Platelet Rich Plasma for Uterine Scar

When vessel wall injury occurs, platelets become activated, releasing more than 30 bioactive proteins, many of which have a fundamental role in hemostasis, inflammation and ultimate wound healing. Platelet-rich plasma (PRP), a modification of fibrin glue made from autologous blood, is being used to deliver growth factors in high concentration to sites requiring wound healing. PRP is obtained from a sample of patients' blood drawn at the time of treatment. As the rate of cesarean deliveries has been rising, long-term adverse sequelae due to uterine scar defects have been increasing. PRP might be a simple preventive treatment that potentially can reduce morbidity following cesarean deliveries.

Introduction

Platelets are cytoplasmic fragments of megakaryocytes, formed in the marrow and approximately 2 μm in diameter. When vessel wall injury occurs, they become activated, releasing more than 30 bioactive proteins, many of which have a fundamental role in hemostasis, inflammation and ultimate wound healing. Growth factors released from the platelets include platelet-derived growth factor, transforming growth factor beta, platelet-derived epidermal growth factor, platelet-derived angiogenesis factor, insulin-like growth factor 1, and platelet factor 4. These factors signal the local mesenchymal and epithelial cells to migrate, divide, and increase collagen and matrix synthesis.

Platelet-rich plasma (PRP), a modification of fibrin glue made from autologous blood, is being used to deliver growth factors in high concentration to sites requiring wound healing. Its clinical uses have dramatically increased in the last decade in various fields of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology, dentistry, and diabetic wound healing. Recently, its positive effects in promoting endometrial and follicular growth and gestation in assisted reproduction cycles have also been demonstrated.

PRP is obtained from a sample of patients' blood drawn at the time of treatment. A 30cc venous blood draw will yield 3-5 cc of PRP depending on the baseline platelet count of an individual, the device used, and the technique employed. The blood draw occurs with the addition of an anticoagulant, such as citrate dextrose A to prevent platelet activation prior to its use. The preparation process is known as differential centrifugation. An initial centrifugation to separate red blood cells (RBC) is followed by a second centrifugation to concentrate platelets, which are suspended in the smallest final plasma volume. The upper 2/3 portion of the volume that is composed mostly of platelet-poor plasma (PPP) is removed. Pellets are homogenized in lower 1/3rd (5 ml of plasma) to create the Platelet-Rich Plasma (PRP). A count of 1 million /mL has become the working definition for therapeutic PRP. Activation of the platelets before their application is not required as there is no consensus for better results.

Caesarean delivery is the commonest operation performed on women worldwide with progressively rising incidence. Consequently, long-term adverse sequelae due to uterine scar defect have been increasing. Common gynecological complains include chronic pelvic pain, dyspareunia, dysmenorrhea and postmenstrual spotting and infertility. Obstetric sequelae seem to be increasing such as cesarean scar ectopic pregnancy, placenta previa, and placenta accrete, all associated with major maternal morbidity and even mortality. Given the association between uterine scar defect and gynecological symptoms, obstetric complications and potentially subfertility, it is important to develop preventive strategies.

To the best of knowledge studies using PRP for uterine scars treatment have not been published. Due to the aforementioned, the aim of our study is to learn the effect of PRP use on uterine scar healing.

Material and Methods

This is a prospective randomized single blinded study. Study population will include all women planned to undergo elective cesarean delivery at term with singleton pregnancy. Women meeting inclusion criteria will be offered to participate in the study. After signing informed consent, block randomization will be completed, including: A- administration of PRP following uterine incision repair, B - administration of placebo (0.9% normal saline) on the uterine incision. Women will be blinded to the group they have been randomized to. Blood will be drawn to all women 30 minutes before operation for platelet count and preparation of PRP (in case randomization was for group A). All operations will be performed by highly skilled surgeons of the same team. All other stages of operations will be similar in both of the groups. Operative and post-operative data will be collected from the medical files, including operation duration, estimated blood loss, operation complications (hypotension, bladder gut or vascular perforation), post-operative complications (hemorrhage, endometritis, vascular - thromboembolic event, ileus). All women will be invited to the gynecologic clinics at six weeks, 3 months and 6 months post operation for trans-vaginal sonographic evaluation of the uterine scar. Measurement will include uterine scar residual myometrial thickness (RMT), adjacent myometrial thickness (AMT), depth, length, and RMT/AMT ratio.

Women's reports regarding possibility of uterine scar defect symptoms (heavy menstrual bleeding, intermenstrual spotting, pelvic pain) will additionally be collected on follow-up visit

Eligibility Criteria:
Inclusion criteria:

* Women undergoing elective cesarean delivery
* Term pregnancy (≥37 weeks of gestation)
* Singleton pregnancy

Exclusion criteria:

* Thrombocytopenia (CBC Platelet count \<70,000)
* Connective tissue disease
* Uterine scars other than cesarean (s/p myomectomy, s/p cornual resection)
* Malformed uterus (unicornuate, bicornuate, didelphic)