Sepsis is a high morbidity and mortality in critical care unit. Clinically, we found that
secondary thrombocytopenia was common in the patients with sepsis, and the incidence can be
as high as 55%. Moreover, many studies have shown that thrombocytopenia is an early
prognostic marker in sepsis and an independent risk factor for the mortality of sepsis.
Furthermore, sepsis patients with severe thrombocytopenia(PLT< 50×10^9/L) have the higher
mortality of 50%-90%. And then, it has been reported that early recovery from
thrombocytopenia helps to prevent the coagulopathy and decreases the mortality. Until now,
the treatment of thrombocytopenia are mainly platelet transfusion and platelet-increased
drugs. Because of source scarcity, transfusion-related infectious and immunological
complications, platelet transfusion is limited in the clinical treatment. So, the use of
platelet-increased drugs for replacement therapy becomes an inevitable trend. The primary
purpose of this study is to explore the effect of platelet-increased drugs (rhTPO) on sepsis
patients with severe thrombocytopenia.
The study is designed as a prospective, multi-center, open-label, randomized, controlled
trial in 7 tertiary academic medical centers which are medical, surgical or general ICUs.
Patient enrollment is expected to last up to 30 months. Eligible patients will be randomly
assigned to the control and rhTPO add-on treatment in a dynamic random and competitive design
in clinical trial sites. Sequential organ failure assessment (SOFA), Acute Physiology and
Chronic Health Evaluation II (APACHE II) scores are as the dynamic equilibrium factors.
Randomization will be done after the first assessment, ensuring that the assessing
occupational therapist will not be biased at this time by knowing the group assignment. Both
groups receive appropriate medical support and treatment based on guidelines issued by the
surviving sepsis campaign.
The intervention group will receive rhTPO at a dose of 15000u/d, subcutaneous injection, for
7 consecutive days. It will be terminated when platelet counts (PCs) reach the standard of
clinical recovery of platelets: increased by 50×10^9/L for 3 consecutive days compared with
PCs at baseline, or PCs are more than 100×10^9/L, or the duration of rhTPO is more than 7
days. The time from randomization to administration of rhTPO will be within 24 hours. The
control group will not use any platelet-increased drugs.
Platelet transfusion is advised to be administered when PCs are below 10×10^9/L in the
absence of apparent bleeding; or below 20 ×10^9/L if the patient has a significant risk of
bleeding in both two groups; or below 50 ×10^9/L if the patient has active bleeding or need
invasive operation.
Patients will be followed for 28 days. PCs will be monitored every day until the first 7
days, followed by tests once a week. Liver and renal function, coagulation function,
inflammatory biomarkers (CRP, PCT), and the severity of the disease (SOFA, APACHEǁ) will be
monitored before treatment, followed by tests once a week. And then, the number of blood
transfusion (including platelets), the length of ICU stay, days free from advanced
cardiovascular/respiratory/renal support, bleeding events, and any adverse effects will be
recorded after treatment.