Fibrinogen and Management of Peripartum Life-Threatening Hemorrhage

Peripartum Life-Threatening Hemorrhage and Associated Coagulopathy

Peripartum life-threatening hemorrhage (PŽOK) refers to critical bleeding during childbirth that requires rapid transfusion therapy with not only red blood cell concentrates but also fresh frozen plasma (FFP) or platelet concentrates. Coagulopathy can easily develop in PŽOK due to physiological changes in coagulation and fibrinolytic parameters in pregnant women during late pregnancy. Besides the amount of blood loss, determining the fibrinogen concentration in the blood appears to be a suitable indicator for assessing the severity of PŽOK.

Two specific coagulopathies can also occur in PŽOK. One is consumptive coagulopathy, where tissue factor flowing into the maternal bloodstream activates exogenous coagulation factors forming a complex with activated factor VII, leading to increased fibrinogen consumption. The other is dilutional coagulopathy, where there is extensive loss of coagulation factors associated with massive blood loss, which is replaced by infusions and transfusions without replenishing coagulation factors. The common link between both types of coagulopathy is that the fibrinogen concentration in the blood serves as an indicator of critical PŽOK and that timely fibrinogen supplementation can be a crucial step in preventing PŽOK.

Hypofibrinogenemia

To timely normalize fibrinogen levels, it is essential to know its current level. The value requiring massive transfusion is a fibrinogen concentration of < 200 mg/dl, or indirect determination via A5_FIMBTEM < 10 mm (a parameter assessed by rotational thromboelastometry). In the third trimester of pregnancy, normal fibrinogen concentrations rise to nearly 500 mg/dl. The minimum amount of fibrinogen necessary for normal hemostasis represents 40−50% of the normal concentration.

Efficacy of Fibrinogen Concentrate

Rapid normalization of fibrinogen levels reduces the volume of lost blood. Currently, fresh frozen plasma can be used to compensate for lost fibrinogen; however, due to higher concentration, it is more appropriate to administer fibrinogen concentrate. Other risks of FFP therapy include volume overload, which can lead to pulmonary edema. One must also consider the time-consuming plasma preparation before administration.

Studies show that prophylactic administration of 2 g of fibrinogen concentrate had no effect on postpartum hemorrhage in women with normal blood fibrinogen levels. However, when the concentrate is given to patients with PŽOK and severe hypofibrinogenemia (< 150 mg/dl), fibrinogen levels increase. This also reduces the volume of FFP units administered during continued care.

Point-of-Care Fibrinogen Testing

Prognosis for patients can be improved by quick identification of low fibrinogen levels in plasma and timely intervention. Viscoelastic systems (TEG, ROTEM) can evaluate fibrinogen levels through point-of-care testing (POCT, in vitro measurement at the point of care) and are a suitable screening method. These bedside methods allow fibrinogen level measurement within 10−20 minutes, thus providing information on the severity of coagulopathy in its early stage, estimating the necessary volume of transfusion products, and enabling timely initiation of appropriate therapy.

Conclusion

Administering fibrinogen concentrate is most effective in patients with severe hypofibrinogenemia. Prophylactic administration of fibrinogen concentrate to women with normal plasma fibrinogen levels proved ineffective in preventing significant blood loss. Viscoelastic methods are suitable techniques for early screening and intervention in PŽOK.

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Source: Matsunaga S., Takai Y., Seki H. Fibrinogen for the management of critical obstetric hemorrhage. J Obstet Gynaecol Res 2019; 45: 13−21, doi: 10.1111/jog.13788.