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Megakaryocyte colony stimulating activity (MK-CSA) and megakaryocyte progenitors (CFU-MK) in bone marrow transplantation
SYMPOSIUM IX:
MEGAKARYOCYTE PATHOPHYSIOLOGY THURSDAY, June 5, 1986 Abstract No. 245 - Abstract No. 249
245 FEEDBACK RESPONSES TO THROMBOCYTOPENIA. C.W. Jackson. Dept. Hematology/ Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Acute thombocytopenia produces multiple changes in megakaryocytopoiesis. The number and extent of changes is related to the severity of thrombocytopenia. With severe thrombocytopenia in rodents (platelet count <5 of baseline), there is an increase in number, DNA content and size and a decrease in the maturation time of megakaryocytes. An increase in small marrow cells bearing platelet markers (immediate megakaryocyte antecedents) is discernible within 2 hr and peaks at 6-10 hr. By 18 hr, both endomitotic activity and average DNA content of megakaryocytes is increased. The peak in endomitotic activity occurs at 32-36 hr while the largest increase in megakaryocyte DNA content is observed at 48-72 hr. An increase in megakaryocyte size is detectable by 24 hr and is greatest at 2-3 days. An increase in megakaryocyte number is also observed by 24 hr and peaks at 2-2 l/2 days. Megakaryocyte maturation time is shortened during the 1-3 day period. Colony-forming marrow megakaryocyte progenitors do not increase in number in mice until 4 days after induction of acute thrombocytopenia; however, the proportion of these cells in DNA synthesis at 1-2 days is increased. The megakaryocyte response to less severe thrombocytopenia includes an increase in endomitotic activity and size and a decrease in maturation time, all proportionate to the decrease in platelet count, but no increase in immediate megakaryocyte precursors or in megakaryocytes has been detected. In summary, thrombocytopenia causes several changes in megakaryocytopoiesis,all of which facilitate the more rapid production of platelets. 246 MEGAKARYOCYTE COLONY STIMULATING ACTIVITY (MK-CSA) AND MEGAKARYOCYTE PROGENITORS (CFU-MK) IN BONE MARROW TRANSPLANTATION. PA de Alarcon, JA Schmieder. University of Iowa, Iowa City, IA 52242, USA. Platelet recovery after bone marrow (BM) transplantation lags behind myeloid and erythroid recovery. To define the role of CFU-Mk and Mk-CSA in the recovery of megakaryocytopoiesis after BM transplantation we studied 12 consecutive patients. Serum samples were obtained the day of transplantation and 3 times weekly thereafter until platelet recovery. BM samples from seven patients were obtained for CFU-Mk assay and histopathology. BM mononuclear cells from healthy adult volunteers were used as targets for the Mk-CSA assay. The in vitro plasma clot colony assay for CFU-Mk was used in this study. Serum samples from patients on days 0 or 1 posttransplantation stimulated 35.6 (23.5) (standard deviation) colonies. Serum from days 9 to 16 produced 42.4 (35.6) colonies. These numbers are significantly different, ~~0.025 and ~~0.05 respectively, from those produced by normal serum 16.6 (8.53). On day 28 three patients had no colony growth and absent Mk in the BM. One of these patients recovered. Four patients had from 8-24% of the normal number of CFU-Mk and present but markedly decreased Mk. Mlc-CSAin the serum of all 12 patients showed a biphasic pattern with an early peak followed by a valley and delayed second peak. In the patients studied beyond 30 days there was persistent activity. The presence of CFU-Mlcand Mk in BM foretells a prompt platelet recovery and their absence may represent a poor prognostic sign. The Mk-CSA response after BM transplantation is adequate. 124
MEGAKARYOCYTE PATHOPHYSIOLOGY THURSDAY, June 5, 1986 Abstract No. 245 - Abstract No. 249
245 FEEDBACK RESPONSES TO THROMBOCYTOPENIA. C.W. Jackson. Dept. Hematology/ Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Acute thombocytopenia produces multiple changes in megakaryocytopoiesis. The number and extent of changes is related to the severity of thrombocytopenia. With severe thrombocytopenia in rodents (platelet count <5 of baseline), there is an increase in number, DNA content and size and a decrease in the maturation time of megakaryocytes. An increase in small marrow cells bearing platelet markers (immediate megakaryocyte antecedents) is discernible within 2 hr and peaks at 6-10 hr. By 18 hr, both endomitotic activity and average DNA content of megakaryocytes is increased. The peak in endomitotic activity occurs at 32-36 hr while the largest increase in megakaryocyte DNA content is observed at 48-72 hr. An increase in megakaryocyte size is detectable by 24 hr and is greatest at 2-3 days. An increase in megakaryocyte number is also observed by 24 hr and peaks at 2-2 l/2 days. Megakaryocyte maturation time is shortened during the 1-3 day period. Colony-forming marrow megakaryocyte progenitors do not increase in number in mice until 4 days after induction of acute thrombocytopenia; however, the proportion of these cells in DNA synthesis at 1-2 days is increased. The megakaryocyte response to less severe thrombocytopenia includes an increase in endomitotic activity and size and a decrease in maturation time, all proportionate to the decrease in platelet count, but no increase in immediate megakaryocyte precursors or in megakaryocytes has been detected. In summary, thrombocytopenia causes several changes in megakaryocytopoiesis,all of which facilitate the more rapid production of platelets. 246 MEGAKARYOCYTE COLONY STIMULATING ACTIVITY (MK-CSA) AND MEGAKARYOCYTE PROGENITORS (CFU-MK) IN BONE MARROW TRANSPLANTATION. PA de Alarcon, JA Schmieder. University of Iowa, Iowa City, IA 52242, USA. Platelet recovery after bone marrow (BM) transplantation lags behind myeloid and erythroid recovery. To define the role of CFU-Mk and Mk-CSA in the recovery of megakaryocytopoiesis after BM transplantation we studied 12 consecutive patients. Serum samples were obtained the day of transplantation and 3 times weekly thereafter until platelet recovery. BM samples from seven patients were obtained for CFU-Mk assay and histopathology. BM mononuclear cells from healthy adult volunteers were used as targets for the Mk-CSA assay. The in vitro plasma clot colony assay for CFU-Mk was used in this study. Serum samples from patients on days 0 or 1 posttransplantation stimulated 35.6 (23.5) (standard deviation) colonies. Serum from days 9 to 16 produced 42.4 (35.6) colonies. These numbers are significantly different, ~~0.025 and ~~0.05 respectively, from those produced by normal serum 16.6 (8.53). On day 28 three patients had no colony growth and absent Mk in the BM. One of these patients recovered. Four patients had from 8-24% of the normal number of CFU-Mk and present but markedly decreased Mk. Mlc-CSAin the serum of all 12 patients showed a biphasic pattern with an early peak followed by a valley and delayed second peak. In the patients studied beyond 30 days there was persistent activity. The presence of CFU-Mlcand Mk in BM foretells a prompt platelet recovery and their absence may represent a poor prognostic sign. The Mk-CSA response after BM transplantation is adequate. 124