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- idiopathic thrombocytopenic purpura
- antiphospholipid syndrome
- systemic lupus erythematosus
- inferior vena cava thrombosis
A 23-year-old woman was admitted in January 1983 with complaints of purpuric spots all over her body for 4 days prior to admission. She had been married for 3 years, had undergone three spontaneous abortions (one first trimester and two second trimester), and had one live birth. On examination, she had no splenomegaly. Investigations revealed a haemoglobin of 11.2 g/dl, total leukocyte count 4 × 109/l (polymorphs 64%, lymphocytes 36%), erythrocyte sedimentation rate 12 mm in first hour, platelets 40 × 109/l. Blood film showed isolated thrombocytopenia. Renal function, liver function tests, chest X-ray and ultrasound of the abdomen were normal. Bone marrow aspiration showed increased megakaryocytes while other cell lines were normal. Antinuclear antibody (ANA) and dsDNA were negative. A platelet antibody test was not available. The patient had isolated thrombocytopenia without any systemic illness. A diagnosis of idiopathic thrombocytopenic purpura (ITP) was considered. The patient was started on 60 mg prednisolone per day. The platelet count had risen to 70 × 109/l by the 10th day and she was discharged.
In March 1983, she was re-admitted with falling platelet counts, mucosal and gingival bleeding, and epistaxis. The platelet count was 15 × 109/l. The dose of oral steroid was increased and platelet concentrate was transfused. The platelet count did not increase and the patient developed menorrhagia and haematuria while still in the hospital. She was referred to a surgeon and, in view of the refractory thrombocytopenia, a splenectomy was performed. Postoperatively, her platelet count increased transiently for 1–2 days and then stabilised at 15–20 ×109/l. She was put on danazol and cyclophosphamide after a period of 12 days postoperatively. Platelets were monitored and there was gradual but definite improvement. Six months after surgery, the platelet count was 150 ×109/l and the medicines were tapered gradually.
Between January 1984 and September 1997, she did not return for follow-up. She had eight more spontaneous abortions, six of which were in the second trimester. The cause of this was investigated. Gynaecological examination and her husband's semen analysis were normal. Abdominal ultrasound was also normal and TORCH test was negative. Her platelet count, bleeding time and clotting time were normal.
In October 1997, the patient was re-admitted with complaints of gradually increasing abdominal distension and low-grade fever. She was febrile with no pallor or lymphadenopathy. Her abdomen was distended, the umbilicus was stretched transversely and there were no dilated veins over the abdomen or back. The liver was palpable and non-tender with evidence of free fluid in the abdomen. Investigations showed normal complete blood counts including platelet count, renal and liver function tests; urine examination revealed trace proteins and chest X-ray was normal. An ascitic tap showed 150 cells, 90% lymphocytes, and was transudative in nature. Contrast abdominal computed tomography (CT) scan (figure 1) showed gross ascites; the liver was enlarged and there was inferior vena cava (IVC) thrombosis. There were prominent retroperitoneal collateral vascular channels. On magnetic resonance angiography (MRA) (figure 2) the IVC was well visualised from its formation at the L5 level up to the L2 vertebral level. There was no evidence of flow intensity noted above L2 level. The flow in the inferior vena cava appeared slow and contained a central area of thrombus formation. The findings were suggestive of IVC thrombosis with collateral formation.
Contrast CT scan of abdomen showing hepatomegaly, ascites and inferior vena cava thrombosis (seen as hypodense eccentric filling defect)
MRA, flash 2-D sequence, showing dark signal flow void in aorta, heterogenous slightly hyperintense signals in the intrahepatic part of the IVC due to thrombus formation. Intense bright signals are seen in portal vein and prominent paraspinal
The patient's blood was screened for a hypercoaguable state. The activated partial thromboplastin time was 54 s (control 23 s), lupus anticoagulant was 55.8 s (control 37 s), anticardiolipin antibody IgG 64.413 g/l (normally less than 10). The levels of protein C, S, antithrombin and fibrinogen were normal. ANA and dsDNA were both positive. Echocardiography showed pericardial effusion and 24-h urinary proteinuria was 1.2 g.
Questions
- 1
- What was the cause of the initial episode of severe thrombocytopenia?
- 2
- What is the diagnosis?
Answers
QUESTION 1
This patient had isolated thrombocytopenia with no systemic involvement. She was diagnosed as a case of ITP. Both ANA and dsDNA were negative initially.
QUESTION 2
This patient had IVC thrombosis due to antiphospholipid syndrome (APS), as both lupus anticoagulant and IgG anticardiolipin antibodies were positive. She had underlying evidence of systemic lupus erythematosus (SLE) as she had pericardial effusion, significant proteinuria, and both ANA and dsDNA were ultimately positive.
Outcome
The patient was diagnosed as having IVC thrombosis due to APS with SLE. She was started on deltaparin 5000 units bid, with prednisolone 40 mg/day, low-dose aspirin, and diuretics. On this treatment ascites decreased and she improved symptomatically. She was discharged on request on the 18th day of treatment on deltaparin and steroids. She discontinued the treatment on her own in the next 10 days and died 6 weeks later, probably due to pulmonary embolism.
Table Thrombocytopenia in ITP and APS
Discussion
The triad of thrombosis (arterial and venous), foetal loss and thrombocytopenia constitutes APS. Our patient had historically all components of this syndrome but the initial event of thrombocytopenia was probably due to ITP and not to APS. An antiplatelet antibody test, if avaliable, would have supported the diagnosis. Thrombocytopenia may be the first manifestation of SLE but when it was present in our patient, there were no systemic manifestations of SLE and both ANA and dsDNA were negative. The differentiating features between thrombocytopenia in a patient with APS and due to ITP are shown in the table. In APS associated with SLE thrombocytopenia is usually mild and seldom requires treatment.1 However, our patient presented with severe thrombocytopenia which had a stormy course. Another differentiating feature is that splenectomy is not the long-term solution for thrombocytopenia in case of APS.2 Our patient had two rare coexisting diseases. The presence of these diseases simply reflect an underlying autoimmune disease. About 30% of patients with ITP may have elevated IgG antiphosholipid antibodies at the time of diagnosis.3 Coexistent APS would increase the risk of thrombosis following splenectomy as was seen in our patient. Such patients should be given prophylactic anticoagulants.4
The term refractory ITP is applied to cases that do not respond to standard doses of steroid and splenectomy and require some other form of therapy to raise their platelet count.5 Therapy for such patients is divided into four levels, depending on the severity of side-effects (box FB1).
The treatment of acute thrombotic attack is not different from thrombosis elsewhere. Low molecular weight heparin is preferred because of a more predictable response and less incidence of thromboctyopenia. After an acute event of thrombosis, high-intensity warfarin has to be given on a long-term basis.2
It has been suggested recently that testing of lupus anticoagulant and antiphospholipid antibodies may be unnecessary for the diagnosis of ITP (box FB2).6 We would conclude by recommending these tests to be done in all patients with ITP at the time of diagnosis and particularly before pregnancy or any surgical procedure.
Final diagnosis
Refractory idiopathic thrombocytopenic purpura with inferior vena cava thrombosis due to antiphospholipid syndrome and systemic lupus erythematosus.