Unexplained fever can be due to thromboembolic disease.1,2,3
CASE HISTORY
A man of 55 was admitted after ten days of fever, lethargy and nausea. Six weeks previously, while on holiday in Turkey, he had fallen and sustained fractures of ribs and pelvis, requiring an emergency splenectomy. His recovery was uneventful and postoperatively he received Pneumovax and Haemophilus influenzae b immunization; also, daily prophylactic oral penicillin was prescribed. His medical history included seronegative rheumatoid arthritis, epilepsy and two deep vein thromboses requiring brief periods of anticoagulation.
On examination he appeared well but his temperature was 38.2°C. He was hypoxic when breathing air, PaO2 9.82kPa, oxygen saturation 94%. Findings on respiratory examination were unremarkable apart from tachypnoea.
Blood results including renal function, glucose, protein strip, tumour markers, thyroid function tests, full blood count (platelets 284 × 109/L) and erythrocyte sedimentation rate were normal. C-reactive protein was 76 mg/L (normal 0-5). His alkaline phosphatase (ALP) was 442 IU/L (normal 30-95) and aspartate transaminase (AST) was 130 IU/L (normal 12-14). Multiple urine, blood and stool specimens, serum viral titres (including hepatitis screen) and atypical bacterial serology were all negative. His chest and pelvic X-rays were normal apart from multiple healing fractures. Transthoracic echocardiography and abdominal ultrasound were also normal. He was treated with intravenous cephalosporin and metronidazole for 10 days.
Two weeks after admission his temperature continued to spike up to 39.5°C. A contrast enhanced CT scan at this time revealed extensive thrombus within the right pulmonary artery extending to the right lower lobe (Figure 1). There was further thrombus within both common iliac veins and within the inferior vena cava. He was started on subcutaneous low-molecular-weight heparin and warfarin. The temperature settled within 24 hours of anticoagulation and subsequently remained normal. C-reactive protein, AST and ALP also declined to the normal ranges. The patient was discharged one month after admission with advice to remain on warfarin lifelong.
Figure 1.
Contrast CT scan showing occlusion of the right main pulmonary artery (arrow)
COMMENT
A low-grade pyrexia, less than 38.3°C, is seen in up to 14% of patients with pulmonary embolism, but a temperature exceeding 38.9°C, as in the patient reported here, is seen in less than 2%.4 In any patient with fever of unknown origin, the possibility of pulmonary embolism must be borne in mind.
The presence of fever cannot distinguish pulmonary infarction from pulmonary haemorrhage nor does it indicate the extent of pulmonary embolism.5 The fever is probably due to an acute inflammatory response from endogenously produced chemotactic factors, possibly through tissue injury and/or complement activation.6 It usually subsides after anticoagulant treatment.7 The rapid resolution seen in our patient is hard to explain in terms of the underlying lesion. The explanation may lie in the anti-inflammatory and anti-pyretic properties of heparin. The exact mechanisms are unknown, but possibilities include blockade of activity or reduced synthesis of tissue necrosis factor alpha7 and inhibition of inflammatory cell adhesion by blockade of P- and L-selectins.8
References
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