An 18-year-old man with a history of type 3 von Willebrand disease (VWD) presented with a spontaneous pyohaemothorax. Type 3 VWD may present with both mucocutaneous and deep-seated bleeds, such as visceral haemorrhages, intracranial bleeds and haemarthrosis. There have been very few cases described in children of spontaneous pyohaemothorax. Management of this patient was challenging due to risks of bleeding following surgical drainage, requiring constant replacement with von Willebrand factor concentrate, while monitoring factor VIII levels to balance the risks of thrombosis.
- haematology (incl blood transfusion)
- paediatrics (drugs and medicines)
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An 18-year-old man with a known history of type 3 von Willebrand disease (VWD), hypertension, obesity (body mass index 39.7) and anxiety, presented to an outside hospital with report of chest pain of 3 days, fever and haemoptysis of 1 day. Previous treatment for VWD included on-demand von Willebrand factor (VWF) concentrate for oral and soft tissue bleeds. On physical examination, the patient was tachypnoeic and diaphoretic with increased work of breathing. A chest CT scan was performed, which showed a very large left pleural fluid collection with mediastinal shift to the right. The Hounsfield units were above that of simple fluid. He was given a dose of vancomycin and levofloxacin for concern of parapneumonic effusion and transferred to our hospital for further care. On arrival, vital signs showed a heart rate of 133 beats/min, temperature 98.4°F, blood pressure 143/80 mm Hg and respiratory rate 20 breaths/min. A bedside chest X-ray revealed complete obscuration of the left hemithorax and mediastinal shift to the right (figure 1).
Investigations revealed a white blood cell count of 33.76 X 109/L (4.5 to 11 109/L), haemoglobin 134 g/L (138 to 17.2 g/L), platelet count 471 X 109/L (155 to 369 X 109/L), C reactive protein 37.5 mg/dL, (0–0.9 mg/dL) and procalcitonin 0.77 ng/mL (<0.15 ng/mL). The rest of the labs were within normal limits. Repeat CT chest confirmed the findings of a very large left pleural fluid collection, likely a large haemothorax, with significant displacement of mediastinal structures (figure 2).
The patient remained tachycardic, but normotensive in the initial few hours. Supportive management was initiated with oxygen via high-flow nasal cannula. He was given a dose of 5000 units (45 RCo/ kg) of plasma-derived, VWF containing, factor VIII concentrate (Humate-P). Primary video-assisted thoracoscopic surgery (VATS) with chest tube placement was performed according to paediatric surgery recommendation. The patient was intubated and started on mechanical ventilation prior to the procedure. Intraoperatively, he received an additional dose of 5000 units of Humate-P. The fluid had a blood purulent appearance, and microscopic examination showed numerous polymorphonuclear neutrophils, confirming the diagnosis of pyohaemothorax.
The patient was weaned off the ventilator to oxygen via nasal cannula over the following days. Throughout his hospital stay, his factor VIII and VWF levels were closely followed, and clotting factor dose and frequency adjusted accordingly. He received a total of 16 doses of Humate-P over 22 days (figure 3). He was treated with broad-spectrum antibiotics and supportive management, including 2 units of packed red blood cells on day 5 and 12 of admission to maintain haemoglobin above 70 g/L. He did not experience any further bleeding or thrombotic events during his treatment, and haemoglobin remained subsequently stable. Blood cultures and pleural fluid cultures did not grow any pathogen. Repeat chest ultrasound following chest tube removal on day 9 of admission showed resolution of the pyohaemothorax. He was transferred to the paediatric floor after a 12-day stay in the paediatric intensive care unit. He received rehabilitation and was discharged home on nighttime oxygen, which was weaned off in 2 weeks.
VWF is a protein that acts as a tether between the platelets and collagen in the subendothelial matrix, thus playing an important role in retaining the platelets at the site of the vascular injury and subsequently activating the platelets at the start of the haemostatic process.1 VWF also acts as a carrier for factor VIII. Low VWF levels lead to an increased factor VIII clearance causing low factor VIII levels despite normal production. VWD may be due to insufficient production of VWF (type 1), dysfunctional VWF (type 2) or complete to near-complete absence of VWF (type 3). Type 1 and 2 VWD present with mucocutaneous bleeds (ecchymoses, purpura, gastrointestinal bleeding, menorrhagia and epistaxis) as well as increased bleeding with trauma, surgeries and dental extractions.2 Type 3 is rare, representing only 1% of all cases of VWD,3 and can present with a combination of the mucocutaneous bleeds characteristic for VWD, and deep-seated bleeds (haematomas, haemarthroses) similar to the ones encountered in moderate-to-severe factor VIII deficiency.
Trauma, pulmonary infarctions, infections, pleural and other anatomical abnormalities, malignancies and coagulopathies may present with haemothorax.4 Coagulopathies like immune thrombocytopenic purpura, haemorrhagic disease of the newborn related to vitamin K deficiency and haemophilia, have all also been reported to be complicated by haemothorax.4 5
A spontaneous pyohaemothorax is a very rare presentation even for type 3 VWD. This unique presentation is important to discuss as the management can be challenging. In general, treatment of VWD is based on normalising levels of VWF and factor VIII in an event of bleeding, as well as before surgical intervention.6 Consensus guidelines published in January 2021 endorse the use of either desmopressin or factor concentrate, with the choice based on VWD subtype and severity. For patients undergoing major surgery, the panel suggests targeting both factor VIII and VWF activity levels of 0.50 IU/mL (50%) for at least 3 days after the procedure (conditional recommendation based on very low certainty in the evidence of effects).7 In type 3 VWD and some patients with type 2 VWD, a VWF containing concentrate is the treatment of choice, as desmopressin is likely to be either ineffective (type 3) or potentially harmful (type 2C).6 7 There are various plasma-derived concentrates of factor VIII and VWF commercially available8 as well as one product that contains only VWF produced through recombinant DNA technology. The dosing is dependent on the concentrate. We used Humate-P, which is an antihaemophilic factor complex concentrate containing VWF and factor VIII in an average ratio of 2.4:1.9 We aimed to maintain the VWF activity and factor VIII activity above of 0.50 IU/mL (50%), meanwhile keeping the factor VIII levels less than the upper limit of normal. When using concentrates that have both factor VIII and VWF, there is a risk that with repeated administration, the factor VIII activity progressively increases, putting the patient at risk for a thrombotic event.10 In order to maintain appropriate levels, we checked the factor VIII activity and VWF antigen daily and titrated our doses accordingly.
We found five published paediatric cases with bleeding disorders (haemophilia A, VWD, Glanzmann thrombasthenia) who developed a haemothorax in the absence of trauma, as described in table 1. In one of the patients described, there was no apparent cause, while infection is insinuated in the rest of the patients as a likely inciting event. The treatment involved thoracocentesis and haemostatic therapy along with antibiotics in the cases associated with suspected infection. A retrospective study published in 2008 emphasised the importance of early recognition and early surgical intervention by VATS or thoracotomy in patients with spontaneous haemopneumothorax.11 It was noted that VATS was the preferable method over thoracotomy as it causes lesser blood loss in a shorter operative time, as well as easy accessibility to the most likely bleeding point near Sibson’s fascia.11 This was applicable to our patient who benefitted from an early VATS procedure to evacuate his lung haematoma. Hence, the surgical intervention performed is also important to note. So, we emphasise the importance of early recognition and prompt surgical intervention by VATS or axillary thoracotomy. Of the five reported paediatric case reports of spontaneous haemothoraces, the patient with type 3 VWD was treated with Humate-P replacement (similar to our patient) and antibiotics, but did not require thoracentesis or any surgical intervention. None of the case reports described previously had a documented spontaneous pyohaemothorax. The 3-year-old patient with haemophilia A did have a concern of an infected pleural effusion and later a large haematoma, which was evacuated surgically; this is the closest comparison to the unique presentation of our patient.
A spontaneous haemothorax may present with a rapid sequence of symptoms, including dyspnoea and chest pain, sometimes progressing to haemodynamic instability and life-threatening hypovolemic shock.12 The risks related to endotracheal intubation and mechanical ventilation, and risks of bleeding post surgery in patients with such haematological diseases, make management difficult and often complicated. Replacement of VWF in a constant manner and monitoring of haemodynamic and respiratory status are key to successfully managing such patients. To the author’s best knowledge, this report reflects the first report of a paediatric patient with a spontaneous pyohaemothorax who required surgical intervention and critical medical management.
Type 3 von Willebrand disease (VWD) is the most severe type of VWD, which can present with both mucocutaneous and deep-seated bleeds like haemarthrosis, gastrointestinal bleeding, intracranial bleeding and occasionally haemothorax.
Spontaneous bleeding into body cavities can be expected in patients with inherited bleeding disorders like haemophilia, VWD, Glanzmann thrombasthenia, factor VIII, X and V deficiencies, and afibrinogenemia.
Management of bleeding in VWD type 3 involves careful replacement of von Willebrand factor and factor VIII using plasma-derived or recombinant concentrates with constant measurement of factor activity levels.
Prompt surgical intervention in case of a haemothorax is important via video-assisted thoracoscopic surgery or thoracotomy for early improvement of outcomes.
Contributors VDN coauthored this article with AS, LB and VCR. There are no prior publications or submissions with any overlapping information. The idea for the article was conceived by all four authors. VDN did the literature search. VDN wrote the initial draft and the coauthors revised the complete draft multiple times. As the first and corresponding author, VDN will be the guarantor and responsible for all further communications. The case was managed by all the authors in different roles.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer-reviewed.