202410111818

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Tags: Obstetrics

Postpartum haemorrhage

defined as

• cumulative blood loss >1,000 mL
• blood loss with signs or symptoms of hypovolemia within 24 hours after vaginal or cesarean delivery

PPH is one of the leading causes of pregnancy-related deaths

Elements of NPMS (National partnership for Maternal Safety):

Antenatal anaemia

Antenatal anemia has been a/w PPH
antenatal hemoglobin <9 g/dL conferring a 2‐fold increased risk of severe PPH requiring transfusion
severe antenatal anemia (hemoglobin <7 g/dL) increasing the risk of PPH 10‐fold

Although studies have hypothesized that severe anemia may impair myometrial contractility ∵ reduced oxygenation, ↑ risk of uterine atony, the precise mechanism(s) through which anemia heightens PPH risk are unclear

Coagulopathy during PPH

The majority of obstetric hemorrhage is caused by uterine atony, surgical and/or genital tract trauma (>80%), yet coagulation is often preserved unless bleeding is massive

Abnormal placental implantation is the leading cause of massive blood loss. In cases of abnormal placental implantation, precipitous blood loss can rapidly induce coagulopathy due to both depletion and dilution of clotting factors.

Hypofibrinogenaemia

In patients with moderate to severe PPH, one of the most notable hemostatic changes is the decrease in the plasma fibrinogen level

Among patients who experience 1000-1500mL blood loss the incidence of hypofibrinogenemia (<2g/L) is around 4-5%

hypofibrinogenemia occurs in 17% of PPH cases with blood loss exceeding 2500mL and in 26% of cases with a blood loss surpassing 3000mL

Findings from several studies indicate that pre-emptive exposure to fibrinogen concentrate in patients with mild or moderate PPH does not reduce the risk of transfusion or additional blood loss compared to placebo

Thrombocytopenia

Thrombocytopenia is relatively uncommon in patients with mild to moderate PPH (1.3 – 5.1%), but the incidence substantially increases (up to 50%) in patients with severe or life-threatening hemorrhage

platelet transfusion was only required with large volume blood loss (>5000mL) or if bleeding was associated with placental abruption or pre-existing thrombocytopenia

↓ clotting factors

The incidence of a prolonged PT or aPTT is very low in patients with mild-to-moderate PPH (0.2 – 0.5%)

Dilutional coagulopathy

While this phenomenon has been studied in hemorrhage during major surgery and trauma settings, evidence in PPH is relatively limited

Coagulopathy unrelated to blood loss

placental abruptio
AFE
sepsis
HELLP

Coagulopathy has been described in cases of placental abruption and amniotic fluid embolism (AFE)

In both etiologies, coagulation impairment can occur early or even before bleeding is observed and is often unrelated to blood loss volume, with disproportionately low fibrinogen levels and signs of hyperfibrinolysis being recurrent features

Alternative causes of coagulopathy unrelated to volume of blood loss include sepsis and pre-eclampsia incorporating hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome

In a recent prospective observational study by De Lloyd et al, a distinct coagulopathic phenotype – Acute Obstetric Coagulopathy (AOC) - was characterized, with no correlation with blood loss volume

Guidelines

Coagulopathy identification predominantly relies on laboratory test thresholds, notably

• fibrinogen level <2 g/L,
• platelet count < 75x10^9/L
• PT/aPTT values 1.5 times higher than the non-pregnant reference range.

definitions for PPH-related coagulopathy are inconsistent across national obstetric societies

POC tests / VHA

Longitudinal studies investigating maternal coagulation profiles using TEG and ROTEM have demonstrated increased coagulability and decreased fibrinolysis with advancing gestation

Results of ROTEM parameters should therefore be considered within device specific reference values since the correlations for individual parameters, including CT and FIBTEM values, may vary between the ROTEM sigma and delta devices

Prolongation of the ROTEM EXTEM CT and the TEG R can therefore suggest clotting factor deficiency, but these derangements may also be corrected by fibrinogen infusion alone, further complicating interpretation.

The Pltem (EXTEM A10 - FIBTEM A10) also has a high NPV (0.99) in identifying thrombocytopenia although only moderate correlation was observed between Pltem and platelet count (r=.42)

current reference ranges for ROTEM LY30 are not able to distinguish between normal lysis and hyperfibrinolysis during pregnancy

severe hyperfibrinolysis has been identified using TEG and ROTEM in patients with life-threatening PPH from amniotic fluid embolism

Outcome w/ VHA guided resus

limited evidence
likely ↓ blood product transfusion

Taken together, these data provide important evidence supporting the clinical utility of POC tests in ruling out coagulopathy among patients with mild-to-moderate PPH. By excluding coagulopathy, these tests have the potential to prevent unnecessary plasma or platelet transfusion, particularly in hospitals adhering to formulaic approaches to blood product transfusion, such as 1:1:1 for RBC: plasma: platelet transfusion.

This approach is a vital component of patient blood management, ensuring that individuals requiring only RBCs for anemia receive appropriate treatment without unnecessary exposure to other blood products.

OBS UK trial

just registered

In cases of ongoing bleeding, repeat POC tests every 20-30 minutes or after every 500-1000 mL blood loss until successful cessation of bleeding is confirmed.

The accuracy of POC testing in detecting thrombocytopenia and clotting factor deficiencies is uncertain and therefore laboratory tests of coagulation should be performed at the same time as POC testing during active periods of blood loss.

ROTEM protocol

TEG6S protocol

CFF A10

• 17mm (or fibrinogen >2g/L) → no fibrinogen replacement required

• <=17mm (or fibrinogen <=2g/L) → give fibrinogen conc.
  • CFF A10 10-17mm = 4g
  • CFF A10 <10mm = 6g

CK-R

Review CK-R after CFF A10 >17mm and/or fibrinogen >2g/L

• <= 7.6min (or normal PT/APTT) → no FFP

• 7.6min (or ↑PT/APTT) → give FFP

  • booking weight <=50kg = 3u
  • booking weight >50 = 4u

Quantitative blood loss

Quantification of blood loss is a key element of the NPMS bundle and is recommended for all deliveries by national societies, including the American College of Obstetricians and Gynecologists (ACOG), AWHONN, and the California Maternal Quality Care Collaborative (CMQCC)

While visual EBL is readily available, feasible, and easy to perform, it has been shown to underestimate large volume loss while overestimating small volume loss

Fibrinogen

When acquired hypofibrinogenemia occurs during PPH, FFP is not the preferred method for fibrinogen replacement due to its low fibrinogen concentration and the large volume required for fibrinogen repletion

Administration of FFP in early PPH can paradoxically lower fibrinogen levels, as the fibrinogen concentration in FFP is lower than the maternal serum fibrinogen level at term gestation

the high volume of FFP required to raise the fibrinogen level exacerbates dilutional anemia to the point of increasing pRBC transfusion requirement

Cryoprecipitate requires a smaller transfusion volume but is pooled from multiple donors

Fibrinogen concentrate reduces the risk of infectious transmission and immunologic reaction from exposure to multiple donors required for cryoprecipitate

Fibrinogen concentrate is a human plasma-derived, pasteurized concentrate powder. Each vial contains approximately 1 gram of fibrinogen concentrate

Fibrinogen concentrate is reconstituted with 50 mL of sterile water and can be rapidly administered over 10 minutes during hemorrhage

The study used to develop the dosing equation for fibrinogen concentrate was performed in 12 non-pregnant patients with hypofibrinogenemia

In massive hemorrhage, repletion with fibrinogen concentrate may not be optimal, as it lacks von Willebrand factor and, depending on the formulation, factor XIII, which is necessary for clot stabilization.

No benefit was found for the use of pre-emptive treatment of PPH with fibrinogen concentrate (2 g)

VHA

data support moving away from fixed ratio transfusion methods in PPH and use of POC VHA-guided therapy to enable individualized, targeted hemostatic treatment and avoid unnecessary transfusion and associated transfusion morbidity.

TXA

The World Maternal ANtifibrinolytic trial (WOMAN trial), an international, multicenter placebo-controlled study, investigated the effect of TXA compared to placebo in 20,060 patients who experienced PPH after vaginal or cesarean delivery in predominantly low- and middle-income countries.

The study found that TXA reduced the risk of death from PPH compared to placebo (mortality rate, 1.5% vs 1.9%; relative risk (RR) = 0.81; 95% CI: 0.65-1.00; P = 0.045), when administered within 3 hours of birth (RR = 0.69; 95% CI: 0.52-0.9). There was no difference in morbidity outcomes of transfusion or hysterectomy.

counter-argument: may not apply in high resource settings (i.e. ?poor external validity)

TRAAP trial

• vaginal delivery
• no difference in PPH
  meta-analyses: conflicting results

TRAAP2 trial

• CS
• no difference in postpartum transfusion requirement
  meta-analyses suggest some benefit but criticised for:
• substandaard trials
• unreliable data
• reporting bias

TXA as prophylaxis is unwarranted

MoA

The minimum serum level of TXA to achieve antifibrinolytic effect is thought to be 10-20 mcg/mL

Seifert et al. demonstrated that administration of 1g IV TXA to patients at high risk for PPH having cesarean delivery yielded a peak serum level of 59.8 mcg/mL 3 minutes after administration, with serum levels sustained higher than 10 mcg/mL for more than one hour during surgery

In patients having cesarean delivery randomized to receive TXA 1 g, TXA 0.5 g, or placebo, d-dimer as a surrogate for hyperfibrinolysis were increased in placebo, and lowered with superior dose response to 1 g TXA

Safety

Vigilance on drug error

intrathecal administration of TXA can be highly fatal

Neuro & cardiac manifestation:

• convulsion, immediate back/gluteal pain, leg myoclonus
• VF, cardiac arrest

An intravenous injection of 1 g tranexamic acid results in a concentration of 0.9 μg/l in the CSF 9 h after injection. Administration of 1 g of tranexamic acid evenly distributed throughout the normal CSF volume of 150 ml would therefore be expected to produce a CSF concentration of approximately 6600 μg/ml – approximately 7000 times higher than after intravenous injection. A patient who died after spinal injection of 200 mg tranexamic acid had a CSF tranexamic acid concentration of 432 μg/ml at post-mortem

The mechanisms for tranexamic acid-induced seizures and muscle spasms include a direct ↑ in excitability of neuronal networks

Tranexamic acid directly inhibits GABA type A and glycine receptors located on the postsynaptic sites of spinal dorsal horn neurones, resulting in increased excitability
→ back/gluteal pain, LL myoclonus

Generalised convulsions are due to ↓ inhibitory neurotransmission as a result of direct competitive antagonism of γ-aminobutyric acid type A receptors and glycine receptors within the brain

Cerebral vasoconstriction, ischaemia and raised intracranial pressure may also play a role following systemic administration of higher doses

Cardiovascular effects may result from centrally mediated massive sympathetic activation due to seizure activity

Mx

Management remains symptomatic and supportive

Seizures could often not be terminated even using multiple routine anticonvulsants

Toxic effects of spinal tranexamic acid may be reduced if its CSF concentration is reduced by concomitant or subsequent administration of local anaesthetic or CSF lavage

A volume of 10 ml of CSF is removed and replaced with 10 ml of saline; this may be repeated up to four times

Insertion of a spinal catheter may facilitate this. Careful asepsis will be required during these procedures

PPH in PAS

Median blood loss for patients with PAS undergoing cesarean hysterectomy has been reported to range from 2 to 10 L

Depending on the degree of invasion, 4 to 8 units of pRBCs should be in the operating room, checked and ready to transfuse if needed. FFP, platelets, and cryoprecipitate should also be easily acquirable

Cell salvage may be most beneficial for cases with higher anticipated blood loss to ensure that enough red cells are collected for reinfusion. In these cases, cell salvage may decrease the amount of allogenic blood transfused

There is a paucity of evidence-based trauma-informed guidelines and recommendations for patients with PAS

References

Postpartum Hemorrhage Assessment and Targeted Treatment - BPRCA

Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia - Patel - 2019 - Anaesthesia - Wiley Online Library

315. Postpartum Hemorrhage

Episode 159 — Postpartum Hemorrhage With Juanita Henao

Navigating Coagulopathy in Obstetric Hemorrhage The Role of Point-of-Care Testing - BPRCA