Shock Syndromes II

Tranexamic acid in postpartum hemorrhage:

In the WOMAN trial, a tranexamic acid 1-g bolus (which may be repeated at 30 minutes

if bleeding persisted after the initial dose) did not affect all-cause mortality but did reduce

mortality from postpartum hemorrhage if administered within 3 hours compared with placebo

(1.2% vs. 1.7%; RR 0.69; 95% CI, 0.52–0.91; p=0.008).

ii.

The World Health Organization strongly recommends tranexamic acid within 3 hours for

postpartum hemorrhage.

The importance of early tranexamic acid was evaluated in an integrated analysis of both the

WOMAN trial and the CRASH-2 trial. For every 15-minute delay to tranexamic acid, the overall

benefit was decreased by around 10%, highlighting the importance of early administration.

In cardiac surgery, perioperative tranexamic acid reduced blood product transfusions and rates

of major hemorrhage without a higher risk of death from thrombotic complications, but with an

increased risk of seizures (0.7% vs. 0.1%; p<0.01).

Of note, the tranexamic acid doses of 50–100 mg/kg used in this study are much higher than

those used in trauma.

ii.

The increased risk of seizures may be unique to cardiac surgery because the risk of stroke and

seizures has been described after cardiac surgery, independent of tranexamic acid use.

A lysine analog that is 10-fold less potent than tranexamic acid

Recommended dose is a 150-mg/kg bolus, followed by a 15-mg/kg/hour infusion.

Compared with tranexamic acid, aminocaproic acid may cause more adverse drug reactions,

including hypotension and bradycardia, with rapid administration and rhabdomyolysis.

patient.

Recombinant Activated Factor VIIa (rFVIIa)

Activates hemostasis through the extrinsic pathway of the coagulation cascade by interacting with

tissue factor to activate factor X to factor Xa and factor IX to factor IXa. Adequate concentrations of

platelets and fibrinogen are needed to support activity.

In trauma, a randomized controlled trial (CONTROL trial) was terminated early because of the futility

for the primary end point of mortality, though investigators did find a reduction in PRBC transfusion

with rFVIIa (200 mcg/kg followed by 100 mcg/kg at 1 hour and 3 hours) in patients with blunt trauma.

There is no consensus on rFVIIa use for acute bleeding. Institutional protocols vary with respect to

appropriate indication, timing, dosing, and readministration of rFVIIa.

Database reviews document an increased incidence of venous and arterial thromboembolic events with

off-label rFVIIa use for non-hemophilia indications.

In trauma, rFVIIa should only be considered if major bleeding and traumatic coagulopathy persist

despite all other attempts to control bleeding and optimize the physiologic environment, including

correction in acidosis, hypothermia, and hypocalcemia.

Although rFVIIa may reduce transfusion requirements, its lack of consistent mortality benefit limits its

widespread adoption in trauma care.

A combination of concentrated clotting factors II, VII, IX, and X and proteins C and S

Four different forms of PCC are available in the United States. Factor content of the PCCs varies,

particularly for factor VII (Table 5).

FEIBA (factor eight inhibitor bypassing activity) is the only PCC composed of activated clotting

factors, making it an activated prothrombin complex concentrate (aPCC). Although theoretically

more efficacious, this may also lead to increased thrombotic events.