Prophylactic Fresh Frozen Plasma Research Articles

Futility of fresh frozen plasma in the correction of coagulopathy prior to image-guided drainage of infected collections: Results from a prospective case–control study

Abstract BACKGROUND: Fresh frozen plasma (FFP) is frequently used as prophylactic hemostatic therapy for correction of periprocedural coagulopathy. This practice is frequently based on the assumption that deranged international normalized ratio (INR) predicts the risk of periprocedural bleeding and that FFP transfusion is effective in mitigating the procedure-associated bleeding risks. There is limited evidence to support both these assumptions in the context of image-guided drainage of infected collections. AIMS: The study aimed to analyze the efficacy of weight-based standard FFP dose for correction of infection-associated coagulopathy in patients with clinicoradiologically diagnosed infected collections planned for image-guided drainage. MATERIALS AND METHODS: In this prospective case–control study, 229 patients with clinicoradiologically diagnosed infected abdominal collection(s) planned to undergo image-guided drainage were included. Cases and controls were defined as patients with baseline INR >1.2–3 (in the absence of any other bleeding diathesis) and INR ≤1.2, respectively. Cases received 10–15 mL/kg of FFP before drainage. Costs and time delays in drainage among the two groups, efficacy of plasma transfusion in the correction of coagulopathy, incidence of transfusion reactions, bleeding complications, and inhospital mortality were analyzed. RESULTS: There were 117 cases and 112 controls. A total of 445 FFP units were utilized. The median (interquartile range) time required from diagnosis of collection to the procedure was 25.3 (20.8–40.3) hours among cases and 16.4 (8.7–20.1) hours among controls (P < 0.001). FFP transfusion resulted in INR normalization (≤1.2) only in 7.9% of cases (n = 9). Among the 81 cases who had pretransfusion INR ≥1.5, INR improved to ≤1.5 in 49 (60.4%) patients. There was an average of 2.9% decrease in INR per unit of FFP transfused. No bleeding complications were noted in patients undergoing drainage despite a persistent deranged INR (>1.5) postplasma transfusion. Transfusion reactions occurred in 17/117 (14.5%) patients. There were no deaths among the controls while five patients died among the cases. CONCLUSION: Prophylactic FFP transfusion for infection-associated coagulopathy leads to a significant delay in lifesaving drainage procedures. Minority of patients attain normalization of INR with FFP transfusion.

Clinical Manifestations, Current and Future Therapy, and Long-Term Outcomes in Congenital Thrombotic Thrombocytopenic Purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an extremely rare disease characterized by the severe deficiency of a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13), caused by ADAMTS13 mutations. While ADAMTS13 supplementation by fresh frozen plasma (FFP) infusion immediately corrects platelet consumption and resolves thrombotic symptoms in acute episodes, FFP treatment can lead to intolerant allergic reactions and frequent hospital visits. Up to 70% of patients depend on regular FFP infusions to normalize their platelet counts and avoid systemic symptoms, including headache, fatigue, and weakness. The remaining patients do not receive regular FFP infusions, mainly because their platelet counts are maintained within the normal range or because they are symptom-free without FFP infusions. However, the target peak and trough levels of ADAMTS13 to prevent long-term comorbidity with prophylactic FFP and the necessity of treating FFP-independent patients in terms of long-term clinical outcomes are yet to be determined. Our recent study suggests that the current volumes of FFP infusions are insufficient to prevent frequent thrombotic events and long-term ischemic organ damage. This review focuses on the current management of cTTP and its associated issues, followed by the importance of upcoming recombinant ADAMTS13 therapy.

Management of a patient with factor X deficiency with FEIBA: a case report

Abstract Hereditary factor X (FX) deficiency is a rare autosomal recessive disorder that increases bleeding tendencies, ranging from epistaxis to intracranial haemorrhage (ICH), which can be life-threatening. Single factor concentrates are recommended for treating rare bleeding disorders; however, in India most people with FX deficiency are treated with fresh frozen plasma (FFP). We report a case of FX deficiency in a child with a history of intracranial bleeding who was found to have a novel mutation in the F10 gene. Although managed with weekly prophylactic FFP infusions, he continued to experience regular bleeding including two further instances of ICH. Other therapeutic options were unavailable or unaffordable. When the Indian Government added FEIBA to the essential drug list, a decision was made to try FEIBA prophylaxis to better manage his bleeding. In 2019, he was started on a weekly dose of FEIBA, 500 IU (20 IU/ kg and his prophylactic FFP transfusion regimen was stopped. His bleeding episodes started to reduce after two months of starting FEIBA prophylaxis. Over the last three years he has had only four minor bleeding episodes and has remained completely free of major bleeding. He is now able to receive home-based therapy and his prognosis can be considered to be improved. FEIBA may be a useful medicinal therapy for FX-deficient patients who suffer severe haemorrhagic episodes in countries where plasma-derived factor X (pdFX) is not available.

Splenic kaposiform hemangioendothelioma presenting as insidious consumptive coagulopathy

Splenic kaposiform hemangioendothelioma presenting as insidious consumptive coagulopathy

A multicenter analysis of the role of prophylactic transfusion of blood products in patients with cirrhosis and esophageal varices undergoing endoscopic band ligation

Background & AimsProphylactic administration of platelets and fresh frozen plasma (FFP) has been recommended in patients with cirrhosis with low platelets and/or prolonged international normalized ratio (INR) without scientific evidence to support this practice. In this analysis, we evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation (EBL).MethodsThis is a multicenter retrospective analysis of consecutive EBL procedures in patients with cirrhosis at 4 hospitals in Spain from 01/2010-01/2017. FFP and/or platelet transfusion were given at the discretion of the physician if INR was >1.5 and/or platelet count <50x109/L. Patient demographics, endoscopic findings, bleeding events after EBL, and the use of prophylactic FFP or platelets were recorded.ResultsA total of 536 patients underwent 1,472 EBL procedures: 72% male; main etiology HCV and alcohol (72%); median MELD score 11; Child-Pugh A/B/C (59/33/8%). EBL procedures were performed for primary (51%) or secondary (49%) prophylaxis. A median of 2 procedures per patient were performed.1-4 FFP and/or platelets were administered in 41 patients (7.6%). The prophylactic transfusion protocol was followed in 16% and 28% of procedures with high INR and/or low platelets, respectively. Post-EBL bleeding occurred in 26 out of 536 patients (4.8%) and in 33 out of 1,472 procedures (2.2%). Bleeding was due to post-EBL ulcers in 21 patients and due to band dislodgment in 5. In 6 patients, bleeding occurred within 24 hours and in the remaining patients it occurred within 2 weeks after EBL. In those that bled, 7 met criteria for transfusion (2 for FFP and 5 for platelets), of whom only 1 received FFP and 4 received platelets; the remaining 19 patients did not meet criteria for transfusion. There was no association between INR or platelet count and bleeding events. Univariate and multivariate analysis revealed that Child-Pugh and MELD scores were risk factors for post-EBL bleeding.ConclusionsThe incidence of post-EBL bleeding is low and is associated with advanced liver disease. Post-EBL bleeding was not related to baseline INR/platelet count and most outpatients with post-EBL bleeding did not meet criteria for prophylactic transfusion.Lay summaryPatients with chronic liver disease or cirrhosis and enlarged veins (varices) of the esophagus that can potentially bleed commonly need an endoscopy to treat these varices with elastic rubber bands (endoscopic band ligation). Some patients have low platelet counts or prolonged coagulation tests. This analysis of 4 centers evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation. The results showed that bleeding after band ligation is uncommon and that if bleeding occurs it does not seem to be related with coagulation tests or the administration of blood products to prevent bleeding after band ligation of esophageal varices.

Prophylactic fresh frozen plasma and platelet transfusion have a prothrombotic effect in patients with liver disease

Background and AimsPatients with liver disease acquire complex changes in their hemostatic system, resulting in prolongation of the international normalized ratio and thrombocytopenia. Abnormalities in these tests are commonly corrected with fresh frozen plasma (FFP) or platelet transfusions before invasive procedures. Whether these prophylactic transfusions are beneficial and truly indicated is increasingly debated. In this study, we studied ex vivo effects of FFP and platelet transfusions in patients with liver disease‐associated hemostatic changes in a real‐life clinical setting. MethodsWe included 19 patients who were deemed to require prophylactic FFP transfusion by their treating physician and 13 that were prescribed platelet transfusion before a procedure. Hemostatic status was assessed in blood samples taken before and after transfusion and compared with healthy controls (n = 20). ResultsEx vivo thrombin generation was preserved in patients with liver disease before FFP transfusion. Following FFP transfusion, both in and ex vivo thrombin generation significantly increased, as evidenced by a 92% and 38% increase in thrombin‐antithrombin and prothrombin fragment 1 + 2 levels, respectively, and a 20% increase in endogenous thrombin potential. Platelet counts increased from 28 [21‐41] × 109/L before to 43 [39‐64] × 109/L after platelet transfusion (P < .01), and was accompanied by increases in in vivo markers of hemostatic activation. ConclusionsFFP and platelet transfusion resulted in increased thrombin generation and platelet counts in patients with liver disease, indicating a prothrombotic effect. However, whether all transfusions were truly indicated and had a clinically relevant effect is questionable.

Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura

BackgroundCongenital thrombotic thrombocytopenic purpura (cTTP), otherwise known as Upshaw‐Schulman syndrome, is an extremely rare hereditary disease. Pregnancy is identified as a trigger for TTP episodes in patients with cTTP. ObjectivesTo investigate the ideal management of pregnant patients with cTTP. Patients/MethodsWe identified 21 patients with a reproductive history (38 pregnancies) in a Japanese cTTP registry. Fetal outcomes were compared between two groups: group 1 (n = 12), pregnancy after diagnosis of confirmed cTTP by ADAMTS13 gene analysis; and group 2 (n = 26), pregnancy before diagnosis of confirmed cTTP. ResultsIn group 1, ADAMTS13 activity was closely monitored until delivery in most cases. Among 10 pregnancies in group 1, prophylactic fresh frozen plasma (FFP) infusions during pregnancy were performed to replenish ADAMTS13. In group 2, prophylactic FFP infusions were not administrated in 23 pregnancies and FFP test infusions were performed in only three pregnancies. The live birth rate of group 1 was significantly higher than that of group 2 (91.7% vs 50.0%, respectively, P = .027). The fetal survival rates of women without FFP infusions were dramatically decreased after 20 weeks of gestation. The FFP infusion dosage in group 1 was generally higher than 5 mL/kg/wk by 20 weeks of gestation. ConclusionsOur results indicate that FFP infusions of more than 5 mL/kg/wk should be initiated as soon as patients become pregnant. However, even with these infusions, patients with repeated TTP episodes before pregnancy might have difficulty giving birth successfully. Recombinant ADAMTS13 products might be new treatment options for pregnant patients with cTTP.

Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures.

Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures.

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy.

BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy.

G121(P) Service evaluation of management of term neonates with major perinatal blood loss

Aims Clear guidelines exist for the management of major haemorrhage in adults. These include a strong emphasis on early transfusion of Fresh Frozen Plasma (FFP) in conjunction with Packed Red Cells (PRC) in order to avoid/treat possible accompanying coagulopathy. Current practice within the local neonatal population is to await clotting profiles and administer FFP if coagulation is found to be abnormal. This practice may lead to a significant delay in treatment. The aim of this service evaulation was to identify whether term neonates with major haemorrhage around the time of delivery required support with coagulation factors. This may support the use of prophylactic FFP alongside RBC transfusion prior to results becoming available helping to stabilise the infant sooner. Methods Data was requested from our local blood transfusion laboratory for all requests for blood products made for patients on the neonatal unit between April 2011 to December 2013. Further details regarding antenatal and neonatal course were then taken from the Badger database on all babies that were identified to have received blood products on their date of birth or following day. Babies born at less than 37 weeks were excluded. Results We identified 7 term babies with a clear history of major perinatal blood loss. 5/7 (71%) required transfusion of FFP in addition to PRC on the basis of abnormal clotting profile. All babies receiving FFP needed extensive resuscitation at birth followed by intensive care support, whereas the 2 babies that were not transfused were clinically stable. One of the babies not receiving FFP did not have their clotting profile checked. All babies received Vitamin K post delivery as standard. Conclusion Term infants with a clear history of perinatal blood loss who are compromised at delivery and require packed red cell transfusion should be considered for early transfusion of FFP without awaiting coagulation profiles.

Prophylactic Fresh Frozen Plasma Infusion is Ineffective in Reversing Warfarin Anticoagulation and Preventing Delayed Intracranial Hemorrhage After Falls.

Elderly patients, with considerable fall risk, are increasingly anticoagulated to prevent thromboembolic disease. We hypothesized that a policy of prophylactic fresh frozen plasma (FFP) infusion in patients having falls would reverse vitamin K antagonists (VKAs) and that reversal would decrease delayed intracranial hemorrhage (ICH). A retrospective review of patients with trauma admitted to a level 2 community trauma center was performed from January 2010 until November 2012. Inclusion criteria were: ground level fall (GLF) with suspected head trauma, on VKA, an international normalized ratio (INR) of >1.5, and a negative head computed tomography (CT). Patients were transfused with FFP to a goal INR of <1.5 while observed. Patients were classified as reversed (REV) if the lowest INR achieved within 4 to 24 hours after initial INR was <1.5 or unreversed (NREV) if lowest INR achieved was >1.5. Chi-square and logistic regression were performed. A total of 194 patients met the criteria. In all, 43 (22%) patients were able to be REV, and 151 (78%) patients remained NREV. Unreversed patients were male and younger (P < .05). There was no difference in mean FFP received. Unreversed patients had a higher initial INR of 3.0 compared to REV patients (2.5; P = .018). One patient developed a delayed ICH and belonged to the REV group. The incidence of delayed hemorrhage was 0.5%. A strategy of prophylactic FFP infusion was ineffective in VKA reversal. We recommend against prophylactic infusion of FFP during a period of observation for patients on VKA with suspected head trauma and a negative initial CT.

Interpretation of clotting tests in the neonate

There are significant differences between the coagulation system in neonates compared with children and adults. Abnormalities of standard coagulation tests are common within the neonatal population. The laboratory tests of...

HSCT-Associated Hepatic VOD Is Initiated With Preceding Appearance Of Unusually Large Von Willebrand Factor Multimers In Patient Plasmas

Backgrounds and AimsHepatic veno-occlusive disease (VOD) associated with hematopoietic stem cell transplantation (HSCT) is characterized by a clinical triad of jaundice (total bilirubin, >2 mg/mL), hepatomegaly with right upper quadrant pain, and ascites and/or unexplained body weight gain (>5% of baseline) within 30 days after operation. Although the pathogenesis of hepatic VOD has not been fully elucidated, the common pathological features are thrombi formed in hepatic central vein.We previously reported that a significant decrease of plasma ADAMTS13 activity was noted in patients undergoing HSCT, who subsequently developed VOD (Park et al, BMT 2002). Then, we showed that plasma antigen levels of von Willebrand factor (VWF) has been kept higher in HSCT-patients with VOD than in those without, and in fact prophylactic infusions of fresh frozen plasma (FFP) with a dose of 10 ml/kg body weight 3 times per week were effective to reduce the frequency of VOD occurrence in high risk patients (Matsumoto et al, BMT 2007). However, more recent studies by ours indicate that FFP infusion alone is not enough to totally eliminate the occurrence (unpublished). Recently, it has been shown that the treatment with recombinant soluble thrombomodulin (rTM) is sometimes highly efficient to reverse VOD progression. But its pharmacokinetics and regimen for the treatment has not been established. As a first step to elucidate a possible combination regimen of FFP and rTM to VOD patients, here we have analyzed the transitional changes of unusually large VWF multimers (UL-VWFMs). The UL-VWFMs are released from damaged endothelial cells and induce platelet hyperagglutination under high shear stress generated in microvasculatures, and are often observed in patient plasmas undergoing HSCT. Patients and MethodsDuring 2011-2012, 45 patients were received allogenic HSCT in the second internal medicine department of our university hospital. None of these patients ,however, were received planned prophylactic FFP infusions, and as a result six patients undergoing allogenic cord blood transplantation (CBT) developed VOD. Clinical features of these 6 patients are shown in Table 1. [Display omitted] Under approval of Ethics Committee of Nara Medical University, we consecutively collected patient's citrated plasmas (ca 2.5 ml) and stored at -80°C until use. Using these deep-frozen plasma samples, we here extensively analyzed plasma levels of ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag), and VWF collagen binding activity (VWF: CBA), together with VWF multimer analysis. More importantly, we also measured the corrected platelet count increment (CCI) to evaluate the efficiency of Platelet trsnsfusions. Then, we comprehensively evaluated these data with routine clinical and laboratory findings. Results and Discussion1) Plasma levels of ADAMTS13:AC were moderately but consistently decreased during two months after HSCT, whereas those of VWF:Ag were kept high, usually more than 200% and often 500% of the normal. 2) The UL-VWFMs appeared soon after HSCT, and continued at least until absolute neutrophil count (ANC) increased to >500 (usually 20-30 days after HSCT). 3) Until platelet engraftment (usually 40-60 days after HSCT), platelet transfusions (every 2-3 days interval) are usually performed to prevent the bleeding complications. During that period, the CCI values were consistently low, but those values were significantly increased during the administration of rTM. 4) Excess platelet transfusions before platelet engraftment induced the consumption of larger VWFMs in patient's plasmas, and often almost simultaneously hepatic VOD developed. Thus, platelet transfusions during the appearance of UL-VWFMs in patient's plasmas may induce platelet clumping in microvasculatures, and lead to the development of thrombotic complications including hepatic VOD. 5) The measurement of plasma levels of VWF:CB activity appeared to well predict the presence of UL-VWFMs. A representative case is shown in Figure. [Display omitted] Thus, a combination regimen of FFP and rTM might be advisable when the patients show the early clinical signs of hepatic VOD and the laboratory data such as VWF:CBA suggest the presence of UL-VWFMs in patient's plasmas. Disclosures:Matsumoto:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees. Fujimura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees; Baxter International Inc: Membership on an entity's Board of Directors or advisory committees.

Reference intervals for common coagulation tests of preterm infants (CME)

Fresh-frozen plasma (FFP) is sometimes administered to nonbleeding preterm neonates who are judged to be at risk for bleeding because they have abnormal coagulation tests. The benefits/risks of this practice are not well defined. One limitation to progress is lack of reference intervals for the common coagulation tests, thus limiting precision about whether coagulation tests are indeed abnormal. In a sequential observational study, fetal blood was drawn at preterm birth (≤ 34 weeks) from the umbilical vein near the placenta. Fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, platelet (PLT) count, and mean PLT volume were measured. Reference intervals were constructed using 5th and 95th percentile values. Associations were then sought between abnormal coagulation values at birth and bleeding problems identified during the first week. Coagulation tests were drawn at 175 preterm deliveries and the results were organized into reference intervals by gestational age. No abnormal coagulation value, either alone or in combination, predicted hemorrhage (intraventricular, gastrointestinal, or pulmonary) during the first week. However, fibrinogen exceeding the 95th percentile was associated with evidence of in utero infection/inflammation (correlations with elevated C-reactive protein, p<0.01, and elevated immature to total neutrophil ratio, p<0.001). Abnormal coagulation values at preterm birth do not predict bleeding during the first week. This suggests to us that bleeding in the days after preterm birth is not generally the result of in utero coagulopathy. These findings bring into question the value of coagulation screening of nonbleeding preterm infants and prophylactic FFP administration to those with abnormal values.

Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

Treatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle 1 of ALL treatment in adult patients. Secondly, we explored potential etiologic factors for VTE and the clinical impact of VTE on ALL outcome. We retrospectively assessed symptomatic VTE incidence and use of thromboprophylaxis in 240 adults treated for newly diagnosed ALL in the Dutch-Belgian HOVON-37 multicentre study (1999-2005). Potential etiologic factors were explored by analysis of patient and disease characteristics, impact of VTE on ALL outcome by analysis of complete remission and overall survival rates. Symptomatic VTE was observed in 24 of 240 patients (10%). Thromboprophylaxis differed by centre (prophylactic fresh frozen plasma (FFP) supplementation or no thromboprophylaxis) and was applied only during L-asparaginase in cycle 1. VTE incidence was significantly lower with FFP supplementation than without FFP (6% vs. 19%; adjusted odds ratio [OR] 0.28; 95% confidence interval [CI] 0.10-0.73). FFP did not influence antithrombin or fibrinogen plasma levels. Patients with VTE in cycle 1 had a significantly poorer complete remission rate (adjusted OR 0.18; 95% CI 0.07-0.50), particularly patients with cerebral venous thrombosis (adjusted OR 0.17; 95% CI 0.04-0.65). Our study suggests that prophylactic FFP supplementation effectively reduces symptomatic VTE incidence during ALL treatment in adults. This should be confirmed in a randomised controlled trial.

Inappropriateness of fresh frozen plasma for abnormal coagulation tests

There is increasing evidence to suggest that the use of fresh frozen plasma (FFP) as a prophylaxis to bleeding is ineffective. However, a high proportion of FFP transfusions still occur in non-bleeding patients despite the high risk of adverse events. The aim of the study was to assess compliance with current prophylactic FFP guidelines at a large tertiary centre. Data were collected retrospectively over a 16-month period from May 2010 to August 2011. Information collected included patient characteristics, indications for and details of FFP use, and the ordering of coagulation screens before and after transfusion. Over this period, FFP was used in a total of 573 transfusion episodes, 88 of which were prophylactic. This use deviated from the British Committee for Standards in Haematology guidelines in three main areas: indications for FFP use (89%), dose prescribed (49%) and the measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) after transfusion (66%). There were no significant differences in compliance with guidelines between different hospital departments, suggesting a culture of widespread inappropriate FFP use and a general lack of understanding among clinicians. Physician training and increased enforcement of existing guidelines could reduce FFP usage and expenditure.

Factors associated with prophylactic plasma transfusion before vascular catheterization in non-bleeding critically ill adults with prolonged prothrombin time: a case–control study

Fresh-frozen plasma (FFP) is widely used in critically ill patients, despite a weak evidence base. Factors that influence the decision to transfuse FFP before intravascular catheter insertion are poorly described. We undertook a case-controlled study based on a prospective cohort study of 1923 admissions to 29 intensive care units in the UK. Non-bleeding patients with an international normalized ratio (INR) ≥1.5 who underwent intravascular catheterization, but no other invasive procedure, were identified. We compared patient characteristics, illness-related factors, and biochemical and haematological variables between patients who did or did not receive pre-procedural FFP. One hundred and eighty-six patients fulfilled the criteria; 26 received FFP during the 24 h before line insertion (cases) and 160 did not (controls). Factors associated with greater use of prophylactic FFP by clinicians were pre-existing chronic liver disease (P=0.01), higher serum bilirubin before procedure (P=0.01), lower platelet count (P=0.01), higher activated partial thromboplastin time (P=0.001), lower fibrinogen (P=0.01), and concurrent red cell transfusion despite the absence of bleeding (P=0.001). There was no difference in pre-procedural INR [median (1st, 3rd quartile) cases: 1.95 (1.85, 2.6); controls 1.8 (1.6, 2.3); P=0.19]. The mean FFP dose was 11.1 ml kg(-1) (sd 5.7 ml kg(-1)); 53.8% of cases were transfused <10 ml kg(-1). Chronic liver disease and more abnormal coagulation tests were associated with greater probability of pre-procedural FFP administration before vascular catheterization, whereas the severity of prothrombin time prolongation alone was not. FFP was more likely to be administered when red cells were also transfused, even in the absence of bleeding.

Two newborn-onset patients of Upshaw–Schulman syndrome with distinct subsequent clinical courses

Upshaw-Schulman syndrome (USS) is caused by a congenital deficit in ADAMTS13 activity owing to genetic mutations. USS is characterized by severe neonatal jaundice with a negative Coombs test and repeated childhood episodes of thrombocytopenia reversible by fresh frozen plasma (FFP) infusions. We present two patients with USS, both of whom underwent exchange blood transfusions as newborns, although the disease subsequently developed along different clinical courses. USS-CC5 initially received a diagnosis of neonatal jaundice due to fetomaternal ABO incompatibility with an indirect positive Coombs test, which masked the diagnosis of USS. Before prophylactic FFP infusions were initiated, USS-CC5 had chronic thrombocytopenia. In contrast, thrombocytopenia developed in USS-HH4 only in response to infections and spontaneously normalized without FFP infusions. Analyses of the ADAMTS13 genes in USS-CC5 and USS-HH4 revealed compound heterozygotes of p.R398C/p.Q723K and p.Q449X/p.Q1374Sfs, respectively. Analysis of von Willebrand factor (VWF) multimers in plasma samples taken from both patients in remission showed single symmetrical multimer bands, which differ from the triplet structure of bands observed in normal samples. These data suggested that plasma VWF multimers in the patients had not been proteolytically modified. Our results indicate the presence of a previously unknown regulatory mechanism for VWF-dependent high-shear stress-induced platelet aggregation.

Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

BackgroundFresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure.MethodsA non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay.DiscussionThe Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure.Trial RegistrationTrial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909

Impact of Prophylactic Fresh Frozen Plasma On Venous Thromboembolism in Adults Treated for Acute Lymphoblastic Leukemia Receiving Asparaginase,

Abstract 3345 Background:Acute lymphoblastic leukemia (ALL) is frequently complicated by venous thromboembolism (VTE). The reported incidence varies from 2% to 37%, with the highest risk arising in the first weeks after treatment initiation. VTE leads to morbidity, mortality and premature termination of therapy. Prevention of VTE in ALL is complicated, as thrombotic and bleeding factors need to be balanced. The efficacy of prophylactic antithrombotic measures is not clear yet, and standardized guidelines are lacking. We assessed the effect of various prevention protocols on the VTE risk in adults treated for ALL. Methods:Between April 1999 and November 2005, 240 consecutive patients aged 16–59 years with newly diagnosed ALL were treated with the same anti-leukemic protocol in a Dutch-Belgian multicenter study, which included L-asparaginase in cycle 1 (5000 U/m2/day, day 15–28). All VTE events during treatment were prospectively recorded. VTE prophylaxis was applied only in cycle 1 during asparaginase administration, and varied between different centers: no prophylaxis, fresh frozen plasma (FFP), or antithrombin (AT) concentrate. A centers’ prevention protocol was used as a proxy for all patients treated in that center. AT plasma levels were assessed of patients with VTE and 22 controls without VTE. We determined VTE incidence in cycle 1, the impact of the various prophylactic measures, and VTE incidence during the total treatment period for ALL. Secondly, we assessed the clinical relevance of VTE on ALL outcome. Results:25 of 240 patients (10.4%; 95% CI 6.6–14.3) experienced objectively diagnosed, symptomatic VTE in cycle 1 (10 cerebral thromboses of which 8 in the sagittal sinus, 11 upper limb vein thromboses (10 central venous catheter (CVC)-related), 3 deep vein thromboses of the leg, 1 pulmonary embolism). VTE incidence in patients receiving FFP prophylaxis was reduced by 70% as compared to patients without prophylactic measures (7.2% vs. 23.9%; RR 0.3; 95% CI 0.1–0.6; Table 1). Age, sex, ALL-type and CVC-placement did not differ significantly between patients with and without FFP prophylaxis. The effect of prophylactic AT concentrate could not be properly assessed as it was only rarely given in two centers. Mean AT plasma levels did not differ significantly between VTE patients with or without FFP, neither between patients with VTE and controls without VTE (Figure 1). During the total treatment period, VTE occurred in 36 of 240 patients (15.0%; 95% CI 10.5–19.5). Patients with VTE in cycle 1 were less likely to obtain complete remission after cycle 1 (HR 0.5; 95% CI 0.3–0.9), but did not have a significantly decreased overall survival (HR 1.5; 95% CI 0.9–2.6).Table 1Effect of FFP prophylaxis on VTE incidence during ALL treatment cycle 1ALL patients with VTE in cycle 1Total number of ALL patientsVTE incidenceFFP prophylaxis141947.2%No FFP prophylaxis114623.9%Total2524010.4%RR = 0.3 (95% CI 0.1 – 0.6)ALL = acute lymphoblastic leukemia; FFP = fresh frozen plasma; VTE = venous thromboembolism; RR = relative risk [Display omitted] Conclusions:FFP significantly reduced VTE incidence by 70% during ALL treatment, without reversing the AT deficiency induced by asparaginase. Our observation is in contrast with two previous studies on the effect of FFP on VTE in ALL. The mechanisms by which FFP accomplishes this antithrombotic effect are not clear yet and require further investigation. Since this was a retrospective, observational study, the effect of prophylactic FFP on VTE risk in adults treated for ALL should be confirmed by a randomized controlled trial. Disclosures:No relevant conflicts of interest to declare.