The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.
Humans ; Anticoagulants/therapeutic use* ; Thrombomodulin/therapeutic use* ; Blood Coagulation Disorders ; Disseminated Intravascular Coagulation/drug therapy* ; Sepsis/drug therapy* ; Heparin/therapeutic use* ; Recombinant Proteins

BACKGROUNDUp to date, there is few satisfactory pharmacotherapy, except for aspirin and heparin, to stop the preeclampsia progression. Although the mechanism of preeclampsia is poorly understood, it has been proven to be associated with coagulation activation. Researches on prophylactic and therapeutic application of anticoagulants may benefit the clinical aspects of preeclampsia individuals. This study aimed to evaluate the effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine (PS/PC) microvesicle induced-mouse model.

METHODSSixty-six preeclampsia-like pregnant mice, induced by PS/PC microvesicle administration, were randomly divided into six groups. From days 5.5 to 16.5 of pregnancy, each group was respectively treated as follows: a) mice in group C (n = 12, control group) were injected with 100 microl of filtered phosphate-buffered saline into the tail vein every day; b) group PE (n = 15, preeclampsia model group) were injected in the same way with 100 microl of filtered PS/PC vesicle suspension; c) group H (n = 9, group treated with heparin) were injected with 1 unit heparin together with PS/PC vesicle suspension; d) group A (n = 10, group treated with aspirin) were injected with 20 microg/g aspirin-DL lysine as well; e) group LD (n = 10, group treated with low-dose Danshensu) were injected with 10 microg/g Danshensu; and f) group HD (n = 10, group treated with high-dose Danshensu) were injected with 30 microg/g Danshensu. Systolic blood pressure, total urinary protein levels, blood tests for some hemostatic function parameters (mean platelet counts, plasma antithrombin III activity (AT-III), D-D dimmer levels, and thrombin time), fibrin deposition by phosphotungstic acid hematoxylin staining, and thrombomodulin expression by immunohistochemistry staining in placentas were examined as indices for maternal syndrome.

RESULTSHeparin showed significant effects on maternal syndrome of preeclampsia such as hypertension and proteinuria, and different doses of Danshensu also presented the certain effects. High-dose Danshensu and aspirin all demonstrated better effects than low-dose Danshensu on decreasing blood pressure to normal level, while high-dose Danshensu demonstrated better effects than aspirin and low-dose Danshensu on decreasing proteinuria to normal level. As to Danshensu's effects on hemostatic function, high- and low-dose Danshensu's marked effects on increasing the plasma AT-III activity were the same as that of aspirin and inferior to that of heparin. High-dose Danshensu's better effect on elevating the platelet counts was superior to low-dose Danshensu and aspirin. Low-dose Danshensu's obvious effect on decreasing D-D levels was close to heparin and superior to high-dose Danshensu and aspirin. High- and low-dose Danshensu's significant effects on reduced thrombin time level are same to heparin. Different anticoagulants all played improvement roles in placental fibrin depositions, but heparin and high-dose Danshensu's roles on lowering thrombomodulin expression in placentas were superior to low-dose Danshensu and aspirin. However, anticoagulant function of high-dose Danshensu was still inferior to heparin. We found long-term use of heparin and aspirin, in spite of low-dose administration, could raise the risk of bleeding such as placental abruption and intestinal hemorrhage. But no any side effect was observed in mice treated with different doses of Danshensu in our study.

CONCLUSIONSDanshensu has proven to be effective and safe in ameliorating the prognosis of maternal syndrome in a preeclampsia mouse model. We suggest long-term provision of low-dose Danshensu in pregnancy, leading to an improvement of preeclampsia syndrome with considerable maternal safety.

Animals ; Anticoagulants ; therapeutic use ; Aspirin ; therapeutic use ; Disease Models, Animal ; Female ; Heparin ; therapeutic use ; Lactates ; therapeutic use ; Mice ; Mice, Inbred ICR ; Phosphatidylcholines ; adverse effects ; Phosphatidylserines ; adverse effects ; Placenta ; metabolism ; Pre-Eclampsia ; chemically induced ; prevention & control ; Pregnancy ; Random Allocation ; Thrombomodulin ; metabolism

OBJECTIVETo observe the clinical effect of TCM treatment for dissolving phlegm and dispelling stasis (DP-DS) on acute cerebral infarction (ACI) and its influences on plasma protein C and S and soluble thrombomodulin (TM).

METHODSOne hundred and twenty-two patients were randomly assigned to two groups, the treated group (62 cases) and the control group (60 cases). They were all treated with the conventional treatment, and DP-DS treatment was given to the treated group additionally. The treatment course was 14 days. The changes in scores of TCM syndrome and neurofunction impairment (NIHSS), levels of plasma protein C (PC), protein S (PS) and TM before and after treatment in the two groups were observed.

RESULTSThe total effective rate of TCM syndrome in the treated group was higher than that in the control group (P= 0.00). After treatment, NIHSS in the two groups was significantly different (P=0.00), and the score in the treated group was superior to that in the control group (P = 0.00). NIHSS score and levels of PC and PS were improved in both groups (P = 0.024, 0.028), and the improvement of PC in the treated group was superior to that in the control group respectively (P = 0.049). But no significant change of TM was shown after treatment.

CONCLUSIONTCM DP-DS treatment shows significant effect in improving TCM syndrome and neurofunction impairment of the patients with acute cerebral infarction, and raise the levels of PC and PS.

Aged ; Cerebral Infarction ; blood ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; Protein C ; metabolism ; Thrombomodulin ; blood

Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less likely to develop complications of inactivity, not only venous thrombosis, but also contractures, decubitus ulcers, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.
Anticoagulants ; therapeutic use ; Factor Xa Inhibitors ; Heparin ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Orthopedic Procedures ; adverse effects ; Postoperative Complications ; epidemiology ; Pulmonary Embolism ; prevention & control ; Recombinant Proteins ; therapeutic use ; Risk Factors ; Thrombomodulin ; therapeutic use ; Vena Cava Filters ; Venous Thrombosis ; epidemiology ; prevention & control ; Vitamin K ; antagonists & inhibitors ; Warfarin ; therapeutic use

BACKGROUNDPrevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.

METHODSSeventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated.

RESULTSThe PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group.

CONCLUSIONSResveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.

Animals ; Disease Models, Animal ; Femur Head Necrosis ; chemically induced ; prevention & control ; Lipopolysaccharides ; toxicity ; Magnetic Resonance Imaging ; Methylprednisolone ; toxicity ; Plasminogen Activator Inhibitor 1 ; blood ; Rabbits ; Stilbenes ; pharmacology ; therapeutic use ; Thrombomodulin ; blood ; Tissue Plasminogen Activator ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo observe the expression and effect of thrombomodulin (TM) mRNA and endothelial protein C receptor (EPCR) mRNA in lung tissue of acute paraquat poisoned rats, and intervention of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODSEighty male SD rats were randomizedly divided into four groups: the normal control group (n=8), the Na-DMPS control group (n=8, administered with 200 mg/kg Na-DMPS intraperitoneally), the PQ group (n=32, administered with 20 mg/kg 1% PQ intraperitoneally), the NA-DMPS protected group (n=32, administered with 200 mg/kg Na-DMPS intraperitoneally before with 20 mg/kg 1% PQ). The expression of TM mRNA and EPCR mRNA in the PQ group and the Na-DMPS protected group was evaluated at the six hour, on the first, third and seventh day.

RESULTSThe expression of TM mRNA and EPCR mRNA in lung tissue of poisoned rats, was significantly increased and reached the peak at the six hour, was decreased slowly on the first day, and returned to normal level on the seventh day. In the Na-DMPS protected group, at the six hour and on the first day, the expression of TM mRNA (1.071 +/- 0.097, 1.055 +/- 0.051) was less than that in the PQ group (P<0.05 or P<0.01). EPCR mRNA (0.678 +/- 0.005), (0.650 +/- 0.007) at the six hour and on the first day in the Na-DMPS protected group was less than that in the PQ group (P<0.05 or P<0.01).

CONCLUSIONThe expression of TM mRNA and EPCR mRNA of rats after PQ intoxication is increased, and can significantly be decreased after administered with Na-DMPS.

Animals ; Antigens, CD ; genetics ; metabolism ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Paraquat ; poisoning ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; genetics ; metabolism ; Thrombomodulin ; genetics ; metabolism ; Unithiol ; therapeutic use