Color profile: Generic CMYK printer profile Composite Default screen 8 PATHOPHYSIOLOGY OF POSTPARTUM HEMORRHAGE AND THIRD STAGE OF LABOR R.-U. Khan and H. El-Refaey INTRODUCTION uterine volume leads to a reduction in placental site surface area. As the placenta is a relatively The physiology of postpartum hemostasis rigid and inelastic structure, the surface area of depends primarily upon mechanical events its attachment site decreases when it is tightly mediated by hormones, which induce strong compressed. uterine muscular contraction. Virtually all According to Brandt, compression of the recent studies focus on the latter, but the placenta forces placental blood back into the phenomenon cannot be understood without sinuses in the decidua basalis6. These sinuses examining why uterine contraction stops become blocked by the action of strong bleeding. Broadly speaking, myometrium and myometrial contraction, and thus the com- decidua are arranged such that powerful muscu- pressed placenta attempts to force blood back lar contractions after delivery favor hemostasis into a high-resistance system. Ultimately, the (Figure 1)1–3. Spiral arteries ‘fan out’ to create a sinuses become so congested that they rupture. low-resistance vascular bed in the intervillous The blood from the ruptured sinuses tears the space, which facilitates placental blood flow. fine septae of the spongy layer of the decidua This flow has been shown to decrease with basalis, and thus the placenta is sheared off7. muscular activity4. Third-stage contractions Dieckmann and colleagues implied that this are powerful and prolonged: they act to stop ‘retroplacental hematoma’ has no functional placental blood flow and to separate the value, and a subsequent investigation suggested placenta and membranes. that it is the contraction and retraction of the uterine wall itself that cause it to rend itself PLACENTAL SEPARATION AND apart from the placenta8. UTERINE ACTIVITY Ultrasonographic investigations recently corroborated that the Dieckmann theory is Mechanical events correct. Herman and colleagues conducted The biomechanical events which lead to real-time ultrasonographic imaging of the delivery of the placenta and its membranes third stage of labor and identified a ‘detach- begin to take place even before the start of the ment phase’, wherein the placenta completes second stage of labor. Membrane detachment its separation9. This detachment is preceded by starts during the first stage and slowly spreads a ‘contraction phase’, in which the placental- upwards from the internal os5. site uterine wall undergoes thickening. How- As the trunk of the baby is delivered, the ever, the ‘latent phase’ before this thickening uterus muscle fibers undergo a very powerful occurred varied between patients and was contraction. Muscle fibers shorten, and the thought to determine the overall length of the uterus is reduced in size and volume, a process third stage. Of interest, neither the latent phase characterized as retraction. These events are nor the contraction phase was associated probably facilitated by the spiral arrangement of with ultrasound evidence of retroplacental uterine muscle fibers, whereby the reduction in hematoma formation. 62 84 Z:\Sapiens Publishing\A5211 - Postpartum Hemorrhage\Make-up\Postpartum Hemorrhage - Voucher Proofs #T.vp 30 August 2006 14:19:44 Color profile: Generic CMYK printer profile Composite Default screen Pathophysiology of postpartum hemorrhage membranes which follow the placenta and may form a retroplacental clot, whereas this blood escapes immediately in the Matthew Duncan method. Second, placental separation is slower in the Matthew Duncan method, allowing more time for bleeding10. As clinicians are able to nei- ther predict nor alter the method of placental separation, the distinction between the Schultze and Matthew Duncan methods is most proba- bly clinically irrelevant. Control of postpartum bleeding occurs by contraction and retraction of the interlacing myometrial fibers surrounding maternal spiral arteries of the placental bed. Myometrial con- traction compresses the spiral arteries and veins, thereby obliterating their lumina. It is for this reason that the myometrial fibers involved are often referred to as ‘living ligatures’10. In addi- tion, it is thought that some hemostasis occurs by means of direct pressure as the uterine walls are forced to firmly oppose one another as a result of myometrial contraction. It is worth noting the physiological effect of early cord clamping, a common intervention which is part of the active management of the third stage of labor, is to retain blood in the pla- centa, which prevents it from being so tightly Figure 1 (a) Circular uterine muscle at rest: two compressed by the uterus. This, in turn, reduces sets of crossing spiral; (b) at term: stretching of the the amount of myometrial retraction and con- 1 spirals (Goerttler, 1931 ). The innermost part of the traction, leading to more, not less, bleeding. muscular layer has been described as superficially However, this blood is thought to form a retro- ‘circular’ musculature, which is in fact two sets of placental clot, which speeds up the shearing off crossing spirals2. An alternative description of muscle fibers travelling in all directions has been of the placenta. Ultimately, the consequent described3. Both descriptions suggest that blood speedy delivery of placenta should lead to vessels are compressed during contraction of muscle quicker hemostasis, but the intervention of cord cells clamping is a paradox in that it involves causing increased initial bleeding to lessen ultimate total bleeding. The two classical methods of placental deliv- Unfortunately, apart from the recent ultra- ery result in different bleeding patterns. In the sound studies mentioned above, there is a dis- Schultze method, separation begins in the cen- tinct paucity of information about the physical ter of the placenta (the fetal surface), and this changes which lead to hemostasis and placental part descends first, with the remainder follow- separation. ing. The Matthew Duncan separation method involves detachment of the leading edge of the Endocrine mechanisms leading to placenta, and the entire organ slips down and mechanical events out of the uterus sideways. The latter method is much less common (20% of the total), but is Like all muscular activity, uterine contractility supposed to result in more bleeding for two pos- depends on both electrical and hormonal sible reasons. First, in the Schultze method, any stimuli. ‘Intrinsic’ activity may be mediated by extravasated blood is trapped within the stretch receptors, although it is unclear whether 63 85 Z:\Sapiens Publishing\A5211 - Postpartum Hemorrhage\Make-up\Postpartum Hemorrhage - Voucher Proofs #T.vp 30 August 2006 14:19:45 Color profile: Generic CMYK printer profile Composite Default screen POSTPARTUM HEMORRHAGE such mechanisms are neural or neurohormonal. both to prevent and to treat postpartum hemor- Two classes of hormones have been implicated rhage. At the same time, however, therapeutic in third-stage uterine contractility, namely oxytocic agents used to augment labor are oxytocin and prostaglandins. sometimes associated with uterine atony in the third stage. In this latter circumstance, the non-pulsatile administration of these agents Oxytocin may be leading to down-regulation of oxytocin Interest in the role of oxytocin in the third stage receptors, as has been demonstrated in in vitro has been partly motivated by the long-standing studies15. Despite the acknowledged therapeu- experience with therapeutic oxytocin to prevent tic role of oxytocic agents in the third stage of postpartum hemorrhage. Broadly speaking, labor, the true physiological role of oxytocin in oxytocin causes increased uterine contractions the third stage remains unclear. It appears to by acting on myometrial oxytocin receptors. have an inconsistent or paradoxical relationship However, research has failed to show a clear with the third stage. and simple relationship between physiological oxytocin action and third-stage events for a Prostaglandins number of reasons. Oxytocin assays are notori- ously unreliable, because the decidua synthe- Prostaglandins are potent stimulators of sizes its own oxytocin. As a result, plasma levels myometrial contractility, acting via cyclic AMP- do not reflect oxytocin concentrations at the mediated calcium release. The therapeutic use- myometrium. Moreover, plasma oxytocin levels fulness of prostaglandin agents in postpartum take no account of the density of myometrial hemorrhage lends credence to the possibility oxytocin receptors, which has been shown to of a physiological role for prostaglandins in participate in a complex control mechanism the third stage of labor. The prostaglandins with oxytocin itself and other factors. Finally, involved in uterine contraction are produced in oxytocinase, a plasma enzyme, denatures decidual tissue, placental tissue and fetal oxytocin before it reaches its site of action11. membranes16. The uterotonic action of prosta- During labor, oxytocin is released in a glandins does not depend on gestation. There pulsatile manner, and both the pulse frequency are many classes of prostaglandin; the two and duration increase12. Exactly what triggers classes implicated in uterine contraction are the pulsatile oxytocin release is presently PGE2 and PGF2α. unclear. Ferguson speculated that uterine Several observers have noted that large stretching of the cervix stimulates oxytocin