PMC10029757_01
Inflammatory, coagulation function, and hematologic responses to HLH therapies: Day 0 corresponds to ruxolitinib (RUX) initiation. Treatment schedules, lines, and bars represent continuous therapy and individual doses of drugs with intermittent schedules. Arrows indicate that treatment was continued. (A-D) The laboratory assessments of Case 1. The levels of platelet (PLT), prothrombin time (PT), active thromboplastin time (APTT), C-reactive protein (CRP), fibrinogen (FIB),
ferritin, soluble CD25 (sCD25), and triglyceride were abnormal before Day 0 and gradually improved after therapy. But he developed a fever again on Day 28. The levels of ferritin and CRP were all elevated. The values of FIB and PLT were reduced again. (E-H) The laboratory assessments of Case 2. The dexamethasone (DXM) dose was reduced by half every three days, finally reaching a reduced dose of 1.5 mg on Day 42. It was replaced by methylprednisolone on Day 43. Inflammatory, coagulation function, and hematologic parameters were abnormal before Day 0, and gradually improved after therapy.
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A month later, she developed a high fever, fatigue, headache, and pancytopenia with an absolute neutrophil count (ANC) of 0.3 x 109/L, HGB of 93 g/L, and PLT of 37 x 109/L ( Figure 1E, H ). The CRP level was 131 mg/L (normal: 0-8 mg/L) ( Figure 1E ). H ). Her ferritin level was 12459 microg/L and the TG level (7.04 mmol/L) was four times higher than normal ( Figure 1G ). The PLT and ANC counts had normalized on Day 7 ( Figure 1E, H ). The ferritin, fibrinogen, and TG level improved on Day 14 ( Figure 1G, H ). The ferritin level, liver function, coagulation, and hematologic parameters were normal at the last follow-up on Day 353 ( Figure 1E, F, G, H ).
PMC10029757_02
Inflammatory, coagulation function, and hematologic responses to HLH therapies: Day 0 corresponds to ruxolitinib (RUX) initiation. Treatment schedules, lines, and bars represent continuous therapy and individual doses of drugs with intermittent schedules. Arrows indicate that treatment was continued. (A-D) The laboratory assessments of Case 1. The levels of platelet (PLT), prothrombin time (PT), active thromboplastin time (APTT), C-reactive protein (CRP), fibrinogen (FIB),
ferritin, soluble CD25 (sCD25), and triglyceride were abnormal before Day 0 and gradually improved after therapy. But he developed a fever again on Day 28. The levels of ferritin and CRP were all elevated. The values of FIB and PLT were reduced again. (E-H) The laboratory assessments of Case 2. The dexamethasone (DXM) dose was reduced by half every three days, finally reaching a reduced dose of 1.5 mg on Day 42. It was replaced by methylprednisolone on Day 43. Inflammatory, coagulation function, and hematologic parameters were abnormal before Day 0, and gradually improved after therapy.
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A month later, she developed a high fever, fatigue, headache, and pancytopenia with an absolute neutrophil count (ANC) of 0.3 x 109/L, HGB of 93 g/L, and PLT of 37 x 109/L ( Figure 1E, H ). The CRP level was 131 mg/L (normal: 0-8 mg/L) ( Figure 1E ). H ). Her ferritin level was 12459 microg/L and the TG level (7.04 mmol/L) was four times higher than normal ( Figure 1G ). The PLT and ANC counts had normalized on Day 7 ( Figure 1E, H ). The ferritin, fibrinogen, and TG level improved on Day 14 ( Figure 1G, H ). The ferritin level, liver function, coagulation, and hematologic parameters were normal at the last follow-up on Day 353 ( Figure 1E, F, G, H ).
The perforin protein (PRF1) expression and DeltaCD107a in natural killer (NK) cells of Case 2: (A) Flow cytometry analysis revealed the decreased expression rates of PRF1 in NK cells of Case 2. The expression rates of PRF1 were 7.09% of the negative control and 33.08% of the patient sample. The negative control was treated with isotype-control antibodies to eliminate the false positive interference caused by the non-specific binding of antibodies to the cells. Thus, the actual expression rates of PRF1 were 25.99% (i.e., 33.08% - 7.09% = 25.99%, normal: >=81%). (B) The NK cells stimulation test showed severe dysregulation of the immune response. The expression rates of CD107a in the NK cells of Case 2 were 0.90% (before stimulation) and 3.33% (post-stimulation). Thus, DeltaCD107a was 2.43% (DeltaCD107a >10% indicates normal degranulation function).
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NK cells ( Figure 2A ). NK cells stimulation test showed severe dysregulation of immune response ( Figure 2B ) on Day 352.