APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of ...familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency.
The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277–14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP).
Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.
•APO CII deficiency is an ultra-rare autosomal recessive cause of hypertriglyceridemia.•Despite a low-fat diet and fibrate therapy, severe hypertriglyceridemia may persist.•Fatty liver and pancreatitis are challenging complications.•Fibrate helped reduce TG but was associated with cholelithiasis and rhabdomyolysis.
Ligneous Conjunctivitis is an autosomal recessive, chronic form of conjunctivitis characterized by formation of pseudo-membrane particularly over tarsal conjunctiva attributed to plasminogen ...deficiency. Various forms of medical and surgical treatment modalities have been reported. We are reporting a case of ligneous conjunctivitis in a nine month old baby managed successfully with both topical and intravenous fresh frozen plasma, topical heparin and cyclosporine.
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•FFP transfusion before invasive procedures enhanced the total amount of generated thrombin by 5.7%.•Transfusion slightly decreased thrombin generation in a subgroup of patients, ...presumably by replenishing protein C.•Responses to FFP transfusion were similar in patients with compensated/decompensated cirrhosis, ACLF, infection or shock.•Benefit of FFP transfusion in cirrhosis was too modest to justify its indiscriminate use.
The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients.
Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures – if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 – were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion.
FFP enhanced ETP-TM by 5.7%, from 973 (731–1,258) to 1,028 (885–1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 1,071–1,537 to 1,124 812–1,370 nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5.
FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases.
Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.
The indications for transfusing fresh‐frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of ...transmitting infection are similar to those of other blood components unless a pathogen‐reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion‐related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near‐patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non‐UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.
Background and objectives
Freeze‐dried plasma (FDP) has logistical advantages in terms of storage and reconstitution time compared to fresh‐frozen plasma. In vitro studies show FDP to be equivalent ...to fresh‐frozen plasma regarding coagulation and clotting capacities. FDP is used in an increasing number of countries. We wanted to evaluate the clinical effects of FDP in major haemorrhage compared to standard care.
Methods
MEDLINE, Embase, Central, Biosis Previews, WHO ICTRP, Clinical Trials and Open Grey were systematically searched from inception until September 2018, without language restriction. Studies were eligible if they examined haemorrhagic adult patients transfused with FDP. Our primary outcome was mortality. Two reviewers independently assessed studies for eligibility, extracted data and assessed bias.
Results
Nine studies were eligible for inclusion. Three studies had a comparison group: one was a randomized controlled trial and two were before and after comparisons. Six studies were uncontrolled. A total of 606 patients received FDP, while 72 patients received non‐FDP transfusion. In total, five minor adverse effects were documented. Two studies compared FDP to fresh‐frozen plasma and found no difference in 30‐day mortality between the groups. The included studies were heterogenous and had several methodological weaknesses, such as no control group, missing data or no protocol.
Conclusions
The available research does not document the clinical effects of FDP. We cannot recommend or discourage use of FDP in major haemorrhage on base of available research.
Objective Allergic reactions are a severe complication of plasma exchange (PEx). Few reports have analyzed allergic reactions during PEx using fresh-frozen plasma (FFP) as a replacement solution. We ...therefore clarified the relationship between risk and exacerbation factors that lead to the onset of PEx-related allergic reactions, particularly PEx, using FFP, and examined whether or not allergic reactions were predictable. Methods This retrospective study included 88 consecutive patients who underwent PEx with FFP as a replacement solution at Kitasato University Hospital. The patients were grouped according to the presence of allergic reactions and compared. Data were analyzed using the χ2 test, Mann-Whitney U test, and a binomial logistic analysis. Statistical analyses were performed using EZR software program, version 1.54, with p <0.05 considered statistically significant. Results There were 44 allergic reaction cases. The average time to the onset of an allergic reactions was 63.5 (45-93) min. The allergic reaction-onset group had significantly higher average albumin (Alb) levels than did the non-allergic reaction-onset group. The binomial logistic analysis identified Alb levels as independent risk factors for allergic reactions. The receiver operating characteristic analysis identified an Alb level ≥3.4 g/dL as a risk factor for allergic reactions (area under the curve: 0.731; 95% confidence interval: 0.622-0.84). Conclusion Allergic reaction onset occurred approximately one hour after PEx initiation in the critical period. A serum Alb level ≥3.4 g/dL was identified as a risk factor for predicting allergic reactions. Patients with Alb levels ≥3.4 g/dL at the first PEx should be monitored for allergic reaction symptoms.
The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It is comprised of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and ...adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, including controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion.During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as metalloproteinases, heparanase, and hyaluronidase. These sheddases are activated by reactive oxygen species and pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. Inflammation-mediated glycocalyx degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion. Clinical studies have demonstrated the correlation between blood levels of glycocalyx components with organ dysfunction, severity, and mortality in sepsis.Fluid resuscitation therapy is an essential part of sepsis treatment, but overaggressive fluid therapy practices (leading to hypervolemia) may augment glycocalyx degradation. Conversely, fresh frozen plasma and albumin administration may attenuate glycocalyx degradation. The beneficial and harmful effects of fluid and plasma infusion on glycocalyx integrity in sepsis are not well understood; future studies are warranted.In this review, we first analyze the underlying mechanisms of glycocalyx degradation in sepsis. Second, we demonstrate how the blood and urine levels of glycocalyx components are associated with patient outcomes. Third, we show beneficial and harmful effects of fluid therapy on the glycocalyx status during sepsis. Finally, we address the concept of glycocalyx degradation as a therapeutic target.
Given the pathophysiological key role of the host response to an infection rather than the infection per se, an ideal therapeutic strategy would also target this response. This study was designed to ...demonstrate safety and feasibility of early therapeutic plasma exchange (TPE) in severely ill individuals with septic shock.
This was a prospective single center, open-label, nonrandomized pilot study enrolling 20 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE; > 0.4 μg/kg/min) out of 231 screened septic patients. Clinical and biochemical data were obtained before and after TPE. Plasma samples were taken for ex-vivo stimulation of human umbilical vein endothelial cells (HUVECs) to analyze barrier function (immunocytochemistry and transendothelial electrical resistance (TER)). Cytokines were measured by cytometric bead array (CBA) and enzyme-linked immunosorbent assays (ELISAs). An immediate response was defined as > 20% NE reduction from baseline to the end of TPE.
TPE was well tolerated without the occurrence of any adverse events and was associated with a rapid reduction in NE (0.82 (0.61-1.17) vs. 0.56 (0.41-0.78) μg/kg/min, p = 0.002) to maintain mean arterial pressure (MAP) above 65 mmHg. The observed 28-day mortality was 65%. Key proinflammatory cytokines and permeability factors (e.g., interleukin (IL)-6, IL-1b, and angiopoietin-2) were significantly reduced after TPE, while the protective antipermeability factor angiopoietin-1 was not changed. Ex-vivo stimulation of HUVECs with plasma obtained before TPE induced substantial cellular hyperpermeability, which was completely abolished with plasma obtained after TPE.
Inclusion of early septic shock patients with high doses of vasopressors was feasible and TPE was safe. Rapid hemodynamic improvement and favorable changes in the cytokine profile in patients with septic shock were observed. It has yet to be determined whether early TPE also improves outcomes in this patient cohort. An appropriately powered multicenter randomized controlled trial is desirable.
Clinicaltrials.gov, NCT03065751 . Retrospectively registered on 28 February 2017.
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