Platelet storage pool disorder: multidisciplinary planning in pregnancy
- Sadia Khakwani ,
- Claire Winton ,
- Nosheen Aslam and
- Suzanne Taylor
- Department of Obstetrics, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
- Correspondence to Dr Claire Winton; claire.winton@nhs.net
Abstract
A 32-year old primigravida woman presented for antenatal care giving a history that her mother had platelet storage pool disorder (PSPD). The patient was subsequently diagnosed with PSPD during her pregnancy and had a caesarean delivery for breech presentation at 39 weeks. In this paper, we discuss the basic science, inheritance pattern, symptoms and management of this condition, alongside the antenatal and intrapartum and postnatal management specific to it, highlighting the need for a multidisciplinary approach to care. PSPD refers to a group of rare conditions involving defects in platelet granule storage or secretion, which leads to abnormal aggregation and activation of platelets. There are both genetic and acquired forms of the condition. It is a functional platelet disorder, meaning platelet counts will usually remain in the normal range. The diagnosis may be suspected due to characteristic signs and symptoms, but patients may also be asymptomatic. There have been only a few documented cases of pregnant women with PSPD; therefore, management is not clear. Vaginal delivery is not contraindicated, however, postpartum haemorrhage should be anticipated and planned for the use of deamino D-arginine vasopressin (DDAVP), tranexamic acid, prophylactic oxytocics and prompt access to blood products, including platelets, if required. This case highlights the need for effective multidisciplinary teamwork between obstetricians, anaesthetists and haematologists to ensure high-quality care and enable careful intrapartum management planning.
Background
Platelet storage pool disorders (PSPDs) are a rare group of bleeding disorders, which have implications for the health of both mother and baby. Multidisciplinary input is required especially during intrapartum care. There are only a few reported cases of this condition in pregnancy, hence the importance of this case report in adding to the literature on managing PSPD in pregnancy.
Case presentation
A 32-year old primigravida woman booked with her community midwife at 8 weeks gestation and was referred to a consultant-led antenatal clinic after reporting her mother had a diagnosis of PSPD. The pregnancy was planned, and the patient was taking folic acid and multivitamins, including vitamin D. The patient was White British, had a booking BMI of 26 and was an ex-smoker. She had a history of migraine and polycystic ovarian syndrome. Booking blood showed a haemoglobin of 131 g/L and normal platelets of 290×109/L. At her first antenatal clinic appointment at 21 weeks gestation, she was reviewed by an obstetric consultant. The patient had no symptoms or signs of a bleeding disorder. We liaised with the regional haematology centre, and the local haematology team, for further information and guidance. The regional centre carried out testing, which confirmed a diagnosis of PSPD; normal aggregation of platelets to agonists, but decreased release to epinephrine and collagen, was displayed. Due to the risk of PSPD in the fetus, the local haematologist advised to avoid fetal scalp electrodes, fetal blood sampling, rotational and mid-cavity instrumental deliveries. As the booking platelets were normal, the regional haematology centre advised for no extra haematological investigations. The platelet count and haemoglobin remained normal throughout the antenatal period as checked at booking, 28 weeks and in the third trimester. PSPD is not an indication for serial growth scans, so these were not arranged. However, she was advised to attend the hospital in case of antepartum haemorrhage.
The woman presented with reduced fetal movements at 30 weeks, and a subsequent ultrasound scan (USS) showed a baby with a normal estimated fetal weight but in a footling breech presentation. At a consultant antenatal clinic at 32 weeks, a referral was made to the antenatal high-risk anaesthetic clinic, and a neonatal alert was completed. At 34 weeks, a review in the antenatal high-risk anaesthetic clinic by a consultant obstetric anaesthetist took place. Thorough communication took place with the patient at this point regarding the risk of postpartum haemorrhage (PPH), the management to reduce this risk and after liaising with the regional haematology centre, the advice for general anaesthetic if an operative procedure was necessary.
The fetus remained in the breech presentation, and at 36 weeks, the options for management of breech presentation were discussed, and the patient opted for an elective caesarean section. This was booked at 39 weeks after a further review at 38 weeks when repeated USS showed persistent breech presentation. Arrangements were in place for the provision of DDAVP, prophylactic syntocinon infusion and tranexamic acid as well as packed red cells and platelets not only on the day of caesarean but also if she presented in an emergency. Postnatal management was also discussed including oral tranexamic acid, along with judicial use of fluids in the postnatal period.
The patient was admitted on the day of surgery and received antacid prophylaxis and a preoperative subcutaneous dose of DDAVP (0.3 μg/kg) 1 hour before the operation. Two units of packed red cells and an adult dose of platelets were immediately available, but neither were given prophylactically. General anaesthesia was uneventful with administration of 1 g of tranexamic acid at induction, and careful fluid balance (replacing intraoperative loss and only 1.5 L of crystalloid in first 24 hours) was maintained. A male infant was born in good condition, the total weighed blood loss was 500 mL and there were no surgical complications. A syntocinon bolus (5 international units) was administered at the time of delivery followed by a syntocinon infusion to optimise uterine tone. The postoperative analgesia was managed without nonsteroidal anti-inflammatory drugs. Postnatal oral tranexamic acid was given for 4 days (1 g eight hourly). The platelet count was 149×109/L 1 day after the caesarean section, and haemoglobin level was 103 g/L. The patient was discharged with her baby 3 days after the caesarean, her postoperative stay was being slightly prolonged due to a delay in resuming normal bladder and bowel function.
Outcome and follow-up
The patient remains well and asymptomatic.
Discussion
PSPDs are a rare group of bleeding disorders, which are caused due to the dysfunctional granules within the platelets. Platelet granules are tiny storage sacs within platelets, which release various substances to help stop bleeding and aid coagulation. There are two main types of platelet granule: alpha and dense. Alpha granules are the most abundant.1 Some PSPDs are related to deficiency of the granules, and others occur when platelets are unable to empty their contents into the bloodstream.2 There can be deficiency of either alpha and dense granules, or both, and the condition can affect both men and women.3 The number of platelets usually remain normal, or there can be mild thrombocytopenia.
PSPD can be inherited or acquired. Inheritance patterns include autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive and sporadic. Acquired forms of PSPD can be linked to systemic lupus erythematosus, cardiovascular bypass and hairy cell leukaemia.2 Within the inherited forms, they can be part of a syndrome or isolated PSPD. The genetic syndromes whose causative genes are known include Chediak-Higashi syndrome, thrombocytopenia-absent radius syndrome, Hermansky-Pudlak syndrome and Wiskott-Aldrich syndrome (X-linked thrombocytopenia).2 4 5 However, the majority of cases are nonsyndromic isolated forms of PSPD and the genes responsible for the condition are not yet known.6 The transmission risks to the offspring depend on the pattern of inheritance. In this case, the regional haematology centre considered this to possibly be an autosomal dominant form due to the mother of the patient having a diagnosis, therefore, giving a 50% risk of the fetus being affected.
The majority of patients are asymptomatic and the condition is often identified when screened due to a family member being diagnosed. If symptoms do occur, they can include menorrhagia since menarche, nose and gum bleeds, easy bruising, joint bleeds, prolonged bleeding during child birth and dental procedures and recurrent anaemia. In obstetrics, a previous history of PPH should raise the suspicion of a haematological disorder, such as PSPD.
Diagnosis of PSPD is complex and the methods of diagnosis are not standardised across all laboratories.6
Further testing may include7 8:
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Full blood count—platelet count will usually be normal.
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Peripheral blood smear—the platelet morphology is usually normal.
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Bleeding time studies—will be prolonged. In the presence of prolonged bleeding time with normal platelet morphology and platelet count >100, after ruling out von Willebrand disease (most common bleeding disorder), the possibility of PSPD should be considered.4
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Platelet aggregation studies—there will be dysfunctional aggregation response to adenosine diphosphate (ADP), epinephrine and collagen.4 In a small number of patients, the aggregation response will be normal.9
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Flow cytometry—is a simple and efficient tool of diagnosis in PSPD, especially where the aggregation test is normal. It detects the mepacrine-loaded platelets and is reduced in PSPD.10
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Electron microscopy –detects platelet granule subtypes affected—dense or alpha.
In this case, it was shown that the patient had normal platelet aggregation to platelet agonists, but had decreased release of serotonin (5-HT) to both epinephrine and collagen. These are classic features of PSPD and indicate deficiency of platelet dense granules. Platelet count was normal, and morphology was normal, which excluded grey platelet syndrome. Neither she nor anyone in the family had a history of the above-mentioned genetic syndromes. Electron microscopy was not performed. Therefore, it is not known if the patient had deficiency of only the dense granules or both dense and alpha granules. The regional haematology centre advised testing for the child would be carried out if there were symptoms or signs or bleeding, or if planning surgery as this would pose a significant haemostatic challenge. In the absence of these factors, it is usual to defer testing until adolescence, which would enable consent to be taken and adult normal ranges to be used.
Management
The management of PSPD in pregnancy requires a multidisciplinary approach involving obstetricians, anaesthetists, haematologists and neonatologists.11 Early diagnosis is a key, allowing adequate time for antenatal surveillance and intrapartum management planning. As specific guidelines for PSPD in pregnancy management are not available, components of the plans will be extrapolated from guidelines, and evidence, of other known bleeding disorders.12 13 We have developed a proposed pathway for management of PSPD in pregnancy (figure 1).
Proposed pathway for management of PSPD in pregnancy. Hb, haemoglobin; PSPD, platelet storage pooldisorder; PPH, postpartumhaemorrhage.
If the patient is known to have a condition that predisposes them to bleeding risk, the Royal College of Obstetricians and Gynaecologists (RCOG) guidance on bleeding disorders recommends prepregnancy counselling from a multidisciplinary team.14 Pregnancy causes no effect on PSPD, neither affecting the course of the pregnancy nor mode and timing of delivery. The mainstay of antenatal management will involve optimising haemoglobin levels as well as ensuring appropriate management in the case of an antepartum haemorrhage and planning intrapartum and postnatal care. For the management of breech presentation, the RCOG Greentop guideline advises to consider avoiding external cephalic version.14
PSPD alone is not a contraindication to vaginal delivery, and caesarean delivery should be undertaken only for obstetric indications.11 However, prolonged labour should be avoided if possible, and genital and perineal trauma should be minimised to reduce the risk of excessive bleeding.10 The fetus is at risk of having PSPD and bleeding, therefore, it is advised to avoid fetal scalp electrodes, fetal blood sampling, vacuum extraction and mid-cavity or rotational forceps. Low-cavity forceps could be considered and may be less traumatic than a caesarean at full dilatation.8 11
Patients will require delivery in a consultant-led unit with availability of blood products. There is no specific requirement for delivery in a tertiary setting, however, each case has to be individualised and guided in liaison with haematology and anaesthetic specialists. Delivery in a nontertiary setting may impact on prompt availability of certain blood components, including platelets.
The use of regional anaesthesia in women with bleeding disorders is controversial. The RCOG guidelines state that for mild platelet dysfunction, central neuraxial anaesthesia can be considered in individual circumstances if the benefits outweigh the risks.12 Some anaesthetic teams would decide that regional anaesthetic should not be performed, as you cannot correct or replace the platelets in this functional disorder, and there is a risk of epidural, or spinal, haemorrhage or haematoma, which can lead to permanent neurological damage.8 11 However, as one of the key principles of management is minimising blood loss, regional anaesthetic may be preferred due to the association with lower rates of haemorrhage and transfusion.12 The risks and benefits will need to be discussed on an individual case basis. In labour, patient-controlled analgesia would be an alternative to epidural analgesia.11
A recent case report12 discussed the use of point of care thromboelastrography (TEG) to quantify patient’s haemorrhage risk and aid in the management of these cases. TEG is used to assess clot formation, strength and breakdown. It gives an overall guide to haemostasis and is often used in the management of PPH. Timing of the TEG would need to be considered, and the utilisation does require expertise of this technique within the department. At the time of writing, the hospital trust caring for this particular patient did not have point of care coagulation testing available.
There are a number of different pharmacological treatment options to prevent, or treat, PPH in PSPD. First, the mainstay treatments of PPH should not be forgotten. Management of PPH involves an MDT approach, prompt assessment, resuscitation and the possibility of requiring surgical intervention. This includes the prophylactic administration of an uterotonic medication at delivery (usually syntometrine or syntocinon), along with active management of the third stage of labour. Other uterotonic medications used in the treatment of PPH will include ergometrine, misoprostol and carboprost.
Tranexamic acid is an antifibrinolytic agent, which works by inhibiting the enzymatic breakdown of fibrinogen and fibrin by plasmin. It has been recommended for use both to treat PPH, and also for women having a caesarean who are at increased risk of PPH.15 High-dose tranexamic acid has been shown to reduce blood loss, fall in haemoglobin and need for blood transfusion.16 A large multicentre trial (WOMAN trial) showed that tranexamic acid reduced deaths due to bleeding with no increase in thromboembolic events.17
DDAVP is often used in the treatment of mild haemophilia and von Willebrand’s disease, as it causes a two five-fold increase in factor 8 and von Willebrand’s factor from stores. The mechanism of action in PSPD is unclear and a response is not guaranteed. However, the RCOG guidance on bleeding disorders states that although DDAVP does not appear to have a direct effect on platelets, the increase in ultra large VWF multimers improves platelet adhesion, and a good response is usually obtained with DDAVP in patients with mild platelet function defects.14 It is thought to reduce bleeding time by improving the platelet adhesiveness.8 It can be given intravenously, subcutaneously or nasally, with the subcutaneous route less likely to cause side effects of headaches and flushing. The antidiuretic effect of DDAVP requires that careful consideration be given to fluid balance and it should be avoided in cases of pre-eclampsia.14 Testing of DDAVP prior to treatment may also be a consideration to confirm whether there is response to treatment.18
Due to the significant risk of PPH, blood products including platelets may be required. Therefore when a patient with PSPD is in labour, or attending for a caesarean delivery, red cells and HLA matched platelets must be available. Transfusion of platelets may be required in a major PPH, but are generally not considered prophylactically as the benefits do not outweigh the risks which include neonatal alloimmune thrombocytopenia (NAT)19 Maternal sensitisation can occur to paternally derived fetal platelet antigens, and alloantibodies can develop to HLA antigens. If these antibodies are present then they can also limit the maternal response to platelet transfusions. Management of NAT is beyond the scope of this review, but requires intensive monitoring and a multidisciplinary approach.20 Use of recombinant factor VIIa (rFVII) would be off-licence for PSPD. There is limited data on it’s use in this condition but one case reports on its use where the patient had previous allergic reactions to conventional therapies.21
There are no specific guidelines for PSPD postnatal care. However some guidance can be extrapolated from the RCOG Greentop guideline on inherited bleeding disorders in pregnancy.14 Women should be advised to take tranexamic acid following delivery until bleeding becomes their usual menstrual period or has stopped. After caesarean, it is advised to be taken for a minimum of 7 days to reduce the risk of secondary PPH. Women with bleeding disorders are considered to have a low risk for venous thromboembolism (VTE). However, replacement therapy, transfusion and other interventions may increase this risk. Therefore, VTE prophylaxis (mechanical and pharmacological) should be considered in relation to thrombosis risk factors as well as considering the risk of bleeding.11
Learning points
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Platelet storage pool disorders (PSPDs) are a rare group of bleeding disorders caused by dysfunctional granules within the platelets.
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PSPD can be inherited or acquired, as well as a part of various genetic syndromes, therefore, a fetus may be affected.
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The management of PSPD in pregnancy requires a multidisciplinary approach involving obstetricians, anaesthetists, haematologists and neonatologists.
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It is important to make individualised decisions regarding the place and mode of delivery, use of analgesia and anaesthesia, pharmacological interventions and use of blood products.
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PSPD can increase the risk of postpartum haemorrhage.
Acknowledgments
Dr KK Hampton, consultant haematologist and honorary senior lecturer, Sheffield Haemophilia and Thrombosis Centre—for further information on diagnosis and investigation.
Footnotes
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Contributors All named authors contributed to the conception and design of the case report, as well as the drafting and revisions of the article. All authors gave final approval of the version published, and agreement to be accountable for the article and to ensure that all questions regarding the accuracy or integrity of the article are investigated and resolved. CW—conception, planning, literature review, design, drafting and revisions. SK—conception, planning, literature review, design drafting and revisions. NA—drafting and revisions. ST—drafting and revisions.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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