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Placenta percreta is an obstetric complication, where the placenta invades through the myometrium into adjacent organs, is often associated with life-threatening torrential haemorrhage. The bleeding is usually controlled by medical treatment including oxytocin and prostaglandins; or surgical means including ligation of uterine or internal iliac arteries, hysterectomy or intra-arterial embolisation (). However, in severe cases, it usually requires intensive resuscitation, blood components and coagulation factors. Massive transfusion often leads to disseminated intravascular coagulopathy (DIC) because of haemorrhage secondary to coagulation and platelet consumption.
Our massive transfusion protocol currently relies on conventional coagulation test results before preparing blood components. This ultimately leads to major delays in administering components which then, may not be relevant to the current clinical situation. For the case documented below, where massive haemorrhage was anticipated, we decided to use a predetermined blood product administration protocol in an effort to mitigate and treat coagulopathy by early, adequate coagulation factor administration, thus removing the delay in ordering, preparing and subsequent administration of blood components.
However, in some cases, even adequate replacement therapy fails to control life-threatening bleeding resulting in exsanguination. Alternative haemostatic treatments, which are efficacious in such a setting, might be life-saving and reduce red cell transfusion requirements. Fibrinogen concentrate (Haemocomplettan®) and activated recombinant factor VII (rFVIIa, Novoseven®) may be potential candidates. The experience of using fibrinogen concentrates and rFVIIa in obstetrics is very limited. However, other surgical specialties have successfully used both products in both prophylactic and therapeutic indications (Wissa 2009). This report will also examine our experience of the use of fibrinogen concentrate together with rFVIIa in an attempt to control massive haemorrhage.
A 29-year-old para one, with one previous caesarean section was scanned at 21 weeks' gestation. The ultrasound scan revealed a low-lying placenta. Serial scans showed placenta previa with the anterior placenta covering the os, full thickness invasion of the myometrium and indentation of the bladder. She was otherwise well with no history of PV bleeding or abdominal pain. At 33 weeks' gestation she was admitted and caesarean section planned for 3 weeks later.
A lower transverse incision through the previous incision was made in the uterus to deliver the baby. Following delivery the bleeding from the placental bed was brisk and heavy as attempts were made to remove the placenta. A decision for a peripartum hysterectomy was agreed in view of the uncontrollable haemorrhage and failure of other medical and surgical haemostatic techniques.
29 units of red cells were transfused, together with 14 units of fresh frozen plasma, 4 units of pooled cryoprecipitate, and 6 units of platelets. Haemostasis was eventually achieved following the administration of 3 doses of 8mg rFVIIa (Novoseven) and 6g of fibrinogen concentrate (Haemocomplettan®, CSL Behring, Marburg, Germany). The patient spent 2 days in the intensive care unit. The postoperative recovery was uneventful and the patient was discharged 9 days after delivery.
Haemoglobin, platelet count and prothrombin time were monitored throughout the procedure (figure 1). rFVIIa was given at xxx and fibrinogen concentrate at xxx.
Placenta percreta is defined as a morbidly adherent placenta (accrete) that penetrates through the uterine muscle into the bladder and/or other adjacent organs (Miller 1997). The incidence of placenta accreta is 1 in 2,500 deliveries. Placenta percreta occurs in 5-7% of all abnormal placentations. Parallel with the dramatic and persistent rise in caesarean delivery rates, the incidence of placenta accreta is increasing (Oyelese 2006). However, limited data is available to guide optimal management and, in particular, transfusion management. The purpose of this study was to review our experience with placenta percreta and evaluate the transfusion strategies employed.
Major obstetric haemorrhage can often lead to consumptive coagulopathy, increased fibrinolysis, and impaired function of platelets and coagulation factors. Emerging practice requires the early and aggressive use of blood components. It was agreed pre-operatively that packed red cells in a 2:1 ratio with plasma would be used since it has been associated with a reduction in mortality in the exsanguinating patient (Kushuk 2008). This initially worked well, however bleeding continued in spite of optimal blood component replacement, hysterectomy and internal iliac artery ligation. A decision was made to treat more aggressively using newer haemostatic agents, rFVIIa and fibrinogen concentrate. rFVIIa has been shown to provide effective haemostasis in a wide range of bleeding conditions. It is often used as a last resort and is found that bleeding decreases in most cases leading to significant reductions in red cell transfusion requirements.
The first dose of rFVIIa given to the patient did not appear to act sufficiently due to the loss of coagulation factors and platelets during sustained haemorrhage. The efficacy of rFVIIa is largely dependent on the presence of high levels of fibrinogen. A sufficient haemostatic effect was obtained with rFVIIa during the administration of the second dose because both platelets and cryoprecipitate were transfused immediately prior to administration. By the time the third dose was given normal haemostasis was achieved, bleeding was dramatically reduced and the surgery was completed. No further blood components were required.
Prior to the third dose of rFVIIa, fibrinogen concentrate was administered. Haemocomplettan is a highly purified, lyophilised, virally inactivated fibrinogen concentrate obtained from human plasma that can be rapidly reconstituted without the need for thawing and crossmatching. Fibrinogen concentrate was originally reserved for replacement therapy in congenital fibrinogen deficiency, and in the UK, Haemocomplettan is only approved for this indication. However the role of fibrinogen, a crucial haemostatic coagulation factor in ensuring haemostasis during serious bleeding, has been a subject of increasing interest.
The main finding from this case study was that substitution therapy with fibrinogen concentrate was associated with a significant reduction in blood loss, so much so that no further blood components were used. There was also a significant improvement in coagulation parameters. No serious adverse events were recorded.
Fibrinogen constitutes an important component of the haemostatic process, including its roles in formation of platelet aggregates and generation of a sufficiently stable fibrin network. Adequate amounts of functional fibrinogen are also required to achieve an optimal effect of other haemostatic interventions such as infusion of antifibrinolytic drugs, rFVIIa and platelet transfusions. During progressive blood loss, fibrinogen appears to represent the coagulation factor first reaching a critical low threshold and notably hypofibrinogenaemia may emerge before the development of significant thrombocytopenia. In addition, haemodilution with colloid plasma expanders predisposes to development of a functional fibrinogen deficiency. Hence, it seems reasonable to predict an overall beneficial haemostatic effect of fibrinogen administration as supplementary treatment in massive bleeding patients. Serious bleeding in obstetric complications is often associated with hyperfibrinolysis resulting in very low levels of plasma fibrinogen and high levels of fibrin D-dimer that makes fibrinogen substitution even more reasonable in this cohort of patients.
In conclusion, the present case suggests that substitution therapy with fibrinogen concentrate may contribute to reduced transfusion requirements and decreased blood loss. Prospective clinical trials aiming at evaluating the haemostatic potential of fibrinogen substitution therapy in massively bleeding patients are highly desirable.