prospective Investigation of Pulmonary Embolism Diagnosis criteria) were detected in two patients, one of whom had PHT. In HbSS/HbSβ0-thalassemia patients with PHT, 19 patients (86%), 2 patients (9%), and 1 patient (5%) had low-, intermediate-, or high-probability scan results as compared to 30 patients (97%), 1 patient (3%), and 0 patients (0%) in HbSS/HbSβ0-thalassemia patients without PHT (p = 0.31). In HbSC/HbSβ+-thalassemia patients with PHT, 3 patients (100%), 0 patients (0%), and 0 patients (0%) had low-, intermediate-, and a high-probability scan as compared to 19 patients (90%), 1 patient (5%), and 1 patient (5%) in HbSC/HbSβ+-thalassemia patients without PHT (p = 0.86). There were no statistical differences in irregular distribution of the radiopharmaceutical or nonspecific signs associated with PHT between patients with and without PHT. Conclusions: Although small pulmonary artery obstruction cannot be excluded, large to medium-sized pulmonary artery obstruction is an unlikely primary causative factor in SCD-related PHT

Splenectomy for the treatment of thrombotic thrombocytopenic purpura.

Contains fulltext : 47353.pdf (publisher's version ) (Closed access)Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial. We report on a series of 33 patients with TTP who were splenectomised because they were plasma refractory (n = 9) or for relapsed disease (n = 24). Splenectomy generated prompt and unmaintained remissions in all except five patients, in whom remission was delayed (n = 4) or who died with progressive disease (n = 1). Four postoperative complications occurred: one pulmonary embolism and three surgical complications. Median follow-up after splenectomy was 109 months (range 28-230 months). The overall postsplenectomy relapse rate was 0.09 relapses/patient-year and the 10-year relapse-free survival (RFS) was 70% (95% CI 50-83%). In the patients with relapsing TTP, relapse rate fell from 0.74 relapses/patient-year before splenectomy to 0.10 after splenectomy (P < 0.00001). Two patients died from first postsplenectomy relapse. Although these results are based on retrospective data and that the relapse rate may spontaneously decrease with time, we conclude that splenectomy, when performed during stable disease, has an acceptable safety profile and should be considered in cases of plasma refractoriness or relapsing TTP to reach durable remissions and to reduce or prevent future relapses

Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial

A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion. More than 50% of the PCT platelet components were stored for 4 to 5 days prior to transfusion. The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups (13,100 +/- 5400 vs 14,900 +/- 6200, P =.11). By longitudinal regression analysis for all transfusions, equal doses of test and reference components did not differ significantly with respect to the 1-hour (95% confidence interval [CI], -3.1 to 6.1 x 10(9)/L, P =.53) and 24-hour (95% CI, -1.3 to 6.5 x 10(9)/L, P =.19) posttransfusion platelet count. Platelet transfusion dose, pretransfusion storage duration, and patient size were significant covariates (P <.001) for posttransfusion platelet counts. Clinical hemostasis, hemorrhagic adverse events, and overall adverse events were not different between the treatment groups. Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components