Thrombocytopenia in Pregnancy, Diagnosis and Initial Management (453)

Objectives

The aim of this guideline is to provide a framework for the investigation and management of thrombocytopenia in pregnancy. The guideline applies to clinicians who may encounter women with thrombocytopenia in pregnancy. It should also provide guidance for referral to the Haematology Obstetric Clinic.

Audience

This guidance is written for the benefit of all staff involved in caring for pregnant women and new parents, this includes obstetricians, midwives, maternity care assistants and other members of the maternity multi-disciplinary team. The focus in this guidance is for obstetricians and midwives involved in care of women found to have thrombocytopenia in pregnancy

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Thrombocytopenia is a common finding in pregnancy, occurring in approximately 7–10% of pregnancies. It may be a diagnostic and management problem, and has many causes, some of which are specific to pregnancy. Although most cases of thrombocytopenia in pregnancy are mild and have no adverse outcome for either mother or baby, occasionally a low platelet count may be part of a more complex disorder with significant morbidity and may be life-threatening. This condition requires multi- disciplinary team management throughout pregnancy and the peripartum period. The ranges described below should be referred to when deciding when a referral to the Haematology/Obstetrics clinic should be made. Management for women that fall within these platelets ranges is discussed in section 2(III) below.

1. Diagnosis of thrombocytopenia

1. Normal platelet range	150–400 x 10⁹/l
2. Mild thrombocytopenia	>80 x 10⁹/l
3. Moderate thrombocytopenia	50–80 x 10⁹/l
4. Severe thrombocytopenia	<50 x 10⁹/l

As for the non-pregnant patient, a careful history, examination, and laboratory workup is helpful. An approach to diagnostic assessment is summarised in the Table below, and a flow diagram is provided in Appendix I to aid management. The extent of testing for each woman should be individualised depending on the platelet count and clinical features.

The key initial assessment is a blood film to confirm that the thrombocytopenia is genuine and to urgently exclude the presence of microangiopathy.

In those with no adverse features, antenatal management depends on both the extent and timing of the thrombocytopenia. In general, in women with platelet counts above 100 x 10⁹/l, monthly checks by the midwife are sufficient, with instructions to liaise with the specialised Haematology Obstetric clinic if platelet counts fall below 80 x 10⁹ /l, or if there is unexplained bleeding or extensive bruising. Women who present with low platelet levels at booking (80-100 x 10⁹/l) should be referred to the haematology obstetric clinic as this can be indicative of ITP. For further guidance, follow Table 1.

Table 1

1. History:

Document any previous obstetric experience, neonatal platelet counts; past response to treatment, such as corticosteroids for immune thrombocytopenia, family history of bleeding, auto-immune disorders

2. Physical examination:

Usually normal aside from bleeding manifestations; these are unusual unless the count is very low. Check blood pressure (pre-eclampsia), and for abdominal tenderness (HELLP syndrome)

3. Relevant laboratory tests depend
on the stage of pregnancy and other factors:

At all stages:

Repeat full blood count (FBC), LFTs & U&Es
Blood film to confirm thrombocytopenia, and urgently exclude presence of red cell fragments (microangiopathies)
Group & Save (crossmatch only if imminent delivery expected),
Coagulation screen – care in interpretation as APTT shortens through pregnancy.
Consider checking auto-immune profile in selected cases

If there is a family history of thrombocytopenia: von Willebrand screen for type 2B; blood film for hereditary macrothrombopathies

Changes in white cell count +/- lymphadenopathy: consider bone marrow disease. N.B. left shift in white cell series is normal in pregnancy

Check all women with an historical platelet count <150 for Hepatitis C antibodies.

2. Symptoms

Women with a low platelet count in pregnancy are generally less symptomatic than non-pregnant women due to the procoagulant state induced by increased levels of fibrinogen, factor VIII and Von Willebrand factor (VWF), suppressed fibrinolysis and reduced protein S activity.

Common symptoms of thrombocytopenia include:

petechiae, epistaxis and more rarely, haematuria and gastrointestinal bleeding.

Symptoms are uncommon with a platelet count ≥ 50 x 10⁹/l

3. Causes of thrombocytopenia

75% are caused by gestational thrombocytopenia,
15-20% are secondary to hypertensive disorders such as PET and HELLP
3-4% are caused by immune processes e.g. ITP
1-2% are derived from rare constitutional thrombocytopenias, infections, or malignancies.

4. Antenatal management levels and investigations

Patients with known platelet disorders should be discussed with medical obstetric clinic for ongoing management plan.

If a patient presents at booking with thrombocytopenia, the routine booking bloods should be taken along with haematinics (Vit B12, folate and ferritin), U+E’s LFTs, blood film and coagulation screen. Once results are known, patients should be discussed with the medical obstetric team.

If a patient with thrombocytopenia develops a fever with raised creatinine +/- neurological symptoms, urgent discussion with haematology regarding TTP is required.

The presence of red cell fragments on a blood film should prompt urgent discussion with haematology and the medical obstetric team.

PLATELET COUNT DURING PREGNANCY	RECOMMENDED ACTION
>140 x 10⁹/L	Normal. No action required unless unexpected bruising or bleeding
80 - 140 x10⁹/l	Completed antenatal check as per gestation with urinalysis and blood tests for: FBC, U&Es, LFT's & blood film Repeat FBC every 4 weeks and if presenting in spontaneous labour Repeat FBC prior to any invention with an associated bleeding risk Advise the woman to seek medical attention in the event of any associated bleeding symptoms
<80 x10⁹/l	Completed antenatal check as per gestation with urinalysis and blood tests for: FBC, U&Es, LFT's & blood film Refer to Haematology/Obstetric Antenatal clinic Refer for Anesthetic review
<50 x10⁹/l	Completed antenatal check as per gestation with urinalysis and blood tests for: FBC, U&Es, LFT's & blood film Contact Haematology/Obstetric team for urgent review Refer for Anesthetic review

5. Management in pregnancy and intrapartum period

1. Safe platelet levels for intervention

INTERVENTION	PLATELET COUNT
Antepartum, non invasive procedures planned	≥ 20 x10⁹/l
Vaginal Birth	≥ 40x 10⁹/l
Operative or Instrumental birth	≥ 50x 10⁹/l
Regional Anaesthesia	≥ 70x 10⁹/l

Management of gestational thrombocytopenia, PET and HELLP does not require a consultant haematologist, except when there is doubt regarding the diagnosis. All other causes of thrombocytopenia must involve a consultant haematologist.

6. Management of women with ITP (immune or congenital)

1. Emergency treatment Recommendations for life-threatening bleeding in women with ITP

A combination of initial treatments, including IV corticosteroids and, usually, IVIg, should be used in emergency situations in which there is an urgent need to increase the platelet count within 24 hours. Platelet transfusions may be helpful and must not be postponed in cases of life-threatening bleeding, especially haemorrhage. In the case of life-threatening bleeding and the absence of a significant response to IVIg and platelet transfusion in a patient on corticosteroids, the use of a TPO-RA should be considered. Additional options may include vincristine or vinblastine, antifibrinolytics in combination with other initial therapies, and, rarely, emergency splenectomy.

Below are recommendations for the management of ITP during pregnancy, but a haematologist should always be consulted in such cases.

2. Recommendations for the treatment of maternal ITP

1. Counselling for women with ITP wishing to become pregnant is recommended.

2. A platelet count between 20-30 x 10⁹ /L in a non-bleeding patient is safe for most of pregnancy. A platelet count ≥ 50 x10⁹ /L (see separate anaesthesia recommendation above) is required for delivery.

3. Initial treatment is with oral steroids or IVIg.

4. IVIg can provide a rapid, but often very transient, increase in platelet count and can be used to urgently increase platelet counts during bleeding or for delivery.

5. Combining therapies may elicit a response in patient’s refractory to single agents alone. High-dose methylprednisolone, in combination with IVIg and/or azathioprine, is suggested for ITP refractory to oral corticosteroids or IVIg alone.

6. Rituximab can be considered in pregnancy for very severe cases, but perinatal and neonatal immunosuppression and subsequent infection are potential complications and require monitoring.

7. TPO-RAs may be considered in late pregnancy when other treatments have failed, but published information is limited.

8. In the rare instances when splenectomy is required, it should be performed in the second trimester.

9. Vinca alkaloids, danazol, and immunosuppressive drugs not listed in these recommendations should be avoided in pregnancy.

3. Recommendations for management of birth of newborn infants to mothers with ITP

1. Neonatal alloimmune thrombocytopenia should be excluded by parental testing if the neonate presents with severe thrombocytopenia.

2. The mode of birth should be determined by obstetric indications, not by anticipation of the neonatal platelet count.

3. Procedures during labour that may be associated with increased hemorrhagic risk to the fetus should be avoided, specifically the use of fetal scalp electrodes, fetal blood sampling, assisted vaginal birth with ventouse, and assisted vaginal birth with rotational forceps.

4. Previous maternal splenectomy can be associated with a higher risk for neonatal thrombocytopenia even if the mother now has a normal platelet count.

5. A mother with a previous newborn, thrombocytopenic or not, is likely to have a second baby with a similar platelet count. Umbilical cord platelet count should be obtained at the time of birth or as soon as possible afterwards

6. Repeat the platelet count as needed depending on platelet levels, trends in the count, and response to treatment (if any). If cord platelet count is ≤ 150 x 10⁹ /L, repeat the platelet count daily until stable. The incidence of pseudothrombocytopenia is high in neonates because of the difficulties encountered in obtaining unclotted blood with blood draws.

7. If platelet count is ≤ 50 x 10⁹ /L at birth, perform a cranial ultrasound. Magnetic resonance imaging for confirmation or clarification can be performed without anaesthesia using the sleep and swaddle approach 30 to 60 minutes prior.

8. In the case of ICH, give IVIg and limited steroids to maintain platelet count ≥ 100 x 10⁹ /L for 1 week if possible and ≥ 50 x 10⁹ /L for another week. The use of platelet transfusion may increase neonatal risk.

7. If there is symptomatic bleeding or if platelet count is ≤ 30 x 10⁹ /L, with or without platelet transfusion, give IVIg.

8. If severe thrombocytopenia continues for 1 week in a breast-fed infant, consider pausing breastfeeding for a few days to see whether platelet count increases.

Appendix 1 Antenatal management flow chart

Last reviewed: 13/06/2024

Next review date: 13/06/2027

Author(s): Christine Cree, Dr. Catherine Bagot, Dr. Fiona Hendry.

Version: 2

Approved By: Maternity Clinical Governance Group

Document Id: 453

References

American College of Obstetrics and Gynaecology, (2019), Practice Bulletin: Thrombocytopenia in Pregnancy, ACOG; 207; 133; 3: e181- e184

Eslick, R et al, (2021), HOW Collaborative position paper on the management of thrombocytopenia in pregnancy, ANZJOG 2021; 61: 195-204

Myers,B, (2012), Diagnosis and management of maternal thrombocytopenia in pregnancy, BJH; 158: 3-15

NICE (2019). Intrapartum care for women with existing medical conditions or obstetric complications and their babies (NG121) > Section 1.6: Bleeding disorders

Park, Y.H., (2022), Diagnosis and Management of thrombocytopenia in pregnancy, Blood research, 2022; 57: S79- S85

Provan, D., Arnold, D.M. et al (2019) Updated international consensus report on the investigation and management of primary immune thrombocytopenia, Blood Advances; 2019; 3: 22; 3780-3815

University Hospitals of Leicester (2022), Thrombocytopenia in pregnancy and the peripartum period