BACKGROUND: Glanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αIIbβ3 integrin. Concizumab,a monoclonal antibody specific for Tissue Factor Pathway Inhibitor (TFPI), abolishes its anticoagulant effect.
OBJECTIVE: To evaluate the in vitro ability of concizumab to improve haemostasis in GT.
METHODS: The effects of concizumab were evaluated in whole blood or platelet-rich plasma (PRP) from GT patients (n=5-9) using a thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), a global fibrinolytic capacity assay and a flow-chamber assay (T-TAS). Washed platelets (WP) and 20 nM recombinant activated factor VIIa (rFVIIa) were included for comparison.
RESULTS: The lag time in the TGA was significantly longer (+85%, p<0.0001) in GT patients than in controls. WP, rFVIIa and concizumab each significantly improved thrombin generation profiles. The ROTEM clotting time was significantly longer in GT patients than in controls (677 s vs 523 s; p=0.03). However, CT improved after adding WP, rFVIIa or concizumab. Under flow, occlusive thrombi were present in all healthy controls after 10 min, whereas platelet-fibrin depositions were not seen in GT patients. Sub-occlusive or occlusive thrombi formed when GT blood was mixed with WP, rFVIIa or concizumab. Clots in GT PRP were more susceptible to fibrinolysis and were improved by WP, rFVIIa or concizumab.
CONCLUSIONS: Concizumab enhanced thrombin generation, decreased the ROTEM CT, improved thrombus formation under flow and reduced clot lysis. Our results demonstrate the potential of concizumab for subcutaneous prophylaxis in GT patients.

Glanzmann\'s Trombasthenia (GT) is a genetic disorder, that develops with a tendency toward bleeding and is characterized by the absence or decrease in platelet aggregation. Surgical bleeding may be difficult to control. Platelet transfusion is the main treatment, albeit refractoriness can occur. We describe the case of a patient with GT and platelet refractoriness, who was submitted to radical prostatectomy and dental extraction. The perioperative treatment with apheresis platelet concentrate and activated recombinant factor seven allowed the procedures to be performed uneventfully. We discuss the complexity of the case and the treatment option.

UNASSIGNED: Diffuse alveolar hemorrhage (DAH) is a rare and frequently life-threatening complication of a variety of conditions. DAH may result from coagulation disorders, inhaled toxins, or infections. We report a series of patients who developed DAH after receiving a tissue-type plasminogen activator (tPA) for acute cerebral infarction. We aimed to find risk factors of DAH in patients receiving tPA and the effectiveness of activated recombinant factor VII (rFVIIa) treatment for the same.
UNASSIGNED: A total of 1023 acute ischemic stroke (AIS) patients who received tPA in our department from January 2006 to December 2018 were enrolled in this study. Four of the 1023 patients (0.39%) developed DAH. The modified Rankin scale was used to assess clinical severity. Infarction volume was assessed upon follow-up using DWI (diffusion-weighted imaging). Atherothrombotic brain infarction cases were excluded from the study. The age, sex, occlusion site, area of infarction, emphysema, intracranial hemorrhage, and neurological outcomes were analyzed. Patients who developed DAH were more likely to have a history of emphysema. We administered rFVIIa to three DAH patients with good prognosis.
UNASSIGNED: The inclusion/exclusion criteria of tPA were based on the AHA/ASA Guidelines for the early management of patients with AIS.These patients had no evidence of infections, bronchoscopy, autoimmune diseases, HIV, and transplantations. Our study suggests that systemic administration of rFVIIa for DAH is effective. Emphysema may be a risk factor for the development of DAH following tPA. When we use tPA for emphysema patients, we must be careful about DAH enough.

BACKGROUND: Postoperative bleeding after cardiac reoperations is among the most complicating problems, both for the physicians and for the patients. Many modalities have been used to decrease its adverse effects and the need for blood products administration.
OBJECTIVE: In a randomized double-blinded clinical trial of redo cardiac valve surgery in adult, the effect of active recombinant factor VII (rFVIIa) on postoperative bleeding was compared with placebo. Chest tube drainage was used for comparison of bleeding between the two groups.
METHODS: Two groups of 18 patients undergoing redo valve surgeries were treated and compared regarding chest tube drainage, need for blood products, prothrombin time (PT), partial thromboplastin time (PTT), hemoglobin and hematocrit, platelet count, and international normalized ratio (INR) in first 24 hours after surgery. Bleeding was assessed at 3rd, 12th, and 24th hour after operation. In rFVIIa group, 40 µg/kg of AryoSeven was administered before end of surgery and same volume of normal saline was administered as placebo in the control group.
RESULTS: Study groups showed no difference regarding baseline variables. Three patients in rFVIIa group (16.67%) and 13 in placebo group (72.23%) received blood products (P < 0.01). Chest tube blood drainage at 24th hour after operation was 315 ± 177 mL in rFVIIa group and 557 ± 168 mL in control group (P = 0.03). At third and 12th hour after operation, the difference was not statistically significant (P = 0.71 and P = 0.22, respectively). Postoperative ICU stay was not different; while extubation was longer in the placebo group (352 ± 57 vs. 287 ± 46 minutes; P = 0.003).
CONCLUSIONS: Our study demonstrated the efficacy of rFVIIa in controlling postoperative bleeding in redo cardiac valve surgeries regarding subsequent blood loss and transfusion requirement; however, outcome results remains to be defined.

Consensus on management of complicated cases of dengue infection is evolving. Dengue hemorrhagic fever (DHF) occasionally progress to fulminant liver failure with high fatality rate. Inadvertent use of blood products to control massive bleeding in dengue shock syndrome may worsen fluid overload and subsequently the multi-organ dysfunction. We report a case of 37-years-old Sri Lankan man who developed fulminant liver failure and massive bleeding associated with DHF, subsequently recovered completely with supportive measures including administration of N-acetyl cysteine and activated recombinant factor VII. In conclusion, prevention of ischemic injury to liver and adoption of early aggressive supportive measures in complicated cases of dengue hemorrhagic fever is crucial for a favorable outcome. Indications for rFVIIa to arrest uncontrolled internal bleeding and use of NAC in non-acetaminophen-induced acute liver failure in complicated DHF are a platform for discussion.

BACKGROUND: Dabigatran etexilate, a pro-drug of a direct thrombin inhibitor, was approved a few years ago for non-valvular atrial fibrillation and deep venous thrombosis. Rapid monitoring of the dabigatran level is essential in trauma and bleeding patients but the traditional plasma-based assays may not sufficiently display the effect. Furthermore, no antidote exists and reversal of the anticoagulant effect is impossible or difficult. The present study investigated the in vitro effect of dabigatran on whole blood thromboelastography (TEG) and its reversal by recombinant activated factor VII and prothrombin complex concentrate.
METHODS: Blood was collected from 10 healthy donors and spiked in vitro with therapeutic doses of dabigatran to a plasma concentration of 200 ng/ml, followed by therapeutic doses of recombinant activated factor VII (corresponding to 100 μg/kg) and prothrombin complex concentrate (corresponding to 50 IE/kg) and evaluated by TEG.
RESULTS: Compared to baseline, dabigatran changed all TEG parameters in a hypocoagulable direction corresponding to increased R time and time to maximum rate of thrombus generation, reduced angle, A5, A10, maximum amplitude and maximum rate of thrombin formation. Recombinant activated factor VII had a procoagulant effect on the majority of the investigated TEG parameters when added to dabigatran spiked samples. Prothrombin complex concentrate appeared not to have a procoagulant effect on TEG even when the heparin content in the formulation was neutralized by heparinase.
CONCLUSIONS: TEG displays the presence of dabigatran in whole blood in vitro and the anticoagulant effect of dabigatran is partly reversed by spiking with recombinant activated factor VII.