PCC has been available in India for a few years and not much of literature is available to support its use and efficacy in obstetric patients presenting with haemorrhage. Use of PCC should be kept in mind in patients with severe DIC needing massive blood transfusion, patients with signs of fluid overload or patients with poor cardiac reserve presenting with DIC.This case report is aimed at presenting a case of an obstetric patient who presented with pregnancy induced hypertension (PIH) and acute liver failure with intrauterine foetal death (IUFD) who had to be delivered normally in view

Of IUFD but was having deranged coagulation profile. While correcting disseminated intravascular coagulation (DIC), she developed signs of fluid overload and she responded to a single dose of prothrombin complex concentrate (PCC) which helped to control the continuous oozing post her Normal delivery.  

Case Report

We report a case of PIH who presented with DIC and acute liver failure, in whom labour was induced for IUFD.

Anaesthesia on-call team was called to evaluate a 34 weeks primigravida (G1P0A0) who was transferred from another hospital for further management. She was 25 years old and weighed 72 kgs. She was diagnosed to have Pregnancy induced hypertension (PIH), intrauterine foetal death

(IUFD) and acute liver failure (ALF). She also complained of fever and nausea vomiting since the last 2 days. She had no H/O bleeding per vaginum or any other site. She was on T. Labetalol for PIH.

On examination, she was anxious, tachypnoeic and icteric. She had pedal oedema. Her pulse ratewas 103/ min and feeble. Her blood pressure was 70/48 mmHg, Spo2 on room air was 96% and urine output was 200 ml since the last 5 hrs. Obstetrician’s per abdominal findings confirmed 32 weeks gestation and absent FHS. The head was engaged and mild uterine activity was present. On PV examination, there were no signs of bleeding. Labour was induced with sublingual misoprostol and Inj. Oxytocin infusion in view of IUFD.Her investigations were as follows:

Investigations

• HB: 10.9 g/dl

• TLC:19000 cells/mm3

• Platelet Count:35,000/mm3

• Pt/Inr:36.1 s/3.61 s

• Total Bilirubin: 27.4 mg/dl

• Direct Bilirubin: 12.9 mg/dl

• S. Creatinine:3.1 mg/dl

• Bun:43 mg/dl

• Sodium: 123 meq/l

• Potassium:4.9 meq/l

• Fibrinogen:Less than 35 mg/dl

• Ddimer:7556 ng/ml

• Blood Sugar:82 mg/dl

ABG on room air:

• Ph:7.30
• pO2: 95 mmHg
• pCO2:28 mm Hg
• HCO3:17 mmol/L
• BE:6
• Lactate: 5 mmol/L

Her ABG and peripheral smear for malarial parasite, IGM and Leptospirosis tests were also sent in view of fever. She was started on Inj. Noradrenaline 4 mg/ 100 ml NS at 0.03 mcg/kg/min through peripheral IV cannula and the dose was titrated further as per her BP. In view of deranged INR [13], low platelet count (35,000), deranged LFT and fibrinogen (<35) and raised D-dimer, she received 3 U PRBC, 6 FFP, 16 U platelets and 25 U cryoprecipitate (total volume of 3700ml) over 6 hours to correct her coagulopathy.. Inj Vit K IV was given stat. 10% Dextrose infusion and inj Sodabicarb 50 ml were also given.She had a normal vaginal delivery of a single dead foetus, 4 hrs after starting the blood and blood products. Soon after her delivery, she started showing signs of fluid overload and pulmonary oedema which might have resulted from massive transfusion. Her saturation dropped and she was put on non-invasive ventilation (NIV). There was continuous oozing from the sutured episiotomy site,following the delivery. Tocolytics like Tablet misoprostol 800 mcg per vaginum, Inj. Oxytocin 40 units in 20ml NS was given over 1 hour, Inj. Methylergometrine 0.2 mg intramuscular and Inj. Carboprost 250 mcg intramuscular were given to control the bleeding. Also, Inj. Tranexamic acid 1 gm and inj. Botropase were given IV stat. She kept oozing for almost half an hour postpartum. More blood products could not be given as she was showing signs of fluid overload which was treated with Inj. Furosemide 80 mg and subsequently continuous infusion of Inj furosemide 20 mg/hour was given to improve her urine output. NIV was started in view of pulmonary oedema. She was maintaining 100% saturation with 40% FiO2 on NIV.At this point of time, it was decided to give her Prothrombin complex concentrate (PCC). 80 ml of PCC (2000 IU) was given. She was taken to the operation theatre to look for any other bleeders and resuturing of episiotomy. At this point, she was on NIV with 40% Fio2, maintaining 100% saturation,

On infusion noradrenaline at 0.03mcg/kg/min with BP 114/76mmhg, Pulse rate 95 /min. Also, things were kept ready for obstetric hysterectomy and the cath lab was kept ready for uterine artery embolisation. NIV and inotropic supports were continued. She was drowsy and tachypnoeic and an

Airway cart and drugs for GA were kept ready in view of change in surgical plan if bleeding continued. Bleeding had almost stopped after resuturing of the episiotomy under local infiltration.She responded well to the single IV dose of PCC and further doses were not required. Repeat blood parameters showed improvement with INR 1.34; fibrinogen 201 and platelet count

55,000. Next day by morning, her peripheral oedema started settling. Ionotropic supports were reduced and there were no signs of bleeding. NIV support was given intermittently and her coagulopathy was corrected as per thromboelastography (TEG) for 7-8 days after the delivery pics. She was also found to be positive for Leptospirosis and was treated for the same. The patient was discharged home after 22 days.

Her 2 D echocardiography evaluation was done the next day, which revealed normal findings.

Prothrombin complex concentrates (PCCs) are purified drug products which are obtained from a plasma pool [4-5].It contains a mixture of vitamin K-dependent coagulation factors (II, VII, IX and X) and natural coagulation inhibitors like protein C and protein S, protein Z in variable amounts and also

        Heparin to prevent activation of these coagulation factors factors is 25% higher than the normal plasma. PCCs are alternative to FFP for rapid and reliable substitution of clotting factors [3]. Recommended dose is 35-50 IU/kg.

Indications

• For rapid reversal of warfarin-induced bleeding (7,3-5). Apart from FFP and Vit.K, which are commonly used for the reversal of Warfarin induced bleeding, 4 factor PCC can also be used

• For reversing the effect of newer anticoagulants where the specific antidote is not available like Dabigatran [3]

• Congenital deficiency of any vitamin K-dependent coagulation factors (II, VII, IX, X) [4]

• Prophylactic use of PCC can be considered in the perioperative period in patients with coagulopathy to reduce intra and postoperative bleeding [4]

• Massive blood transfusion

• In emergency situations in case of life threatening bleeding in polytrauma(7) along with FFP transfusion as PCC is devoid of factor V

Advantages

• Rapid reversal: PCC administration takes less time compared to FFP for reversing the anticoagulant effects of warfarin [5]

• Time saving: PCC administration can be done over a few minutes and can save time required for procuring the blood and the blood products [4]

• Safety: It's safe to use PCC in patients with poor cardiac and renal reserve to prevent them from going into fluid overload. [4]

• Leukocyte free: PCC is leucocyte free and hence is safe in post-transplant patients and alsohas less risk of viral transmission [5]

• It prevents Transfusion related lung injury (TRALI) in patients with massive transfusion [4-5]

Adverse Effects

• Allergic reactions [4]

• Thromboembolic complications [8,3-4]. Like pulmonary embolism, DVT, stroke, sagittal sinus thrombosis, myocardial infarction. This risk is reduced with newer preparations as they contain heparin

Relative Contraindications

• Past history of DIC [4]

• Recent history of myocardial infarction or stroke [4]

• In pregnancy- The effect of PCC on the foetus is not known and hence its use in obstetric cases should be considered in conditions where the benefits are more compared to the risks [4]

        In our case, after overzealous transfusion of blood and blood products over a short span of time,patient developed signs of pulmonary oedema and had fluid overload. She needed NIV to maintain the oxygen saturation and was als treated with diuretics. It was decided to use prothrombin complex.

        Concentrate (PCC) as further transfusion of blood and blood products was not possible due to fluidoverload [3]. PCC was used here as a last resort as its use does not find place in obstetric hemorrhage guidelines. The bleeding reduced after the first dose of PCC and further doses were not needed.

Though there is a scarcity of literature on the use of PCC in obstetric hemorrhage, if kept in mind,can reduce the use blood products like FFP and cryoprecipitate to control the bleeding and hence,can prevent complications like fluid overload and transfusion related acute lung injury (TRALI) [4].

1. Pacheco L.D. et al. “An update on the use of massive transfusion protocols in obstetrics.” American Journal of Obstetrics and Gynecology, vol. 214, no. 3, 2016, p. 340.

2. Glynn J.C. et al. “Prothrombin complex for massive obstetric haemorrhage.” Anaesthesia, vol. 62, no. 2, 2007, pp. 202–203.

3. Samama C.M. et al. “Prothrombin complex concentrates: a brief review.” European Journal of Anaesthesiology, vol. 25, no. 10, 2008, pp. 784–789. Doi: 10.1017/S0265021508004675.

4. Baskaran J. et al. Prothrombin Complex Concentrate. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2020. https://www.ncbi.nlm.nih.gov/ books/NBK539716/.

5. Franchini M. et al. “Prothrombin complex concentrates: an update.” Blood Transfusion, vol. 8, no. 3, 2010, pp. 149–154. doi:10.2450/2010.0149-09.

6. Preston F.E. et al. “Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients.” British Journal of Haematology, vol. 116, 2002, pp. 619–624. https://doi.org/10.1046/j.0007-1048.2001.03295.x.

7. Köhler M. et al. “Thrombogenicity of prothrombin complex concentrates.” Thrombosis Research, vol. 95, no. 4, suppl. 1, 1999, pp. S13–S17.