Case 109 – summary

Thanks for all your help this week. This week’s case focused on Thrombocytopenia pregnancy that ultimately was ITP responsive to steroid therapy.

Mild gestational thrombocytopenia (with platelet counts <150×10^9/L) is common affecting up 5-10% of pregnant women.

Pregnant women with mild thrombocytopenia of platelets 100-150×10^9/L and normal blood film/screening blood tests should stay in primary care with monthly FBC and advice to refer to secondary care if platelet counts fall below 100×10^9/L.

Only 1% of pregnant women will have a platelet count less than 100×10^9/L which is the international working groups definition of thrombocytopenia and this is the range where further specialist investigation and referral to secondary care is appropriate.

A suggested approach to thrombocytopenia in preganancy is outlined below:

History:

• Previous FBC results: Thrombocytopenia prior to pregnancy points to causes other than gestational thrombocytopenia.

• Family history: Type IIb VWD although rare can present as thrombocytopenia in pregnancy.

• Medication History: Any changes in medications. Many drugs in common use can cause isolated thrombocytopenia – worth checking a patients medications.

• Features of Connective tissue diseases (CTD): Fatigue, Rashes, Joint stiffness, sore eyes etc.

• Gestation at onset: Later in pregnancy more likely to be due to pregnancy specific causes like Pre-eclampsia, HELLP, Acute Fatty liver of pregnancy etc. Gestational thrombocytopenia is more common in second and third trimesters.

• Personal Bleeding history: BAT score may help indicate if underlying bleeding disorder, particularly useful if no previous blood tests available and family history of bleeding.

 

Initial investigations:

• FBC repeat plus CD61 platelet count or citrate count: Confirm genuine thrombocytopenia.

• Blood film: Film crucial to exclude underlying marrow disorder and to look for fragmentation, signs of haemolysis, hereditary thrombocytopenia with giant platelets or white cell inclusions or for signs of infection.

• U&E, LFT’s: May be abnormal if HELLP/Pre-eclampsia/HUS.

• Coagulation screen inc D-Diner: Abnormal if DIC/HELLP.

• VWD screen: Useful particularly if family history to exclude type IIb VWD.

• Antiphospholipid antibodies

• ANA

• HIV, Hep B, Hep C

• B12/Folate: Rarely a cause of isolated thrombocytopenia

• Physical examination: Look for mucosal bleeding petichiae and any signs of Connctive tissue diseases.

Optional testing depending on findings:

  • TFT’s: Thyroid problems may be associated with ITP in pregnancy as part of autoimmune spectrum.
  • Ig levels: If history of frequent infections.
  • Other viral serology: if indicated from history or film.
  • H.Pylori serology.
  • DAT, LDH and Retics: If concern Evans syndrome due to spherocytes on film.
  • ADAMTS 13 testing if fragmentation on film.
  • Bone Marrow: If suspicion of primary blood disorder from film.

 

Establishing the Diagnosis:

Broadly speaking thrombocytopenia in pregnancy is best thought of in five distinct categories depending on the investigations above.

 

1) Normal Blood film and other investigations (most likely scenario):

• Gestational thrombocytopenia (GT) – accounts for 75% total

• ITP – 5%

 

Useful features to distinguish the two diagnoses:

Rare for GT to cause platelet count <50×10^9/L.

GT usually occurs mid-late second trimester and during the third trimester where as ITP can occur earlier (as in this case).

There may also be a history of previous thrombocytopenia in pregnancy that fully resolves post-partum in GT. hence very important to monitor platelet counts post partum.

 

2) Atypical lymphocytes on film, raised inflammatory markers:

• Infection

 

3) Microspherocytes, agglutination or clumping on film and positive DAT:

• Evans syndrome

 

4) Blasts on film

• Pimary bone marrow disorder

 

5) Schistocytes on film – 15% of patients

• TTP

• HUS

• DIC

• Pre-eclapsia/HELLP/Acute fatty liver of pregnancy

 

The rest of this case focuses on our lady who had a normal blood film and isolated thrombocytopenia. It is important that the possible cause of thrombocytopenia is established before embarking upon management as the approaches for management of HELLP or TTP vary greatly to the management of ITP for example.

 

Monitoring patients with Isolated thrombocytopenia thought to be ITP:

All patients should be referred for secondary care review if platelets <100×10^9/L and have an antenatal anaesthetics review.

There is little evidence to suggest what appropriate monitoring should be and it should be tailored to platelet count and the rates of decline seen rather than a rigid time based check for example every 4 weeks. The consensus seems to be monitoring should be somewhere between 2-6 weekly Depending on the individual. In the third trimester particularly after 34 weeks weekly checks if plt <80×10^9/L are suggested especially if treatment is given.

Patients with thrombocytopenia in pregnancy should be advised of who to contact in case of bleeding or concerns. They should also be asked to avoid IM injections, though BCSH guideline makes it clear low dose aspirin prescribed for obstetric reasons should not be automatically withheld unless high bleeding risk.

All patients should have repeat FBC 1-3 months post-delivery to check for spontaneous resolution of thrombocytopenia. This is important particularly if GT was thought to be the cause of thrombocytopenia as by this timepoint the thrombocytopenia should have resolved.

Treating patients with Isolated thrombocytopenia thought to be ITP:

BCSH guidelines suggest treatment for ITP should be in order to achieve “safe” platelet counts and not necessarily normalise platelet counts.  BCSH guidelines state that although no robust trials it is reasonable to leave asymptomatic pregnant women with platelet counts of 20-30×10^9/L without treatment until the third trimester.

Treatment approaches for ITP during pregnancy vary slightly but generally treatment is with prednisolone first line starting at 10-20mg dose of prednisolone with IVIG reserved in case of bleeding or as second line therapy.

Treatment is usually prednisolone for a week, adjusting to minimum dose of prednisolone that maintains a response. Response time is usually around 3-7 days. It is recommended that tapering of doses is suspended near term as often platelet count falls at term. Slow taper also recommended post-partum as quick tapering can affect the mother’s psychological state.

The treatment aims to achieve  a minimum platelet count of 50×10^9/L for vaginal delivery. Platelet counts of >80×10^9/L will usually be needed for neuroaxial anaesthesia.

Although steroids are relatively safe in pregnancy common side effects are impaired glucose tolerance, hypertension, mood change and weight gain.

Second line therapies and agents for ITP are less clear and would require discussion in an MDT setting depending on the individual patient.

Delivery planning for patients with ITP:

Mode of delivery should be based on obstetric indications there is no need for Cesarean section in ITP patients as no evidence to show this reduced ICH rates in thrombocytopenic neonates.

Ideally delivery should be in a hospital with Haematology and obstetric care.

General consensus both in How I treat and RCOG review of thrombocytopenia in pregnancy is that a platelet count >50×10^9/L is required for vaginal and operative delivery. For epidural anaesthesia platelet count needs to be >80×10^9/Land an anaesthetic review before delivery is recommended to discuss alternative analgesia if thrombocytopenia at delivery.

Platelet transfusions should be available in case of complications but should not be routinely administered.

Neonates born to mothers who have ITP do have a risk of thrombocytopenia due to passage of Ig G Ab across the placenta. 15-30% of babies born to mothers with ITP are thrombocytopenic though only 5% have counts <20×10^9/L. It is worth stating that antenatal steroids and IVIG have no effect on the fetal platelet counts. The passage of antibodies is unpredictable therefore mothers platelet counts won’t always indicate the likelihood of associated thrombocytopenia in the baby. A history of sibling with thrombocytopenia at birth, mother with previous splenectomy or platelet count <50×10^9/L at delivery are predictors of an increased risk of neonatal thrombocytopenia. This means all babies born to mothers with presumed ITP should be treated as possibly being thrombocytopenic. Fetal scalp electrodes and instrumental deliveries are ideally avoided and cord blood should be taken at delivery to confirm the platelet count. IM vitamin K should also be avoided. Platelet counts should also be checked at day 1 and 4 post delivery, as platelet nadir around this time. If platelets less than 50×10^9/L or symptomatic transcranial USS should be performed.

Postnatal care should include daily FBC of mother until day 5 post partum.

Prenatal counselling of mothers with ITP:

Pre-pregnancy counselling for a lady with ITP as recommended by RCOG should include:

• Discussion that ITP relapses may occur during pregnancy.

• Around a third of women will need treatment in pregnancy usually in third trimester.

• An epidural may not be possible if thrombocytopenic.

• There is an increased chance of a sibling being affected with thrombocytopenia if a mother has had splenectomy or previous baby with neonatal thrombocytopenia.

• Risk of adverse delivery outcomes for mother or major bleeding in neonates is thankfully low with correct planning and monitoring.

 

References:

Provan et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010 115:168-186.

B Myers. Diagnosis and management of maternal thrombocytopenia in preganancy. BJHaem, 2012, 158, 3-15.

B.Myers. Review Thrombocytopneia in pregnancy. RCOG 2009.

T Gernsheimer et al. How I treat thrombocytopenia in pregnancy. Blood 2013. 121.

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