Blood
Vol. 24 No 1 | Autumn 2022
Feature
Thrombocytopenia in pregnancy
Dr Simon Kavanagh
MBBS, FRACP, FRCPA

Thrombocytopenia (defined by a circulating platelet count <150 x 10^9/L) is a common finding in pregnancy, affecting 5–10% of all pregnancies. The platelet count rarely falls below 100, with approximately 1% of pregnant women having a platelet count below this threshold.1

Pregnancy-associated thrombocytopenia may not require treatment but almost always requires additional surveillance and, if more severe, may have implications for delivery.

Aetiology

Common or clinically relevant causes of thrombocytopenia in pregnancy are shown in Table 1. This paper focuses primarily on causes of thrombocytopenia that are common (or of particular significance) in pregnancy.

Table 1. Common/important causes of thrombocytopenia in pregnancy.

Pregnancy-specific Not specific to pregnancy
Isolated thrombocytopenia
  • Gestational thrombocytopenia
  • Artefactual thrombocytopenia
  • Immune thrombocytopenia (ITP)
  • Medication therapy/drugs
  • Type 2B von Willebrand disease
  • Inherited thrombocytopenia
Thrombocytopenia associated with systemic disorders
  • Pre-eclampsia
  • HELLP* syndrome
  • Acute fatty liver of pregnancy
  • TTP/HUS†
  • Autoimmune disease (SLE, APS‡)
  • Infection (especially viral)
  • Bone marrow disorders
  • Nutritional deficiency
  • Liver disease/splenic sequestration

* Haemolysis, Elevated Liver enzymes, Low Platelets
† Thrombotic Thrombocytopenic Purpura/Haemolytic Uraemic Syndrome
‡ Systemic Lupus Erythematosus, Antiphospholipid Syndrome

 

Gestational thrombocytopenia

Gestation thrombocytopenia (GT) accounts for ~75% of all thrombocytopenia in pregnancy.2 3 It usually presents with mild and isolated thrombocytopenia developing during the second or third trimester. The platelet count tends to fall with advancing gestation. The pathogenesis of GT is incompletely understood but may reflect a combination of haemodilution (due to plasma volume expansion) and increased platelet clearance.4

Though GT is usually mild, platelet counts as low as 50–70 have been reported. A platelet count <50 is unlikely to be gestational and alternative causes should be pursued.

Thrombocytopenia associated with systemic disorders

Disorders in this group differ widely in aetiology and pathogenesis but share a number of clinical features. Thrombocytopenia, hypertension, red blood cell (RBC) fragmentation, elevated liver enzymes, renal failure, abdominal and neurological symptoms may all be seen.5 These conditions often follow an aggressive clinical course and require urgent investigation and treatment. A multi-disciplinary approach is essential to improve maternal and fetal outcomes.

Immune thrombocytopenia

While not unique to pregnancy, immune thrombocytopenia (ITP) is the most common cause for a platelet count <50 in the first and second trimesters.6 It occurs due to IgG antibody binding to the platelet surface, accelerating clearance of the platelet-antibody complex by splenic/hepatic macrophages.7 ITP may be detected in isolation but may also be seen in viral (hepatitis C, HIV) infection and in some autoimmune disease.

Investigation

A detailed clinical history, particularly relating to medication therapy, personal/family history of thrombocytopenia, diet and the presence of other illness (eg. infection, skin rash, arthritis) is essential. The gestational age at onset and severity of thrombocytopenia must be established. Pre-pregnancy blood counts, if available, should be reviewed.

In vitro platelet aggregation, most often seen in EDTA-anticoagulated samples, warrants special mention. This is a common cause of artefactual thrombocytopenia. When platelet aggregation is identified on blood film review, or if there is onset of unexpected thrombocytopenia, repeat counts – including one collected into citrate anticoagulant – are recommended. Discussion with the haematology laboratory is often useful.

Not all women who develop thrombocytopenia during pregnancy need extensive investigation. One study demonstrated that, of 621 women with platelet counts between 116–149, none had obstetric complications related to thrombocytopenia.8 Some authors have suggested that a count of 115 be considered the lower bound for the reference interval at term.9

Mild and late-onset thrombocytopenia in a well woman suggests GT and surveillance alone may be appropriate. Thrombocytopenia should generally be further investigated if it develops before or during the first trimester, is associated with systemic illness or the platelet count is <80. Initial investigation is context dependent but common initial investigations are shown in Table 2.

Detection of an autoantibody (eg. positive ANA) supports, though does not prove, an immune cause. Negative results do not exclude ITP. Antiphospholipid antibodies are particularly important to detect given their association with thrombotic risk. Helicobacter pylori serology (or urease breath test) is of use in confirmed ITP. Haemolytic markers (eg. direct antiglobulin test, haptoglobins) and ADAMTS13 assay should be performed where there is significant RBC fragmentation.

Table 2. Initial investigation of thrombocytopenia in pregnancy.

FBC + blood film Lupus anticoagulant
Reticulocyte count Antiphospholipid antibodies
Coagulation studies Autoantibodies (eg. anti-nuclear antibody +/- others)
Biochemistry (renal + liver function) Viral serology (HIV, hepatitis B/C)
Lactate dehydrogenase (LDH) Vitamin B12/folate
Thyroid function tests Iron studies

 

Management considerations

In general, a platelet count >100 does not require intervention, though ongoing surveillance blood is warranted. The frequency of testing depends on the platelet count and gestational age. A full blood count (FBC) every four weeks is often adequate in early pregnancy. Fortnightly testing is generally performed from 32–34 weeks gestation; weekly counts are advised when thrombocytopenia is more severe or if the clinical situation is unstable.

Delivery

Patients with a platelet count <100 should generally deliver in a hospital with obstetric experience and 24-hour access to laboratory testing and blood bank support. Significant bleeding is unlikely with either C-section or vaginal delivery with a stable platelet count of >50.10 The decision between these modes of delivery should be based on obstetric factors. Rapidly progressive thrombocytopenia, or milder thrombocytopenia with platelet dysfunction, may be associated with higher risk of bleeding and caution used in these scenarios. Use of a ROTEM-guided critical bleeding protocol is recommended if significant bleeding is observed. Platelet transfusion may be needed.

Anaesthesia

Thrombocytopenia increases the risk of bleeding in neuraxial anaesthesia, particularly when epidural catheters are placed. The ‘safe’ platelet count depends on multiple factors including anaesthetist experience, procedure (spinal vs. epidural), use of medication/s that may impair platelet function, tempo of onset of thrombocytopenia and the presence of other medical issues. A recent position paper suggests that a neuraxial anaesthesia be considered in women with a platelet count >70, a normal coagulation profile and absence of other risk factors for bleeding 11

Venous thromboembolism

Thrombocytopenia does not provide adequate protection against venous thrombosis. The risk of thrombosis should be considered ante- and postpartum and weighed against the perceived risk of bleeding. Pharmacological thromboprophylaxis is generally safe when the platelet count is >50. Antiphospholipid syndrome, which may result in thrombocytopenia and heightened thrombotic risk, is a particularly challenging scenario requiring specialist input.

Neonatal management

Implications for the neonate depend on the cause of maternal thrombocytopenia. True gestational thrombocytopenia does not impact the newborn and measurement of the neonatal platelet count is not required if this diagnosis is secure.

In contrast, ITP may affect the newborn when antibodies of IgG isotype cross the placenta. Reported severity varies. Platelet counts <50 have been reported in ~10% of newborns of mothers with ITP while platelet counts <20 are reported in ~1% of neonates.12 13 The maternal platelet count does not correlate with neonatal thrombocytopenia and only a history of a previously affected sibling is predictive. Unlike neonatal allo-immune thrombocytopenia (NAIT), which is not associated with maternal thrombocytopenia, intracranial haemorrhage due to maternal ITP is rare (<1%).14 A platelet count should be performed at delivery. If thrombocytopenic, repeat counts in the first few days of life are recommended. As exposure to maternal antibody stops at delivery, serial testing of the neonate is not required if the initial platelet count is normal.

Treatment

Treatment is dependent on the cause and severity of thrombocytopenia. Availability of pharmacological and blood products – particularly intravenous immunoglobulin (IVIg) and platelets – should be considered in advance of delivery.

A trial of corticosteroids is often considered as the platelet count falls, especially if neuraxial anaesthesia is desired and ITP cannot be excluded. A significant increment in platelet count supports a diagnosis of ITP. Prednisolone at doses between 10–40mg is often used. In the absence of high-quality data on the optimal schedule, dosing depends on clinical urgency and other factors (eg. gestational diabetes). Following response, the dose should be tapered to the lowest effective dose. Non-response to steroids does not exclude ITP with at least one study suggesting that response rates to steroids are lower in pregnant (vs. non-pregnant) women.15

IVIg is often administered as second-line therapy in ITP. Response rates are in the order of 40%, somewhat lower than seen in non-pregnant populations.16 While generally well-tolerated, responses to IVIg are often transient and repeat dosing may be required. ITP refractory to steroids and IVIg is a challenging scenario. Splenectomy, preferably in the second trimester, may be considered. Immunosuppression or thrombopoietin mimetics are uncommonly used in pregnancy. Platelet transfusion is typically reserved for when delivery or neuraxial anaesthesia are required and there has been refractoriness to (or insufficient time to trial) alternate therapies.

Treatment of thrombocytopenia associated with systemic disorders differs. In selected cases of pre-eclampsia expectant management may be appropriate. Delivery must be expedited if there is worsening thrombocytopenia, HELLP or other deterioration in maternal/fetal condition. Other disorders (eg. TTP/HUS, HELLP) typically require urgent delivery and additional specific therapy depending on the diagnosis. TTP is generally treated with plasma exchange (+/- other agents) while atypical haemolytic uraemic syndrome (aHUS) often requires renal support and use of inhibitors of complement activation. These conditions must be managed in a tertiary hospital environment.

Conclusion

Thrombocytopenia is a common finding in pregnancy. Establishing a diagnosis hinges on the time of onset, severity of thrombocytopenia and presence of other abnormalities. While surveillance is often sufficient, clinicians must remain alert to the possibility of other systemic disturbance that might indicate a more serious disease process. Treatment must be individualised and take into consideration preferences regarding neuraxial anaesthesia and availability of blood products.

 

Our feature articles represent the views of our authors and do not necessarily represent the views of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), who publish O&G Magazine. While we make every effort to ensure that the information we share is accurate, we welcome any comments, suggestions or correction of errors in our comments section below, or by emailing the editor at [email protected].

 

References

  1. Reese JA, Peck JD, Deschamps DR, et al. Platelet Counts during Pregnancy. New England Journal of Medicine. 2018;379(1):32–43.
  2. Burrows RF, Kelton JG. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. Am J Obstet Gynecol. 1990;162(3):731–4.
  3. Boehlen F, Hohlfeld P, Extermann P, et al. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol. 2000;95(1):29–33.
  4. Cines DB, Levine LD. Thrombocytopenia in pregnancy. Blood. 2017;130(21):2271–7.
  5. Cines DB, Levine LD. Thrombocytopenia in pregnancy. Blood. 2017;130(21):2271–7.
  6. Cines DB, Levine LD. Thrombocytopenia in pregnancy. Blood. 2017;130(21):2271–7.
  7. Cines DB, Blanchette VS. Immune Thrombocytopenic Purpura. New England Journal of Medicine. 2002;346(13):995–1008.
  8. Boehlen F, Hohlfeld P, Extermann P, et al. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol. 2000;95(1):29–33.
  9. Pavord S, Hunt B. The Obstetric Haematology Manual. Cambridge University Press; 2018.
  10. Xu X, Zhang Y, Yu X, Huang Y. Preoperative moderate thrombocytopenia is not associated with increased blood loss for low-risk cesarean section: a retrospective cohort study. BMC Pregnancy and Childbirth. 2019;19(1):269.
  11. Eslick R, Cutts B, Merriman E, et al. HOW Collaborative position paper on the management of thrombocytopenia in pregnancy. ANZJOG. 2021;61(2):195–204.
  12. Cines DB, Levine LD. Thrombocytopenia in pregnancy. Blood. 2017;130(21):2271–7.
  13. Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood. 2003;102(13):4306–11.
  14. Eslick R, Cutts B, Merriman E, et al. HOW Collaborative position paper on the management of thrombocytopenia in pregnancy. ANZJOG. 2021;61(2):195–204.
  15. Sun D, Shehata N, Ye XY, et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood. 2016;128(10):1329–35.
  16. Sun D, Shehata N, Ye XY, et al. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood. 2016;128(10):1329–35.

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