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A 34-year-old nulliparous woman from Vietnam presented at 14 weeks gestation in 2021 with a platelet count of 22×109/L. She had a history of chronic thrombocytopenia since 2010 which was identified when she presented with petechiae, gum bleeding and headaches. She had investigations performed in Vietnam, including a bone marrow biopsy which were reportedly normal. The details of her other investigations were not available. In the years that followed, she reported that her platelet count had been stable at approximately 25×109/L, with no bleeding symptoms. She was not taking any medications or supplements at the time.
Prior to attending the haematology clinic, she had been seen by the hepatologists as she had chronic hepatitis B infection with a stable, low viral load (1170 IU/mL) and normal liver function tests apart from a mildly elevated GGT (49 U/L). A baseline ultrasound demonstrated significant splenomegaly (measuring 21 cm with a prominent splenic vein measuring up to 25 mm), splenic varices but with no radiological evidence of cirrhosis or other features of portal hypertension. Further investigations were performed which included a negative result for malaria, HIV, parvovirus, hepatitis D, hepatitis C, arbovirus, and Schistosoma mansoni serologies. CMV and EBV serologies were consistent with past infection.
She had no other significant medical history and only recently had been taking a red ginseng liquid supplement and multivitamins. She was a non-smoker and non-drinker and had only moved to Australia 6 months prior.
On examination, she had a spleen extending to below the umbilicus with no stigmata of chronic liver disease. There was no palpable lymphadenopathy. At the time of review, her blood counts were: haemoglobin 101 g/L, MCV 91, neutrophils 1.37×109/L, platelets 23×109/L.
Given the chronicity of the thrombocytopenia and splenomegaly, an acute malignancy and pregnancy-specific causes were thought unlikely. She had further investigations including haemoglobin studies, ANA, lupus anticoagulant and antiphospholipid antibodies, LDH, vitamin B12, folate, ferritin, all of which were normal. A paraprotein was not identified and the IgG was raised. JAK2 V617F mutation was not detected.
Magnetic resonance imaging (MRI, Fig. 1) showed no evidence of liver cirrhosis, with marked splenomegaly, marked dilation of the splenic vein with tortuosity and varices extending to the gastroesophageal junction. A shearwave elastography was performed to assess for advanced liver fibrosis with a result of 7 kpa.
Fig. 1MRI: T2 weighted coronal view of upper abdomen at 18 weeks gestation.
She was commenced on tenofovir at 15 weeks to treat her chronic hepatitis B to exclude an extrahepatic manifestation of the virus. She was also given a trial of prednisone 40 mg daily for 4 days by the haematology team. Despite these measures, there was no significant change in the platelet count.
Due to concern regarding increased risk of significant bleeding in antepartum and peripartum period due to severe thrombocytopenia relatively early on in her pregnancy, with significant splenomegaly and portal hypertension, and risk of splenic rupture, a multidisciplinary discussion recommended that she should proceed with a splenectomy. She underwent a splenectomy at 20 weeks with one unit of platelets transfused pre-operatively with less than 100 mL estimated blood loss. A gastroscopy was performed prior to the splenectomy which revealed four cords of large, grade 3 varices, all of which had red wale signs, and portal gastropathy. Banding was not performed with the hope that the splenectomy would reduce portal pressures. The liver appeared nodular intra-operatively (Fig. 2) and a liver biopsy was performed. She was commenced on propranolol 10 mg twice daily which was titrated up to 30 mg twice daily by discharge. By day 4 post-operatively, her platelet count normalised to 151×109/L and neutrophils to 10.46×109/L. On day 5 post-operatively, she developed malaena with a 20 g/L haemoglobin drop, secondary to a variceal bleed. She underwent another gastroscopy for variceal ligation. Thromboprophylaxis was not used post-operatively due to the initial thrombocytopenia and subsequent variceal bleed.
Fig. 2Intra-operative appearance of liver and spleen.
Histopathology of the liver (Fig. 3A,B) showed mild nodular regenerative hyperplasia with no cirrhosis or evidence for incomplete septal cirrhosis, and mild inflammatory changes consistent with inactive chronic hepatitis B. Histopathology of the spleen (Fig. 3C,D) showed chronic fibro-congestive splenomegaly without neoplasia or other specific features.
Fig. 3(A) H&E stain (V, central vein; P, portal tract). Liver biopsy demonstrating absence of fibrosis or cirrhosis with nodular transformation of the parenchyma characterised by small monoacinar regenerative nodules bordered by atrophic and compressed liver cell plates at the peripheral acinar regions with compressed slit-like central vein. The parenchymal nodularity is subtle and difficult to appreciate on routine stains but is highlighted on a reticulin stain (see B). (B) Reticulin stain highlights the presence of hyperplastic regenerative nodules with atrophy and compression of liver cell plates in the peripheral acinar regions. (C) H&E stain. The spleen demonstrates dilation of the veins and red pulp sinuses with congestion, fibrosis of the red pulp, accumulation of haemosiderin-containing macrophages and sclerosiderotic nodules (Gamna–Gandy bodies, see D). (D) H&E stain, higher power. Iron incrustation of the connective tissue and sclerosiderotic nodules, often with associated foreign body reaction, (Gamna–Gandy bodies) develop due to focal haemorrhages.
The remainder of her pregnancy was unremarkable, and she had a repeat elective endoscopy for further variceal ligation. The patient was induced at 37 weeks' gestation for suspected placental dysfunction (small for gestational age and borderline fetoplacental Doppler abnormalities) which could possibly have been related to the beta-blockade. She had an uncomplicated caesarean section for a failed induction and had an uncomplicated recovery with 5 days prophylactic enoxaparin postpartum.
The baby was well, weighing 2070 g (3rd percentile) at birth, apart from mild hypoglycaemia which resolved with breastfeeding assistance. The patient is now well and asymptomatic with a normal platelet count and with no residual gastro-oesophageal varices on endoscopy.
The most common cause of severe thrombocytopenia in early pregnancy is immune thrombocytopenia (ITP) with pre-eclampsia surpassing ITP in the third trimester.
The differential diagnosis of splenomegaly includes chronic infections, chronic liver disease with portal hypertension, a haematological malignancy (e.g., myeloproliferative neoplasm or lymphoma), an infiltrative disorder (e.g., sarcoid, amyloid), or connective tissue disorders.
Nodular regenerative hyperplasia (NRH) is a rare disease characterised by micronodular transformation of the liver without fibrosis and is one of the more common causes of non-cirrhotic portal hypertension.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
The nodular areas likely correspond to hypertrophic response to normal or slightly increased blood flow. It has been associated with rheumatological and autoimmune disorders, drugs, haematological disorders and HIV.
In our patient, a clear aetiology for the NRH was not identified. A bone marrow biopsy was not performed again as it was thought that this would not alter the course of her management and it was thought that the splenectomy may be both therapeutic and diagnostic.
Indications for treatment of thrombocytopenia in pregnancy include platelet count <50×109/L and impending delivery or invasive procedure, active bleeding due to thrombocytopenia or severe thrombocytopenia (<20–30×109/L).
In this case, given the chronicity of her presentation, the fact that she was asymptomatic, and that the underlying pathology was unlikely to be ITP, we did not pursue therapy immediately. The standard management of pregnant patients with portal hypertension involves screening for gastro-oesophageal varices, particularly in the second trimester. Had this patient not been pregnant, her management would likely have been different and not involved splenectomy so early on.
While ‘common things occur commonly’, this case is an important reminder that uncommon disorders do occur and that not all cases of thrombocytopenia in pregnancy are due to immune thrombocytopenia or pregnancy-related disorders.
Massive splenomegaly in pregnancy adds complexity to the situation due to the myriad of possible aetiologies and potential added risk. Our case demonstrates that pregnant women with massive splenomegaly can be safely managed. A multidisciplinary approach to complex cases such as this, in a tertiary centre is recommended.
Conflicts of interest and sources of funding
The authors state that there are no conflicts of interest to disclose.
References
Pishko A.
Devine L.D.
Cines D.B.
Thrombocytopenia in pregnancy: diagnosis and approach to management.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
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