Units Of FFP Research Articles

Use of Activated Recombinant Factor VII for the Control of Post Partum Hemorrhage (PPH).

Objective: To evaluate the efficacy and safety of activated recombinant factor VII (rFVIIa) in the control of PPHPatients and Methods: All patients with massive PPH who failed medical and surgical treatment were eligible for the investigation. Massive PPH was defined as loss of > 1000 ml of blood within 24 h after delivery. Patients were considered for treatment with rFVIIa after failure of conventional measures such administration of myotonic agents including oxytocin, ergotamine, misoprostol and failure of other interventions aimed at controlling blood loss such as ligation of uterine and ovarian vessels, or ligation of internal iliac artery. The primary outcome measures were control of the bleeding episode and reduction in the number of administered blood products.Results: A total of 16 patients with massive PPH were eligible for the current study. Vaginal and vacuum delivery was used in 6 patients while 10 patients underwent C-section. The mean dose of rFVIIa was 68 mcg/kg administered intravenously as a single bolus injection. Mean time of diagnosing PPH and administration was 5.5 hours (+/−2). The mean number of blood products used prior the administration of rFVIIa was 14 units RBC and 12 units of FFP. Cessation of blood loss was achieved in 14 patients within an average of 20 minutes after the administration of rFVIIa. The blood products utlilized after the administration of rFVIIa in these patients were 2 URBC and 2UFFP. The uterus was conserved in 7 patients who received rFVIIa prior to hysterectomy. While in 9 patients rFVIIa was administered after failure of hysterectomy to control blood loss. Of the 16 patients, 3 died because of multiorgan failure following severe blood loss. No adverse events including thromboembolic phenomena were observed.Conclusion: Massive PPH is the most common cause of maternal mortality in developing countries. The use of rFVIIa in patients with massive PPH can achieve hemostasis with a single dose only. The administration of rFVIIa in patients with massive PPH may avoid the need for hysterectomy. There were no safety issues in the current study. Further trials should address the dose and timing of administration of rFVIIa in patients with massive PPH.

Sequential Use of Recombinant Factor VIIa and FEIBA in a Pediatric Patient with Disseminated Intravascular Coagulation.

The persistence of abnormal coagulation test results and bleeding after standard treatment in the setting of disseminated intravascular coagulation (DIC) can pose a significant challenge. Recombinant Factor VIIa (Novo Nordisk) has been used in the pediatric population for treatment of hemophilia patients with inhibitors and in various other instances as a single agent to manage coagulopathy. (1) The use of NovoSeven and FEIBA (Baxter Hyland Immune) has been reported in use of adult patients with factor deficiencies and coagulation factor inhibitors. (2) The synergistic use of NovoSeven and FEIBA to improve clinical bleeding caused by DIC in a pediatric patient is being described.A 15 year old African American male presented with a 2 month history of leg pain and a WBC of 400K. He was diagnosed with Philadelphia chromosome positive CML and treated with Allopurinol and Imatinib. After 7 months on Imatinib, he presented in septic shock. His WBC increased to 50.8K with 44% myeloblasts. Flow cytometry confirmed myeloid blast crisis. The patient was admitted to the PICU on broad spectrum antibiotics. Within 12 hours of admission, he required ventilatory assistance. Central lines were placed in the right subclavian vein, right femoral vein and left radial artery. He began bleeding from his nostrils, endotracheal tube and all of his central line sites. Mitoxantrone and Cytarabine were started. Patient was noted to have DIC with PT> 20 sec, APTT> 40 sec, platelets of 23K and D-Dimers of 11.86 (normal <0.42 mcg/ml). His Fibrinogen level was maintained above 300mg/dl during the first 8 days of admission. By hospital day 2, the patient received numerous units of FFP, platelets and PRBC, but he continued to bleed. NovoSeven was started due to volume concerns and increased bleeding. He had improvement in his coagulation tests but no improvement in his bleeding. On hospital day 3, NovoSeven was given intravenously alternating with FEIBA. The patient received NovoSeven 100 micrograms/kg IV q 12 hours. About 6 hours from the NovoSeven dose, FEIBA was given on a q 12 hour schedule at 50 units/kg IV. Significant improvement was seen with the coagulation profile immediately and the bleeding improved in 6 hours. The patient was discharged from the PICU 15 days from his admission with no clinical adverse events associated with the administration of the NovoSeven and FEIBA. He has subsequently tolerated a haploidentical transplant from his sister and he remains in continuous remission.Nigel Key and colleagues have described improved clinical clotting response with prothrombin complex concentrate (PCC) and NovoSeven. They hypothesized that the coagulation proteins in PCC have a longer half life impacting on the effectiveness of NovoSeven. (2) The use of FEIBA and NovoSeven is risky without a widely available clinical assay to assess responsiveness to NovoSeven. This anecdotal report suggests that FEIBA and NovoSeven can be given sequentially without adverse thrombotic events. Further study in monitoring NovoSeven and using sequential agents may be helpful in patients who prove unresponsive to NovoSeven alone.

P15 Transfusion Related Acute Lung Injury (TRALI) or Other Acute Lung Injury (ALI)?

Transfusion related acute lung injury (TRALI) is a form of acute lung injury (ALI) occurring within 6 h of transfusion. Patients presenting with TRALI are often indistinguishable from other causes of ALI. It is an increasingly recognized severe complication of transfusion. We present two cases where TRALI was strongly clinically suspected but only one case was serologically proven to be TRALI. Case 1: A 51 year old lady sustained a massive haemorrhage following an elective gynaecological procedure. 48 h later she returned to theatre and received 4 units of FFP and developed ALI. Case 2: A 28 year old had a postpartum haemorrhage following an emergency caesarian section. After receiving 3 units of RBC she developed respiratory failure. Both patients required ventilation but made a full recovery. Fluid overload, cardiogenic pulmonary oedema, sepsis and pulmonary thromboembolism were excluded and the cases were referred to the NBS for investigation of TRALI. In both cases, the expert panel consulted by the NBS was doubtful about the likelihood of TRALI since all 4 FFP units were collected from male donors and red cells are thought less likely to be implicated. However, all donors were contacted and investigated for WBC antibodies in their serum. Serology did not confirm the diagnosis in Case 1 but TRALI was confirmed in the second case where anti‐HNA1 antibodies were identified in one of the red cell donors and the patient typed as HNA‐1a positive. The diagnosis of TRALI is one of exclusion of other causes of ALI. Here we illustrate that despite the clinical similarities between the two patients, both strongly suspected of TRALI, only one was serologically confirmed to have TRALI. This highlights the difficulties in deciding which cases should be referred for further investigation. Although the referral process is complicated and requires a great deal of clinical input, TRALI needs to be considered as a cause of ALI following transfusion with all blood products, including RBCs. Finally, it is important to reach a diagnosis for both the patient concerned, as this may impact on their future management, and to exclude the implicated donors from further donations.

Treatment of Non-Endemic Hepatolithiasis in a Western Country. The Role of Hepatic Resection

The aim of this study was to assess the safety and the efficacy of hepatic resective surgery in the treatment of single lobe hepatolithiasis. Retrospective analysis and comparison between hepatic resections in patients with hepatolithiasis (hepatolithiasis group [HG]) and liver masses (control group [CG]). Seventeen consecutive Caucasian patients with single lobe hepatolithiasis (HG) and 30 patients with liver masses without chronic liver disease and previous chemotherapy (CG), were operated during the 5-year period 2000-2005, inclusive. Major hepatic resections including 4 right hepatectomies, 10 left hepatectomies, and 3 left lateral sectionectomy in HG, and 12 right hepatectomies, 3 extended right hepatectomy, 5 left hepatectomies, 4 left lateral sectionectomy, 5 bisegmentectomy, and 1 mesohepatectomy in CG. The main outcome measures were: type and length of surgical procedures, intra- and postoperative blood losses and transfusions (packed red blood cells [PRBC] and fresh frozen plasma [FFP]), intra- and postoperative course and complications (within 30 days of the operation), length of hospitalisation, histopathology, and recurrence of hepatolithiasis. Mean operation time was 6.21 +/- 2.38 h in HG versus 7.10 +/- 2.21 h in CG (P = 0.33). Mean intra-operative blood loss in CG was higher than in HG (1010 +/- 550 ml versus 560 +/- 459 ml; P = 0.035). The other variables considered in the two groups were not statistically different. Intra-operative transfusion were 0.50 +/- 0.85 units in HG versus 1.35 +/- 2.25 units of PRBC in CG (P = 0.06), and 0.66 +/- 1.34 units in HG versus 0.68 +/- 1.20 units of FFP in CG (P = 0.44), respectively. No cases of death were registered. Postoperative complications occurred in 12 patients (25.5%) - 5 cases (10.6%) in HG and 7 cases (14.8%) in CG (P = 0.18). Mean postoperative transfusions were 0.47 +/- 1.24 units in HG versus 1.10 +/- 1.18 units of PRBC in CG (P = 0.35), and 0.65 +/- 1.40 units in HG versus 0.46 +/- 0.82 units of FFP in CG (P = 0.25), respectively. Difference in median hospitalisation was not statistically significant (14 +/- 10 days versus 12 +/- 9 days; P = 0.28). Histopathology showed cholangiocarcinoma in 2 cases (11.7%). During the follow-up period (range, 5-127 months; mean, 50.4 +/- 41.9 months), 1 patient had lithiasis recurrence and 1 patient died for the co-existing cholangiocarcinoma. Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

Efficacy of Low-Dose Recombinant Activated Factor VII (rFVIIa) in Massively Transfused Trauma Patients with Coagulopathy.

Introduction: Coagulopathy in the setting of massive transfusion is multifactorial: the dilutional effect of blood loss and inadequate replacement of coagulation factors and platelets, DIC from hypotension and tissue injury, consumption of coagulation factors and platelets at multiple sites of endothelial damage, hypothermia, and impaired hepatic synthesis of coagulation factors in severe hepatic injury are all contributing factors. rFVIIa in "standard" or higher doses (90 μg/kg is the approved dose for hemophilia patients with inhibitors) has been reported to reverse coagulopathy in trauma-related massive transfusion. We postulate that lower doses of rFVIIa may be efficacious.Case series: 8 patients (M:F 1:1, age range 17–78, mean 52 yrs) with blunt trauma and multiorgan injury excluding head injury (Injury Severity Score 18–43, mean 30) had received massive transfusion within the first 24 hr of admission and had persistent bleeding despite resuscitative surgery. The first 3 patients had severe hepatic injury. Blood component support (mean number of units) included: 24 units of packed red cells (range 10–46), 12 units of FFP (range 5–32), 19 units of platelets (range 5–35), and 14 units of cryoprecipitate (range 0–20). Mean INR was 1.42 (range 1.24–1.90). Hematology consultation was obtained, and patients received 1.2 or 2.4 mg rFVIIa with the goal of achieving a dose of 20 μg/kg. Weight-based dosing was calculated post-hoc and the mean dose for the series was 21 μg/kg (range 11–37 μg/kg). Mean post-rFVIIa INR was 0.95 (range 0.84–1.08; vs 1.42, p=0.0002); INR correction apparently persisted for 10–12 hr in 7 out of 8 patients. There was good correlation between INR correction and bleeding cessation. Mean blood component usage (in 7 patients) in the 24-hr period post-rFVIIa included: 5 units of packed red cells (range 2–10; vs 24, p=0.01), 2 units of FFP (range 0–6; vs 12, p=0.04), and 5 units of platelets (range 0–10; vs 19, p=0.02). In one patient outlier, who had liver, spleen, kidney, pelvic and long bone fractures, the effect of rFVIIa was attenuated by surgical washout; INR correction and bleeding cessation were short-lived. The overall mortality in this series was 25% (2/8, including one patient whose care was withdrawn on hospital day 15 at the family's request); this compares favorably to the 40%–50% mortality quoted in massively transfused trauma patients. There were no thromboembolic complications in this group of patients (myocardial infarction, stroke, and extremity thrombosis were specifically sought in all cases). Of note, during this time, 2 other patients were considered for rFVIIa by the trauma team, but additional blood component therapy as recommended by hematology consultation led to bleeding cessation.Discussion: Low-dose rFVIIa (on the order of 20 μg/kg) used after appropriate blood component resuscitation appears to correct the coagulopathy of massive transfusion in critically injured blunt trauma patients. In this setting, rFVIIa can be very cost-effective. Collaboration between the trauma team and hematology or transfusion medicine specialist is important to guide the timing, dosing, and laboratory monitoring of rFVIIa.

Rituximab in Three Cases of Refractory Thrombotic Thrombocytopenic Purpura.

Thrombotic Thrombocytopenic Purpura (TTP) etiology remains elusive, recently has been associated with von-Willebrand Factor-cleavage protein inhibitory antibodies. Plasma exchange (PE) remains the gold standard therapy, however there are some cases resistant to it. Rituximab has been proved useful in antibody mediated immune disorders. We report our experience in 3 consecutive TTP patients, refractory to PE and successfully treated with Rituximab 375 mg/m2 weekly x 6.Case 1. A 41 years old female diagnosed with Hasimoto thyroiditis 4 years before. In January 2003 she was admitted to hospital with headache, abnormal behaviour, 16x109/L platelets and 4–5% schistocytes. 47 PE sessions with a total of 235 fresh frozen plasma units (FFP) for replacement were made. Corticosteroids, IVIG and vincristine were added, but no improvement was achieved. Then, Rituximab was administered, after the second dose a complete clinical response was attained, and she remains well by now.Case 2. A 21 years old female was into hospital in October 2003 with bruises, paraesthesia, skin pallor and jaundice. Hb 6.5 g/dL, platelets 4.6x109/L, LDH 1223 U/L and 13% schistocytes. She received 24 PE with 96 FFP units, plus corticosteroids and vincristine, with no response. Rituximab was administered, after the third dose she experienced a complete response, and remains stable since then.Case 3. female, 35, she was into hospital in January 2005 with diarrhoea, vomiting, jaundice, seizures and bruises, Hb 4.5 g/dL, platelets 10x109/L, LDH 2486 U/L and 20% schistocytes. She received 43 PE with 129 FFP units and corticosteroids, but her neurological situation worsened. Rituximab was administered, after the first dose she experienced a complete response which maintains nowadaysConclusions: intense PE remains the gold standard therapy, it is expensive, scarce, and not free of secondary effects. In a group of patients refractory to PE Rituximab is emerging as useful safe option, it was very well tolerated in ours cases. Unfortunately, we were not able to test the vWF-CP activity and its inhibitor. Our results encourage us to use Rituximab earlier than the first case, in order to avoid too much PE, and now we are considering Rituximab as a second option in patients refractory to PE, but much more cases must be considered.

Administration of FFP Repletes and Sustains the Megakaryocyte/Platelet-Derived Factor V Pool To Confer Hemostatic Competence in a Factor V-Deficient Individual.

Recent studies by our laboratory have demonstrated unequivocally that factor V is endocytosed by megakaryocytes from plasma to form the platelet-derived factor V pool. In the current study, we have determined the time-dependent acquisition of factor V by platelets in a 67 year old factor V-deficient patient, previously shown to be completely devoid of plasma- and platelet-derived factor V. The patient now receives weekly tranfusions of two units of FFP to prevent gastrointestinal bleeding. Plasma and platelet lysate samples were prepared from fresh, whole blood drawn prior to (0 hrs), and following (2, 6, 24, 96, 168 hrs) patient transfusion. A factor V radioimmunoassay (RIA), which can detect factor V concentrations as low as 0.075 μg/mL, a standard factor V clotting-based activity assay, and/or western blotting analyses, which utilize a mixture of anti-human factor V light chain and heavy chain mAbs, were used to evaluate the appearance, and subsequent disappearance, of factor V in these two blood compartments. Prior to transfusion (t = 0 hr), the patient's plasma-derived factor V could not be detected by any of the three factor V assays. The patient's plasma-derived factor V level peaked immediately following transfusion (t = 2 hr) reaching a concentration of 1.3 +/− 0.08 μg/mL as measured by RIA, and declined until it reached an undetectable level at 96 hrs post transfusion. These data were confirmed by the results of both the clotting-based assays and western blotting analyses. As the patient's platelet-derived factor V levels were below the sensitivity of both the RIA and clotting assay, they were analyzed by western blotting. Such analyses confirmed that subsequent to its endocytosis, the patient's platelet-derived factor V is stored in a partially protelytically activated form similar to that of a control individual. Due to the partially proteolytically activated state of the platelet-derived cofactor, platelet lysates treated with thrombin to activate the factor V to factor Va were used for quantative western blotting. Interestingly, and perhaps consistent with the patient's receipt of weekly FFP transfusions, factor V/Va could still be detected in platelets immediately prior to transfusion. Subsequent to transfusion and in marked contrast to changes in the plasma-derived cofactor pool, a significant increase in the patient's platelet-derived factor V/Va level was not observed until 24 hrs post transfusion. These data are consistent with previous studies demonstrating that platelets do not endocytose factor V. Although the concentration of the platelet-derived factor V/Va pool decreased over the subsequent 6 days, antigen remained detectable even though the plasma-derived pool had been depleted 3 days earlier. These combined observations indicate that, subsequent to FFP administration, the patient's megakaryocytes acquire and proteolytically process plasma-derived factor V normally. Furthermore, the consistent presence of factor V/Va within the patient's platelets is in all likelihood preventing gastrointestinal bleeding in this individual, which supports the concept that platelet-derived factor V represents the hemostatically relevant factor V pool.

Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy

We prospectively studied presentation biological differences and the response to therapy in patients with thrombotic thrombocytopenic purpura (TTP) associated with, or unrelated to human immunodeficiency virus (HIV) infection. TTP patients underwent standard evaluations and were treated with prednisone 1 mg/kg in addition to infusions of fresh frozen plasma (FFP; 30 ml/kg/d) until normalization of the platelet count. Unresponsive patients were referred for plasma exchange. Compared with HIV- TTP patients (n=23), in HIV+ subjects (n=21) microangiopathy was dominant among Black females, who had lower presentation Hb (median 5.8 g/dl; P=0.03), platelet count (13 x 10(9)/l; P=0.05) and a CD4 count of 0.096 x 10(9)/l. HIV+ individuals responded to FFP faster than HIV- patients and none of them required apheresis. Ten HIV- TTP patients required apheresis (P=0.03) and four died. Responses in the HIV+ and HIV- groups occurred after treatment with a median of 33 and 55 units (one unit=320 ml) of FFP (P=0.004) respectively. Response to this protocol was seen in 84% (95% response in HIV+ patients). Regression analysis showed that survival was associated with younger age (P=0.001), rapid platelet (P=0.001) and Hb (P=0.0009) recovery, and fewer FFP units to normal lactate dehydrogenase levels (P=0.006). We conclude that in HIV+ individuals, microangiopathy is highly responsive to plasma infusions. This observation is important particularly when apheresis is not available.

Case report: immune anti-D stimulated by transfusion of fresh frozen plasma

Abstract FFP has occasionally been reported to generate an immune response to RBC antigens (e.g., anti-D and anti-Fya). The Council of Europe requires that each unit of FFP have less than 6 × 109/L RBCs. However, there is considerable variation internationally in the method of production and the level and assessment of RBC contamination of FFP. This study reports the case of a 63-year-old group B, D– man who received multiple transfusions of D– blood products over a 4-month period. Seven months later the patient’s antibody screen remained negative and he was transfused with seven units of D– RBCs and six units of FFP, four of which were D+. Two months later anti-D, -E, and -K were detected in his plasma. Although the anti-E and anti-K could have resulted from transfusion of antigen-positive RBCs, the anti-D could have resulted only from transfusion of the D+ FFP. The D status of FFP is currently not considered when selecting products for transfusion even though the D antigen is highly immunogenic and the level of RBC contamination of FFP is not always known. This case highlights that transfusion of FFP is a stimulus for RBC antibodies and that when a patient has had a recent transfusion of FFP, consideration should be given to obtaining a sample for pretransfusion testing within 3 days before a scheduled RBC transfusion. In addition, the D status of FFP should be considered before administering FFP to premenopausal D– women. Immunohematology 2005;21:149–51.

Hemostatic Levels of Coagulation Factors in Patients with Mild Prolongation of Prothrombin Time / INR: Implications for Transfusion Medicine Practice.

OBJECTIVE: To investigate hemostatically important clotting factors in patients with mild to moderate prolongation of PT/INR, who generally receive prophylactic FFP transfusions, especially in neurosurgery, because there is scant data in the literature supporting prophylactic plasma therapy. METHODS: 36 plasma samples from 31 neurosurgical patients with PT/INR 12.5–15.0/1.3–1.5 were separated and frozen within 8 hours of collection; these were tested for coagulation factors II, VII and VIII levels, and PT/INR/PTT values were correlated with the factor levels. Retrospective analysis of all neurosurgery patients for whom FFP was ordered with similar PT/INR values was performed both during 5 months of study period and 5 months post-study period, when changes were implemented in FFP administration guidelines. The PT/INR/PTT values were studied 24 hours following the FFP requests in order to evaluate the effect of plasma infusion. Each group was divided in two subgroups: those who received FFP transfusion within 24 hours of the FFP requests, and those who did not. RESULTS: PT/INR/PTT and coagulation factor levels of the 36 samples are seen in Table 1.PT mean13.78INR mean1.38PTT mean29.29PT median13.5INR median1.3PTT median29.5PT range10.7–18.6INR range0.9–1.9PTT range19.3–37.9FII mean68%FVII mean53%FVIII mean156%FII median66%FVII median51%FVIII median126%FII range34–107%FVII range28–124%FVIII range55–547%There was no correlation between PT/INR with FVII levels (p>0.05). All patients had FVII > 15–25%, level recommended as safe for surgery. FII was also hemostatically normal, whereas mean factor VIII level was elevated, that correlated with shortened PTT in many of these patients. Retrospective analysis revealed that during the study period there were a total of 99 FFP requests (69 patients). Of these 68 requests (46 patients) did and 31 (29 patients) did not receive FFP transfusions within the next 24 hours. Mean number of FFP units transfused was 3.03 (median 2, range 1–7). During the post study period a total of 15 requests (for 14 patients) were received; of these 2 did and 13 did not receive FFP transfusions within the next 24 hours. Mean and median number of FFP was 2. PT/INR/PTT at time of request and 24 hours post transfusion are presented in the Table 2Study Period (99 FFP requests)Post Study Period (15 FFP requests)Transfused (68)Non-Transfused (31)Transfused (2)Non-Transfused (13)At FFP RequestAt 24 hrsAt FFP RequestAt 24 hrsAt FFP RequestAt 24 hrsAt FFP RequestAt 24 hrs13.42*12.111.911.2914.112.812.2211.541.3†1.181.161.11.41.31.181.1428.9♠27.9827.6527.4326.627.127.426.99*PT;†INR;♠PTTCONCLUSION: In patients with a mild prolongation of PT/INR, plasma levels of FII and FVII were hemostatically normal, whereas FVIII levels were increased. After FFP transfusions, PT/INR and PTT values did not change suggesting that plasma therapy in these patients was not warranted. After the study there was a drastic reduction (85%) in FFP orders for prophylactic plasma transfusions.

A novel method of preoperative autologous blood donation with a large volume of plasma for surgery in gynecologic malignancies

The objective of this study was to establish a novel method of preoperative autologous blood donation (PAD) for surgery of gynecologic malignancies, which requires considerable amounts of plasma relative to the red blood cell component. To collect a double volume of plasma over the amount obtained from whole blood without using an aphaeresis system, we first collected 500 ml of whole blood (2.5 units), and centrifuged it. We gave back the resultant red cell component alone, and retained the plasma component. We further collected an additional 500 ml of whole blood, and centrifuged it. The red cell component (2.5 units) was stored in the refrigerator (as a concentrated red cell, CRC). The resultant plasma together with the plasma collected first (5 units) was frozen and stored in the freezer (fresh frozen plasma, FFP), We repeated this procedure at most three times at intervals of 1 week. Erythropoietin was injected once a week and iron tablets were prescribed. Ninety-nine patients undergoing surgery for a gynecological malignancy were subjected to this method and 86 patients without PAD served as a control. We conducted the procedure for PAD without any noticeable side effects. The amount of actual use of allogeneic CRC and FFP were significantly reduced in the PAD group compared with the control group. In particular, 93.6% of the PAD cases who gave 10 or less units of FFP could go without allogeneic FFP. Postoperative serum albumin levels were higher in the PAD group compared with the control. We have established a novel PAD method which can yield a greater volume of FFP relative to CRC, thus meeting requirements for surgery for gynecological malignancies.

An unsuspected case of placenta accreta

Case report A 29-year-old school-teacher presented in her second pregnancy at term + 6 in spontaneous labour, with an undiagnosed breech presentation. A detailed ultrasound at 20 weeks had shown the placenta to be fundal. She had had an uneventful antenatal period. Her previous pregnancy had been uncomplicated and ended in a forceps delivery at term. Subsequently she developed postpartum endometritis, which was treated by antibiotics. She had wellcontrolled asthma and was a non-smoker. Vaginal examination revealed that the cervical os was 8 cm dilated. After discussing the mode of delivery she opted for caesarean section, which was performed under spinal anaesthesia. The placenta was removed manually but was apparently complete. The estimated blood loss was 800 ml. Intraoperatively, a slight tear of right uterine angle was noted and was sutured. A drain was left intra-abdominally and syntocinon infusion of 40 units in 500 ml of normal saline was administered. Two hours postoperatively she started bleeding vaginally. On examination abdomen was soft, nondistended and the drain contained only 30 ml of serous blood. Initial management included intravenous oxytocin; bimanual uterine compression and intramuscular prostaglandin F2 alpha (carboprost) did not arrest the bleeding. She was taken back to theatre for laparotomy. There was no intra-abdominal bleeding. The uterus was reopened. No obvious source of bleeding was identified; therefore all uterine and abdominal layers were closed again. The vaginal bleeding ceased, but soon after laparotomy she then started bleeding intra-abdominally due probably to disseminated intravascular coagulation (DIC), and finally a subtotal hysterectomy was performed. The estimated blood loss was approximately 6 l. In total she received 15 units of blood, 12 units of FFP, 9 units of cryoprecipitate and 2 units of platelets. Her postoperative care was managed jointly in the intensive care unit, and the high-dependency area of the labour ward, by the anaesthetist, haematologist and obstetrician. She made a good recovery. Pathological examination showed a uterus weighing 628 g and measuring 15 6 9 6 6 cm. The endometrial cavity contained blood and the endometrial lining was ragged. There was no residual placental tissue identified and there were no leiomyomata or other abnormalities seen. Random blocks were sampled from around the uterine cavity and in the blocks from the fundus two foci of residual chorionic villi were identified, the largest 6 mm across. These chorionic villi were lying in close proximity to the myometrium with some large veins and there was a cytotrophoblastic reaction nearby. There was minimal decidual change in this area, although elsewhere decidua up to 2 mm thick was present. The changes were considered consistent with placenta accreta (Figure 1).

Vitamin K-dependent coagulation factors and fibrinogen levels in FFP remain stable upon repeated freezing and thawing.

FFP is considered adequate for transfusion up to 24 hours after thawing and is currently used most often to replace deficient clotting factors, such as in warfarin overdose. We set to examine the levels of vitamin K-dependent factors (i.e., prothrombin, FVII, F IX, FX), as well as fibrinogen, upon twice freezing and thawing of FFP. If factor levels in refrozen FFP remain within normal limits, this component can possibly be transfused, thus avoiding wastage of precious blood components. Twenty units of FFP, five units of each blood group A, B, AB, and O, were thawed, and aliquots were taken for measurement of coagulation factors. The plasma units were then kept for 24 hours at 4 degrees C, at which point a second aliquot was taken, The remaining FFP units were refrozen and kept at -80 degrees C for 1 week. The above procedure was then repeated. Coagulation-factor activity and fibrinogen level were measured by the coagulation analyzer. The mean levels of prothrombin, FVII, F IX, FX, and fibrinogen of each blood group (A, B, AB, and O) were calculated for each of four time points and found not statistically different (p > 0.05). Therefore, the rest of the analysis was done for all 20 FFP units as one group. The mean +/- SD levels of each coagulation factor at each time point demonstrated that all levels were within normal limits of all factors measured and that for none of the factors was there a significant decay of activity. The levels of prothrombin, FVII, F IX, FX, and fibrinogen remain stable and adequate for transfusion in twice-thawed-and-refrozen FFP. This component can be safely used for transfusion as a source of vitamin K-dependent clotting factors and fibrinogen.

Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients.

Epstein-Barr virus (EBV) infection is recognized as the principal aetiological factor in the pathogenesis of post-transplant lymphoproliferative disease (PTLD), particularly when primary EBV infection occurs after transplantation. We analysed, using a time-dependent proportional hazards model, the factors associated with development of PTLD in 40 adult liver transplant recipients who were seronegative for EBV prior to transplantation. Of 40 patients, 13 (33%) had a tissue diagnosis of PTLD at a median time of 126 days after transplantation. The multivariate analysis showed that prior CMV disease, the number of steroid boluses given and the number of units of RBC and FFP transfused were significant risk factors for development of PTLD.

"Goal-directed" transfusion management leads to distinct reduction of fluid requirement in liver transplantation.

Complications in patients undergoing OLT, such as hemorrhagic events, are caused not only by surgical problems but also by the profound functional disturbances arising from hepatic insufficiency, which are at least partially cured by the procedure itself. Preoperative clotting data give insight only into the dysfunction of the explanted organ. Hence, we tried to perform a standardized, "goal-directed" anesthesiologic management in the perioperative phase in OLT, following strict indications for blood replacement according to diuresis, hemoglobin level, and hemodynamic parameters. We performed 200 OLTs in 185 patients, according to usual methods. The mean intraoperative fluid requirement was 884 ml of balanced salt solution, 8.1 units of RBC, and 9.4 units of FFP. During the first 24 hours postoperatively, an average of 2.4 units of RBC and 5.6 units of FFP had to be transfused. Currently, 170 of the 185 patients (91.9%) are alive and well. Our data demonstrate that a distinct reduction of transfusion rates in OLT is possible, neglecting clotting data and improving clotting function by avoiding hemodilution.

Rapid thawing of fresh frozen plasma in two-liter bags

The authors hypothesized that plasma could be rapidly thawed in two-liter Transfer Pack Units, because of their greater surface area (993 cm 2) compared to standard satellite bags (348 cm 2) of Blood Pack Units (both from Fenwal, Baxter Healthcare Corp, Deerfield, IL). Five units of FFP were prepared in each bag. The Sterile Connection Device (DuPont, Wilmington, DE) was used to transfer plasma from the satellite to transfer pack units, and these were put in metal canisters before all units were frozen at −65°C. Thawing time was 4.8 ± 1.3 (SD) minutes and 15 ± 3.2 (SD) min. for units prepared in modified and standard methods respectively ( t = 6.33, P < .01). The thermal rate constants were calculated as 0.0034 and 0.0033 for the two methods. The finding of similar values substantiate the theory that thawing time is related to the volume to surface area ratio.

Transfusion Pattern of Fresh Frozen Plasma at Medical University Hospital in Bangladesh

This cross sectional study was carried out at Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of November 2008 to April 2009 on patients who received fresh frozen plasma. Relevant information of those patients was noted from the records kept at the Department of Transfusion Medicine. The collected data was statistically analyzed.In this study it was observed that 939 units of FFP were required in BSMMU during study period. 289 patients required these units of FFP. The age of the patients that required FFP ranged from 1 day to 75 years. Among them highest 99 (34.25%) were in the age group1 day to. 10 years. There were178 (61.59%) males and 111 (38.41%) females. Out of 289 patients 111 (38.41%) was B+ve, 86 (29.76%) was O+ve, 66 (22.84%) was A+ve and 26 (08.99%) was AB+ve. According to Rh typing maximum unit 930 (99.04) units were Rh D +ve, 9 units (00.96%) were Rh D-ve. Highest number of FFP Unit 329 (35.04%) was used in day care center in transfusion medicine department. Followed by Gastro-enterology 188 (20.02%), Burn &amp; Plastic surgery 140(14.91%), Paediatrics &amp; allied 106 (11.29%), Rest 176 units by other departments.According to clinical indication highest number of FFP Unit 271 (28.86%) was used for Hemophilia A, followed by CLD 210 (22.36%), Burn140 (14.91%). Distribution of the units of FFP according to rational use it was found that a large number of unit 386 (41%) use was not clinically justified. Study shows 60 (20.77%) patients was not supplied with correct documentation. According to requirement Transfusion Medicine alone uses 35%, other dept of university uses 46%, 19% of unit is supplied to other medical centers. Key words: Fresh frozen plasma; Transfusion; Clinical audit. DOI: 10.3329/jdmc.v18i2.6273 J Dhaka Med Coll. 2009; 18(2) : 132-135