COVID-19 complicated by immune thrombocytopaenic purpura and internal jugular vein thrombosis

Background

COVID-19 has caused a public health emergency of international concern, with millions of infections and deaths worldwide. COVID-19 has been shown to have many effects on multiple bodily systems; this includes haematological and thrombotic manifestations.

Immune thrombocytopenia purpura (ITP) is characterised by an immune-mediated reaction resulting in a significant reduction in platelet counts. The normal platelet range for a healthy individual is 150–400×10⁹/L. Mild thrombocytopenia, such as platelet counts of 100–150 × 10⁹/L, has been frequently reported in patients with COVID-19; however, more severe thrombocytopenia has rarely been seen.1 2

Our patient was found to have bilateral deep vein thrombosis (DVTs) in the internal jugular veins likely secondary to COVID-19, ITP or both. A focus of this case is to increase awareness of haematological complications of COVID-19 infection including ITP and thromboembolism. As the rates of COVID-19 continue to increase, complications of COVID-19 are likely to continue to emerge.

Case presentation

A 61-year-old woman with a background of hypertension, fibromyalgia and previous lumbar spinal fusion surgery due to prolapsed disc presented with a sudden onset of severe occipital headache associated with nausea and mild photophobia. She was also noted to have a mild breathlessness and productive cough with white sputum for 3 days. She had a positive nasopharyngeal PCR swab for COVID-19 in the community 5 days prior. On admission, she was afebrile, with normal oxygen saturations. Her full blood count was normal with haemoglobin (Hb) 134 g/L (normal range 117–155 g/L), white cell count 3.4×10⁹/L (normal range 3.8–10.8×10⁹/L), neutrophils 2×10⁹/L (normal range 2–7×10⁹/L), lymphocytes 0.7×10⁹/L (normal range 0.8–3.9×10⁹/L), platelets 153×10⁹/L (normal range 140–400×10⁹/L), C reactive protein <5 mg/L (normal range 0–5 mg/L).

A CT scan of the brain was performed, this showed no abnormality. Her chest X-ray was also unremarkable. Due to previous lumbar spinal fusion surgery, she had an X-ray of the lumbar spine to identify whether a lumbar puncture would be possible to investigate further the cause of her headaches, specifically querying subarachnoid haemorrhage. X-ray lumbar spine showed four-level posterior transpedicular screw fixation from L3 to S1, with anterior lumbar interbody fusion at L3-L4. After discussions with the neurology team, it was agreed for the patient to have an magnetic resonance venogram (MRV) rather than fluoroscopic-guided lumbar puncture to reduce the risk of postprocedure complications.

While the patient was awaiting the MRI scan, she did not have blood tests for 3 days as she was otherwise clinically stable with mild COVID-19 symptoms. The repeated blood test showed an acute marked thrombocytopenia; platelets were 5×10⁹/L. The rest of the blood results were unremarkable.

Investigations

The new acute thrombocytopenia was urgently discussed with the haematology team. A blood film was requested, which showed true thrombocytopenia with no red blood cell fragments or schistocytes present (figure 1).

An urgent repeated CT head was performed to rule out acute intracranial bleeding following a significant drop in platelets, this was reported as normal. Further investigations including rheumatological markers, viral panel (hepatitis B, hepatitis C, HIV, cytomegalovirus, Epstein-Barr virus), haematinics, thyroid function, coagulation screen and helicobacter pylori faecal antigen were all unremarkable.

Due to nonresolving headache, she underwent an MRV, which showed bilateral internal jugular vein occlusion with no evidence of infarct or haemorrhage.

Differential diagnosis

The haematology team agreed that the acute reduction in patient’s platelet counts was most likely due to ITP secondary to COVID-19 infection. It is not clear if COVID-19 or ITP had led to the occurrence of jugular venous thrombosis as both these conditions are associated with increased thromboembolic tendency.

The patient had been started on low-molecular weight heparin (LMWH) for venous thromboembolism (VTE) prophylaxis as per hospital protocol on admission. Therefore, heparin-induced thrombocytopenia (HIT) was also considered as a potential cause, but HIT usually occurs 5–14 days after heparin exposure. Patients with HIT usually have moderate platelet counts (50–80×10⁹/L).3 Using the 4Ts score, which calculates the risk of HIT based on the timing of heparin therapy, complications of thrombosis or thrombocytopenia, and likelihood of other causes, the differential of HIT could be excluded given the patient was low risk, so no HIT assay was conducted.4

Thrombotic thrombocytopenic purpura was also excluded as patient was clinically well with no evidence of microangiopathic haemolytic anaemia, red cell schistocyte or low ADAMDS13 (A Distntegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity.

Drug-induced thrombocytopenia was excluded as patient did not receive any medication such as quinine, sulphonamides, statin, gold, valporic acid or any antibiotics or other drugs known to cause low platelet counts.5 She was on amlodipine 5 mg/day and pregabalin prior to admission.

Secondary ITP can occur alongside autoimmune disorders like lupus, Sjorgen’s syndrome, antiphospholipid syndrome, dermatomyositis and seemingly in rarer cases of rheumatoid arthritis.6 These were excluded as patient’s rheumatologic markers were negative.

Thrombocytopenia can also be associated with malignancy. This is often caused by myelosuppression due to bone marrow infiltration or myelodisplasia, for example, from acute leukaemia. It can also be caused by specific cancers, including small-cell lung cancer, and more rarely, paraneoplastic syndromes such as idiopathic ITP as part of an association with some solid tumours such as breast and lung cancers.7 This was excluded as patient did not have any evidence of malignancy on examination or investigations.

Given the above differential diagnoses were excluded, the haematology team felt that the acute reduction in the patient’s platelet counts was most likely due to ITP. Investigations to screen for common causes of ITP were unremarkable, for this reason, the ITP was thought to be likely secondary to COVID-19 infection.

Treatment

The patient had headaches throughout the admission. They were described as intermittent to severe, frontal headaches. She had ongoing mild COVID-19 symptoms—shortness of breath on exertion and cough but did not have any fevers and no oxygen requirement.

For ITP, she was treated with intravenous immunoglobulin (IVIG) 1 g/Kg for 2 days. IVIG is often used in those with a high risk of bleeding, due to platelet counts responding and rising quickly, usually within 12–48 hours.8 9 It was decided that the patient did not need a platelet transfusion as she had no bleeding and her CT brain was normal. Platelet transfusions have the effect of increasing circulating platelet mass straight away, however, have short-lived effects and hence are only used in cases of life-threatening bleeds.8 After 1 day of IVIG, blood showed an improvement in platelets to 10×10⁹/L.

Neurology advised for a conservative approach for headaches, recommending symptomatic treatment with analgesia.

Outcome and follow-up

The patient was followed up in haematology clinic the day after discharge; platelets had increased to 41×10⁹/L. A further haematology appointment was booked for 5 days later, which showed an improvement in platelets back to the normal range, platelets were 213×10⁹/L (figure 2).

She was commenced on anticoagulation low molecular weight heparin (LMWH); enoxaparin for jugular venous thrombosis. This was switched to a direct oral anticoagulant; apixaban 5 mg two times per day on the follow-up appointment 1 week postdischarge. Anticoagulation is to be continued for at least 6 months, pending further discussions at the thrombosis multidisciplinary team meeting.