Bleeding is frequent among patients with thrombocytopenia. We studied whether in vitro platelet function predicts future bleeding in patients with acute myeloid leukemia (AML), and thrombocytopenia. Adult AML patients with platelet count <5.0 × 1010/L were included. Detailed bleeding history and blood samples were collected at inclusion and every 7 days. We analyzed hematology and coagulation parameters. With flow cytometry we evaluated platelet activation (activated GPIIb/IIIa, P‐selectin, and CD63 expression), and platelet aggregation. Agonists were thrombin‐receptor activating peptide (TRAP) and collagen‐related peptide (CRP‐XL). During 18 months, sixty participants were enrolled and followed for a total of 114 weeks. Bleeding occurred in 52 weeks, and was not associated with clinical, hematology or coagulation parameters. Predictors of bleeding were assessed using multivariate logistic regression, adjusted for platelet count, sex, and age. Bleeding history and receiver operating curves were compared using c‐index. Reduced TRAP‐induced platelet aggregation had Odds ratio 3.00 (95% confidence interval [CI] 1.38‐6.60). Reduced CRP‐XL‐induced platelet aggregation had Odds ratio 4.00 (95%‐CI 1.70‐9.20) for bleeding. Overall, C‐index was 0.71 for the models including platelet aggregation results, 0.72 for activated GPIIb/IIIa‐positive platelets after stimulation with TRAP, 0.68 for percent P‐selectin positive platelets with TRAP and 0.63 for the platelet count. Among patients receiving no platelet transfusion, C‐index was 0.83–0.91 for bleeding; highest for models using platelet aggregation. Change in platelet aggregation did not correlate with the number of platelet concentrates administered. In conclusion, platelet aggregation and platelet activation results predict bleeding better than platelet count alone, among AML patients with thrombocytopenia.
Acute toxic leukoencephalopathy (ATL) and delayed post-hypoxic leukoencephalopathy (DPHL) are two possible adverse entities related to opioid intoxication (OI), each having a distinct clinical course. While ATL shows a monophasic course with gradual neurological deterioration, DPHL has a distinct biphasic course. We report a case of ATL along with a case of DPHL happening in young male patients with OI, including their clinical courses as well as imaging characteristics with comparable time intervals. Initially, both leukoencephalopathies typically show magnetic resonance imaging findings with confluent and symmetric white matter (WM) abnormalities in the periventricular regions on T2 and fluid-attenuated inversion recovery images along with restricted diffusion on diffusion-weighted imaging. The DPHL patient however also presented with WM cystic substance loss in the deterioration phase, several weeks after hospital admission, which was previously described in a case of DPHL. Interestingly, similar WM changes have recently been observed in virus-associated necrotizing disseminated acute leukoencephalopathy in patients with coronavirus disease 2019 which may suggest a common pathophysiological mechanism. Knowing the distinct imaging features of ATL and DPHL along with their typical clinical courses can provide a faster and more reliable differentiation between these two entities.
Mycophenolate mofetil (MMF) raises platelet counts in patients with primary immune thrombocytopenia. However, studies indicate that MMF inhibits collagen-induced platelet aggregation, potentially increasing bleeding risk following MMF therapy. OBJECTIVE:The study evaluates the in vitro effect of MMF on platelet function. Blood samples (n=6) from healthy donors were incubated with vehicle, MMF or mycophenolic acid (MPA) at clinically relevant concentrations. Platelet aggregation was measured with flow cytometry and 96-well light transmission aggregometry (LTA). Using flow cytometry, we measured the expression of platelet glycoprotein receptors GPVI, CD49b, CD42b, CD42a, CD61 and CD41. Platelet activation was measured as the expression of P-selectin and the active form of the GPIIb/IIIa receptor following agonist stimulation. Agonists were: Adenosine diphosphate, thrombin receptor-activating peptide, collagen, collagen-related peptide and U46619. The Platelet Function Analyzer-200 was used to measure global platelet function RESULTS: MMF and MPA did not change platelet aggregation regardless of the agonist used. An exception was a significant, but minor decrease in platelet aggregation induced by a low collagen concentration. MMF (6±3%, p=0.02) and MPA (8±4%, p=0.01) compared with vehicle (22±11%). However, this was not observed 3 using the lesser sensitive LTA method. Compared with vehicle, MPA led to a significantly lower relative disposition of the surface collagen-receptor GPVI (7.8±1.8 versus 8.8±2.1 mean fluorescence intensity, p<0.001). In all other platelet related tests, neither MMF nor MPA showed any effect. CONCLUSION: MMF and MPA only had a minor effect on collagen-induced platelet aggregation, with MPA reducing the relative disposition of surface GPVI receptors.
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