Blood Coagulation & Fibrinolysis最新文献

Background: The Western diamondback rattlesnake ( Crotalus atrox ) is a medically important venomous snake in the Southwestern United States, injuring humans, and their companion animals. The goals of this investigation were to utilize a rabbit model of subcutaneous envenomation to assess Crotalus atrox venom coagulopathy and determine the efficacy of a ruthenium-containing antivenom (RA) in attenuating it.

Methods: Sedated New Zealand White rabbits had viscoelastic measurements of whole blood coagulation kinetics obtained from ear artery samples. Crotalus atrox venom (4 mg/kg) was injected subcutaneously and changes in coagulation determined over three hours and compared to samples obtained prior to envenomation. Other rabbits had site-directed RA injected 5 min after venom injection.

Results: A significant decrease in the velocity of clot growth and thrombus strength was observed in animals injected with venom alone. Site-directed administration of RA resulted in no change in coagulation over the 3 h following venom injection. The interaction of antivenom administration and time was significantly different in the cases of clot growth velocity and strength.

Conclusions: A novel rabbit model was used to define the toxicodynamic profile of coagulopathy of Crotalus atrox venom and demonstrate the efficacy of RA. Future investigation is planned involving other medically important venoms and RA administration.

Objective: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH).

Methods: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC.

Results: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]).

Conclusion: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Objectives: Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO).

Methods: The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 10 9 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs.

Results: Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD).

Conclusions: The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

Inferior vena cava thrombosis (IVCT) is rare. Thrombophilia is one of the important risk factors. It is also uncommon for gene mutations in F9 gene to cause thrombosis but not hemorrhage. A 35-year-old male patient was admitted to our department with left lower limb swelling without an obvious cause for 1 day. Through contrast-enhanced computed tomography and color Doppler ultrasound, he was found to have lower extremity deep vein thrombosis, IVCT and pulmonary embolism. Through whole-exome sequencing analysis, he was found to carry a 925.7 kb duplication (chrX:137939698-138865419, hg19) encompassing ATP11C , SRD5A1P1 , MCF2 , FGF13 and F9 genes. This duplication of F9 gene was not detected in his parents. Other thrombophilic genes defects were not found. The factor IX activities of this patient, his father and mother were 194, 70 and 148, respectively. He was treated with catheter-directed thrombolysis, AngioJet-assisted pharmaco-mechanical thromboectomy and manual aspiration thromboectomy. Complete recanalization of left femoral, iliac veins and inferior vena cava was achieved. F9 gene duplication is a rare mutation, which can induce multiple venous thrombosis through increasing the activity level of factor IX in plasma. IVCT is a serious type of venous thrombosis. Personalized intervention treatment plans should be developed based on the different clinical characteristics of each case to achieve a higher benefit-risk ratio.

An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.

The aim of our study was to evaluate the efficacy of this therapy in patients with refractory primary immune thrombocytopenia. It is crucial to develop alternative treatment methods for this patient group in order to achieve better response. This combination therapy combines two different mechanisms of action, which is promising in terms of targeting pathophysiology of immune thrombocytopenia. We conducted a retrospective study, which included all patients who were diagnosed with refractory primary immune thrombocytopenia and received TPO-RA and rituximab at the General Hematology Department, Copernicus Memorial Hospital in Lodz, Poland. We assessed the response, time to response and treatment-free remission (TFR). After 1 month of treatment, the complete response (CR1, PLT >100 g/l) was achieved in 62.5% patients, and response (R1, PLT >30 g/l) was achieved in 62.5% patients. The median PLT was 175 × 10 9 /l. Within 1 month of treatment, 87.5% of patients achieved TFR. Adequately, after 6 months, CR6 and R6 was 62.5 and 75%. The median PLT was 182 × 10 9 /l. Treatment-free remission 6 months after completion was in 50% of patients. The study group achieved response to treatment, which suggests that combination of TPO-RA and rituximab is effective and relatively well tolerated. Prospective study on larger group of patients is needed to better evaluate the efficiency and safety of this treatment.

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.

The prothrombin time (PT) test is commonly used to monitor deficiencies in coagulation factors. A prolonged PT may indicate a deficiency of factors II, V, VII, X, and fibrinogen, or the presence of an inhibitor. However, further tests are required to differentiate between a true factor deficiency and the presence of an inhibitor. It is important to note that falsely prolonged PT can lead to misdiagnosis and inappropriate clinical intervention that can have life-threatening consequences. A 19-year-old woman with elevated hematocrit levels and prolonged PT was diagnosed with secondary erythrocytosis due to cyanotic congenital heart disease with ventricular septal defect (VSD). However, further investigation revealed that the prolonged PT result was false. Excess citrate in the blood sample, caused by polycythemia, led to this misleading outcome, resulting in unnecessary and potentially harmful treatment. This incident emphasizes the importance of laboratory personnel and clinicians being aware of the test's limitations. Not only should specialists in thrombosis and hemostasis possess this knowledge, but it is also pertinent for general laboratory staff, as well as laboratory directors and specialists. The significance of accurate laboratory testing for the proper diagnosis and treatment of patients is highlighted in this case.

As bleeding disorders are a worldwide health concern, Saudi Arabia is experiencing a notable prevalence of such disorders. Studying the frequency and cause of hemostatic disorders is the key to successful clinical interventions and instigating effective public policies that limit the spread of such disorders. The current review aims to highlight the major findings of the body of literature that has investigated the causes, prevalence, and major challenges associated with bleeding disorders in the country. The current review summarizes the major findings of different studies that have been conducted in Saudi Arabia regarding different bleeding disorders. Multiple causes and symptoms of bleeding disorders have been reported by different studies. Some studies investigated the genetic aspect of bleeding disorders and revealed specific mutations in coagulation factor genes influencing the symptoms of different bleeding disorders. Moreover, rare bleeding disorders such as Glanzmann thrombasthenia and Henoch-Schönlein purpura, have been reported in different regions of Saudi Arabia. Combining clinical presentations, genetic factors, and epidemiological data, the current review of the literature provides a comprehensive insight into bleeding disorders in the kingdom. This will help in advancing the diagnostic capabilities and genetic counseling enhancing management strategies and therapeutic interventions benefiting bleeding disorder patients and the kingdom.