Acquired Factor VIII Inhibitors: A Case Study.

The physiology of hemostasis is one of high complexity that involves the initiation, amplification, and propagation of the many moving parts of the hemostatic system and its regulatory mechanisms. It is imperative that clinical laboratory professionals have a strong understanding of the many intricacies of the physiology of coagulation and its in vitro testing. An elongated activated partial thromboplastin time can have several causes, and the correct cause must be elucidated in a timely manner for proper treatment. A mixing study with normal pooled plasma should be performed to evaluate for the presence of an inhibitor vs factor deficiency. Factor inhibitors, specifically factor VIII in this case study, should be titered so that the clinician can decide which treatment may work best for the patient. Continued monitoring of factor levels and inhibitor titers should be conducted to follow the resolution or progression of inhibitor presence.

Assessment of FVIII, D-dimer, S. ferritin, and lactate dehydrogenase in hospitalized patients with 2019 coronavirus disease

BACKGROUND: Corona virus disease 2019 (COVID-19) is a coronavirus that can produce a variety of symptoms, ranging from asymptomatic carrier status to severe respiratory failure, multiple organ dysfunction, and death, it might be associated with hypercoagulability as increase in coagulation factor 8 (FVIII). OBJECTIVES: This study was carried out to investigate markers of hypercoaguablility (factor VIII activity, D-Dimer) in hospitalized adult patients with COVID-19, evaluation of certain markers of inflammation (S. ferritin, lactate dehydrogenase [LDH], C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]) and correlate those markers with each other. PATIENTS AND METHODS: This cross-sectional study included 70 adult hospitalized patients with COVID-19. Blood samples were obtained for FVIII, D. dimer, and ESR. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 23 and Microsoft Office Excel 2010. RESULTS: The mean age of enrolled 70 patients was 60.22 +/- 14.43 years. 44 (62.9%) of patients had neutrophilia and lymphopenia was seen in 41 (58.6%). High ratio of N/L was seen in 66 (94.3%). Low count of eosinophil was seen in 44 (62.9%), high LDH level was seen at 57 (81.4%). Regarding serum ferritin, high level was seen 64 (91.4%) and high level of CRP was seen in 56 (80%). High level of ESR was seen in 64 (91.4%) and high level of D. dimer was seen in 55 (78.6%), while the high level of FVIII was seen in 30 (42.9%) and low FVIII level was seen in 4 (5.7%). CONCLUSIONS: The majority of patients had neutrophilia, lymphopenia, high N/L ratio, and eosinopenia. Markers of inflammation (S. ferritin, LDH, CRP, and ESR), which were elevated. FVIII level and D. dimer were elevated in the majority of patients with COVID-19. Few of the patients were had a low level of FVIII, which might be related to abnormal function of the liver or might be attributed to autoantibodies directed against FVIII.

A Delphi Consensus Approach for Difficult-to-Treat Patients with Severe Hemophilia A without Inhibitors.

INTRODUCTION: Over the past decade, there has been an increase in novel therapeutic options to treat hemophilia A. It is still unclear how these novel treatments are used in the management of patients with hemophilia A, particularly those with challenging clinical scenarios who are typically excluded in clinical trials. PURPOSE: This study aimed to understand the areas of consensus and disagreement among hematologists regarding the preferences toward therapeutic approaches for difficult-to-treat patients with severe hemophilia A without inhibitors. PATIENTS AND METHODS: During February-June 2020, a three-round modified Delphi study was conducted to generate consensus among 13 US experts in the field of hemophilia. Experts were asked about their preferences toward therapeutic options for patients with challenging clinical situations, including age-related morbidities (eg, myocardial infarction, joint arthropathy), increasing demand for high-impact physical activities, early onset osteoporosis, and newborns with hemophilia A. Consensus was defined as ≥75% agreement between the panelists. RESULTS: Consensus was reached on many, but not all cases, leaving uncertainty about appropriateness of therapeutic approaches for some patients where clinical evidence is not available or driven by physicians' or patients' preferences toward therapeutic options. A majority of panelists preferred FVIII replacement therapy rather than emicizumab prophylaxis for the challenging cases presented due to established evidence on safety, efficacy, and level of bleed protection for FVIII treatment. CONCLUSION: Recommendations emerging from this study may help guide practicing hematologists in the management of challenging hemophilia A cases. Future studies are needed to address treatment options in the clinical cases where no consensus was reached.

Low FXIII activity levels in intensive care unit hospitalized COVID-19 patients.

BACKGROUND: COVID-19 infection is associated with a hypercoagulable state. Severe COVID-19 patients present with high plasma fibrinogen levels, continuous deposition of fibrin and the presence of microthrombi in their lungs, accompanied by significant fibrinolysis, resulting in high D-dimer levels. Due to the role of FXIII in fibrin crosslinking and clot stabilization, we analyzed its activity levels and dynamics in COVID-19 patients hospitalized in the intensive care unit (ICU). METHODS: FXIII levels were measured in thirty four COVID-19 patients hospitalized in the ICU and in fourteen non-severe COVID-19 patients. FVIII levels were measured for comparison. Laboratory data and clinical variables were recorded. RESULTS: The average FXIII activity level in 34 ICU hospitalized COVID-19 patients was 69.9±33 %, significantly lower compared to an average of 120±20.9 % FXIII activity in 14 non-severe COVID-19 patients. FXIII activity levels were below the low normal value (< 79 % FXIII activity) in 74 % of the ICU hospitalized COVID-19 patients. In contrast, high FVIII activity was measured among all severe COVID-19 patients. Consecutive measurements, performed in fourteen ICU hospitalized COVID-19 patients, pointed to a significant decrease in FXIII activity from the average of 85.7±28.2 %, (which is in the normal range), to an average of 68.0±20.4 %, below the low normal range, within 6.4±3.4 days of ICU hospitalization. Liver functions did not differentiate between patients with low and normal FXIII activity. No inhibitor to FXIII activity was found in the plasma of severe COVID-19 patients. Levels of FXIII-A antigen correlated with FXIII activity, and were low in severe COVID-19 patients. CONCLUSIONS: Low FXIII activity levels were found in COVID-19 patients hospitalized in the ICU, with gradual decline during their hospitalization. A mechanism of consumption may account for the low FXIII activity in these patients.