Prolonged isolated thrombocytopenia after hematopoietic stem cell transplantation: morphologic correlation

Abstract

Summary:Prolonged isolated thrombocytopenia, defined as recovery of other cell counts with continuous dependence on platelet transfusions for greater than 90 days after hematopoietic stem cell transplantation (HSCT), develops in approximately 5% of patients who undergo HSCT. Although the clinical conditions associated with prolonged isolated thrombocytopenia have been studied, a systematic review of bone marrow biopsies has not been performed and the pathophysiologic basis has not been defined. We reviewed all HSCT at one center from 1990 to 1995 (n = 454) and found 12 cases that met criteria for prolonged isolated thrombocytopenia (incidence = 12/454 or 3%). Bone marrow core biopsies from 12 patients with prolonged isolated thrombocytopenia were reviewed to determine cellularity, numbers of megakaryocytes, the presence of atypical forms, and clusters of megakaryocytes. These marrow megakaryocyte counts were compared to age and disease matched controls, and 11 normal donors. Patients (aged 1-56 years, mean 32 years) who underwent HSCT (four sibling HLA-identical, five autologous bone marrow, three autologous peripheral stem cell) with prolonged isolated thrombocytopenia had a statistically significant lower absolute megakaryocyte count in bone marrow biopsies performed before transplantation and more than 30 days after transplantation compared to control patients (aged 4 months to 50 years, mean 31 years) who underwent HSCT (four sibling HLA-identical, four autologous bone marrow, four autologous peripheral stem cell) for similar conditions. No apparent differences were seen in size of megakaryocytes, nuclear-cytoplasmic ratios, or clustering of megakaryocytes. Overall marrow cellularities were similar in the three groups. These findings suggest that decreased differentiation of megakaryocytes from stem cells, rather than ineffective platelet production or peripheral destruction of platelets, causes prolonged isolated thrombocytopenia in HSCT patients. Low megakaryocyte counts prior to HSCT may be a useful prognostic indicator, as this feature was associated with the development of prolonged isolated thrombocytopenia.

Determinants of peripheral blood count value in long‐term survivors of allogeneic hemopoietic stem cell transplantation

“…Concomitant lower recipient Hb, ALC, ANC and Plt readings signified poorer 'overall' marrow engraftment. Although the marrow assessments in these patients were reported as within normal limits, subtle variations in cellularity may be difficult to discern [6]. Unlike studies on early engraftment or survival, we showed that in patients achieving long-term disease free survival, stable cell counts are not affected by blood group matching or the volume of stem cells infused.…”

Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation

“…Thrombocytopenia after allogeneic HCT is classified as PIT or SFPR [20,21]. Bielinski et al reported that PIT was observed in 3% patients undergoing HCT [20].…”

“…Thrombocytopenia after allogeneic HCT is classified as PIT or SFPR [20,21]. Bielinski et al reported that PIT was observed in 3% patients undergoing HCT [20]. Three reports have described a total of 4 patients with PIT who were treated with a TPO-R agonist after HCT (Table 3) [13,23,24]; 2 were treated with romiplostim and 2 received eltrombopag.…”

“…Eltrombopag was used for patients who developed prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR). PIT was defined as dependence on platelet transfusion for 90 days or longer after HCT [20]. SFPR was defined as a decline of platelet counts to 20,000/mL lasting at least 7 consecutive days or requiring platelet transfusions within 7 days after achieving primary platelet recovery [21].…”

Persistent thrombocytopenia post auto-SCT for AML treated with romiplostim in a patient with HIV

“…2 There are numerous causes, including drugs, hypersplenism, low CD34 counts in the graft, disease relapse and autoimmune disease. An autoimmune cause seemed the most likely cause in our patient after exclusion of other causes.…”