Zeigler Z R, Kelton J G, Moore J C, Shadduck R K, Andrews D F, Nath R, Agha M
Adult Bone Marrow Transplant Program of the Western Pennsylvania Hospital Western Pennsylvania Cancer Institute, Pittsburgh, PA 15224, USA.
Bone Marrow Transplant. 1999 Sep;24(6):641-5. doi: 10.1038/sj.bmt.1701928.
The pathophysiology of thrombotic thrombocytopenic purpura (TTP) is not well understood. Recent studies have described a platelet aggregating factor which has been characterized as a calcium-dependent cysteine protease (calpain) in patients with TTP. A type of TTP, sometimes called secondary TTP, has been associated with bone marrow transplantation (BMT). However, unlike primary adult TTP, BMT-TTP has important differences and often does not respond well to plasma exchange. We describe the measurement of calpain activity in a group of BMT patients (with and without the clinical syndrome of transplant-associated TTP). Calpain was measured using a functional assay (14C-serotonin platelet release with inhibition by the cysteine protease inhibitor, leupeptin) in the sera of patients following autologous (auto) or allogeneic (allo) BMT. We also independently diagnosed and graded the BMT-TTP on the day of blood sampling using a scale that related to the percentage schistocytes and lactic dehydrogenase level. Calpain activity was detected in 1/8 (13%) grade 0-1 (6 auto, 2 allo); 6/16 (38%) grade 2 (3 auto, 13 allo) 9/16 (56%) grade 3 (2 auto, 14 allo) and 8/8 (100%) grade 4 BMT-TTP. Pre-BMT samples were tested in 10 allo-BMT patients who had positive calpain results post-BMT. One patient gave positive results before the transplant. This patient developed grade 4 BMT-TTP (day 24 post-BMT) and died despite apheresis. Positive calpain results were highly associated with neurologic symptoms, P < 0.001. Nineteen of 24 (79%) patients with positive results had neurologic symptoms compared to three of 21 (14%) patients with negative results. In conclusion, calpain was detected in half of the BMT patients with mild to moderate BMT-TTP (grades 2-3) and was uniformly found in those with severe (grade 4) BMT-TTP. Typically the calpain activity develops as TTP complicates the transplant process. It is unknown whether calpain contributes to the pathogenesis of this disorder, or is a secondary event.
血栓性血小板减少性紫癜（TTP）的病理生理学尚未完全明了。最近的研究描述了一种血小板聚集因子，在TTP患者中其被鉴定为一种钙依赖性半胱氨酸蛋白酶（钙蛋白酶）。一种有时被称为继发性TTP的TTP类型与骨髓移植（BMT）有关。然而，与原发性成人TTP不同，BMT - TTP有重要差异，且对血浆置换往往反应不佳。我们描述了一组BMT患者（有和没有移植相关TTP临床综合征）中钙蛋白酶活性的测定。在自体（auto）或异体（allo）BMT后的患者血清中，使用功能测定法（14C - 血清素血小板释放，用半胱氨酸蛋白酶抑制剂亮抑酶肽抑制）测量钙蛋白酶。我们还在采血当天使用与裂体细胞百分比和乳酸脱氢酶水平相关的量表独立诊断并分级BMT - TTP。在0 - 1级的8例患者中有1例（13%）检测到钙蛋白酶活性（6例自体，2例异体）；2级的16例中有6例（38%）（3例自体，13例异体），3级的16例中有9例（56%）（2例自体，14例异体），4级BMT - TTP的8例患者中8例（100%）检测到钙蛋白酶活性。对10例BMT后钙蛋白酶结果呈阳性的异体BMT患者检测了BMT前样本。1例患者在移植前呈阳性结果。该患者发生4级BMT - TTP（BMT后第24天），尽管进行了血液成分单采仍死亡。钙蛋白酶阳性结果与神经症状高度相关，P < 0.001。结果呈阳性的24例患者中有19例（79%）有神经症状，而结果呈阴性的21例患者中有3例（14%）有神经症状。总之，在半数轻度至中度BMT - TTP（2 - 3级）的BMT患者中检测到钙蛋白酶，在重度（4级）BMT - TTP患者中均检测到钙蛋白酶。通常钙蛋白酶活性在TTP使移植过程复杂化时出现。尚不清楚钙蛋白酶是否促成这种疾病的发病机制，还是一个继发事件。
